Accelerating_Successes_Against_Cancer_Report by blindlove200

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									National Cancer Institute




                                                        Recommendations from the
                                            NCI-designated Cancer Center Directors


                                AccelerAting
                                    SucceSSeS
                              AgAinSt cAncer


                            U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
                            National Institutes of Health
            2 ContributorS
            4 StAtement of PurPoSe
                 The Cancer Centers Directors’ Working Group
             8 exeCutive SummAry
            14 Prevention
                 Summary
                 Introduction
                 Current Knowledge, Issues and Problems
                 Accomplishments
                 Emerging Therapeutic and Interventional Strategies
                 Identification and Prioritization of Opportunities for Advancement
                 Action Items for NCI-designated Cancer Centers
                 Anticipated Outcomes and Potential Impact
                 References


 Table of
            30 eArly DeteCtion
                 Summary
                 Introduction


ConTenTs
                 Current Knowledge, Barriers, and Opportunities
                 Emerging Technologies
                 Imaging for Early Detection
                 High-Risk Populations for Early Detection Screening
                 Opportunities to Impact Early Detection and to Reduce the Cancer Burden
                 Anticipated Outcomes and Potential Impact
                 References
            40 treAtment
                 Summary
                 Introduction
                 Current Knowledge, Barriers and Opportunities
                 Emerging Therapeutic and Interventional Strategies
                 Identification and Prioritization of Opportunities for Advancement
                 Anticipated Outcomes and Potential Impact
                 References
            48 SurvivorShiP
                 Summary
                 Introduction
                 Current Knowledge, Issues, and Problems
                 Emerging Therapeutic and Interventional Strategies
                 Identification and Prioritization of Opportunities for Advancement
                 Anticipated Outcomes and Potential Impact
                 References
            54 CollAborAtionS
                 Summary
                 Introduction
                 Current Knowledge, Issues, and Problems
                 Emerging Therapeutic and Interventional Strategies
                 Identification and Prioritization of Opportunities for Advancement
                 Key Challenges Requiring Large-Scale Collaborations
                 References
            64 DiSSeminAtion
                 Summary
                 Introduction
                 Current Knowledge, Barriers and Opportunities
                 Emerging Dissemination Strategies
                 Anticipated Outcomes and Potential Impact
                 References
            70 APPenDiCeS
                  70    Appendix A: Selected Chemoprevention and Nutritional Intervention Trials
                  72    Appendix B: IOM Survivorship Report Executive Summary
                  88    Appendix C: PCP Survivorship Report Executive Summary
                  99    Appendix D: Survivorship Activities at Cancer Centers
                 100    Appendix E: Summary of Survivorship Activities at Cancer Centers
                 116    Appendix F: Summary of Shared Resources Survey at Cancer Centers


                                                                          Accelerating Successes Against Cancer 
ConTribuTors
Cancer Center Directors Working Group
Steering Committee members
Chair: John Mendelsohn, MD, Director, MD Anderson Cancer Center
Martin Abeloff, MD, Director, Sidney Kimmel Cancer Center, Johns Hopkins University
David Alberts, MD, Director, Arizona Cancer Center, University of Arizona
William Dalton, MD, PhD, Director, Moffitt Cancer Center, University of South Florida
Judith Gasson, PhD, Director, Jonsson Comprehensive Cancer Center, University of California, Los Angeles
Stanton Gerson, MD, Director, Case Comprehensive Cancer Center, Case Western Reserve University
Leland Hartwell, PhD, Director, Fred Hutchinson Cancer Research Center
Ronald Herberman, MD, Director, University of Pittsburgh Cancer Institute
John Kersey, MD, Director, University of Minnesota Cancer Center


Subcommittee members
Prevention
Chair: David Alberts, MD, Director, Arizona Cancer Center, University of Arizona
Randall Burt, MD, Interim Director, Huntsman Cancer Institute, University of Utah
Grover Bagby, Jr., MD, Director, Oregon Health Sciences University Cancer Institute
Raymond Dubois, MD, PhD, Director, Vanderbilt-Ingram Cancer Center, Vanderbilt University
Deborah Helitzer, PhD, University of New Mexico
Lisa Hess, MS, University of Arizona
H. Kim Lyerly, MD, Director, Duke Comprehensive Cancer Center, Duke University
Frank Meyskens, Jr., MD, Director, Chao Family Comprehensive Cancer Center, University of California, Irvine
Cosette Wheeler, PhD, University of New Mexico
Cheryl Willman, MD, Director, University of New Mexico Cancer Research and Treatment Center

early Detection
Chair: Stanton Gerson, MD, Director, Case Comprehensive Cancer Center, Case Western Reserve University
Louise Acheson, MD, Case Western Reserve University
James Basilion, PhD, Case Western Reserve University
Zaver Bhujwalla, PhD, Johns Hopkins University
Jeff Bulte, PhD, Johns Hopkins University
Thomas Chenevert, PhD, University of Michigan
Greg Cooper, MD, Case Western Reserve University
Kenneth Cowen, MD, PhD, Director, Eppley Cancer Center, University of Nebraska
Jeff Duerk, PhD, Case Western Reserve University
Sam Gambhir, PhD, Stanford University
Robert Gillies, PhD, University of Arizona
William Hait, MD, PhD, Director, Cancer Institute of New Jersey
John Hazle, PhD, MD Anderson Cancer Center
Tom Meade, PhD, Northwestern University
Mark Pagel, PhD, Case Western Reserve University
Marty Pomper, PhD, Johns Hopkins University
Brian Ross, PhD, University of Michigan
Georgia Weisner, MD, Case Western Reserve University


 Accelerating Successes Against Cancer
George Wilding, MD, Comprehensive Cancer Center, University of Wisconsin
Max Wicha, MD, Director, Comprehensive Cancer Center, University of Michigan

treatment
Chair: Martin Abeloff, MD, Director, Sidney Kimmel Cancer Center, Johns Hopkins University
Michael Caligiuri, MD, Director, Comprehensive Cancer Center, Ohio State University
John Glick, MD, Director, Abramson Cancer Center, University of Pennsylvania
John Ruckdeschel, MD, Director, Barbara Ann Karmanos Cancer Institute, Wayne State University

Survivorship
Chair: William Dalton, MD, PhD, Director, Moffitt Cancer Center, University of South Florida
Lucile Adams-Campbell, MD, Howard University Cancer Center
Patricia Ganz, MD, Jonsson Comprehensive Cancer Center, University of California, Los Angeles
Mark Israel, MD, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center
Paul Jacobsen, PhD, Moffitt Cancer Center, University of South Florida
Les Robison, PhD, St. Jude Children’s Research Hospital
Steven Rosen, MD, Director, Robert H. Lurie Comprehensive Cancer Center, Northwestern University
Ellen Stovall, National Coalition of Cancer Survivorship
Stephen Williams, MD, Director, Indiana University Cancer Center
Cheryl Willman, MD, Director, University of New Mexico Cancer Research and Treatment Center
Linda Jacobs PhD, Abramson Cancer Center, University of Pennsylvania

Collaborations
Chair: Leland Hartwell, PhD, Director, Fred Hutchinson Cancer Research Center
David Alberts, MD, Director, Arizona Cancer Center, University of Arizona
Steven Burakoff, MD, Director, New York University Cancer Institute
Walter Eckhart, PhD, Director, Cancer Center, Salk Institute
Peter Emanuel, MD, Acting Director, Comprehensive Cancer Center, University of Alabama at Birmingham
William Hait, MD, PhD, Director, Cancer Institute of New Jersey
Peter Jones, PhD, Director, USC/Norris Comprehensive Cancer Center, University of Southern California
Russell Kaufman, MD, Director, The Wistar Institute Cancer Center
Theodore Krontiris, MD, PhD, Director, City of Hope National Medical Center
Janet Leeds, MBA, Fred Hutchinson Cancer Research Center
Peggy Means, MHA, Fred Hutchinson Cancer Research Center
Myra Tanita, MHA, Fred Hutchinson Cancer Research Center

Dissemination
Chair: Ronald Herberman, MD, Director, University of Pittsburgh Cancer Institute
Paul Bunn, Jr., MD, Director, University of Colorado Cancer Center
Frank Meyskens, Jr., MD, Director, Chao Family Comprehensive Cancer Center,
University of California, Irvine
Carl-Wilhelm Vogel, MD, PhD, Director, Cancer Research Center of Hawaii, University of Hawaii at Manoa
George Weiner, MD, Director, Holden Comprehensive Cancer Center, University of Iowa
Robert Young, MD, Director, Fox Chase Cancer Center



                                                                                    Accelerating Successes Against Cancer 
sTaTemenT of PurPose
                                          n
                                                 ever has there been such opportunity and promise for
                                                 improving outcomes for patients with cancer. The human
                                                 genome project and other recent accomplishments in
                                          molecular biology and technology development have made it
                                          possible to revolutionize the way physicians and researchers can
                                          address the challenge of preventing and curing cancer.

                                          In 1971, with the passage of the National Cancer Act, the Na-
                                          tional Cancer Institute (NCI) initiated creation of centers of ex-
                                          cellence and charged them with gathering together the expertise
                                          to greatly expand research on understanding the causes of cancer
                                          and improving its treatment. Initially the centers of excellence
                                          consisted of three NCI-designated Cancer Centers. Today there
                                          are 61 Centers, spread widely across the United States.

                                          As a result of the government’s increased investment in research
                                          over a period of more than three decades, we now know that
                                          cancer is caused by mutations or abnormal functioning of critical
                                          genes which control the replication and behavior of the cells in
                                          our bodies. This statement could not have been made in 1971.

                                          The National Institutes of Health (NIH) Director Dr. Elias Zer-
                                          houni’s new NIH Roadmap Initiative contains three key concepts:
                                          1) exploring new pathways to discovery focusing on molecular
                                          networks associated with disease, imaging technologies, and nano-
                                          medicine; 2) creating interdisciplinary research teams of the future;

 Accelerating Successes Against Cancer
and 3) re-engineering the clinical      and cancer is a disease whose risk      The total impact of cancer on
research enterprise and incorporat-     increases with aging. We can sub-       health is high. It was recently
ing community-based physicians,         stantially reduce deaths from cancer    reported that for Americans under
in order to place more patients         just by broadening the application      the age of 85, cancer is the lead-
in innovative clinical trials. The      of knowledge we have today. By          ing cause of death. The American
Nation’s Cancer Centers and             expanding our knowledge through         Cancer Society reported that last
academic cancer research programs       further research, even greater gains    year there were 1,399,790 new
are leading the way in all three of     are well within our reach.              cases of cancer and 564,830 deaths.
these areas, and have been doing so                                             Economists at the University of
for decades. By their very
nature, research programs
in NCI-designated Cancer
Centers bring together
basic, clinical, and popula-
tion scientists to focus on
cancer. Since their incep-
tion, the Cancer Centers
have been peer-reviewed
and scored by NCI based
upon the strength of their
intra- and interprogram-
matic interactions. This
model has contributed sig-
nificantly to the successes
that have been achieved
in understanding the
molecular basis of cancer
and in developing targeted thera-       The Cancer Centers Directors            Chicago estimate that a 1% reduc-
pies and new imaging modalities.        working group, described below,         tion in cancer deaths would be
The nationwide program of clini-        was not in a position to pursue an      worth over $400 billion.
cal trials investigating new cancer     independent economic analysis of
treatments on many thousands            the benefits of improving cancer        NCI was created as a governmental
of patients is a model of clinical      care. However it is worth making a      agency to lead cancer research, not
investigation.                          few points from the available litera-   to deliver health care. In contrast,
                                        ture. The cost of caring for patients   most of the Nation’s NCI-designat-
While our knowledge of cancer           with cancer reached $40 billion in      ed Cancer Centers are imbedded
will never be complete, we have         1996. Medicare bears over one-          in academic medical centers which
reached the point where medical         third of these costs. This figure has   have the dual missions of leading
researchers can at last envision        increased during the past decade to     the fundamental study of disease
ways to greatly improve our ability     $72 billion. This does not include      and translating new knowledge to
to reduce death and suffering from      the cost of screening and the value     change the delivery of health care.
cancer. The age-adjusted rate of        of time lost from work during treat-    The NCI’s Strategic Plan published
cancer mortality has been falling for   ment, as well as the cost of prema-     in January 2006 outlines a bold
a decade. Recently, it was reported     ture death with loss of productivity.   vision of strategies to investigate
that in 2003, for the first time, the   As an example, the cost of treating     cancer in the laboratory, in the
absolute number of cancer deaths        an early stage breast cancer patient    clinic, and in the community, and
in the United States was reduced        over her lifetime is over $70,000.      states clearly that dissemination
from the previous year. This is         There were 213,000 new cases of         and application of research dis-
despite the fact that as a whole the    this disease alone in 2006.             coveries are required for success.
U.S. population is living longer                                                The Nation’s Cancer Centers are


                                                                                         Accelerating Successes Against Cancer 
uniquely positioned to both lead          prevention, detection, treatment,        That leaves room for helping the
in cancer research and lead in this       survivorship, collaboration, and         24% of women who currently do
dissemination process.                    dissemination. The subcommittee          not receive the benefits of early
                                          reports were presented and discussed     detection.
                                          at the NCI Cancer Center Directors
the Cancer Centers                        Retreat in May 2006 and the final        For colon cancer, the 50% trend for
Directors’ Working                        report of recommendations was re-        reduced deaths is attributed almost
Group                                     viewed by all of the Cancer Center       entirely to colon endoscopy with
                                          directors.                               polypectomy. Polypectomy reduced
At the November 7, 2005 meeting                                                    the incidence of cancer by 80%
of the NCI Director with the direc-                                                in two large studies. Only about
tors of the NCI-designated Cancer         We have made Progress                    50% of Americans over the age of
Centers, a small working group            Progress has been made during            50 undergo colon examination, so
– chaired by Dr. John Mendelsohn,         the 35 years since passage of the        there is high potential for further
President, University of Texas, MD        National Cancer Act in 1971. Dur-        improvement in death rates.
Anderson Cancer Center – was              ing the 10 years between 1990 and
asked to write a report providing a       2002, the age-adjusted death rate        For male lung cancer, the 50%
blueprint on how the Cancer Cen-          from cancer declined 1% per year.        trend for reduced death is attribut-
ters can contribute to achieving the      This translates into over 315,000        ed primarily to reduced tobacco use.
following goals:                          lives saved or prolonged beyond          There is likely to be a downward
                                          that period of time. In 2004, the        trend in lung cancer death rates
  1. Reduce the burden of cancer          total deaths from cancer, which had      for women, because lung cancer
     through research in the areas of     been leveling off for a number of        incidence rates have begun to fall
     prevention, detection, treat-        years, fell to levels slightly below     for women in recent years, parallel-
     ment, and survivorship, and          the previous year’s figures.             ing the earlier fall for men. These
     create a strategy for success.                                                gains have resulted from an enlight-
                                          The American Cancer Society re-          ened behavior on the part of the
  2. Identify ways in which NCI-          cently published a midpoint analysis     public, supported by educational
     designated Cancer Centers can        of progress towards its goal of reduc-   campaigns, clean indoor air laws,
     enhance collaboration with           ing cancer deaths by 50% over the        cigarette taxes, improved access to
     each other and with other            25 year period between 1990 and          counseling and pharmacologic aids,
     stakeholders in the pursuit of       2015. If trends over the first 12        and increased commitment of time
     our shared mission.                  years continue, the projection is for    and effort by the medical profes-
                                          a 23% reduction in cancer deaths by      sion. Obviously, a great deal more
  3. Suggest initiatives that will        2015. However, for breast cancer,        can be accomplished. It must be
     enable the Cancer Centers to         colon cancer, and lung cancer in         emphasized that nearly one-third
     extend their research beyond         males, the trends predict a 50%          of all cancer deaths in the United
     their local communities and to       reduction.                               States (over 180,000 people last
     provide leadership in the wide                                                year) are directly attributed to
     dissemination of best practices      It is worthwhile considering why         tobacco, with lung cancer leading
     in cancer care and prevention.       these significant levels of reduction    the list.
                                          are being achieved and what more
  4. Create a realistic vision of the     can be expected. For breast cancer,      It is apparent that most of the sub-
     potential for future successes       the improvement is attributed to         stantial reduction in cancer deaths
     and identify the roadblocks          a combination of early detection         over the past 12 years has resulted
     that must be dealt with.             due to mammography and manual            from prevention and increased use
                                          palpation and improved therapy.          of effective diagnostic studies. This
The working group was subdivided          Significantly, only 58% of women         report will present measures to fur-
into six subcommittees concen-            had mammograms in 1970 while             ther enhance prevention and early
trating on the outlined goal areas:       by 2002 the number reached 76%.          detection of cancer, as well as new


 Accelerating Successes Against Cancer
approaches to the treatment of can-    importantly – patient advocacy
cer, and management of survivors.      groups and the public. These stake-
While it is impossible to precisely    holders will need to synchronize
quantify the anticipated impact        their goals and actions. From the
on death rates, it is reasonable to    beginning of planning the National
predict that if research efforts and   Cancer Act, and continuing up
use of evidence-based clinical prac-   to the present, patient advocacy
tices are increased in the areas we    groups have played a critical role
outline, we will reduce the burden     in bringing together the public, the
of cancer far more rapidly and come    government, and the biomedical
closer to achieving the American       research community, and reminding
Cancer Society’s goal for 2015.        us all to focus on the patient.


Conclusion
We conclude that the Nation’s
                                       references
35-year-old cancer plan can be         Murphy K, et al. Diminishing
re-energized to increase the pace      returns? The costs and benefits of
of discovery and dissemination         improving health.
of improvements in cancer care.        Perspect Bio Med 2003; 46(3
This document is presented as a        Suppl): S129-37.
blueprint for accelerating successes
against cancer, both by expanding      NIH Cost of Illness Report to the
knowledge of cancer and by apply-      U.S. Congress, (FY 2000).
ing these discoveries expeditiously
to improving the care of cancer        Warren JL, et al. Costs of treat-
patients. Our report of recommen-      ment for elderly women with
dations builds on and expands the      early-stage breast cancer in fee-for-
NCI Strategic Plan.                    service settings. J Clin Oncol 2002;
                                       20(1):307-316.
NCI-designated Cancer Centers
are in the privileged position of      Byers T, et al. A midpoint assess-
being able to contribute to both       ment of the American Cancer
research and patient care goals, and   Society Challenge Goal to Halve
we make a renewed commitment to        the U.S. Cancer Mortality Rates
do so in partnership with the NCI.     Between the Years 1990 and 2015.
We invite collaborators from the       Cancer 2006; 107(2):396-405.
many sectors of our society with
an interest in reducing the burden     Marks JS, et al. On the Thresh-
of cancer to join in this endeavor     old of a Dream. Cancer 2006;
with renewed commitment of their       107(2):217-220, 2006.
efforts and resources.
                                       Weinberg RA. The Biology of
We wish to emphasize that this         Cancer. Garland Science, Taylor
must be a joint effort, involving      and Francis Group, LLC, 2007.
academia, medical care providers,
professional organizations, gov-       NCI Strategic Plan 2006; http://
ernmental agencies and the U.S.        strategicplan.nci.nih.gov/.
Congress, pharmaceutical and bio-
technology companies, and – most


                                                                               Accelerating Successes Against Cancer 
exeCuTive summary
                                          t
                                               he following is a summary of the major recommendations in
                                               each of the six areas targeted for review by the working group
                                               of the Cancer Center directors.

                                          Prevention
                                          In addressing the challenge of reducing the burden of cancer, pre-
                                          vention is the most desirable goal. Population studies have identi-
                                          fied lifestyle changes that can reduce the risk of cancer, the most
                                          prominent of which is avoidance of tobacco use and exposure.
                                          We also have discovered that molecular and biological changes
                                          in blood and tissue specimens from patients can serve as markers,
                                          identifying individuals who bear higher risk for developing certain
                                          cancers, including those who show the very earliest biological

 Accelerating Successes Against Cancer
changes in the development of                including administration                 medicine” to intraepithelial
cancer. These individuals may                of tamoxifen or raloxifene               neoplasias (IENs) and
benefit from active interventions            to prevent breast cancer in              precancerous conditions, by
in their lifestyle and behavior and,         high-risk postmenopausal                 carrying out clinical trials to
in the future, from treatment with           women and HPV vaccination                discover molecular targets for
agents that can retard or prevent            to prevent cervical cancer in            both early detection of high-
the development of cancer.                   young females.                           risk lesions and targets for
                                         •   Utilize rapidly developing               chemoprevention treatments.
We endorse the recommendations               knowledge of inherited and           •   Increase clinical research in the
of the National Cancer Policy                environmentally induced                  behavioral sciences that will
Board on cancer prevention and               mutations to begin to establish          identify improved methods for
early detection, which are summa-            risk profiles for high-risk              changing personal lifestyles and
rized in this report.                        populations, to set the stage for        promote informed decisions
                                             rational chemoprevention and             about health-related behaviors.
Strategies that Can Immediately Begin        other strategies.                    •   Continue to pursue
to Reduce the Risk of Cancer                                                          chemoprevention clinical
 • Implement known methods and          Cancer Centers can partner with               trials, based on the successes
     investigate improved methods       governmental agencies and health              with anti-estrogen agents in
     for preventing initiation and      care providers to extend these                preventing or postponing breast
     enabling discontinuation of        measures to the entire U.S. popula-           cancer in high-risk groups.
     tobacco use. If successful, this   tion through improved delivery
     measure alone can reduce the       and targeted education. Vaccina-         While Cancer Centers can collabo-
     incidence of cancer by more        tion against certain cancers should      rate in carrying out these large-scale
     than 30%, after an estimated lag   eventually become as standard in         and long duration clinical stud-
     time of about two decades.         medical practice as vaccination          ies, funding will be needed from
 •   Implement other evidence-          against serious viral infections.        governmental agencies or from
     based changes in lifestyle that                                             companies willing to partner in
     will reduce the incidence of       Strategies Involving Either Change       these efforts.
     cancer, including a healthy        in Policies or Further Research and
     diet, avoidance of obesity, and    Requiring a Decade or More Before
                                                                                 early Detection
     increased physical activity.       Clinical Application
 •   Implement scientifically            • Perform research on the               Early detection of cancer can
     established medical strategies,         application of “personalized        enhance the chances of achieving




                                                                                           Accelerating Successes Against Cancer 
cure or prolonging life for indi-           • Cancer Centers should partner              querying histories of patients
viduals diagnosed with cancer.                  with state departments of                and their families in a uniform
In spite of the great interest in               health and medical provider              way that will enable informed
identifying markers in blood or                 systems to disseminate                   communication between
cells that can identify the presence            information on the benefits of           patients and families and their
of cancers at the earliest possible             early detection of cancer and            health care providers, and
time, progress in research has been             on locations where access to             provide data for researchers
slow. This is due to limitations in             these measures are available.            seeking to identify high-risk
available technology and lack of            •   Cancer Centers should partner            populations.
adequate funding to support the                 with each other to develop           •   Standardized and uniformly
large-scale and expensive clinical              collaborative networks and               utilized electronic medical
trials required to first identify and           cross-disciplinary teams that            records would support
then validate these markers.                    can share tissue resources and           initiatives in detection,
                                                advanced technology platforms.           treatment, and survivorship
The effort and expense involved are                                                      and should be a national
highly worthwhile. This is because         Strategies Involving Further Research         priority. Collection, storage,
the chances for cure of most early         and Requiring Up to a Decade or More          and annotation of tissue
stage cancers is typically higher          Before Clinical Application                   specimens from each patient
than 90%, whereas cure rates for            • Cancer Centers should                      in a standardized way would
advanced stage cancers can be                   perform large-scale,                     also support these initiatives.
lower than 5% for most, but not all,            collaborative clinical                   Both initiatives will require
solid tumors. Detection at an early             trials designed to identify              substantial funding, collegiality,
stage can yield tremendous benefits             potential markers, using                 and visionary leadership.
in reducing death rates in cancers              the expanding technologies
of the breast, colon, lung and pros-            of genomics, proteomics,
                                                immunohistochemistry and
                                                                                    treatment
tate, which together account for
nearly two thirds of all cancers.               molecular imaging. These must       There has been tremendous progress
                                                be followed by clinical trials      in research leading to an under-
Strategies that Can Immediately                 validating the capacity of these    standing of the fundamental genetic
Increase Early Detection of Cancer              markers to accurately predict       and molecular causes of cancer and
  • Cancer Centers should                       the presence of cancer. This        the development of new therapies
      partner with governmental                 research will require large-scale   that target these abnormalities.
      agencies and health care                  funding from the NCI or other       This has been accompanied by ad-
      providers to expand the use of            sources.                            vances in surgery, radiation therapy,
      currently validated screening         •   Fundamental research                and systematic therapies which
      methods for early detection,              investigating specific genetic      have already improved outcomes for
      especially in underserved                 and molecular abnormalities         cancer patients.
      populations. These methods                that contribute to the
      include colonoscopy, Pap                  malignant phenotype must            Because it already is uniformly
      tests, mammography, and the               continue full force because         acknowledged that fundamental
      PSA test.                                 this approach will continue         research must continue to be pur-
  •   Cancer Centers should join                to contribute importantly to        sued and funded, this report focuses
      advocacy groups in pursuing               identification of markers that      primarily on the need for collabora-
      payment for validated early               predict risk, prognosis, and        tion, coordination, standardization,
      detection tests by Centers                appropriate therapy.                and infrastructure support in clini-
      for Medicare and Medicaid             •   With guidance and support           cal investigation. This will require
      (CMS), insurance companies                from the NCI, Cancer Centers        participation by all stakeholders,
      and health plans, and for                 should develop and adopt a          including oncology specialists, pro-
      extending access to uninsured             standardized and secure web-        viders, payers, regulatory agencies,
      Americans.                                based tool for collecting and       government sponsors (e.g., NCI),


0 Accelerating Successes Against Cancer
and patients. It also will require            while protecting the interests      frequency with which patients
adequate funding specifically des-            of the inventors.                   change their health care providers,
ignated for these purposes. Cancer                                                there is a serious need for uniform
Centers are in an optimal position       Strategies for Implementation in the     guidelines and electronic summa-
to lead in this effort, but the fund-    Long Term                                ries of medical records to enable
ing for clinical research must come       • Implement the extensive               appropriate follow up for cancer
from outside sources.                         CTWG recommendations,               survivors. In addition, research is
                                              which will lead to more             needed on ways of preventing the
We endorse the findings of NCI’s              efficient investigation of new      late side effects of cancer treat-
Clinical Trials Working Group                 treatments and more timely          ments and for dealing with them
(CTWG) entitled “Restructuring                regulatory approval.                when they occur.
the National Cancer Clinical Trial        •   Investigate new technologies
Enterprise,” which was adopted                and targeted therapies for the      The result of these activities will
by the National Cancer Advisory               treatment of cancer, alone and      be a decrease in deaths from sec-
Board in 2005. The CTWG action                in combination.                     ond cancers due to earlier detec-
items are summarized below.               •   Continue intensive research         tion, and improved duration and
                                              on the genetics and biology         quality of life due to control or
Strategies that Can Be Implemented            of cancer, which will provide       elimination of late sequellae of the
Immediately to Improve Treatment              increased understanding of the      cancer or its therapy.
Research                                      malignant process and identify
 • Activate the recommendations               promising targets for anticancer    Strategies
     of the CTWG for improving                agents.                              • Cancer Centers should
     the NCI’s capacity to lead in        •   Collaborate with the                     collaborate with the NCI
     coordinating and supporting              NCI, FDA, CMS and                        Office of Cancer Survivorship
     innovative clinical research.            pharmaceutical/biotechnology             to establish and populate a data
 •   Place a top priority                     companies in creating a                  warehouse containing clinical
     on supporting clinical                   unified and standardized                 information, research protocols,
     investigators and funding the            web-based clinical trials                educational materials, and
     clinical research infrastructure         information technology system            descriptions of outreach
     needed for Cancer Centers,               for recording, reporting, and            activities for the public and for
     academic medical centers, and            analyzing clinical research data.        medical professionals.
     practicing physicians to carry                                                •   Cancer Centers should
     out innovative and timely
     clinical trials.
                                         Survivorship                                  collaborate with the
                                                                                       American Society of Clinical
 •   Increase collaborations             Today there are over 10 million               Oncology (ASCO) and other
     between Cancer Centers in           Americans who have survived can-              organizations in developing
     designing and performing            cer. A risk of recurrence continues           clinical practice guidelines
     clinical trials, sharing            beyond 5 years for some types of              for long-term follow up of
     specialized core services           cancer. In addition, cancer survi-            cancer survivors and mobilizing
     and new technologies, and           vors have a higher than average               adoption of these guidelines
     exchanging tissue specimens.        risk of a second malignancy. In               by the states and health care
 •   Increase collaboration in           fact, approximately 16% of cancers            providers.
     new drug development                occur in survivors of the disease.        •   Cancer Centers should take
     between Cancer Centers and          Survivors also are subject to long-           leadership in designing
     pharmaceutical/biotechnology        term sequellae caused by either               collaborative clinical trials
     companies. This will be             their cancer or the therapy they              that explore ways of avoiding
     greatly enhanced by agreement       received.                                     late complications of cancer
     on both sides to reach                                                            therapy or evaluate treatments
     compromise with regard to           With the increasing mobility                  which can control them.
     control of intellectual property,   of the U.S. population and the


                                                                                           Accelerating Successes Against Cancer 
Collaborations                             personalize cancer care. Multiple       leading to possible FDA approval is
                                           markers are likely to be required for   typically 10-15 years. Shortening
The Cancer Center directors agree          early detection and for selection of    this timeline will require increased
with the statement in the NCI              therapies for each type of cancer.      collaboration in new drug devel-
Strategic Plan that: “Our success          The economic case has not been          opment between companies and
will depend on our ability to inte-        made adequately for the utility of      academia, collaborative efforts
grate our activities across a seamless     biomarkers for both patient care and    to validate and implement use of
continuum of discovery, develop-           drug development.                       biomarkers and imaging technolo-
ment and delivery.” The academic,                                                  gies as endpoints in clinical trials,
commercial, and governmental               Strategies                              elimination of redundancy in the
sectors each have critical contribu-        • A consortium of companies            numerous reviews required for
tions to make. The effectiveness                should be encouraged to jointly    approval of trials, and the use of
and efficiency of their interfaces              invest in the discovery of new     standardized licensing contracts
need to be addressed with creativity            technologies in proteomics,        that create agreed upon sharing of
and compromise.                                 marker identification, and         intellectual property.
                                                imaging agents as a pre-
Chemoprevention                                 competitive activity, much like    Strategy
Chemoprevention trials involve                  the successful SNP Consortium.      • Facilitate collaboration
large, lengthy, and extremely               •   Research on biomarkers can             between companies and
expensive studies of both high-risk             be expedited by exploring              academic institutions, by
and healthy populations, requir-                many candidate markers at the          developing shared licensing
ing large infrastructures to access             same time in a comprehensive           agreements which can be
and monitor data for many years.                validation trial that provides         used to speed up contract
Collaborations between industry                 long-term follow up of a               negotiations.
and clinical investigators – both               number of surrogate markers
academic and in the community                   and predictors, until mortality    Survivorship
– must be long term, with careful               endpoints are reached.             Research on the factors influencing
prioritization and planning, and            •   Regulatory agencies could          the health of cancer survivors re-
thorough scientific review in order             provide financial and fast-track   quires expensive, long-term studies
to optimize the use of scarce hu-               review incentives for companies    of many patients. As with preven-
man and financial resources.                    to encourage early exploration     tion research, the requirement for
                                                and identification of markers      funding of these extensive studies
Strategy                                        that predict the efficacy of new   and for collaboration between
  • Form a collaborative                        therapies.                         institutions serving cancer patients
      chemoprevention trial                 •   For each of the topics covered     must be acknowledged and dealt
      consortium of Cancer Centers              in this report, research can       with effectively.
      and academic medical centers              be strengthened by bringing
      with centralized infrastructure           together expertise across          Strategies
      and data management, funded               Cancer Centers. Sharing of           • Collaborations led by Cancer
      by the NCI and pharmaceutical             specialized, high-tech core             Centers should develop and
      companies.                                facilities will also enhance the        implement standardized
                                                quality of research.                    databases for collecting and
Biomarkers and Imaging                                                                  analyzing information on
The discovery and validation of            Treatment                                    cancer survivors.
useful biomarkers and imaging tests        Therapeutic clinical trials require       • Research to identify the
are under-explored at companies            a series of contractual partnerships         problems experienced by large
and Cancer Centers because of              between companies and clinical               cohorts of cancer survivors
limited available funding, in spite of     investigators which must last for            and to explore treatments and
the critical role of markers in plans      a number of years. The timeline              interventions that predict or
to speed up drug development and           for preclinical and clinical studies         manage these problems should


 Accelerating Successes Against Cancer
     be carried out collaboratively         disproportionate needs for
     between Cancer Centers, and            cancer prevention and care.
     must be funded adequately from     •   Demonstration of the medical
     external sources.                      and financial benefits of best
                                            cancer control practices
                                            should be accomplished by
Dissemination                               establishing demonstration
Advances in diagnostic tests and            projects in regions served by
treatments for cancer usually are           Cancer Centers, funded by
made available to patients rap-             CMS and led by the Cancer
idly by Cancer Centers, academic            Centers.
medical centers, and major health
care providers. However, reach-
ing all patients with cancer and
their health care providers is a goal
obtainable only through concerted
efforts in education and widespread
adoption of best practices, espe-
cially by physicians for underserved
populations. The Cancer Centers
should insure that opportunities to
participate in clinical trials of new
cancer treatments are made avail-
able to greater numbers of indi-
viduals, including underserved and
diverse populations.

Strategies
 • The Federal government needs
     to designate a lead agency
     within the Department of
     Health and Human Services
     (HHS) to coordinate funding
     and dissemination of cancer
     control efforts to the entire
     U.S. population, by bringing
     together the fragmented efforts
     of NCI, CDC, CMS, and other
     HHS agencies.
 •   Cancer Centers should take the
     lead in disseminating cancer
     care guidelines throughout their
     states, in collaboration with
     state health departments and
     state cancer plans.
 •   Cancer Centers should work
     with state cancer registries to
     convert them into outcomes
     registries, and should use them
     to identify populations with


                                                                             Accelerating Successes Against Cancer 
                                           Summary

                                           i
                                              n addressing the challenge of reducing the burden of cancer,
                                              prevention is the most desirable goal. Population studies have
                                              identified lifestyle changes that can reduce the risk of cancer,
                                           the most prominent of which is avoidance of tobacco use and
                                           exposure. We also have discovered that molecular and biological
                                           changes in blood and tissue specimens from patients can serve as
                                           markers, identifying individuals who bear higher risk for
                                           developing certain cancers, including those who show the very
                                           earliest biological changes in the development of cancer. These
                                           individuals may benefit from active interventions in their lifestyle
                                           and behavior and, in the future, from treatment with agents that
                                           can retard or prevent the development of cancer.


                                           We endorse the recommendations          Cancer Centers can partner with
                                           of the National Cancer Policy           governmental agencies and health
                                           Board on cancer prevention and          care providers to extend these
                                           early detection, which are summa-       measures to the entire U.S. popula-
                                           rized in this report.                   tion through improved delivery and
                                                                                   targeted education.
                                           Strategies that Can Immediately Begin
                                           to Reduce the Risk of Cancer            Strategies Involving Either Change
                                            • Implement known methods and          in Policies or Further Research and
                                                investigate improved methods       Requiring a Decade or More Before

PrevenTion                                      for preventing initiation and      Clinical Application
                                                enabling discontinuation of         • Perform research on the
                                                tobacco use. If successful, this        application of “personalized
                                                measure alone can reduce the            medicine” to intraepithelial
                                                incidence of cancer by more             neoplasias (IENs) and
                                                than 30%, after an estimated lag        precancerous conditions, by
                                                time of about two decades.              carrying out clinical trials to
                                            •   Implement other evidence-               discover molecular targets for
                                                based changes in lifestyle that         both early detection of high-risk
                                                will reduce the incidence of            lesions and chemoprevention
                                                cancer, including a healthy             treatments.
                                                diet, avoidance of obesity, and     •   Increase clinical research in the
                                                increased physical activity.            behavioral sciences that will
                                            •   Implement scientifically                identify improved methods for
                                                established medical strategies,         changing personal lifestyles and
                                                including administration                promote informed decisions
                                                of tamoxifen or raloxifene              about health-related behaviors.
                                                to prevent breast cancer in         •   Implement a strong,
                                                high-risk postmenopausal                molecularly-targeted detection
                                                women and HPV vaccination               and chemoprevention drug
                                                to prevent cervical cancer in           development program.
                                                young females.



 Accelerating Successes Against Cancer
    Continue to pursue promising         the common cancers and the de-          through the basement membrane);
    agents in chemoprevention            velopment of molecularly-targeted       and metastatic disease (Figure 1).
    clinical trials, based on the        biological therapies.                   Precancerous lesions are termed
    successes with anti-estrogen                                                 intraepithelial neoplasias (IENs)
    agents in preventing or              The cancer patient is not well one      and can often be identified through
    postponing breast cancer in          day and the next day diagnosed          increasingly sensitive screening
    high-risk groups.                    with cancer. It is estimated that       technologies, both histologically
                                         in most cases there is an average       and molecularly, using a variety of
While Cancer Centers can collabo-        lag of at least 20 years between the    analytical methods (e.g., cDNA
rate in carrying out these large-scale   development of the first cancer cell    microarrays).
and long duration clinical studies,      and the onset of metastatic disease
funding will be needed from govern-      for a broad range of solid tumors.      The best cancer is that which
mental agencies or from companies        In fact, using sensitive molecular      never occurs, so primary preven-
willing to partner in these efforts.     genetic methods, there is now           tion (e.g., preventing and treating
                                         evidence that potentially neoplas-      tobacco use, reducing sun expo-
                                         tic cell populations can exist at       sure, promoting healthy diets and
introduction                             the time of birth and that only in      exercise) is both the most effective
The goals of cancer prevention are       some cases is there progression to      and least costly approach because
to reduce the incidence, morbid-         full-blown malignancy later in life.    it can reduce the likelihood that
ity, and mortality due to cancer by      Based on the fact that there were       the first initiated tumor cell will
preventing initiation of primary         more than 570,000 cancer deaths         occur. Thus, given the average
tumors (primary prevention), in-         in the United States in 2005, and       20-year cancer lag time, secondary,
traepithelial neoplasias (secondary      given the estimated 20-year lag         and tertiary prevention strategies
prevention), or second cancers or        time, more than 10 million cur-         represent effective and cost-effec-
disease-related complications (ter-      rently “healthy” Americans may          tive opportunities to dramatically
tiary prevention). The incidence         harbor ultimately deadly cancers.       reduce cancer mortality in the
and mortality from cancer has been                                               next decades (Figure 2).
decreasing slowly during the past        It is increasingly apparent that vir-   Unfortunately, a pervasive problem
decade. Unfortunately, our aging         tually all cancers proceed from the     in the United States is poor access
population will reverse this trend       first initiated tumor cell (through     to health care, including prevention
in the next decade, despite recent       somatic mutations); to mild, mod-       measures, because of a lack of
advances in the understanding of         erate, and severe dysplasia; inva-      health insurance. In 2001, an esti-
the genetic and molecular bases of       sive carcinoma (invasion of cells       mated 15% of the U.S. population


                                                                                         Accelerating Successes Against Cancer 
Figure 1. Progression of precancer to cancer in humans is a multi-year process, adapted from O’Shaughnessy et al. (O’Shaughnessy, Kelloff
et al. 2002)



(41.2 million individuals) was unin-                cancer death by far, is predicted to         dietary modification, reducing body
sured during the entire year.                       cause 30% (170,000) of the cancer            weight, increasing physical activity,
                                                    deaths in the United States this year.       or through medical intervention
                                                    It is thought that one of the primary        (e.g., surgery and/or chemopreven-
Current Knowledge,                                  reasons why current knowledge                tion) (Table 1).
issues and Problems                                 and information about cancer and
                                                    its prevention is not applied to the         However, research on developing
The development of effective cancer
                                                    general public is due to an overload         and implementing effective cancer
prevention strategies has the poten-
                                                    of complicated information. The              prevention and control interven-
tial to impact more than 8 million
                                                    dissemination of complicated infor-          tions lags in funding relative to
cancer diagnoses and to prevent
                                                    mation is problematic, but compre-           its potential impact on reducing
more than 5.2 million cancer-related
                                                    hensive information is essential to          the cancer burden in the United
deaths each year worldwide. The
                                                    reduce the burden of cancer.                 States. For example, only one
American Cancer Society (ACS)
                                                                                                 non-nicotine medication is cur-
has estimated that 564,830 cancer
                                                    There are many factors known to              rently approved by the Food and
deaths will occur in the United
                                                    reduce overall cancer incidence,             Drug Administration (FDA) for
States in 2006, and that half of all
                                                    such as minimizing exposure to               smoking cessation, though others
cancer deaths could be prevented.
                                                    carcinogens (e.g., avoiding tobac-           are in the pipeline, and the exist-
Tobacco use alone, which represents
                                                    co), vaccination for some cancers,           ing medications achieve smoking
the greatest preventable cause of
                                                                                                 cessation quit rates of 25% at best.
                                                                                                 Since many health care organi-
                                                                                                 zations do not include smoking
Table 1. Factors associated with cancer risk, adapted from Giovannucci                           cessation medications as a covered
(Giovannucci 1999)                                                                               benefit, the incentive for pharma-
                                                                                                 ceutical companies to prioritize the
   factor           Association to Cancer risk
                                                                                                 development of smoking cessation
   Height           Increases prostate, colon, and breast cancer risk
                                                                                                 medications is not high – thus
   Obesity          Increases colon, breast, kidney, endometrial, and gallbladder cancer risk;   fostering a negative feedback loop
                    may increase ovarian cancer risk                                             that discourages health care organi-
   Physical         Increases colon cancer risk; may increase breast and prostate                zations from covering medications
   inactivity       cancer risk


 Accelerating Successes Against Cancer
Figure 2. Issues in secondary prevention for physicians and the public



because the effectiveness of those              STAR (Study of Tamoxifen and           will likely reduce the risk of attri-
medications is low.                             Raloxifene to reduce the risk of       tion by accruing individuals likely
                                                breast cancer in post-menopausal       to be highly motivated to prevent
Similarly, pharmaceutical com-                  women) and the ongoing SELECT          cancer. However, by reducing the
panies have traditionally been                  (Selenium and Vitamin E to reduce      study population, there is a risk
unwilling to invest in the develop-             the risk of prostate cancer) take      of insufficient statistical power if
ment of chemopreventive agents,                 between 5 and 10 years or more to      the risk is overestimated, and the
because of the required length                  complete, and require thousands of     results of these trials will not be
of time and the size and cost of                participants. The cost to complete     generalizable to the overall popula-
Phase III confirmatory trials.                  such large-scale trials is in the      tion that is potentially at risk.
Furthermore, these companies are                $100- to $200 million range and,
concerned about the uncovering                  of course, a positive outcome may      An alternative solution is the
of unexpected, life-threatening                 not be achieved – e.g., the recently   development of intermediate
toxicities that may be observed                 announced unsuccessful results         biomarker endpoints – whether
with the long-term exposure re-                 of intervention with calcium plus      molecular, biochemical, or image-
quired for many cancer prevention               Vitamin D in the Women’s Health        based – that can serve to reduce the
intervention strategies. This can               Initiative (WHI) to reduce the risk    size, duration, and cost of cancer
have an extremely negative impact               of colorectal cancer.                  prevention trials. One illustra-
on safety profiles of approved drugs                                                   tive example relates to a 2,297
(e.g., celecoxib twice-daily dosing             Obviously, the need to develop         participant trial of oral Vitamin A
increased cardiovascular events in              risk-reducing preventive strate-       standard dose (25,000 IU daily) for
at least two blinded, prospective               gies for large populations who may     up to 5 years (versus placebo) in
trials by 4-5%).                                develop common solid cancers           individuals with moderate to severe
                                                remains a high priority for NCI        actinic keratosis (i.e., a cutaneous
The high “cost” of cancer preven-               and the Cancer Centers. To reduce      IEN associated with a high risk
tion trials and the need to develop             the need for large populations in      for squamous cell cancer of the
reliable and meaningful interme-                chemoprevention studies, there         skin). The primary endpoint for
diate endpoints are significant                 must be a clear identification of      this trial was the risk of developing
barriers that must be overcome.                 high-risk populations for preven-      a squamous cell skin cancer. This
Cancer prevention clinical tri-                 tion efforts. This will reduce the     Phase III chemoprevention trial
als, like the recently completed                size of the study population and       – funded by NCI in the middle


                                                                                                Accelerating Successes Against Cancer 
   Disease site                   00   modalities responsible                       barriers, cancer prevention efforts
   Breast               50%           90%    Screening, Education, Adjunct Therapy        have contributed substantially to
                                                                                          the reduction of morbidity and mor-
   Colon                40%           55%    Screening, Education, Adjunct Therapy
                                                                                          tality due to cancer (Table 2).
   Cervix               60%           90%    Screening, Education, Adjunct Therapy
   Prostate             50%           99%    Screening, Education
                                                                                          Cancer chemoprevention and
   Melanoma             50%           90%    Screening, Education
                                                                                          dietary intervention Phase III trials
   Head/Neck            40%           50%    Education, Early Neoadjuvant Therapy         have been limited by relatively
Table 2. Increase in 5-year cancer survival, 1975-2005                                    small amounts of funding for drug
                                                                                          discovery, preclinical pharmacol-
                                                                                          ogy, and toxicology available in
                                                                                          NCI’s Division of Cancer Preven-
1980s and concluded in the middle                 of Vitamin A. This 1-year trial         tion (DCP). There has also been an
1990s – documented a statistically                required only 130 participants,         almost total lack of interest by the
significant, nearly 30% reduction in              cost approximately one-twentieth        pharmaceutical industry. Neverthe-
the risk of developing a squamous                 as much as the original Phase III       less, there have been an increasing
cell cancer of the skin associated                trial, and successfully established a   number of high-impact interven-
with prolonged Vitamin A dosing                   50,000 IU/day dose of Vitamin A as      tion trials targeting intermediate- to
(HR=0.74; 95% confidence inter-                   both safe and possibly more effec-      high-risk populations for breast,
val, 0.56-0.99; p = 0.04).                        tive than standard dose Vitamin A.      cervix, colorectal, prostate, and skin
                                                  There is an absolute need to identi-    cancers. Listed in Appendix A are
Knowing that standard dose                        fy and validate markers that can be     the primary results of paradigm-
Vitamin A can reduce the risk of                  integrated into chemoprevention         shifting trials funded by the NCI
developing a squamous cell cancer                 research to reduce the cost and du-     and/or the U.S. pharmaceutical
of the skin, there was additional                 ration of these trials while assuring   industry that have been reported
interest to determine if doubling or              that sufficient statistical power to    over the past 10 years. As this table
tripling the Vitamin A dose further               detect change is not compromised.       demonstrates, there is increasing
enhanced its skin cancer preventive               Biomarkers must be necessary steps      evidence that chemoprevention
activity. Thus, a Phase IIb, pla-                 in the pathway of carcinogenesis,       strategies are increasingly effec-
cebo-controlled trial was designed                assays must be accurate, precise and    tive in pre-empting the pathway
to compare the relative activities                reproducible, and biomarkers must       of carcinogenesis in intermediate
of three different doses of Vitamin               be validated.                           to high-risk populations for many
A (i.e., 25,000 IU, 50,000 IU, and                                                        common cancers.
75,000 IU per day). The primary                   Accomplishments
endpoint of the follow-up study                                                           Medications, new screening tech-
was an evaluation of Vitamin A                    As stated earlier, barriers to ac-      nologies, and chemoprevention
effects on sun-damaged skin of the                celerated success in cancer chemo-      agents are critically important tools
lateral forearm, using skin biopsy                prevention include: the relative        to prevent and control cancer,
nuclear chromatin pattern abnor-                  impotency of chemopreventive            but their effectiveness depends on
mality at one year of Vitamin A                   agent drug discovery and early          behavioral and psychosocial fac-
dosing versus baseline. A quantita-               phase drug development programs         tors that are also, by themselves,
tive efficacy endpoint was obtained               in academia, NCI, and in the            important factors in the prevention
through karyometric analysis of                   pharmaceutical industry; the long       of cancer. Patient-provider com-
formalin-fixed, paraffin-embedded,                duration and high cost of Phase III     munications, for example, play a
hematoxylin and eosin (H & E)                     cancer chemopreventive clinical         critical role in determining who will
stained biopsies. The results docu-               trials; and the shrinking NCI bud-      engage in health-enhancing lifestyles
mented that the placebo group’s                   get, coupled with a relatively lower    that reduce cancer risk. They impact
skin damage worsened while there                  priority for cancer prevention, as      the likelihood that a person at risk
was a clear dose-related response                 compared to research funding for        for cancer will seek and engage in
between 25,000 and 50,000 IU/day                  cancer treatments. Despite these        appropriate screening, and they


 Accelerating Successes Against Cancer
also determine whether appropriate               emerging therapeutic                      equivalent to preventing all deaths
pharmacotherapies are used, and                                                            from glioma or ovarian cancer.
used appropriately to effectively                and interventional
blend with critical behavioral and               Strategies                                Each year, approximately 5 million
lifestyle changes. As new genetic                                                          people worldwide die prematurely
and molecular discoveries improve                In the United States, approxi-            due to tobacco exposure and that
our ability to develop personalized              mately 44.5 million adults (21% of        number is expected to exceed 10
treatments, similar advances are                 the U.S. population) continue to          million by 2020 if current tobacco
needed to tailor behavioral and                  smoke, despite current prevention         exposure rates remain unchanged.
psychosocial interventions so that               and cessation efforts. Tobacco use is     In the United States, most smok-
they are individually and cultur-                the leading cause of cancer and the       ers become dependent before the
ally appropriate, work to eliminate              greatest leading cause of prevent-        age of 18, and once dependence
disparities, and assure that personal            able death. Tobacco use causes            occurs, the chances of quitting
responsibility for sustaining and im-            over 440,000 premature deaths             on any one occasion is approxi-
proving health is not outweighed by              – 198,000 of which are cancer             mately 5%. Use of the most
the perception that cancer preven-               deaths from smoking and environ-          effective treatments increases that
tion and control is assured via the              mental tobacco exposure.                  percentage to 15-25%, thereby
medicine cabinet.                                                                          demonstrating that more effective
                                                 According to a 2002 report from           treatment for tobacco dependence
It is important for primary care-                the International Agency for Re-          is needed.
givers, as well as the research                  search on Cancer (IARC), tobacco
community, policy–makers, and                    exposure is a direct causal factor of     A recent NIH State of the Science
government agencies to take a                    at least 13 different cancers, such       conference on tobacco identified
multidisciplinary approach to                    as cancers of the lung, pancreas,         the following priority research
investigating, understanding, and                cervix, liver, stomach, head/neck,        areas to reduce tobacco exposure:
improving the success of cancer                  and leukemia. Nearly 90% of all           (1) developing new pharmacologi-
prevention.                                      lung cancers are directly due to          cal and behavioral treatments;
                                                 tobacco exposure (tobacco use or          (2) community-based interven-
                                                 environmental exposure). As a             tions; (3) assessing cancer risks of
                                                 noted researcher pointed out, if          various smokeless tobacco prod-
                                                 we are able to prevent just 10% of        ucts; (4) implementing policy inter-
                                                 all lung cancer deaths, it would be       ventions that will increase cessation;


Figure 3. Multi-step carcinogenesis pathway, adapted from Alberts, et al. (Alberts 1999)




                                                                                                    Accelerating Successes Against Cancer 
Figure 4. Chemoprevention of intraepithelial neoplasia (IEN)



and (5) studying genetic predisposi-             which is associated with urinary         The vast majority of current treat-
tion to tobacco dependence.                      bladder cancer.                          ment modalities are used to treat
                                                                                          advanced or metastatic cancers.
Many cancers are also now known                  A number of primary prevention           However, now that it is possible to
to be directly attributable to viral             efforts exist or are being developed     identify IENs for many solid tumor
infections. The family of infec-                 such as vaccines against HPV (see        types, lifestyle changes, simple
tious agents most closely linked to              sidebar, “Cervix Cancer Preven-          surgical procedures, and chemo-
cancer are viruses such as: human                tion with HPV Vaccines”) and             preventive agents may be used to
papillomavirus infection (HPV),                  hepatitis B and C, and vaccines          impede the development and pro-
which is a necessary factor in the               against H. pylori to prevent the         gression of potentially dangerous
development of cervical cancer and               development of cervical, liver,          precancerous lesions (Figure 3).
possibly squamous cell carcinomas                and gastric cancers respectively. In
of the oropharynx or anus; hepatitis             some cases, eradication of chronic       Furthermore, multiple lifestyle
B and C virus infection which are                viral or bacterial infections by im-     changes, taken together, could
initiators and promoters for hepato-             munotherapy, antiviral therapy, or       profoundly reduce the risk of the
cellular carcinoma; human T lym-                 antibiotic therapy may be viewed as      first initiated cell progressing to
photropic virus (HTLV-1) which                   a form of secondary prevention. For      mild dysplasia. This would include
has been implicated in the develop-              example, administration of anti-         severely reducing dietary fat intake
ment of T-cell leukemia; human                   EBV specific T-cells in transplant       (e.g., as demonstrated by a 25%
herpes virus type 8 (HHV8) which                 patients known to be high risk for       reduction in the risk of breast
has been implicated in Kaposi’s                  post-transplant lymphoproliferative      cancer recurrence rates in the
sarcoma; Epstein Barr Virus (EBV)                disorders can reduce the circulating     Women’s Interventional Nutrition
which has been implicated in                     EBV viral load, and reduce the rate      Study), increasing the number of
Burkitt’s lymphoma, as well as other             of lymphoproliferative disorders.        servings of fruits and vegetables,
B-cell malignancies and nasopha-                 Research into the biology of these       minimizing alcohol intake, tobacco
ryngeal cancer; and simian virus 40              cancers, strategies to prevent infec-    exposure cessation, and markedly
(SV40) which may be implicated in                tion, and therapies to eliminate         increasing physical activity. These
mesothelioma.                                    chronic infection will all play a role   changes may potentially reduce risk
                                                 in preventing such cancers. Because      for several cancers by up to 60%.
Less commonly, other infectious                  prevention depends on unambigu-
agents may lead to cancer, such as               ously understanding the cause of         Furthermore, the addition of an
bacterial infections of Helicobacter             the disease, basic cancer research       effective chemoprevention agent,
pylori (H. pylori), which may be an              efforts impact cancer prevention         such as tamoxifen for moderately
initiator and promoter for gastric               research in important ways.              or severely dysplastic IENs such
cancer, and helmenth infections                                                           as ductal carcinoma in situ, can
such as Schistosoma haematobium                                                           reduce cancer risk by as much as


0 Accelerating Successes Against Cancer
50%. Figure 4 presents the concept      and early detection interventions.       applied to reduce cancer risk
that an effective chemopreventive       We have adapted these recommen-          among the general population and
agent could prevent IEN growth,         dations to identify and prioritize       among populations at higher risk.
progression, or ultimately, invasion    opportunities to advance cancer            • Obesity and physical activity
through the tissue basement mem-        prevention efforts.                          have recently joined unhealthy
brane (as did Proscar in the 18,000     (1) Congress and state legislatures          diet as leading risk factors for
participant Prostate Cancer Preven-     should enact and provide funding             cancer.
tion). Thus, the concept of cancer      for enforcement of laws to sub-            • Efforts to maintain a healthy
prevention is now entering the          stantially reduce and ultimately             weight that start early in
mainstream of cancer therapeutics.      eliminate the adverse public health          childhood and continue
Of course, any chemopreventive          consequences of tobacco use and              throughout adulthood are likely
agent intervention may be associ-       exposure.                                    to be more successful than
ated with toxicity and the risk to        • Reduction in tobacco use                 efforts to achieve and maintain
benefit ratio for any of these agents        offers the greatest opportunity         weight loss once obesity is
must be taken into consideration             to reduce the incidence,                established.
at both the individual person and            morbidity, and mortality of           • Over time, even a small
larger population levels.                    cancer.                                 decrease in the number of
                                          • Efforts to increase the cost             calories consumed and a small
The National Cancer Policy Board             of tobacco, and to eliminate            increase in physical activity
of the Institute of Medicine (IoM)           environmental tobacco smoke             can help prevent weight gain or
concluded that to save the most              exposure in public places and           facilitate weight loss.
lives from cancer, health care               worksites, and by children in       (3) Sufficient Federal appro-
providers, health plans, insurers,           homes, are effective in reducing    priations should be made to fund
employers, policy-makers, and                cancer risk and in encouraging      NCI-designated Cancer Centers
researchers should be concentrating          a lifestyle that is tobacco free.   to support innovative public and
their resources on helping people to      • Tobacco consumption                  private partnerships to develop,
stop smoking, maintain a healthy             reduction efforts by Cancer         implement, and evaluate com-
weight and diet, exercise regularly,         Centers, the health care            prehensive community-based
keep alcohol consumption at low to           community, policy-makers,           programs in cancer prevention
moderate levels, and to follow rec-          and government agencies             and early detection. Every state
ommendations for breast, prostate,           should apply to U.S. tobacco        should have and implement a com-
skin, cervical, and colorectal cancer        products marketed and sold          prehensive cancer control plan.
screening. Additionally, these ef-           internationally.                        A) Federal Efforts
forts might also help alleviate the       • Although tobacco exposure                   n The Centers for Disease

disproportionate burden of cancer            causes more than 30% of all                  Control and Prevention
borne by members of racial and               cancer deaths, only about 3%                 (CDC), as the Federal
ethnic minority groups.                      of the current NCI budget is                 link to the Nation’s public
                                             directed to tobacco control                  health infrastructure, needs
                                             efforts. There is a tremendous               to build the capacities of
identification and                                                                        states - and, in turn, their
                                             need for behavioral and social
Prioritization of                            research and intervention.                   local partners (Cancer
opportunities for                       (2) A national strategy should be                 Centers, academic medical
                                        developed and coordinated by the                  centers, and health care
Advancement                             U.S. Department of Health and                     systems) - to develop and
IoM’s National Cancer Policy Board      Human Services (HHS) to address                   implement comprehensive
recommended that several steps be       the epidemic of obesity, unhealthy                cancer control plans.
                                        diet, and physical inactivity in                n Support for the CDC’s
taken to increase the rates of adop-
tion, the reach, and the impact of      America. Effective interventions                  National Breast and
evidence-based cancer prevention        need to be identified and broadly                 Cervical Cancer Early
                                                                                          Detection Program


                                                                                          Accelerating Successes Against Cancer 
                                                                                                   (NBCCEDP) should
      Cervix Cancer Prevention                                                                     be increased. The
                                                                                                   NBCCEDP has succeeded
      with HPV Vaccines                                                                            in improving screening
                                                                                                   rates among medically
      The dramatic reduction in the incidence and mortality from cervical cancer in                underserved populations,
      the United States over the past 50 years is a direct result of the widespread                but the program reaches
      and effective screening using cervicovaginal (or Pap) smears. Yet, despite a                 only 15% of eligible
      greater than 70% reduction in death in the U.S., as many as 10,000 women                     women because of
      each year who fail to be screened adequately develop cervical cancer and                     limited financial support.
      nearly 4,000 women still die annually of this disease. Worldwide, deaths from                Under funding of CDC’s
      cervical cancer could reach 1 million per year unless effective screening and                NBCCEDP contributes
      prevention programs are implemented.                                                         to lost opportunities for
                                                                                                   prevention.
      In the past 25 years, tremendous research advances have demonstrated that                  n Because screening for
      virtually all cases of cervical cancer are caused by infection with human papil-             colorectal cancer is
      lomavirus (HPV). A recent series of clinical trials testing HPV vaccines have                a proven strategy for
      yielded dramatic results. As a result, on June 8, 2006, Merck’s quadrivalent
                                                                                                   reducing cancer mortality
      HPV vaccine, Gardasil™, targeting HPV types 6, 11, 16 and 18, was approved
                                                                                                   in people over 50 years
      by the FDA for vaccination of females aged 9 to 26 years of age. In clinical tri-
                                                                                                   of age, a CDC program
      als, Gardasil was 100% effective in preventing HPV 16- or 18-related cervical,
                                                                                                   similar to NBCCEDP
      vulvar, or vaginal intraepithelial neoplasia (IEN) grades 2-3 or adenocarcinoma
                                                                                                   is needed to provide
      in situ (AIS) among women who had not been exposed to HPV. However,
                                                                                                   colorectal cancer
      there was no clear evidence of protection from disease caused by HPV types
      for which subjects were PCR or seropositive at study entry. The efficacy of                  screening to people
      Gardasil was 39% for the protection of HPV 16- or 18-related cervical IENs and               who are uninsured and
      AIS and 69.1% for the prevention of HPV 16- or 18-related vulvar or vaginal                  underinsured.
      IENs grades 2-3 among women with any HPV status at baseline who received                B) State Efforts
                                                                                                 n State efforts in cancer
      at least one vaccine dose. A second HPV vaccine, Cervarix™, manufactured
      by GlaxoSmithKline, is currently being tested in Phase III clinical trials.                  prevention and early
                                                                                                   detection should be
      While the development of HPV vaccines has the potential to eliminate the                     reformed because in many
      majority of cervical cancer cases worldwide, a number of critical questions                  cases current programs are
      remain that provide particular opportunities for research in cancer surveillance,            piecemeal and organized
      prevention, dissemination, communication, HPV persistence and progression                    around categorically-
      – all of which have a tremendous public health impact. Furthermore, there                    funded programs.
      is a need to be engaged in areas of investigation related to co-factors (such        (4) Public and private insurers
      as cigarette smoking) that play a role in viral persistence and progression to      and providers should consider
      cervical cancer.                                                                    evidence-based cancer prevention
                                                                                          and early detection services to
                                                                                          be essential benefits and should
                                                                                          provide reimbursement for them.
                                                                                          These services at a minimum
                                                                                          should include interventions
                                                                                          recommended in the U.S. Public
                                                                                          Health Services’ 2000 clinical
                                                                                          practice guideline on treating
                                                                                          tobacco use and dependence,
                                                                                          screening for breast cancer among
                                                                                          women age 50 and older, screen-
                                                                                          ing for cervical cancer among all


 Accelerating Successes Against Cancer
sexually-active women with an            • The Federal government               provision of cancer prevention and
intact cervix, and screening for             administers or funds programs      early detection services.
colorectal cancer among adults age           that do not always reflect best      • Primary care providers in
50 and older.                                practices in cancer prevention          health care settings are
  • Public and private health                and early detection.                    effective agents of behavioral
    insurers and providers should         • The evidence is clear that               change. When counseled
    include in their benefit                 disease prevention is not               about smoking in clinical
    packages coverage for evidence-          only effective, but highly cost         settings, 5-10% of individuals
    based interventions for cancer           effective. Thus, investments            are able to quit.
    prevention and early detection.          in supporting healthy lifestyles     • Evidence suggests that
  • Nicotine replacement                     and appropriate screening               physicians and other
    therapy and treatment (e.g.,             will have not only improved             practitioners are not providing
    Bupropion SR) and counseling,            the quality and quantity of             effective clinical interventions
    for example, are effective               life, but will save money for           such as counseling and
    in helping individuals quit              the U.S. health care systems.           screening tests as often as
    smoking.                                 Additional research is needed           would be beneficial.
(5) Congress should increase                 to optimize and disseminate        (8) Congress should provide
support for programs that provide            cancer prevention and early        sufficient support to HHS for the
primary care to uninsured and low-           detection approaches to achieve    U.S. Preventive Services Task
income people. These programs                the broadest implementation        Force and the U.S. Task Force on
increase the use of cancer preven-           nationally. Support for            Community Preventive Services
tion and early detection services            programs like the NCI’s            to conduct timely assessments of
among medically underserved                  Cancer Research Network,           the benefits, harms, and costs as-
populations.                                 and collaboration between          sociated with screening tests and
  • The differences in morbidity             organizations like NCI,            other preventive interventions.
    and mortality from cancer                Veterans Administration (VA),      Summaries of recommendations
    among various racial and ethnic          the Agency for Healthcare          should be made widely available to
    groups and among the under-              Research and Quality (AHRQ),       the public, health care providers,
    and uninsured present both a             and CMS to improve and             and state and local public health
    challenge to understand the              expand health care services        officials and policy-makers.
    reasons for and an opportunity           research, will improve cancer        • Evidence-based guidelines
    to reduce the burden of cancer.          prevention and control                  for clinical and community
  • In a Nation of increasing                implementation.                         practice provide maps for
    diversity, interventions to           • The lack of coverage for                 action.
    improve cancer prevention                effective prevention services        • Assessments of prevention
    and early detection must                 in public programs introduces           services (such as those by
    accommodate different                    a significant barrier to those          the U.S. Preventive Services
    languages, cultural values,              most burdened by cancer: the            Task Force) are needed on a
    and beliefs.                             uninsured population and                continual basis to ensure that
  • Public and private initiatives to        members of racial and ethnic            public health recommendations
    reduce disparities in the cancer         minority groups who often               incorporate the latest scientific
    burden (e.g., programs at NCI            depend on government-funded             evidence.
    and the American Cancer                  programs for care.                   • As state efforts to implement
    Society) should be supported.       (7) Programs are needed for health           comprehensive cancer control
 (6) HHS should complete a              care providers to improve their              plans gain momentum,
comprehensive review to assess          education and training, monitor              guidance on the effectiveness
whether evidence-based preven-          their adherence to evidence-based            of public health interventions
tion services are being offered and     guidelines, and enhance their prac-          (such as those identified by the
successfully delivered in Federal       tice environments to support the             U.S. Community Services Task
health programs.                                                                     Force) will be critically needed.


                                                                                         Accelerating Successes Against Cancer 
(9) Public and private organiza-           • The culture of clinical cancer           a recommendation means
tions should take steps to improve             research has been dynamically          reduced funding elsewhere,
the public’s understanding of can-             influenced by advances in              but the evidence is clear
cer prevention and early detection             imaging, molecular validation          that the greatest advances in
with a focus on promoting healthy              studies, the human genome              reducing cancer morbidity
lifestyles and informed decision-              project, and systems biology           and mortality are likely to be
making about health behaviors and              so that it is now possible             achieved by rapidly reducing
cancer screening.                              to discover underlying                 or eliminating preventable
  • Raising public awareness of the            mechanisms for environment-            causes of cancer. More
     benefits of cancer prevention             diet-behaviors-health.                 specifically, we recommend
     and early detection is central to         Companion studies are common           major expanded collaboration
     reducing the cancer burden.               today in the conduct of clinical       between DCP and DCCPS,
  • One barrier to effective                   trials and molecular profiling         particularly via NCI’s
     communication is the                      is also being applied to drug          Rapid Access to Preventive
     contradictory and sometimes               discovery and development.             Intervention Development
     questionable research reported        •   Integration of such studies in         (RAPID) program, to assure
     by the news media.                        the field of cancer prevention         that $50 million is invested per
  • Expanded health                            has not been given the                 year for 10 years with the goal
     communications research,                  prominence it deserves in              of discovering, developing,
     particularly via the Health               NCI’s Division of Cancer               and implementing new
     Communications and                        Prevention (DCP) and                   medications to prevent and/or
     Informatics Branch at                     Division of Cancer Control and         treat tobacco dependence.
     NCI, is needed to improve                 Population Sciences (DCCPS)          • To further strengthen cancer
     understanding of which                    or extramurally in the Cancer          prevention and control
     communications approaches                 Centers and Specialized                research activities within
     – both individual (e.g., patient-         Programs of Research                   the Cancer Centers, we
     provider) and community-                  Excellence (SPOREs).                   recommend that to obtain
     based (e.g., news media) – are        •   NCI should invest in a long-           short-term or long-term
     most effective with specific              term, coordinated national             comprehensive cancer center
     populations to prevent and                program that specifically              designated status by NCI,
     control cancer.                           supports transdisciplinary,            that all comprehensive cancer
 (10) Public and private sponsors              integrated research in cancer          center members must work for
of research should expand their                prevention and control which           the common good, and thus
support of studies that integrate              brings together the biological         establish a major wellness and
cancer control and behavioral                  and behavioral sciences                cancer survivorship site within
research with advanced imaging                 in a way that reflects the             the scope of their clinical
and systems biology technolo-                  critical roles that each play in       trials.
gies. Such integrated strategies               preventing cancer.                 (11) Public and private sponsors
more rapidly advance understand-           •   DCP and DCCPS have been            of research should expand their
ing of some key barriers to the                chronically under funded           support of applied behavioral
development of healthy behaviors               by NCI. This has greatly           research and how best to dissemi-
and other risk-reducing strate-                diminished and slowed progress     nate evidence-based prevention
gies in children and adults, and               in cancer prevention and           interventions. Effective strategies
will foster personalized medicine              control. NCI should increase       are especially needed to encourage
approaches that take into consid-              funding for both divisions by      healthy behaviors among chil-
eration not just unique genetic                at least 100% over the next        dren and their families, medically
characteristics of individuals but             5 years. We recognize that         underserved populations, and the
also the unique behavioral and                 in an environment of flat or       public at large through multicom-
social characteristics of those                decreasing NCI budgets, such       ponent interventions.
individuals.


 Accelerating Successes Against Cancer
• Tobacco use, physical activity,                   to speed efforts to prevent       application of genetic testing
    and diet are among the most                     cancer more effectively. At       when indicated are very poorly
    significant lifestyle behaviors                 present, there is minimal         appreciated or understood
    related to cancer risk. In                      incentive for Cancer              by the public and medical
    addition, alcohol, sun safety,                  Centers to expand their           community.
    and sexual practices are also                   cancer prevention and
    important contributors to                       control portfolio.
                                                                                  Action items for
    cancer risk.                                  n For a number of years,

•   Unfortunately, minimal                          behavioral neuroscientists    nCi-designated
    research resources have been                    have used systems             Cancer Centers
    allocated to understanding the                  biology approaches in
    details of behavioral risk as it                assessing the genetic         (1) Reducing the rate of smok-
    relates to cancer. This includes                basis of behavioral risks     ing toward levels of the recently
    the environmental and societal                  (e.g., studies on alcohol     reported California adult smoking
    aspects of individual behavior                  and drug addiction).          rate of 14% through comprehen-
    and population-wide norms.                      Cancer Centers should         sive efforts to stop tobacco use.
       n It is critical to focus not                be encouraged to              Recent data from the California
         on the basic question of                   integrate such analyses       Department of Health Services
         whether interventions                      collaboratively in their      document that smoking among
         work, but how they work,                   studies on behavioral and     45 to 64 year olds declined from
         for whom, and under                        cancer risk.                  15.3% in 2004 to 13.8 % in 2005.
         which circumstances. This        (12) Governmental health care           This is 25% lower than that rest of
         can be achieved through          policy-makers and professional and      the Nation.
         better research questions        educational organizations should
         and improved measures.           institute programs to educate both      (2) Implement outstanding com-
         Doubling the funding             the public and medical profession-      pliance with the newly FDA-ap-
         to DCCPS (see above)             als that certain persons, families,     proved HPV vaccine for young
         is needed to expand the          groups and even subpopulations are      girls and recommendations for the
         dissemination research           at significantly increased familial     use of raloxifene to reduce the
         PAR into a funded RFA            and inherited risk for cancer and       risk of breast cancer in high-risk,
         mechanism.                       constellations of cancers, and thus     post-menopausal women. There
       n Cancer Centers must              need more aggressive screening and      have been two remarkable cancer
         address primary prevention       surveillance.                           prevention breakthroughs in the
         at the community level             • Familial and inherited              past year. First is the FDA approval
         and must be given greater             predispositions to cancers         of a safe vaccine for HPV types 16
         resources, and this focus             of various types account for       and 18 – which cause most cervical
         must be given greater                 a significant fraction of the      cancers – to be used in adolescent
         attention. Moreover, cancer           overall burden of cancer and       girls. Second was documenta-
         prevention and control                represent a population at          tion that raloxifene was equally
         clinical trial accruals should        significantly higher risk of       as active as tamoxifen in reducing
         not only be considered                certain cancers.                   incidence of breast cancer among
         equal to therapeutic               • Evidence-based studies              high-risk women, but with reduced
         accruals in cancer center             document remarkable decreases      incidences of endometrial cancers,
         core grant renewals, but              of both incidence and mortality    pulmonary emboli, and cataracts
         should be considered                  of cancer in high-risk groups      compared to tamoxifen. The
         for special merit in the              with appropriate surveillance.     Cancer Centers must be heavily
         review process as a means          • The knowledge of the risk           engaged in methods to enforce
         of increasing prevention              groups, the recommended            compliance to these extremely
         and control research at               screening and surveillance         important prevention methods.
         Cancer Centers in order               strategies, and the appropriate


                                                                                          Accelerating Successes Against Cancer 
(3) Strongly support research              accelerated changes in risk behavior     from basic research informs clinical
on the application of “personal-           could halve the number of smok-          and community practice, and that
ized medicine” to IENs for the             ing-related cancers such as lung         clinical and community practices
purpose of identifying high-risk           cancer and reduce the numbers of         inform basic science. Furthermore,
lesions and specific molecular             cases of colorectal cancer by up to      it reflects the need to implement,
targets for both early detection           one-third.”                              whenever possible, community par-
and personalized chemopreven-                                                       ticipatory approaches to discovery
tion. Molecular profiling of IENs          The United States is at a crossroads     so that the public better under-
and determination of susceptibility        in cancer prevention research.           stands and supports science and to
through genetic testing, family his-       Discoveries in basic biological and      foster incorporation of science into
tory, and lifestyle for the purpose        behavioral science, along with           practice whenever feasible. Once
of personalized medicine may have          epidemiology and surveillance, are       programs of support evolve from
an even stronger rationale than            advancing knowledge in a number of       these strategies, our potential to
molecular profiling for early and          areas, from the relationship between     reduce the burden of cancer will be
advanced cancers, because the              cancer and modifiable behavioral risk    very substantially improved.
critical molecular targets are likely      factors all the way to the molecular
better defined and the long-term           pathways that mediate the actions of
impact on cancer outcomes more             those risk factors.
dramatic.
                                                                                    references
                                           At the same time, applied research       Alpha-Tocopherol, Beta Carotene
                                           is illustrating how the already vast     Cancer Prevention Study Group.
Anticipated outcomes                                                                The effect of vitamin E and beta
                                           amount of available evidence can be
and Potential impact                       better used to more rapidly reduce       carotene on the incidence of lung
                                           cancer rates. To effectively reduce      cancer and other cancers in male
IoM’s National Research Coun-
                                           the national cancer burden, there        smokers. NEJM 1994; 330(15):
cil has stated, “The nation needs
                                           needs to be greater emphasis on          1029-35.
new strategies to prevent cancer
and, when cancer occurs, to catch          two key strategies: action-oriented
                                           research and interdisciplinary re-       ACS-American Cancer Society,
it at its earliest stages. Smoking,
                                           search that takes best advantage         Cancer Prevention and Early Detec-
unhealthy diet, obesity, sedentary
                                           of advances in informatics, human        tion Facts and Figures 2006, Atlan-
lifestyles, and failure to get screened
                                           genetics, functional genomics, imag-     ta: American Cancer Society, 2006.
all contribute to the excess burden
of cancer. Failure to implement            ing and systems thinking (biology
                                           and social interaction), and behav-      Alberts, D. S., R.R. Barakat, et al.
proven methods of cancer preven-
                                           ioral sciences.                          Prevention of gynecologic ma-
tion leads to avoidable disease and
                                                                                    lignancies. Gynecologic Cancer:
death. A 19% decline in the rate
                                           The first strategy addresses the prob-   Controversies in Management. D.
at which new cancer cases occur
                                           lem that scientific knowledge about      M. Gershenson, McGuire, W.P.,
and a 29% decline in the rate of
                                           the solutions to health problems and     Gore, M., Quinn, M.A., Thomas, G.
cancer deaths could potentially
                                           their causes do not automatically        Philadelphia, (2004). Elsevier Ltd.
be achieved by 2015 if efforts to
help people change their behaviors         guarantee that appropriate steps are
                                           taken in our clinics and communi-        Alberts DS, Ranger-Moore J,
that put them at risk were stepped
                                           ties to implement the changes re-        Einspahr J, Saboda K, Bozzo P, Liu
up and if behavioral changes were
                                           quired for the conversion of research    Y, Xu XC, Lotan R, Warneke J,
sustained. This would equate to
                                           to practice. The second strategy         Salasch S, Stratton, MS, Levine
the prevention of approximately
                                           addresses the overarching principle      N, Goldman R, Islas M, Duckett
100,000 cancer cases and 60,000
                                           that best practices in cancer preven-    L, Thompson D, Bartels P. Safety
cancer deaths each year by the year
                                           tion will evolve only when etiologi-     and efficacy of dose-intensive oral
2015. The possible reductions in
                                           cal knowledge is linked to cancer        vitamin A in subjects with sun-
cancer incidence are particularly
                                           prevention research projects in an       damaged skin.” Clin Can Res 2004;
striking for certain cancers:
                                           iterative way such that the results      10(6):1875-1880.


 Accelerating Successes Against Cancer
Arber et al. Chemoprevention of        ASCO Annual Meeting Proceed-           Giovannucci E. The epidemiolog-
colorectal adenomas with celecoxib     ings. 23(16S), Part I of II (June 1    ic basis for nutritional influences
in an international randomized,        Supplement):10.                        on the cancer cell. Nutritional
placebo-controlled, double-blind                                              Oncology. Heber D, Blackburn
trial. AACR Annual Meeting,            Colditz GA, et al. Harvard Report      GL, Go VLW. San Diego, Aca-
CP-4 (2006).                           on Cancer Prevention, Volume 5:        demic Press (1999).
                                       Fulfilling the potential for cancer
Arias-Pulido H, Joste N, Wheeler       prevention: policy approaches. Can     Giovannucci E, et al. Height,
CM. Loss of heterozygosity on          Cau Cont 2002; 13(3):199-212.          predictors of C-peptide and cancer
chromosome 6 in HPV-16 positive                                               risk in men. Int J Epidemiol 2004;
cervical carcinomas carrying the       Curry SJ, Byers T, Hewitt M.           33(4):908-10.
DRB1*1501-DQB1*0602 haplo-             Fulfilling the potential for cancer
type. Genes, Chrom and Can 2004;       prevention and early detection.        Go VL, et al. Nutrient-gene inter-
40(4) :277-84.                         Washington DC, National Acad-          action: metabolic genotype-phe-
                                       emies Press, National Cancer           notype relationship. J Nutr 2005;
Baron JA, Beach M, Mandel JS, van      Policy Board, Institute of Medi-       135(12 Suppl): 3016S-20S.
Stolk RU, Haile RW, Sandler RS,        cine (2003).
Rothstein R, Summers RW, Snover                                               Greaves MF, Wiemels J. Origins
DC, Beck GJ, Bond JH, Greenberg        Doll R, Peto R. The causes of          of chromosome translocations in
ER. Calcium supplements for the        cancer: quantitative estimates of      childhood leukaemia. Nat Rev Can
prevention of colorectal adenomas.     avoidable risks of cancer in the       2003; 3(9): 639–649.
Calcium Polyp Prevention Study         United States today. JNCI 1981;
Group. NEJM 1999; 340(2):101-7.        66(6): 1191-308.                       Greenfacts. (2004). Scientific facts
                                                                              on tobacco: active and passive
Bertagnolli MM, Eagle CJ, Hawk         Duffield-Lillico AJ, Dalkin BL, Reid   smoking. Available at: http://www.
ET. Celecoxib reduces sporadic         ME, Turnbull BW, Slate EH, Jacobs      greenfacts.org/tobacco/about-tobacco.
colorectal adenomas: Results from      ET, Marshall JR, Clark LC, Nutri-      htm#1, Accessed July 14, 2006.
the Adenoma Prevention with Ce-        tional Prevention of Cancer Study
lecoxib (APC) trial. AACR Annual       Group. Selenium supplementation,       Harper DM, Franco EL, Wheeler
Meeting, CP-3 (2006).                  baseline plasma selenium status and    C, Ferris DG, Jenkins D, Schuind
                                       incidence of prostate cancer: an       A, Zahaf T, Innis B, Naud P, De
Burton GW, Ingold, KU. Beta-caro-      analysis of the complete treatment     Carvalho NS, Roteli-Martins
tene: an unusual type of lipid anti-   period of the Nutritional Preven-      CM, Teixeira J, Blatter MM, Korn
oxidant. Science 1984; 224(4649):      tion of Cancer Trial. BJU Int 2003;    AP, Quint W, Dubin G; Glaxo-
569-73.                                91(7):608-12.                          SmithKline HPV Vaccine Study
                                                                              Group. Efficacy of a bivalent L1
Bertram JS, Kolonel LN, Meyskens       El-Bayoumy K, Sinha R. Molecular       virus-like particle vaccine in
FL Jr. Rationale and strategies for    chemoprevention by selenium: A         prevention of infection with hu-
chemoprevention of cancer in hu-       genomic approach. Muta Res 2005;       man papillomavirus types 16 and
mans. Can Res 1987; 47:3012-3031.      591(1-2): 224-36.                      18 in young women: a randomised
                                                                              controlled trial. Lancet 2004;
Chlebowski RT, Blackburn GL,           Fisher B, Costantino JP, et al.        364(9447):1757-65.
Elashoff RE, Thomson C, Good-          Tamoxifen for prevention of breast
man MT, Shapiro A, Giuliano AE,        cancer: report of the National Sur-    Harper DM, Franco EL, Wheeler
Karanja, Hoy MK, Nixon DW, The         gical Adjuvant Breast and Bowel        CM, Moscicki AB, Romanowski
WINS Investigators. Dietary fat re-    Project P-1 Study. JNCI 1998;          B, Roteli-Martins CM, Jenkins D,
duction in postmenopausal women        90(18): 1371-88.                       Schuind A, Costa Clemens SA,
with primary breast cancer: Phase                                             Dubin G; HPV Vaccine Study
III Women’s Intervention Nutrition                                            group. Sustained efficacy up to 4.5
Study (WINS). J Clin Onc 2005


                                                                                       Accelerating Successes Against Cancer 
years of a bivalent L1 virus-like par-     National Institutes of Health.          Dawsey SM. Surrogate end points
ticle vaccine against human papil-         State-Of-The-Science Conference         in cancer research: a critique. Can
lomavirus types 16 and 18: follow-         Statement. Tobacco Use: Preven-         Epi Bio Prev 1996; 5(12): 947-953.
up from a randomised control trial.        tion, Cessation, and Control.
Lancet 2006; 367(9518):1247-55.            http://consensus.nih.gov/2006/Tobac-    Schatzkin A, Freedman LS, Schiff-
                                           coStatementDraft061406.pdf, June        man MH, Dawsey SM. The vali-
Holtz, A. Lung cancer: Why doesn’t         12–14, 2006.                            dation of intermediate endpoints
it get the respect its gargantuan toll                                             in cancer research. JNCI 1990;
demands? Onc Times 25(21):10-28.           Omenn GS, Goodman GE, et al.            82(22):1746-1752.
                                           Risk factors for lung cancer and for
Jemal A, Tiwari RC, et al. Cancer          intervention effects in CARET, the      Schiff M,Becker TM, Masuk M,
statistics, 2004. CA Cancer J Clin         Beta-Carotene and Retinol Efficacy      van Asselt-King L,Wheeler CM,
2004; 54(1): 8-29.                         Trial.” JNCI 1996; 88(21): 1550-9.      Altobelli KK, North CQ, Nahmias
                                                                                   AJ. Risk factors for cervical intraep-
Kim H. New nutrition, proteomics,          O’Shaughnessy JA., Kelloff GJ, et       ithelial neoplasia in southwestern
and how both can enhance studies           al. Treatment and prevention of         American Indian women. Am J
in cancer prevention and therapy. J        intraepithelial neoplasia: an im-       Epidemiol 2000; 152(8):716-26.
Nutr 2005; 135(11): 2715-18.               portant target for accelerated new
                                           agent development. Clin Can Res         Shonkoff JP. Still waiting for the
Kim J, et al. Changes in serum             2002; 8(2): 314-46.                     right questions. Am J Prev Med
proteomic patterns by presurgical                                                  2003; 24(suppl 3): 4-5.
alpha-tocopherol and L-seleno-             Parkin DM, Pisani P, et al. Esti-
methionine supplementation in              mates of the worldwide incidence        Sporn M B Approaches to preven-
prostate cancer. Can Epi Bio Prev          of 25 major cancers in 1990. Int J      tion of epithelial cancer during
2005; 14(7): 1697-702.                     Cancer 1999; 80(6): 827-41.             the preneoplastic period. Can Res
                                                                                   1976; 36(7 PT 2): 2699-702.
Koutsky LA, Ault KA, Wheeler               Pisani P, Parkin DM, et al. Esti-
DM, Brown DR, Barr E, Alvarez FB,          mates of the worldwide mortal-          Stoughton RB, Friend SH. How
Chiacchierini LM, Jansen KU, for           ity from 25 cancers in 1990. Int J      molecular profiling could revo-
the Proof of Principle Study Investi-      Cancer 1999; 83(1): 18-29.              lutionize drug discovery. Nat Rev
gators. A controlled trial of a human                                              Drug Discov 2005; 4(4): 345-50.
papillomavirus type 16 vaccine.            Rowell CD, Carpenter M, Lamar-
NEJM 2002; 347(21):1645-1651.              tiniere CA. Chemoprevention of          Thompson IM, Goodman PJ,
                                           breast cancer, proteomic discovery      Tangen CM, Lucia MS, Miller GJ,
Lichtenstein P, Holm NV, et al.            of genistein action in the rat mam-     Ford LG, et al. The influence of
Environmental and heritable factors        mary gland. J Nutr 2005; 135(12         finasteride on the development
in the causation of cancer. NEJM           Suppl): 2953S-9S.                       of prostate cancer. NEJM 2003;
2000; 343(2): 78-85.                                                               349(3):215-24.
                                           Sandler RS, Halabi S, Baron JA,
Moon TE, Levine N, Cartmel B,              Budinger S, Paskett E, Keresztes R,     U.S. Department of Health and
Bangert JL, Rodney S, Dong Q, Peng         Petrelli N, Pipas JM, Karp DD, Lo-      Human Services. (2006). The
YM, Alberts DS. Effect of retinol in       prinzi CL, Steinbach G, Schilsky R.     Health Consequences of Involun-
preventing squamous cell skin cancer       A randomized trial of aspirin to pre-   tary Exposure to Tobacco Smoke:
in moderate-risk subjects: a random-       vent colorectal adenomas in patients    A Report of the Surgeon Gen-
ized, double-blind, controlled trial.      with previous colorectal cancer.        eral—Executive Summary. U.S.
Southwest Skin Cancer Prevention           NEJM 2003; 348(10):883-90.              Department of Health and Human
Study Group. Can Epi Bio Prev 1997;                                                Services, Centers for Disease Con-
6(11):949-956.                             Schatzkin A, Freedman LS, Dorgan        trol and Prevention, Coordinat-
                                           J, McShane LM, Schiffman MH,            ing Center for Health Promotion,
                                                                                   National Center for Chronic


 Accelerating Successes Against Cancer
Disease Prevention and Health
Promotion, Office on Smoking and
Health.

Villa LL, et al. Prophylactic quadri-
valent human papillomavirus (types
6, 11, 16, and 18) L1 virus-like
particle vaccine in young women: a
randomised double-blind placebo-
controlled multicentre phase II
efficacy trial. Lancet Oncol 2005;
6(5):271-8.

Wattenberg LW. Prevention–thera-
py–basic science and the resolution
of the cancer problem. Can Res
1993; 53(24): 5890-6.

Wickerham DL, et al. The study of
tamoxifen and raloxifene (STAR):
Initial findings from the NSABP
P-2 breast cancer prevention study.”
J Clin Onc 2006 ASCO Annual
Meeting Proceedings Part I. Vol
24, No. 18S (June 20 Supplement):
LBA5.

Willett WC. Diet, nutrition and
avoidable cancer. Environ Heal
Persp 1995; 103(Suppl 8):165-70.

World Health Organization (2006).
Why is tobacco a public health
priority? http://www.who.int/to-
bacco/en/.

Xi LF, Koutsky LA, Galloway DA,
Kuypers J, Hughes JP, Wheeler CM,
Holmes KK, Kiviat NB. Genomic
variation of human papillomavirus
type 16 and risk for high grade cer-
vical intraepithelial neoplasia. JNCI
1997; 89(11):796-802.




                                        Accelerating Successes Against Cancer 
                                           Summary

                                           m
                                                    any, but not all cancers are curable through medical and
                                                    surgical intervention after early diagnosis. While methods
                                                    for early detection of cancer, including mammography,
                                           PSA testing, PAP smear, and colonoscopy, have been counted as
                                           important public health approaches to reducing the burden of can-
                                           cer, much remains to be done. Most cancers cannot be detected
                                           early by conventional techniques. Use of screening methodologies
                                           for early detection is far below recommended levels. New meth-
                                           odologies for early detection have not been introduced broadly
                                           into the population, while others have yet to be validated. None-
                                           theless, early detection leading to cure of cancer is likely to be the
                                           most powerful and cost-effective method of reducing the burden
                                           and death rate from cancer in our lifetime.


        early                              The key opportunities for early        in high-risk populations will lead
                                           detection include:                     to improved early detection,
                                            • Improve use of existing             improved cancer cure rates, and
DeTeCTion                                       detection approaches including
                                                mammography, colonoscopy,
                                                                                  decreased rates of suffering from
                                                                                  cancer. The cost-effectiveness
                                                PSA, and PAP smear                of current detection strategies is
                                            •   Promote new technologies          clear, while that of new technolo-
                                                in imaging, proteomics, and       gies will need to be defined.
                                                genomics through biomarker
                                                identification, test population   NCI-designated Cancer Center
                                                validation, and population-wide   Action Plan
                                                screening to define biomarkers     • Cancer Centers should develop
                                                of early disease                       collaborative efforts for
                                            •   Concentrate on high-risk               screening new early detection
                                                populations to evaluate the            technologies
                                                most cost-effective new            •   Cancer Centers should
                                                technologies in early detection        coordinate evaluation of
                                                by identifying and validating          genetic early detection
                                                these technologies in cancer           markers for colorectal, lung
                                                survivors, those with a genetic        and pancreatic cancers,
                                                predisposition, and those with         because preclinical detection
                                                either an environmental or             will increase the potential of
                                                lifestyle exposure or high-risk        curative surgery
                                                family history of cancer           •   Cancer Centers should
                                                                                       promote development
                                           NCI-designated Cancer Centers               of registries of high-risk
                                           have led the discovery of new               populations for colorectal,
                                           markers of cancer, improved image-          breast, ovary, prostate and lung
                                           based detection, and the develop-           cancers who would benefit
                                           ment of genomic and proteomic               from early detection screening.
                                           approaches. Providing resources             Examples include: breast MRI
                                           for this discovery effort and sup-          in carriers of BRCA1 and 2
                                           porting the large-scale validation          genes, and mismatch repair


0 Accelerating Successes Against Cancer
    protein mutation analysis in       We are at an exciting crossroad        cancers, early cervical cancer, and
    families with colon, gastric and   in cancer research. The ability to     many cutaneous malignancies
    endometrial cancers                align outstanding basic discovery      – basal cell, squamous cell, and
                                       of genetic and molecular causes        melanoma – are cured through early
                                       of cancer; imaging, protein and        detection, intervention, and medi-
introduction                           genetic discovery technologies;        cal therapy.
Many, but not all cancers are cur-     and population-based research,
able through medical and surgical      combine to provide a compel-           However, many other cancers need
intervention after early diagnosis.    ling capability to rapidly translate   further investigation into their
While methods for early detection      and disseminate these discoveries      etiology, which would allow early
of cancer, including mammogra-         towards early detection of cancer      screening to have an effective im-
phy, PSA testing, Pap smears, and      in at-risk populations.                pact on overall outcome and suffer-
colonoscopies, have been counted                                              ing. For instance, many early stage
as important public health ap-         The potential impact is enormous.      ovarian cancers are not cured even
proaches to reducing the burden of     Today, early cancers of the skin,      with early surgical intervention.
cancer, much remains to be done.       breast, colon, and bladder can         Likewise, most pancreatic carcino-
Most cancers cannot be detected        be controlled by surgery, chemo-       mas, even when localized, cannot
early by conventional techniques.      therapy, and/or radiation therapy.     be cured by surgical and medical
In addition, usage levels of proven    Early stage disease can be cured by    techniques. Gliomas are almost
screening methodologies for early      rapid intervention. Validating the     never cured, even when diagnosed
detection are far below recom-         most cost effective new methods for    early. Prognoses for leukemias and
mended levels. New methodolo-          cancer detection will have extraor-    lymphomas do not appear to be pri-
gies for early detection have not      dinary impact reducing the burden      marily influenced greatly by stage at
been introduced broadly into the       of cancer in the population.           the time of diagnosis, but rather by
population, while others have                                                 the biology and molecular charac-
yet to be validated. Nonetheless,                                             teristics of molecular abnormalities
early detection leading to the cure
                                       Current Knowledge,                     associated with the diseases.
of cancers is likely to be the most    barriers, and
powerful and cost-effective method     opportunities                          Therefore, efforts at early detection
of reducing the burden and death                                              should be focused on those tumors
rate from cancer in our lifetime.      Stage I and Stage II breast cancer,    in which early detection makes
                                       colorectal cancer, small solitary      a current difference in patient
                                       lung cancers, localized prostate       outcome and survival (see sidebar,

                                                                                       Accelerating Successes Against Cancer 
“Optimizing Current Screening                   undergone sigmoidoscopy or colo-               that have been proposed include
Technologies”). With this in mind,              noscopy. In addition, as currently             high magnification devices and
however, patients with deep tissue              practiced, colonoscopy is associated           chromo-endoscopy with spraying
tumors, such as ovarian cancer and              with a “miss rate” for large polyps of         of the mucosa with stains, which
pancreatic cancer, which are nor-               as high as 12.5% and up to 0.9% of             highlight and thereby facilitate
mally diagnosed later, may still have           patients develop interval cancer fol-          detection of flat or depressed neo-
an improved survival and outcome                lowing a colonoscopy with removal              plastic lesions. Imaging technology
were they to be diagnosed early in              of adenomatous polyps. Thus, im-               is developing “virtual” colonoscopy
the course of the tumor progression,            provements in colonoscopic practice            as a new technology.
even though curative impact is less             and technology are needed, with the
likely to be achieved.                          net result of providing thorough ex-           Pap Testing Pap testing has been
                                                aminations to a greater proportion             widely used for several decades,
Colonoscopy Colonoscopy is con-                 of the population at risk. Although            and currently approximately 86%
sidered by most experts to be the               Medicare has provided coverage for             of women aged 18 and older have
most accurate available procedure               screening colonoscopy since 2001,              been examined within the past 3
for the diagnosis of colonic neopla-            fewer than half of the states have             years. This represents the high-
sia and is the only test that allows            laws that requires this coverage from          est delivery of all cancer screen-
for simultaneous removal of lesions.            private insurers.                              ing services. Despite widespread
However, population-based data                                                                 screening, approximately 10,000
from the Behavioral Risk Factor                 Advances in imaging technology                 American women will be newly
Surveillance System indicate that               are also being applied to enhance              diagnosed with cervical cancer
as recently as 2005, only 53.1% of              detection of colorectal neoplasia.             annually and 3,700 deaths will be
adults aged 50 and older had ever               Variations on standard techniques              attributed to this disease. Inci-




      Optimizing Current Screening Technologies
      Breast MRI screening is more sensitive than mammography and has been shown to have value. For high-risk populations,
      such as Ashkenazi Jewish women who have a 45% to 65% lifetime risk of developing breast cancer, breast MRI screening
      is more cost-effective for BRCA1 carriers than BRCA2 carriers, who have mammographically dense breasts.

      MRI screening is at least 10 times more expensive than standard screening and generates higher diagnostic costs. Adding
      annual MRI screening tests for women aged 25 to 69 years in this high-risk population would cost $88,651 per year of life
      gained for BRCA1 carriers and $188,034 per year of life gained for BRCA2 carriers. As a general rule, breast MRI, as with
      other technologies, becomes more cost-effective as risk of breast cancer increases and is less cost-effective as the risk
      decreases. Genetic screening in this population may increase average survival and may also be cost-effective.

      A second technology for breast cancer is digital mammography. However, fixed costs may be one-and-a-half to four times
      more expensive than film-based systems. While overall the advantage is unclear, digital screening has advantages for
      women under the age of 50 years with radiographically dense breasts. Improved detection using digital mammography has
      reduced cancer mortality in select populations by more than 15%.

      PSA screening of men for prostate cancer has lead to early detection, down-staging of early lesions, a lower rate of radical
      prostatectomies, and a better understanding of the impact of a rising PSA in an asymptomatic male. Nonetheless, PSA
      screening is not uniform and many high-risk populations are not routinely screened. African American males have lower
      screening rates, higher PSA at screening, and a higher incidence of prostate cancer. Research into the proper management
      of the isolated rising PSA, the impact of false negatives using the current PSA cut off of 4 ng/ml, and long-term follow-up of
      individuals identified during screening will help to define the value of population-wide screening of asymptomatic individu-
      als. Refined PSA testing will likely reduce the need for biopsies and improve accuracy.



 Accelerating Successes Against Cancer
dence rates are highest in African       few hours of additional life expec-    was used to quantify mammo-
American and Latino women and            tancy and had costs of more than       graphic findings.
death rates are almost twice as high     $2 million per year of life gained.
in African American women com-           Screening every two years is           PSA Screening PSA screening to
pared to Caucasians.                     slightly more costly and has a cost-   detect prostate cancer has lead to
                                         effectiveness estimate of $257,400     down-staging of early lesions, a
As currently practiced, approxi-         per year of life saved. Of available   lower rate of radical prostatecto-
mately 7% of all Pap tests – or 3.5      options, liquid-based cytology may     mies, and a better understanding
million per year – are abnormal and      be most inexpensive although,          of the impact of a rising PSA in an
require further evaluation. Screen-      when coupled with the HPV test, it     asymptomatic male. Nonetheless,
ing intervals can be increased from      is more accurate.                      many high-risk populations are
every 1 to every 2 years if liquid-                                             not routinely screened. African
based Pap tests are used. HPV test-      Mammography Breast carcinoma           American males have lower
ing identifies high risk individuals     remains the most commonly diag-        screening rates, higher PSA at
since virtually all cases of cervical    nosed cancer and second leading        screening, and a higher incidence
intraepithelial neoplasia (IEN) are      cause of cancer death in women.        of prostate cancer than the general
associated with HPV infection.           Consistent with a greater detec-       population. Research into the
More frequent testing is still recom-    tion of early stage cancer, inci-      proper management of the isolated
mended for members of high risk          dence rates have increased since       rising PSA, the impact of false
groups such as immune suppressed         the 1980’s, but death rates have       negatives using the current PSA
and HIV-positive women and those         decreased over that time inter-        cut off of 4 ng/ml, and long-term
with in utero exposure to DES. It        val. Although African American         follow-up of individuals identified
is recognized that certain subtypes      women have a lower breast cancer       during screening will help to de-
of HPV, specifically types 16 and        incidence than Caucasians, mortal-     fine the value of population-wide
18, are associated with most cases       ity rates are higher which may         screening of asymptomatic indi-
of cervical neoplasia. The recently      relate to a more aggressive genetic    viduals. Refined PSA testing will
approved HPV vaccine will impact         signature of the tumors.               likely reduce the need for biopsies
the rate of cervical cancer but is not                                          and improve accuracy.
effective in women already infected      Population-based rates of mam-
with HPV.                                mography within the previous two
                                         years has increased from 61.5% in
                                                                                emerging technologies
With respect to cervical cancer,         1990 to 75.9% in 2002, but almost
mortality rates have declined by up      one-fourth of women age 40 and         Imaging for Early Detection
to 46% in the United States over         older have not been screened.          Imaging and Cancer Detection
the past four decades. This suc-         Rates of mammography in the            The use of ultrasound, x-ray com-
cess is due to the widespread use of     previous year are especially low       puter tomography, MRI, positron
the Pap smear screening programs.        among uninsured women younger          emission tomography (PET), and
Recently, the FDA approved HPV           than age 65 (33.2%).                   more recently combined imaging
DNA testing with cytology screen-                                               systems, have been the backbone
ing for women more than 30 years         As currently practiced, mammog-        of early detection of cancer. With
of age. Every three year screening       raphy is associated with defined       completion of the sequencing
with liquid-based cytology and           false positive and false negative      of the human genome (and the
screening using HPV DNA testing          rates. For example, in a recent        ongoing cancer genome project),
provided economic benefits greater       large clinical trial of screening      there is little question that the
than those provided by annual tests      mammography, standard film             emerging development of mo-
with costs of $95,300 and $228,700       mammography had an overall             lecular and cellular imaging will
per year of life gained.                 sensitivity of 66%, a specificity      further revolutionize the way we
                                         of 92%, and a positive predictive      treat and manage cancer in the
In comparison, these same tests          value of only 5% when a 5-point        next few decades.
conducted annually only provide a        scoring system (BIRADS score)


                                                                                         Accelerating Successes Against Cancer 
Cellular and Molecular Imaging             of extracellular matrix is believed        biomarker identification/
Molecular imaging techniques must          to be an essential step in both the        qualification, and informatics
be designed to detect a molecular          production of new blood vessels to
signature of cancer, in which the          support tumor growth (angiogen-        Proteomics for Early Detection
combination of multiple molecu-            esis) and the migration of tumor       Proteomics involves the detection
lar biomarkers provide sufficient          cells to distant locations (metasta-   of novel peptides in bodily fluids
accuracies to identify tumor tissues       sis). Recent attention has focused     that provide specific fingerprints
and likely therapeutic responses,          on inhibiting matrix-degrading en-     of various tumors. Advances for
especially at the earliest stages.         zymes in order to halt the progress    early detection currently require
Molecular imaging probes must be           of cancer. The activity of these       improvements in both methodolo-
designed for high throughput, high         enzymes can be detected by high        gies and applications of technology
sensitivity, and specificity to differ-    molecular weight contrast agents or    to noninvasively screen for colon
entiate tumor tissues and normal or        blood flow.                            and ovarian cancer, as well as other
inflammatory tissues.                                                             cancers. At many NCI-designated
                                           Imaging of Tumor-Targeted Peptides     Comprehensive Cancer Centers,
Nanodetectors The most promising           The emerging identification of tu-     active screening programs are
technologies for early cancer detec-       mor-homing peptides for both ther-     underway to discover new peptide
tion will be new developments in           apeutic and imaging purposes offers    markers and improve sensitivity
both in vitro diagnostics and in vivo      exciting opportunities to develop      and specificity of existing mark-
molecular imaging. For example,            novel peptides and small molecules     ers in colon, ovarian, pancreatic,
in the area of in vitro diagnostics,       for early cancer detection. Attach-    prostate, and other cancers. The
the development of new nanosen-            ment of tumor-homing molecules         availability of robust biobanks with
sors utilizing the latest advances in      to nanoparticles and radioactive       consistent collection and annota-
nanotechnology (e.g., magnetonano          labels offers excellent potential      tion is critical to this effort. This
and nanowire) should allow very            for using multimodality imaging        highlights the importance of these
sensitive detection of low levels of       approaches to detect precancer-        resources to the development of
serum proteins. It still remains to        ous and cancerous lesions prior to     novel early detection approaches.
be seen which serum proteins are           existing imaging approaches.           Also, critical to these systems
relevant for early detection, but                                                 biology approaches are the use and
they will likely be discovered over        Novel Development of Imaging           continual improvement of bioin-
the next 5-10 years. Nanosensors,          Technologies                           formatic pathway tools to annotate
coupled to good reagents (e.g.,            Advances in imaging will continue      and organize the targets identified
antibodies and aptamers), should           to be made through investment in       to be up- and down-regulated.
allow for other reliable clinical tools    discovery and validation of cancer
for early detection. In vivo molecu-       specific imaging. Promising areas      Validation Research of Proteomic Bio-
lar imaging with optical and other         include the following:                 markers The goal of these research
technologies could then also be              • “Smart” MR probes                  efforts is to define the capacity of
used to localize disease.                    • New optimized reporter genes       proteomics approaches to identify
                                               (PET, BLI, SPECT, MRI)             novel biomarkers that will provide
Imaging Early Cancers                        • Agents targeted to the cell        better and cost-effective risk assess-
Biomarkers of Disease Altered                  surface                            ments in screening both high-risk
metabolism detected by PET and               • Optimizing agents for              patients and the general patient
altered blood flow detected by                 intracellular targets              population as well as guide thera-
DC-MRI represent two promising               • Incorporating imaging into         peutic decision-making for patients
approaches to imaging early can-               therapy trials for the purpose     undergoing treatment. All of these
cers. An emerging approach and                 of identifying response and        promising leads need to be vali-
intensive area of study is directed            predictive biomarkers              dated in retrospective and prospec-
towards the role of tissue remodel-          • Hardware development (i.e.,        tive cohort trials. The availability
ing in the growth and metastasis of            PET/MR, SPECT/MR systems),         of screening and validation sets of
tumors. The enzymatic breakdown                integration of imaging agents,     blood samples will be needed, with


 Accelerating Successes Against Cancer
attention to proper collection and       Investigators at the Institute for      hampered the approval of research
storage of material, selection of        Advanced Studies and the Cancer         protocols and the enrollment of
patients, and broad distribution of      Institute of New Jersey identified a    patients into these cohorts.
cohorts across populations. Current      common variant in the promoter
barriers exist in the availability of    region of the murine double min-        Validation Process for New
these samples, and the lack of col-      ute gene (mdm2) that blunts the         Technologies
lected samples in populations not        normal physiological response to        Any new technology in the area
yet diagnosed with cancer.               cellular damage. In collaboration       of early detection needs to provide
                                         with investigators at MD Anderson       accurate, cost-effective screening
Genomics in Early Detection              Cancer Center, they found that          for cancer and to be capable of dis-
Single nucleotide polymorphisms          individuals with inherited p53          semination to a broad population.
(SNPs) are variations in DNA             mutations (Li Fraumeni Syndrome)        Mammography and colonoscopy
sequences that occur within the          – who also harbor the mdm2 SNP          have emerged as effective methods
3 billion base pairs of the human        – were prone to the onset of mul-       for screening of large populations
genome. Although 99% of human            tiple cancers at younger ages when      despite their need for advanced
gene sequences are the same, it is the   compared with those with wild-          technology, imaging, and infor-
subtle variations that contribute to     type mdm2 alleles. This likely          matics. With these as examples,
individuality, predispose to cancer,     represents one of many SNPs that        there is a high-cost barrier for
and impact response to treatments.       might be strong predictors of pre-      a new technology, which could
By identifying those who are predis-     disposition to particular malignan-     become a commonplace cancer-
posed, interventions can be carried      cies and who would be identified as     screening device.
out to prevent or delay the onset of     at high risk and in need of intense
cancer, thereby ultimately reducing      cancer screening.                       A major barrier remains in the
the national cancer burden.                                                      area of population validation for
                                         Opportunities for Advancement in        sensitivity and specificity of cross
Current Knowledge, Issues, and           Genomics for Early Detection The        populations and particularly for
Problems in Cancer Genomics The          significance of the SNPs will           high-risk populations (see below).
NIH Human Genome Project and             ultimately depend on their impact       Methods for such validation are not
the SNP Consortium – formed by           on individuals. This will require       commonly employed in academic
collaborating pharmaceutical com-        the formation of research teams         laboratories and require complex
panies – are mapping the SNPs in         that will include statistical geneti-   cross-disciplinary teams including
the human genome. It is estimated        cists, epidemiologists, molecular       medical technology experts, physi-
that there are 3 million SNPs and        biologists, pathologists, informatics   cians, epidemiologists, statisticians,
that these make up 90% of human          experts, pharmacologists, and clini-    human geneticists, and clinical
genomic variation. The ultimate          cians. No better place exists than      laboratory pathology, radiology,
location of these SNPs will serve        the NCI-designated Cancer Centers       and public health experts. Among
as useful sequence landmarks and         to bring these groups together.         available technologies, we would
begin to help define susceptibility to                                           anticipate that validation of a
disease and response to treatment.       Thus, it will be critical for NCI to    novel early detection screen would
Researchers have found SNPs in 40        provide incentives for the forma-       take 2 years at the level of Phase II
candidate genes that appeared to         tion of these collaborative teams,      validation, 3-4 years for Phase III
predispose Japanese men to habitual      through award mechanisms and            validation, and 5-7 years to validate
smoking and drinking. Other inves-       review panels that are familiar with    across populations.
tigators found SNPs that alter the       the complexities of this research.
metabolism of carcinogenic com-          Potential problems exist when-          New Screening Methods
ponents of tobacco smoke, thereby        ever genetic information is being       The NCI-designated Cancer
helping to define smokers at high        requested from patients. Therefore,     Centers will continue to be a nidus
risk for cancer who would be prime       it will be incumbent upon Federal,      for discovery of new technolo-
targets for intensive screening and      state, and local policy-makers to       gies. Efforts are ongoing among
prevention.                              clarify current regulations that have   the Centers to establish the value


                                                                                          Accelerating Successes Against Cancer 
of a number of different approaches        at risk for endometrial and ovarian     40 with such histories should have
towards early detection using lead         carcinoma.                              mammograms. In other instances,
discoveries in genomics, imaging                                                   the optimal target populations still
technology, colonoscopy, ultra-            Underserved Populations While           need to be defined.
sound, and advances in minimally-          the overall incidence of cancer in
invasive technologies – such as            underserved populations is only
CCD color bronchoscopy, MRI of             slightly higher than the general
the breast, and proteomics. New            population, cancers are often de-
scientific discoveries in cancer           tected much later in the course of        Genetic risk easy
etiology and cancer detection will         the disease leading to a much worse
lead to new approaches for early           prognosis, higher rates of metastatic
                                                                                     Assessment tool
detection. These areas include:            disease, increased pain and suf-          (GreAt)
                                           fering, increased need of medical
  • Novel colon cancer blood tests         treatment, higher costs of treat-         The Genetic Risk Easy Assessment
      based on novel gene expression       ment, and higher death rates from         Tool (GREAT) has been developed
  •   Proteomics screening for             cancer. Thus, underserved popula-         at Case Comprehensive Cancer
      ovarian, prostate, lung, and         tions are targets for early detection     Center to facilitate systematic
      head and neck cancers                with the potential for consider-          collection, interpretation, and
  •   DNA methylation analysis of          able financial and socioeconomic          communication about the family
      peripheral blood circulating         benefits. Underserved populations         history of cancer. The web-based
      tumor cells for colon, pancreas,     include minorities, the poor, urban       GREAT tool (https://family.case.
      and perhaps gliomas                  inner city populations, the medi-         edu) allows people to record a
                                                                                     detailed family history via a
  •   Glycomics and metabolomics           cally uninsured, rural populations,
                                                                                     secure Internet connection at a
      as blood screens for a number        and older individuals.
                                                                                     time and place convenient for
      of cancers
                                                                                     them, using a reliable, computer-
                                           Ethnic Groups With Increased Risk
                                                                                     ized questionnaire that has been
                                           for Specific tumors These include
high-risk Populations                      African American males who are at
                                                                                     validated by comparison with
for early Detection                        increased risk of prostate cancer and
                                                                                     genetic counselors. The program
                                                                                     then automatically constructs
Screening                                  American Indians who are at in-           and displays a digital family tree
                                           creased risk for gallbladder cancers.     (pedigree), and automates risk
Cancer Survivors Patients who have
                                                                                     analysis for breast, ovarian, and
survived a diagnosis of cancer, and        Behavioral, Environmental, and Work       colorectal cancer. In 2007, the
now are in clinical remission, have        Place Risk Groups These include           GREAT system could be made
a risk of recurrence and are the           obese patients, smokers, those ex-        available to multiple NCI Cancer
single group at the highest risk for       posed to secondary smoke, and en-         Centers for interest, validation,
developing another primary cancer.         vironmental exposures to pesticides,      utility, and for development of
While this population is often             benzene, and organic molecules.           identifiable families that would
followed either by their medical                                                     then be approached to participate
oncologist or internist, broad-based       Family Cancer History Family his-         in early detection clinical trials.
screening of this population for all       tory has also been identified as a
cancer types is often suboptimal.          demonstrable risk, however, only a
National standards for long-term           few genes accounting for this have
screening of these individuals are         been identified. One of the most
not established. For instance, pa-         important aspects of early detection
tients with lymphoma and chronic           is to identify the target population.
lymphocytic leukemia (CLL) are at          Some early detection studies should
increased risk for skin tumors, while      be performed on all individuals
patients with hereditary nonpolypo-        in an age-dependent fashion. For
sis colorectal cancer (HNPCC) are          instance, all women over the age of


 Accelerating Successes Against Cancer
opportunities to impact                NCI-designated Cancer Centers Action   detection, intervention, cure, and
                                       Plan                                   prolong survival of affected indi-
early Detection and                    Cancer Centers should:                 viduals while providing a strong
to reduce the Cancer                    1. Develop collaborative efforts      support to underserved populations.
                                           evaluating new early detection
burden                                     technologies                       Skin Cancer Skin cancer screening
Resource Allocations                    2. Coordinate evaluation of           efforts can be improved by increas-
 1. Improve use of current early           genetic early detection markers    ing primary care physician detection
    detection screening especially         for cancers because preclini-      capabilities for visual inspections
    for underserved populations            cal detection will increase the    and increasing referrals to derma-
 2. Increase research funding for:         potential of curative treatment    tologists for questionable lesions.
      • Imaging technologies for        3. Promote development of reg-        For cancers like melanoma, this will
         early detection                   istries of high-risk populations   dramatically decrease progression to
      • Genomics for SNPs and              for colorectal, breast, ovary,     local, regional, and metastatic dis-
         other genomic screening           prostate, and lung cancers         ease in the vast majority of patients.
         efforts                           that would benefit from early
      • Development of proteomics          detection screening. Examples      Prostate Cancer Improved prostate
         for screening tests               would include breast MRIs          cancer detection methods would
      • Use of family history to           in carriers of BRCA 1 and 2        allow early intervention against
         define at risk populations        genes, and mismatch repair         high-grade prostate cancer lesions
      • Large-scale, population-           protein mutation analysis in       and reduce the overall morbidity
         based screening initiatives       families with colon, gastric       and mortality from this disease.
         to validate new technology        and endometrial cancers
 3. Coordinate regional and state-                                            Cervical Cancer The underserved
    wide initiatives for population    Anticipated outcomes                   populations continue to have a
    dissemination of early detec-                                             reduced rate of cervical Pap smears
    tion efforts and technology        and Potential impact                   performed, leading to the diagnosis
 4. Develop collaborations with        Colon Cancer Current nationwide        of advanced cervical cancer and
    state departments of public        screening rates for colon cancer       death. Even with the availability
    health, insurance carriers,        by colonoscopy is approximately        of the new HPV vaccine, it is likely
    medical systems                    27% and approximately 40% for          that the underserved populations
 5. Increase the proportion of the     the use of occult blood testing        will be the last to receive this vac-
    population covered for existing    in patients over age 50. Increas-      cine and will receive it at a late
    and standard early detection       ing screening to over 80% of the       date, increasing their overall risk of
    screening including colonos-       population would improve early         cervical cancer and making it quite
    copy, mammogram, PSA, and          detection of colon cancer and          likely that this disease will reseed to
    Pap test                           improve survival rates.                the boundaries of the underserved
 6. Coordinate and support ef-                                                population. Aggressive ongoing
    forts to identify high-risk        Breast Cancer Current methods for      efforts to both vaccinate with the
    populations based on the above     detecting breast cancer by mam-        new HPV vaccine and to screen un-
    criteria                           mography are proven to increase        derserved patients with the cervical
 7. Facilitate and expand efforts to   early detection, decrease late-stage   Pap smear will dramatically decrease
    identify families with cancer      diagnosis, increase cure rates, and    the impact of this disease.
    histories and support develop-     prolong survival. However, mam-
    ment of cancer family his-         mography in underserved popula-        references
    tory registries, allowing such     tions is performed in only 47% of
    high-risk groups to have more      women. Increasing annual mam-          http://apps.nccd.cdc.gov/brfss/
    intensive screening                mography utilization in women
                                       over the age of 40 in underserved      http://www.preventcancer.org/colorec-
                                       populations would improve early        tal/upload/NCCRA_reportcard.pdf


                                                                                        Accelerating Successes Against Cancer 
Berry DA, Cronin KA, Plevritis             screening: a summary of the               results of 4,945 paired examina-
SK, et al. Effect of screening and         evidence for the U.S. Preventive          tions. Radiol 2001; 218(3):873-80.
adjuvant therapy on mortality              Services Task Force. Ann Intern Med
from breast cancer. NEJM 2005;             2002; 137(5 Pt. 1):347-60.                Lindfors KK, McGahan MC,
353(17):1784-92.                                                                     Rosenquist CJ, Hurlock GS.
                                           Innocenti F, Undevia SD, Iyer L,          Computer-aided detection of breast
Bond GL, Hu W, Bond EE, Robins             Chen PX, Das S, Kocherginsky              cancer: a cost-effectiveness study.
H, Lutzker SG, Arva NC, Bargon-            M, Karrison T, Janisch L, Ramirez         Radiol 2006; 239(3):710-7.
etti J, Bartel F, Taubert H, Wuerl P,      J, Rudin CM, Vokes EE, Ratain
Onel K, Yip L, Hwang SJ, Strong            MJ. Genetic variants in the UDP-          Liu Y, Yoshimura K, Hanaoka T,
LC, Lozano G, Levine AJ. A single          glucuronosyltransferase 1A1 gene          Ohnami S, Ohnami S, Kohno T,
nucleotide polymorphism in the             predict the risk of severe neutropenia    Yoshida T, Sakamoto H, Sobue T,
MDM2 promoter attenuates the               of irinotecan. J Clin Oncol 2004;         Tsugane S. Association of habitual
p53 tumor suppressor pathway and           22(8):1382-1388.                          smoking and drinking with single
accelerates tumor formation in hu-                                                   nucleotide polymorphism (SNP)
mans. Cell 2004; 119(5):591-602.           Itzkowitz SH, Present DH, Crohn’s         in 40 candidate genes: data from
                                           and Colitis Foundation of Amer-           random population-based Japa-
Boyd NF, Dite GS, Stone J, et al.          ica Colon Cancer in IBD Study             nese samples. J Hum Genet 2005;
Heritability of mammographic den-          Group. Consensus conference:              50(2):62-68.
sity, a risk for breast cancer. NEJM       colorectal cancer screening and
2002; 347(12):886-94.                      surveillance in inflammatory bowel        Mandelblatt JS, Schechter CB,
                                           disease. Inflamm Bowel Dis 2005;          Yabroff KR, et al. Benefits and costs
Ciatto S, Brancato B, Baglioni R,          11(3):314-21.                             of interventions to improve breast
Turci M. A methodology to evalu-                                                     cancer outcomes in African Ameri-
ate differential costs of full field       Jemal A, Murray T, Ward E, et al.         can women. J Clin Oncol 2004;
digital as compared to conventional        Cancer statistics, 2005. CA Cancer        22(13):2554-66.
screen film mammography in a               J Clin 2005; 55(1):10-30.
clinical setting. Eur J Radiol 2006;                                                 Mysliwiec PA, Brown ML,
57(1):69-75.                               Kauhava L, Immonen-Raiha P,               Klabunde CN, Ransohoff DF.
                                           Parvinen I, et al. Population-based       Are physicians doing too much
Dershaw DD. Film or digital mam-           mammography screening results             colonoscopy? A national survey
mographic screening? NEJM 2005;            in substantial savings in treatment       of colorectal surveillance after pol-
353(17):1846-7.                            costs for fatal breast cancer. Breast     ypectomy. Ann Intern Med 2004;
                                           Cancer Res Treat 2006; 95(1)1-8.          141(9):264-71.
Gail MH, Brinton LA, Byar DP, et
al. Projecting individualized prob-        Koroutsky LA, Ault KA, Wheeler            Noller KL. ACOG technical assess-
abilities of developing breast cancer      CM, et al. A controlled trial of a        ment in obstetrics and gynecology:
for white females who are being            human papillomavirus type 16 vac-         cervical cytology screening, 2002.
examined annually. JNCI 1989;              cine. NEJM 2002; 347(21):1645-51.
81(24):1879-86.                                                                      Pisano ED, Gatsonis C, Hendrick
                                           Ladabaum U, Phillips KA. Colorec-         E, et al. Diagnostic performance of
Grann VR, Panageas KS, Whang               tal cancer screening: differential        digital versus film mammography
W, Antman KH, Neugut AI. Ben-              costs for younger versus older            for breast cancer screening. NEJM
efits and costs of screening Ash-          Americans. Am J Prev Med 2006;            2005; 353(17):1773-83.
kenazi Jewish women for BRCA1              30(5):378-84.
and BRCA2. J Clin Oncol 1999;                                                        Plevritis SK, Kurian AW, Sigal BM,
17(2):494-500.                             Lewin JM, Hendrick RE, D’Orsi CJ,         et al. Cost-effectiveness of screening
                                           et al. Comparison of full-field digital   BRCA1/2 mutation carriers with
Humphrey LL, Helfand M, Chan               mammography with screen-film              breast magnetic resonance imaging.
BK, Woolf SH. Breast cancer                mammography for cancer detection:         JAMA 2006; 295(20):2374-84.


 Accelerating Successes Against Cancer
Poplack SP, Carney PA, Weiss JE,
Titus-Ernstoff L, Goodrich ME,
Tosteson AN. Screening mam-
mography: costs and use of screen-
ing-related services. Radiol 2005;
234(1):79-85.

Rex DK, Johnson DA, Lieber-
man DA, Burt RW, Sonnenberg
A. Colorectal cancer prevention
2000: screening recommendations
of the American College of Gastro-
enterology. Am J Gastroent 2000;
95(4):868-77.

Robertson DJ, Greenberg ER,
Beach M, et al. Colorectal cancer
in patients under close colono-
scopic surveillance. Gastroent 2005;
129(1):34-41.

Smith RA, Cokkinides V, Eyre HJ.
American Cancer Society guide-
lines for the early detection of can-
cer, 2006. CA Cancer J Clin 2006;
56(1):11-25.

Stout NK, Rosenberg MA, Tren-
tham-Dietz A, Smith MA, Robin-
son SM, Fryback DG. Retrospective
cost-effectiveness analysis of screen-
ing mammography. JNCI 2006;
98(11):774-82.

Winawer S, Fletcher R, Rex D, et
al. Colorectal cancer screening and
surveillance: clinical guidelines and
rationale – update based on new
evidence. Gastroent 2003; 124(2):
544-560.

Zhang X, Caggana M, Cutler TL,
Ding X. Development of a real-time
polymerase chain reaction-based
method for the measurement of
relative allelic expression and
identification of CYP2A13 alleles
with decreased expression in human
lung. J Pharmacol Exp Ther 2004;
311(1):373-81.


                                         Accelerating Successes Against Cancer 
                                           Summary

                                           r
                                                  ecent national data indicate that the multimodality treat-
                                                  ment of cancer is making a significant contribution to the
                                                  decline in the overall cancer mortality rate. This is particu-
                                           larly gratifying in that these statistics do not even reflect some of
                                           the exciting recent advances due to the application of molecu-
                                           larly-targeted therapies. These encouraging statistics reflect the
                                           success of multidisciplinary and multimodality therapies which
                                           increasingly include a wide spectrum of combinations of surgery,
                                           radiotherapy, chemotherapy, hormonal therapy, and newer tar-
                                           geted therapy – both small and large molecules.


TreaTmenT
                                           There is a substantial basis for
                                                                                   introduction
                                           optimism for accelerating advances
                                           in the treatment of responsive as       Recent cancer statistics indicate
                                           well as refractory tumors if cancer     continued improvement in sur-
                                           researchers can more efficiently        vival. Between 1991 and 2001, the
                                           and effectively move discoveries in     drop in cancer mortality rate was
                                           cancer biology to clinical trials and   10%, translating into as many as
                                           to ultimate application in the com-     321,000 lives saved. Furthermore,
                                           munity at large. The major thrust       for the first time in over 70 years,
                                           of this commentary on cancer            the absolute number of cancer
                                           treatment is to emphasize that an       deaths dropped in 2003. Certainly,
                                           extraordinary level of collaboration    screening, early detection, and a
                                           – as well as alignment of incentives    wide range of prevention activities
                                           – will be required by all stake-        account for a significant amount of
                                           holders in the cancer therapeutic       this improvement, but it is becom-
                                           enterprise if we are to significantly   ing increasingly clear that cancer
                                           accelerate the rate of progress.        treatment, particularly combined
                                                                                   with early diagnosis, is having a
                                           This section on cancer treatment        major impact on cancer mortality.
                                           presents a broad outline of such a
                                           blueprint and highlights an impor-      The goals of cancer treatment
                                           tant new NCI initiative developed       are to decrease the mortality and
                                           by the Institute’s Clinical Trials      morbidity from cancer by prevent-
                                           Working Group (CTWG) which              ing the emergence of clinical
                                           aims at restructuring the national      metastasis at the time of diagnosis
                                           cancer clinical trials enterprise.      with primary and adjuvant therapy;
                                           This type of national plan for can-     and to eradicate or significantly
                                           cer treatment research – coupled        reduce metastatic disease which
                                           with continued robust support for       has become clinically significant.
                                           fundamental science – has the           At the time of the launching of
                                           potential of revolutionizing can-       the National Cancer Program in
                                           cer treatment during the next few       1971, there had been consider-
                                           decades.                                able improvement and refinement


0 Accelerating Successes Against Cancer
in surgical and radiation therapy       technologies and model systems,        of progress, we must understand
techniques resulting in improved        leading to a large number of           as much as possible about the in-
removal and eradication of the          new approaches to cancer treat-        terventions that have lead to this
primary tumor with decreased            ment. The advent of combination        improvement in survival. There
morbidity. However, the effective-      chemotherapy, multidisciplinary        are now data available from the
ness of systemic therapy was largely    therapy particularly in the set-       Cancer Intervention and Surveil-
limited to a relatively small subset    ting of earlier diagnosis of cancer,   lance Modeling Network (CIS-
of cancers including childhood          newer approaches to endocrine          NET) – a consortium of NCI-
cancers, choriocarcinoma, Hodgkin       therapy, and the remarkable gains      sponsored investigators – whose
and non-Hodgkin lymphoma and            in cellular and molecular biology      purpose is to measure the effect
certain leukemias. There was little     coupled with the introduction of       of cancer control interventions
to offer patients with the common       molecularly-targeted therapy have      on the incidence of and risk of
solid tumors in either the adjuvant     transformed the entire treatment       death from cancer in the general
or advanced settings and the explo-     approach to cancer. This was           population. CISNET data indi-
sion in our understanding of the        made possible by the adoption          cate that screening and treatment
molecular basis of cancer was just in   of formal clinical trials of new       have contributed to the observed
its infancy.                            therapies which are carried out        decline in the rate of death from
                                        in Cancer Centers and academic         breast cancer, and that the decline
In the ensuing three decades, there     institutions, and to some degree       can be explained by a combina-
has been a tremendous increase in       by practicing oncologists.             tion of screening and therapy and
our understanding of the genetic                                               not by either one alone. When
and molecular pathogenesis of           In order to build on these accom-      reviewing the improving survival
cancer, accompanied by new              plishments and accelerate the rate     statistics in breast cancer and


                                                                                       Accelerating Successes Against Cancer 
other malignancies, it should be           an engineering problem. It is also a         be more actively explored to
noted that the impressive benefits         scientific problem.                          make progress in this area.
now being demonstrated with                                                          2. There is not a clear recogni-
targeted therapy (e.g., Herceptin          Our scientific challenge is to               tion that our supply of clinical
in the adjuvant therapy of breast          maximize the number of studies that          and translational investigators
cancer) have yet to be represented         identify targets and their inhibitors        is dangerously low. The “per-
in the survival statistics.                and to get them to clinical trial as         fect storm” of medical schools
                                           expeditiously as possible. Our en-           relying on faculty practice
The opportunities and challenges           gineering task is to find better ways        plans, the Medicare/Medicaid
that now face therapeutic research-        to move the knowledge we already             cuts, the impact of medical
ers include:                               have to the broader and diverse              school costs on career choices,
  • Building on the recent                 community at every level including           and the excessive regulation
     advances in the therapy of            early detection, prevention, and             of clinical research are mak-
     responsive neoplasms                  therapy. The Cancer Centers have             ing the process of identifying,
  • Beginning to make progress in          been steadily growing over the past          training, and retaining investi-
     the cancers refractory to current     40 years in their ability to do cut-         gators extremely difficult.
     therapeutic approaches                ting edge science and translate its       3. Past Federal and state efforts
  • Continuing and enhancing               discoveries into clinical trials. Their      to grow or shrink specific areas
     fundamental research in order         success is a testimony to the wisdom         of the physician work force
     to accelerate translational           of creating the NCI Centers’ Pro-            are now leading us to an era
     research in both responsive and       gram and enhancing the extent of             of critical shortages in several
     nonresponsive cancers                 extramural funding for research.             cancer-related specialties.
  • Significantly improving delivery                                                 4. The grant process at the Federal
     of advances in therapeutics to        The Cancer Centers have not, how-            and state level is focused on
     the community at large and            ever, been as successful in the role         individual outcomes without
     in particular to underserved,         of enhancing care delivery in their          recognizing the critical need for
     minority populations                  respective regions. In part, this is         broader, more flexible funding
                                           because that role has not been ade-          that is critical for the institu-
                                           quately funded by the NCI or other           tions that serve as the backbone
Current Knowledge,                         sources. Perhaps an even greater             for the collaborative activities
barriers and                               impediment to this critical phase of         of these investigators.
opportunities                              translational research is the lack of     5. Mentoring and tenure and pro-
                                           a coherent, effective national health        motion policies at universities
Our current understanding of               system that is designed to provide           are often focused on individual
cancer therapy is in a rapid state of      quality care to all the citizens. Even       accomplishments without ap-
transition. Traditionally, we have         if these barriers are removed, there         propriate recognition of the
employed modalities with minimal           are still fundamental engineering            collaboration required for clini-
or no specificity for a particular         challenges in the process of trans-          cal/translational research.
cancer (e.g., chemotherapy, radia-         lational research and its movement        6. There are limited funds for
tion, surgery) and often with the          into the broader public arena.               pursuit of truly innovative,
inability to avoid damaging normal                                                      risky research. This is also true
cells. With the recent stunning            These challenges include:                    for strategies to move knowl-
advances in molecular genetics, epi-        1. The ability of Cancer Centers            edge out to the community
genetics, and cell biology, the major          and industry to more effectively         where it can ultimately impact
task before us over the next decade            interact. Removal of bureau-             survival curves.
is to sort out the molecular targets           cratic hurdles, standardization       7. The competition for intel-
and the drugs that impact them and             of clinical research and report-         lectual property has reached a
study their role in the therapy of             ing methodologies, and align-            level which inhibits or greatly
patients with cancer. This ‘transla-           ment of incentives between               slows advancements that
tional’ aspect of cancer is not solely         industry and academia should             require collaborations to move


 Accelerating Successes Against Cancer
    novel ideas and agents into         and targets for both therapeutic and   individualized therapy based on the
    clinical trials.                    prevention studies.                    specific molecular abnormalities of
                                                                               a patient’s tumor.
                                        Molecularly individualized therapy
emerging therapeutic                    with its resultant diminished mar-
and interventional                                                             identification and
                                        ket size has the potential to dampen
Strategies                              enthusiasm from the industry’s         Prioritization of
A thorough understanding of mo-
                                        perspective. Current intellectual      opportunities for
                                        property concerns also inhibit the
lecular carcinogenesis (genetic and     use of new agents from differ-         Advancement
epigenetic) has led to the capac-       ent pharmaceutical/biotechnol-         In the 2006 NCI strategic plan, the
ity to identify targets which are       ogy companies in designing novel       NCI leadership highlights general
most suitable for preventive and        combinatorial regimens. A new          principles on which to base the
therapeutic interventions. These        comprehensive therapeutic devel-       overall strategy. These include:
target identification studies need      opment plan that aligns incentives       • Discover, develop, and
to be undertaken on a large scale       between academia, industry, and            validate cancer biomarkers for
cooperative basis and appropriate       government is required to overcome         cancer prognosis, metastasis,
biomarkers identified in order to       these obstacles.                           treatment response, and cancer
evaluate the effectiveness of such
                                                                                   progression. The discovery and
interventions in a timely fashion.      Taking advantage of these op-              application of these markers
                                        portunities and surmounting these          are now possible through
Rapidly evolving technologies to        obstacles are critical if we are to        recent advances in biomedical
sequence the human genome have          achieve multimodality therapy              technology such as genomics,
allowed for the discovery of an         which is designed and targeted for         proteomics, nanotechnology,
abundance of genetic mutations          appropriate cohorts of patients.           molecular imaging; all coupled
in cancer. Structural analysis of       Currently, the therapeutic options         with bioinformatics.
such mutations should result in the     for cancer therapy include:              • Accelerate identification of
discovery and development of drugs        • Surgery                                potential targets for cancer
that are specific for the defined le-     • Radiation therapy                      treatments by integrating
sion and nontoxic for the patient.        • Chemotherapy                           preclinical and clinical
The challenge lies in the heteroge-       • Endocrine therapy                      research.
neity of such mutations under the         • Molecularly-targeted therapy:        • Develop individualized
umbrella of specific cancers. Thus,          small molecules that regulate         therapies tailored to the
proving the efficacy of molecu-              tumor growth, survival, and           specific characteristics of a
larly-targeted cancer therapies will         angiogenesis                          patient’s cancer to cure or
depend on comparable advances in          • Immunotherapy                          prolong survival with little or
molecular diagnostics to ensure that           n Monoclonal antibodies
                                                                                   no adverse effects.
these therapies are tested in cohorts          n Cancer vaccines
                                                                                 • Develop more effective
of cancer patients that have the               n Cytokines
                                                                                   symptom management and
relevant mutation. For successful         • Gene therapy                           palliative strategies to better
development of therapeutic strate-
                                                                                   reduce the toxicities of cancer
gies, acquisition of tissue through     Increasingly, patients receive sev-        therapy to insure the highest
minimally-invasive procedures           eral of these treatment approaches         quality of life.
needs to be combined with out-          in combinatorial regimens. Individ-
standing tissue procurement infra-      ualizing this combination therapy is   In order to achieve these ambitious
structure and molecular diagnostics.    now a feasible way of improving the    translational research goals, Dr.
Technological advancements in           antitumor response while avoiding      Andrew von Eschenbach, former
molecular, cellular, and tissue imag-   adverse effects. New methodolo-        director of the National Cancer
ing may provide opportunities for       gies and paradigms must be pur-        Institute, established in January
noninvasive discovery of markers        sued for designing and evaluating      2004 the Clinical Trials Working


                                                                                       Accelerating Successes Against Cancer 
Group (CTWG) which advised the                • Expand awareness of the                     data comparisons, reduce
National Cancer Advisory Board                    NCI-FDA expedited approval                duplication, and facilitate
(NCAB) on whether and in what                     process to speed trial initiation.        data submission for regulatory
ways the NCI-supported national               •   Work with CMS to identify                 approval.
clinical trials enterprise should be              clinical studies that address         •   Investigate integration of
restructured. The CTWG was a                      both NCI and CMS objectives,              Phase II trials into the overall
broadly constituted panel of experts              and for which CMS may be                  prioritization process to further
from academic research institutions,              able to reimburse some routine            coordinate the national clinical
community oncology practices,                     and investigational costs.                trials system.
pharmaceutical and biotechnology
industries, cancer patient advocacy          Prioritization/Scientific Quality         Standardization Initiatives
groups, NCI, the Food and Drug               Initiatives                                • Create, in partnership with
Administration, and the Center for            • Create an Investigational                   the extramural cancer research
Medicare and Medicaid Services.                   Drug Steering Committee to                community, a national cancer
                                                  work with NCI to enhance                  clinical trials information
The full report titled “Restructuring             the design and prioritization of          technology infrastructure
the National Cancer Clinical Trials               early phase drug development              fully interoperable with NCI’s
Enterprise” was issued in June 2005               trials.                                   Cancer Bioinformatics Grid
and is available online at http://inte-       •   Create a network of Scientific            (caBIG) to improve cost
gratedtrials.nci.nih.gov/ict/CTWG_                Steering Committees, which                effectiveness and comparability
report_June2005.pdf. The summary                  leverage current Intergroup,              of results across trials and sites.
vision of the CTWG is to “enhance                 Cooperative Group, Specialized        •   In consultation with
the best of all the components of                 Programs of Research                      industry and FDA, develop
the NCI-supported clinical trials                 Excellence (SPOREs), and                  standard Case Report Forms
system, to develop a cooperative                  Cancer Center structures, to              incorporating Common
enterprise built on a strong scientific           work with NCI in the design               Data Elements to improve
infrastructure and a broadly engaged              and prioritization of Phase III           information sharing among
coalition of crucial stakeholders.”               trials to better allocate scarce          cancer researchers and optimize
                                                  resources, improve scientific             data requirements.
The detailed blueprint for achiev-                quality, and reduce duplication.      •   Build a credentialing system
ing this vision is described in detail        •   Increase community oncologist             for investigators and sites
in this report in four thematic areas             and patient advocate                      recognized by NCI and industry
which are summarized below:                       involvement in clinical trial             to allow faster trial initiation
                                                  design and prioritization to              and keep the investigative
Coordination Initiatives                          improve the rate of patient               community abreast of legal,
  • Create a comprehensive                        accrual, and better address               safety, and regulatory changes.
      database containing                         practical and quality of life         •   Develop commonly accepted
      information on all NCI-funded               concerns in the design of trials.         clauses for clinical trial
      clinical trials to facilitate better    •   Develop a funding and                     contracts with industry to
      planning and management                     prioritization process to ensure          reduce the lead-time needed to
      across clinical trial venues.               that critical correlative science         open trials.
  •   Realign NCI and academic                    and quality of life studies can be
      incentives to promote                       conducted in a timely manner         Operational Efficiency Initiatives
      collaborative team science.                 in association with clinical          • Restructure the Phase III
  •   Increase cooperation between                trials.                                   funding model to promote
      NCI, FDA, and industry                  •   Develop a standards-setting               rapid patient accrual rates and
      to enhance the focus and                    process for the measurement,              cost-effectiveness.
      efficiency of oncology drug                 analysis, and reporting of            •   Reduce institutional barriers to
      development.                                biomarker data in association             timely trial initiation.
                                                  with clinical trials to enhance


 Accelerating Successes Against Cancer
Table 1. Trends in Cancer Mortality Rates in the U.S. by Cancer Site 1990 to 2002*

                                                                             CANCER SITE/GENDER

                    All                                                                                                                                  All
                    cancer                                                                                                                               other
Year                sites                 Lung/Men              Lung/Women            Colorectal            Breast/Women            Prostate             sites


1990                216.0                 91.9                  37.1                  24.5                  33.3                    38.4                 101.3
1991                215.2                 90.0                  37.8                  23.7                  32.7                    38.9                 101.5
1992                213.5                 88.1                  38.8                  23.4                  31.6                    38.9                 101.0
1993                213.5                 87.6                  39.4                  23.1                  31.4                    39.0                 101.1
1994                211.7                 85.6                  39.7                  22.7                  30.9                    38.2                 100.9
1995                209.8                 84.2                  40.3                  22.4                  30.5                    37.0                 100.1
1996                206.7                 82.6                  40.4                  21.7                  29.5                    35.7                 99.3
1997                203.5                 81.2                  40.9                  21.4                  28.2                    33.9                 98.0
1998                200.7                 79.7                  41.1                  21.1                  27.6                    32.4                 96.9
1999                199.4                 78.1                  40.9                  20.9                  26.5                    30.9                 96.9
2000                198.3                 78.2                  40.9                  20.8                  26.6                    30.0                 95.6
2001                194.3                 78.0                  42.0                  20.1                  25.9                    28.5                 94.3
2002                192.3                 76.2                  41.7                  19.7                  25.5                    27.5                 92.7
Average %           1.0                   1.6                   -1.0                  1.8                   2.2                     2.7                  0.7
decline
per year †

  * Rates are per 100,000 population for all races/ethnicities and were adjusted to the 2000 U.S. age distribution by using the direct method. Rates for the
years 1999 to 2002 were adjusted further to account for the change in coding from the International Classification of Disease, 9th Revision (ICD-9) to the
ICD-10 (see Anderson et al., 2001[13]).
  † The average percent declines per year are the means of the changes across the 12 yearly intervals between 1990 and 2002.
Source: Byers, et al. Cancer, 2006, 107(2) 396-405.




  • Increase patient and public                        the following critical responsibili-                          within these individual Cancer
       awareness and understanding of                  ties and key collaborative efforts of                         Centers and academic medical
       clinical trials.                                the stakeholders:                                             centers to decrease bureaucracy,
  •    Increase minority patient access                  1) Individual Cancer Centers and                            reduce legal barriers, overcome
       to clinical trials to improve the                    academic medical centers must                            potential conflict of interest
       participation of underserved                         work toward achieving the goals of                       problems, facilitate necessary
       and underrepresented                                 the NCI strategic plan and the re-                       preclinical studies, and ensure
       populations.                                         structuring of the national cancer                       the expedited filing of INDs
  •    Promote adoption of the NCI                          clinical trials enterprise The in-                       with the FDA.
       Central Institutional Review                         dividual Cancer Centers must                          2) Collaboration between Cancer
       Board facilitated review                             remain the engines of discovery                          Centers Individual Cancer
       process to reduce the time and                       and see that promising labora-                           Centers must be encouraged
       resources needed to open trials                      tory discoveries are promptly                            and incentivized to work
       at individual sites.                                 taken into early phase clinical                          closely together to implement
                                                            studies with the collection of                           and complete early clinical
The Cancer Center Directors work-                           biological materials for ap-                             trials in an accelerated time-
ing group endorses this restructuring                       propriate correlative research.                          frame. Likewise, an inventory
effort and would like to highlight                          Mechanisms must be developed                             of unique core services at


                                                                                                                           Accelerating Successes Against Cancer 
     individual Cancer Centers                 for combinatorial regimens          trajectory, cancer death rates will be
     should be available for access            – constitute major bureaucratic     50% lower than 1990 only after the
     across the entire Cancer Cen-             impediments to timely devel-        year 2040. It should be noted, how-
     ters network. Mechanisms to               opment of new diagnostics and       ever, that the trends for reduction
     share tissue specimens across             therapeutics.                       in death rates for cancers of the col-
     institutions through biore-            7) Enlightened and responsible         orectum, breast, and prostate have
     positories should be further              behavior of people Improved         been tracking toward the ACS 50%
     developed.                                education of the public is es-      goal while trends for other cancer
  3) Collaboration with other entities         sential to impact on personal       sites have declined at a much slower
     Current relationships between             behavior regarding tobacco use,     rate (Table 1).
     Cancer Centers, cooperative               diet, and other lifestyle issues,
     groups, industry, as well as with         screening and cancer preven-        To predict the potential impact of
     the FDA and CMS should be                 tion as well as to enhance          advances in cancer treatment on
     improved and streamlined par-             the public understanding of         survival statistics, we must be able
     ticularly in the area of develop-         research. Cancer prevention         to assess the current contribution
     ment and implementation of                should be regarded as the lead-     of treatment to improving survival.
     Phase III trials.                         ing edge of a continuum which       In the previously quoted CISNET
  4) Collaboration with the health care        includes cancer treatment. An       study, the proportion of the de-
     providers and payer systems Al-           educated public will take better    crease in the rate of death from
     though progress has been made             care of themselves and can be       breast cancer that was attributable
     in certain areas of the country           a highly effective supporter of     to adjuvant treatment ranged from
     and with specific payers, there           research.                           35% to 72% with a median of 54%.
     must be a coherent national                                                   The authors of this report point out
     approach to approval of the                                                   that in spite of the variability in
     costs of patient care in clinical
                                           Anticipated outcomes                    the quantitative conclusions across
     research approved by the NCI,         and Potential impact                    the seven independent statistical
     NIH, VA, cooperative groups           In 1996, the Board of Directors of      models of breast cancer
     as well as trials approved by an      the American Cancer Society set         incidence and mortality in this
     NCI-designated Cancer Center          an ambitious challenge goal for         study, it demonstrates a significant
     with an approved Protocol Re-         the United States to reduce cancer      interplay between screening and
     view and Monitoring System.           deaths rates by 50% between 1990        treatment. They conclude that
  5) Collaboration with policy-makers      and the year 2015. An article           screening and treatment appear to
     and government agencies The           published in the July 15, 2006 is-      have contributed approximately
     closer ties between FDA and           sue of Cancer provides analysis of      equally to the improvement in
     NCI should be further devel-          progress toward that goal through       survival that has occurred. It does
     oped. The development of a            2002, the mid-point of the chal-        not seem unreasonable to expect
     national clinical trials manage-      lenge. This analysis has shown          that similar conclusions might be
     ment system utilized by Cancer        that if the current rate of decline     reached regarding the analysis of
     Centers, community oncolo-            in death rates continues into the       survival improvement in colorectal
     gists, industry, and government       future, the United States will have     and prostate cancer.
     agencies would have an enor-          approximately a 23% lower age
     mous effect on the ultimate           standardized death rate from cancer     Given the progress that has been
     productivity of translational         in the year 2015 compared to the        made with currently available
     research in the United States.        year 1990. While this is only ap-       treatments in breast, prostate, and
  6) Collaboration with pharmaceu-         proximately half of the ACS’ 2015       colorectal cancer and the advances
     tical/biotechnology companies         goal, it is an impressive decrease.     being made in molecularly-targeted
     Issues surrounding technology         The authors further note that if the    diagnostics and therapeutics, an
     transfer –including intellectual      current overall rate of decrease in     accelerated decline in the rate of
     property, confidentiality, con-       death rates continues on the same       deaths from responsive neoplasms
     flict of interest, access of drugs                                            might well be anticipated. As


 Accelerating Successes Against Cancer
pointed out in this report’s section         Cancer Centers should be a
on Prevention, immediate measures            high priority, despite budgetary
to reduce death rates are available          constraints, with recognition
through application of validated             that translational research
screening procedures to underserved          largely originates in Cancer
and underutilizing populations.              Centers and within cancer pro-
The challenges for treatment of              grams at academic institutions.
cancers that have thus far been              For example, funding:
largely refractory and more dif-               a. Biorepositories
ficult to detect – such as pancreatic          b. Easy access to shared re-
cancer – are obviously more difficult             sources across centers
and require major investment of                c. Enhancement/improvement
resources.                                        of mechanisms like the
                                                  Rapid Access to Interven-
Implementation of the NCI                         tion Development (RAID)
Strategic Plan – with emphasis on                 program
a highly coordinated and collab-
orative national blueprint ac-
                                         references
companied by the recommended
restructuring of the cancer clinical     Berry et al. Effect of screening and
trials national enterprise – can be      adjuvant therapy on mortality
expected to accelerate treatment         from breast cancer. NEJM 2005;
progress in both currently respon-       353(17): 1784-92
sive and nonresponsive neoplasms.
However, unlike the situation with       Byers T, et al. A midpoint assess-
the successful space exploration         ment of the American Cancer Soci-
projects, these accelerated gains in     ety challenge goal to halve the U.S.
cancer therapy are dependent not         cancer mortality rates between the
only on skillful application of what     years 1990 and 2015. Cancer 2006;
we currently know, but also on con-      107(2) 396-405.
tinued fundamental research into
the biologic behavior of cancer.

Three specific action items that
should be advocated and promoted
during the next year are:
  1. Cancer Centers’ leadership
     must play a vital role in priori-
     tizing and implementing initia-
     tives of the CTWG.
  2. A unified national cancer clini-
     cal trials information technol-
     ogy system must be created with
     full collaboration of the Cancer
     Centers, cooperative groups,
     and pharmaceutical companies,
     and coordination with the NCI
     and the FDA.
  3. Investment in translational
     research infrastructure in


                                                                                Accelerating Successes Against Cancer 
                                            Summary

                                            W
                                                    ith an estimated 10 million cancer survivors in the Unit-
                                                    ed States, the demand for addressing the long-term needs
                                                    of cancer survivors is clear and optimally accomplished
                                            through the partnerships of academic medical centers, Cancer
                                            Centers in particular, the community, and cancer survivors.

                                            Cancer Centers, through collaborations with other Cancer Cen-
                                            ters and community providers, play a critical role in survivorship
                                            research, development of evidence-based guidelines for cancer
                                            survivors, and education.




                                            Surveys need to be conducted to          The Survivorship Subcommittee
                                            identify existing resources and          recommends the following action
                                            deficiencies or gaps that must be ad-    items be accomplished over the
                                            dressed to meet the needs of adult       next year:
                                            survivors, such as those unique            1. A shared resource warehouse
                                            needs of survivors with less com-             should be established through
                                            mon forms of cancer, and the gap              the NCI Office of Cancer
                                            related to the period immediately             Survivorship. This warehouse
                                            following completion of initial               would provide for a central
                                            treatment. Adopting the pediatric             source of tools on survivor-
                                            cancer model of survivor programs             ship. Cancer Centers should
                                            and clinics may help address the              collaborate and participate in

survivorshiP
                                            needs of adult cancer survivors.              the establishment and popula-
                                                                                          tion of this data warehouse, to
                                            Partnerships must be developed be-            include the following tools:
                                            tween various stakeholders includ-            a. Research protocols
                                            ing academia, community practices,            b. Educational materials
                                            patient advocacy groups, third-               c. Detailed descriptions of
                                            party payers, and industry (e.g.,                clinical, research, educa-
                                            pharmaceutical and biotechnology                 tional, and outreach activi-
                                            companies) to provide the neces-                 ties being conducted at each
                                            sary infrastructure for research, with           Cancer Center
                                            an emphasis on the development             2. Cancer Centers, in collabora-
                                            of biomarkers for early detection             tion with ASCO and other
                                            and identification of risk factors            professional organizations,
                                            for common problems, including                should take a leadership role in
                                            second primary cancers experienced            the development and imple-
                                            by cancer survivors.                          mentation of clinical practice
                                                                                          guidelines for survivors and
                                                                                          mobilizing adoption of these
                                                                                          guidelines as part of their re-
                                                                                          spective states’ cancer control
                                                                                          plans. This work should also


  Accelerating Successes Against Cancer
   involve looking at model pro-     introduction                          programs at Cancer Centers should
   grams and practices and ways                                            address the uniqueness of each
   to improve reimbursement for      The Cancer Center Director            individual’s disease experience, as
   survivorship services.            Working Group Survivorship            impacted by:
3. Working groups drawn from         Subcommittee adopts the NCI             • Type of cancer
   the Cancer Centers should be      definition that “an individual is       • Stage at diagnosis
   convened to work on imple-        considered a cancer survivor from       • Age or life stage at time of
   menting the two action items      the time of diagnosis, through            treatment
   listed above. Consideration       the balance of his or her life.”        • Long-term disabilities or
   should given to having a meet-    Consistent with the definition,           impairments, including
   ing, hosted by the NCI Office     the domain of cancer survivorship         the risk of second primary
   of Cancer Survivorship, that      covers the physical, psychosocial,        malignancies, caused by
   brings together experts on        and economic issues of cancer,            treatment or disease
   these topics, develops specific   from diagnosis until the end of
   plans on how to achieve these     life. It includes issues related to
   objectives, and establishes a     the ability to get health care and
   process for monitoring and        follow up treatment, late effects
   ensuring progress.                of treatment, second cancers,
                                     and quality of life. Survivorship

                                                                                   Accelerating Successes Against Cancer 
Current Knowledge,                         report), there is a need for cancer      The adoption and refinement of
                                           patients to receive a comprehensive      this pediatric model will allow
issues, and Problems                       care summary and follow-up plan.         Cancer Centers to develop multi-
Over the past 20 to 30 years,              Such a care plan would summarize         disciplinary teams that can provide
Cancer Centers excelled in prepar-         critical information needed for the      not only a comprehensive array of
ing patients for treatment, but the        survivor’s long-term care.               services to meet the needs of adult
time has come to move with greater                                                  survivors, but to do so within a
emphasis towards preparing patients        Moreover, there is a consensus           research-based environment. This
for recovery and survivorship. This        agreement on the need to work            approach provides a foundation
preparation should include the             toward development of evidence-          for research efforts, such as the
implementation of early detection          based clinical practice guidelines for   determination of optimal surveil-
protocols since second primary             the care of survivors.                   lance strategies for survivors and
malignancies among this group ac-                                                   the development of new biomark-
count for approximately 16% of all         Cancer Centers have a substantial        ers to facilitate the early detection
cancer incidence.                          number of activities in survivorship.    of disease recurrence and second
                                           However, for adults in particular,       primary cancers, while facilitating
Cancer survivors, including their          these activities are focused on the      continuity of care.
families, experience a spectrum of         most common forms of cancer and
mental and physical problems in            on longer-term aspects of survivor-      The interventional strategies of-
transitioning from active treatment        ship. Therefore, deficiencies or         fered in these multidisciplinary
to follow-up care. Many find they          gaps may exist in addressing the         clinics should address the common
need assistance in adjusting to their      needs of survivors of less common        acute and long-term problems as-
“new normal.”                              forms of cancer and in the period        sociated with survivorship, such as:
                                           just following completion of initial       • Fatigue
Longitudinal research on quality of        treatment.                                 • Depression
life and symptom management is                                                        • Sexual problems
needed to better serve the needs of        emerging therapeutic                       • Cognitive problems
cancer survivors. This longitudinal                                                   • Second cancer risk
research should begin at the point
                                           and interventional                         • Therapy-related chronic
of diagnosis. The ability to follow        Strategies                                    disease (e.g., cardiac,
these individuals and their families                                                     pulmonary, endocrine)
                                           Many Cancer Centers have                   • Psychosocial function
throughout their life span would be
                                           established programs and clinics              (e.g., education, marriage,
enhanced by the ability of Cancer
                                           for survivors of pediatric cancers,           employment)
Centers to establish affiliations
                                           recognizing the long-term care             • Health behaviors (e.g., tobacco
with community practitioners that
                                           needs of this patient population.             use, diet, exercise, medical
provide ongoing medical care to
                                           This comprehensive approach to                screening)
cancer survivors once active treat-
                                           survivorship research and follow-          • Reproduction and offspring
ment ends.
                                           up care has only recently been
                                           applied to populations diagnosed         Furthermore, as the medical sequel-
According to the Institute of
                                           with cancer in adulthood. As a           lae of treatments become better
Medicine’s (IOM) reports, titled
                                           successful model of a multidis-          understood, research to identify
Childhood Cancer Survivorship:
                                           ciplinary comprehensive cancer           useful interventions during cancer
Improving Care and Quality of Life
                                           survivorship program, we refer to        treatment should be greatly ex-
and From Cancer Patient to Cancer
                                           The Lance Armstrong Foundation           panded in the form of cross-institu-
Survivor: Lost in Transition (see
                                           Living Well After Cancer Program         tional clinical trials.
Appendix B of this report), and con-
                                           at the Abramson Cancer Center
sistent with the President’s Cancer
                                           of the University of Pennsylvania
Panel 2003/2004 Annual Report,
                                           (see sidebar).
Living Beyond Cancer: Finding a
New Balance (see Appendix C of this


0 Accelerating Successes Against Cancer
Lance Armstrong Foundation’s Living Well After Cancer
A model Program in Cancer Survivorship

The Lance Armstrong Foundation (LAF) Living Well After Cancer (LWAC) Program at the Abramson Cancer Center of the Uni-
versity of Pennsylvania is a successful model of a multidisciplinary survivorship program in a large, complex Comprehensive
Cancer Center. The program consists of specialists from medical oncology (physicians and nurse practitioners), cardiology,
rehabilitation medicine, and exercise physiology, psychiatry and behavioral science, social work, nutrition, and primary care
– working in a collaborative environment.

The LWAC team determined that a research focus would be critical to its success and sustainability. To facilitate this, they
have developed databases and chose tools to evaluate medical and psychosocial aspects of survivorship. During the first
2 years of the program, LWAC developed and refined their practice and consultative models of care. They also developed
a transition program for young adult survivors of childhood cancers. LWAC’s strategy is to include treatment teams who
care for a specific population as sub-protocol PIs responsible for identifying eligible patients. This strategy has been well
received by the oncology practice teams at the university.

Developing the LAF LWAC program required that the team members go through a number of cycles of implementing, evalu-
ating, and redesigning their care models and assessment tools. The initial aim was to develop a single clinical care/research
center for cancer survivors. However, after piloting this it was evident that more than one model of care was needed; differ-
ences in patient populations and the needs of providers meant that a ‘one size fits all’ approach to program development
was unlikely to provide the best care possible.

After careful consideration, the LWAC team developed parallel practice and consultative models. The practice model pro-
vides routine follow-up care, surveillance, and an individual risk profile for late effects of treatment based on age, family
history, co-morbidities, and cancer treatment history.

In addition to the large volume of survivors that mandates a separate clinical program, the issue of continuity of care with
the primary oncology practice teams was an important consideration for patients and oncologists. Consequently, LWAC de-
veloped the consultative model to pilot and determine feasibility. LWAC serves as research consultants to the treating teams
to allow for continuity of survivorship care while generating useful data for research.

Patients are followed prospectively from diagnosis with yearly mailings of study packets. These data are combined with
clinical data to provide a prospective understanding of the survivor experience. This approach may prove particularly useful,
as it allows for the use of baseline indicators in the construction of models to predict differing trajectories in the survivor-
ship experience among populations of patients with different cancer diagnoses, which may allow for early identification of
individuals at risk for developing difficulties during survivorship.

The goal of the LAF LWAC Program is to improve the care provided to cancer survivors. To accomplish this, stakeholders are
included in the design and implementation of programs, focusing on issues that they find pressing, and overcoming identi-
fied barriers to uptake of services.




                                                                                                     Accelerating Successes Against Cancer 
identification and                         the goal of ending the suffering         survivors through the monitor-
                                           and death from cancer. The grid,         ing of both health outcomes and
Prioritization of                          found in Appendix E of this report,      processes of care.
opportunities for                          provides a more effective means of
                                           communicating the breadth and            Health Care Providers and Payer
Advancement                                depth of activities currently tak-       Systems
Individual Cancer Centers and              ing place at Cancer Centers, and         Reimbursement for psychosocial
Academic Medical Centers                   identifies opportunities to share best   and palliative care and for symptom
Academic medical centers, and              practice models, as well as provides     management must be integrated
Cancer Centers in particular,              focus on survivorship activities that    into health insurance plans. Cancer
have an important role in survi-           may be lacking.                          Centers can assist advocacy groups
vorship research, clinical care,                                                    in pursuing this activity.
and education. With regard to              The Survivorship Subcommittee
research, studies are needed that          recommends that systematic data          Policy-makers and Government
can contribute to evidence-based           collection occurs using a well-          Agencies
guidelines for the optimal care of         defined, online survey method to         The NCI should consider establish-
pediatric, adolescent, and adult           gather commonly codified data.           ment of survivorship programs and
survivors of cancer. With regard to        This will allow for a deeper analy-      survivorship research as an essen-
clinical care, new service delivery        sis of those activities available at     tial element of an NCI-designated
models are needed that will allow          Cancer Centers, and identify gaps        Comprehensive Cancer Center.
Cancer Centers to work closely             that exist.                              Modest funding of survivorship ac-
with community providers to pro-                                                    tivities by NCI would leverage the
vide follow-up care. With regard           Cancer Center Collaborations             ability of Cancer Centers to attract
to education, Cancer Centers               Cancer Centers can generate the          other funding sources to this area.
need to take the lead in informing         knowledge base related to survivor-
patients, families, and the medi-          ship issues, conduct pilot programs,     Pharmaceutical/Biotechnology
cal community about the common             and coordinate large-scale studies       Companies
problems experienced by cancer             and demonstration projects. In           Pharmaceutical and biotechnology
survivors and their management.            addition to generating new knowl-        companies should be considered
                                           edge, Cancer Centers can utilize         among the stakeholders that have
As an initial effort to describe           and disseminate existing knowledge       a vested interest in survivorship
the survivorship activities at the         to ensure that best practices become     activities. In addition to support
Nation’s Cancer Centers, we                part of routine clinical care.           for educational efforts, assistance
solicited narrative descriptions of                                                 should be sought from pharmaceu-
research, clinical, and education          Community Collaborations                 tical companies for the conduct
efforts in this area. These narra-         Work in survivorship is seen as a        of clinical trials of pharmacologic
tives are found in Appendix D of           continuum that will require part-        agents with the potential to ad-
this report which is available at          nerships of Cancer Centers with          dress common problems of cancer
www.cancer.gov/cancercenters/. We          community care practitioners. Can-       survivorship (e.g., depression and
subsequently developed a template          cer Centers can serve as the hub of      fatigue). In addition, support
that provided an opportunity to            networks involved in clinical care,      should be sought from the biotech-
collect standardized information on        education, and research at it relates    nology industry to support research
these activities. The data submitted       to survivorship. These networks          on development of new biomarkers
by the Cancer Centers were com-            can also serve as the foundation for     for early detection and on identi-
piled into an extensive grid that          the conduct of multisite demon-          fication of genetic risk factors for
provides a basis for further analysis      stration projects. One such dem-         common problems (e.g., second
and interpretation of the various          onstration project should be the         malignancies, cognitive difficulties).
categories of survivorship activities      development of community-based
currently being provided and what          alliance models that evaluate the
may be lacking and needed to reach         quality of care provided to cancer


 Accelerating Successes Against Cancer
Individual Behaviors                   Cancer Centers could provide their
Cancer Centers play a significant      information online, within in a
role in educating cancer survivors,    public domain, which may include
their families, and health care pro-   the following examples:
viders about issues faced by cancer      • Follow up procedures
survivors. Most Cancer Centers           • Common sets of data elements
have already established programs        • Survivorship protocols,
that provide information and sup-          especially coordinated with
port for patients undergoing cancer        prevention activities relative to
treatment. This work now needs to          tobacco use, obesity, etc.
be extended to the post-treatment        • Questionnaires
period. In addition, education           • Definitions
and service programs are needed          • Educational materials
that can foster adoption of posi-
tive health behaviors (e.g., regular   This warehouse would not only
exercise, diets high in fruits and     facilitate Cancer Center collabora-
vegetables) among survivors.           tions, but would also provide an
                                       outstanding resource to disseminate
                                       information to the community.
Anticipated outcomes
and Potential impact
These efforts by Cancer Centers        references
should lead to improvements in the
                                       NCI Strategic Plan 2006; http://stra-
quality of care provided to cancer
                                       tegicplan.nci.nih.gov/
survivors and their families and,
by extension, improvements in the
                                       Travis LB, et al. Cancer survivor-
quality of their lives. Cancer Cen-
                                       ship—genetic susceptibility and
ters are uniquely positioned to lead
                                       second primary cancers: research
these efforts and in doing so, can
                                       strategies and recommendations.
galvanize public and medical com-
                                       JNCI 2006; 98(1): 15-25.
munity support for the view that a
comprehensive approach to cancer
care should extend throughout a
patient’s life span.

The Survivorship Subcommit-
tee recommends evaluating the
establishment of a shared resource
data warehouse containing a single
source of resources for patients,
academic center faculty, and com-
munity practitioners. Such a data
warehouse would create a remark-
able resource to facilitate research
and comparability.




                                                                               Accelerating Successes Against Cancer 
                                            Summary

                                            W
                                                     hile great progress could be made to reduce cancer mortal-
                                                     ity, roadblocks to collaborations exist that will be neces-
                                                     sary to overcome in four primary areas of consideration
                                            – chemoprevention trials, therapeutic trials, deployment of bio-
                                            marker and imaging agents, and survivorship. Below summarizes
                                            these roadblocks, and key action items are proposed that could be
                                            undertaken by Cancer Centers to begin to overcome them.




Collaborations                              Chemoprevention trials
                                            Difficulties in accruing large
                                                                                    Action item: Collaborations
                                                                                    between institutions would be
                                            patient volumes, a lack of infra-       facilitated by a shared licensing
                                            structure within Cancer Centers,        agreement that reduces the burden
                                            declining funding, and the size,        of individual contract negotiations
                                            complexity, and expense of these        with each partner.
                                            trials mandates a need for collabo-
                                            rations between Cancer Centers          Biomarkers and Imaging
                                            to conduct large chemoprevention        Technology advancements are
                                            trials. Liability concerns and lack     acutely needed in the rapid de-
                                            of profitability have made it dif-      velopment of assays for proteins
                                            ficult to engage pharmaceutical and     in blood and other body fluids for
                                            biotechnology companies in large        early detection that are inexpen-
                                            prevention trials.                      sive, sensitive, and quantitative.
                                                                                    One major challenge to the use
                                            Action item: We recommend that          of surrogate biomarkers in clinical
                                            a Cancer Center consortium be           trials is the difficulty of establishing
                                            formed to centralize chemopreven-       a predictive relationship between
                                            tion trial infrastructure activities.   the surrogate and mortality from
                                                                                    the disease.
                                            Therapy trials
                                            It is difficult for partnerships to     Scientists involved in the com-
                                            remain intact for the 10-15 years       mercial side of diagnostic tests
                                            required to take a therapeutic from     complain of an inadequate source
                                            concept to clinical practice. Many      of human samples for marker vali-
                                            industry collaborators are aban-        dation. There is a need for greater
                                            doning their traditional academic       understanding of the value added
                                            partners in therapeutic trials due      by a good diagnostic test because
                                            to difficulties of dealing with legal   currently, there is little economic
                                            issues and the technology licens-       incentive to develop diagnostic
                                            ing and contracting offices of these    tests. For example, the opportunity
                                            institutions.                           for early detection and risk assess-
                                                                                    ment is very poor due to the lack


 54 Accelerating Successes Against Cancer
of reimbursement by Medicare and        verse outcomes of cancer by leading    Many areas of medical science are
Medicaid for disease prevention.        an integrated effort to advance fun-   evolving toward larger scale sci-
                                        damental knowledge about cancer        ence projects motivated by oppor-
The necessary interdisciplinary         across a dynamic continuum of dis-     tunities to apply the abundance of
collaborations needed to discover       covery, development and delivery.”     new knowledge to patient needs.
new imaging agents is lacking in        The strategy for meeting this goal     Application of new discoveries
most Cancer Centers. Regulatory         depends on successful collabora-       into standard medical practice is,
bodies are often overly restric-        tion across the entire spectrum of     by its nature, a much larger un-
tive in their application of vague      stakeholders. “We as a Nation will     dertaking than discovery science,
safety and consent requirements to      achieve this vision by optimizing      requiring highly organized, system-
imaging trials that are designed for    new approaches in interdisciplinary    atic activity involving collabora-
therapy trials.                         collaborations and transdisciplinary   tions across research institutions,
                                        science,” NCI explains. “Our suc-      industry, patient care providers,
Action item: A consortium of            cess will depend on our ability to     governmental agencies, and regu-
companies should be organized to        integrate our activities across a      latory entities.
fund a precompetitive academic          seamless continuum of discovery,
activity to improve the technology      development, and delivery; partner     The subcommittee was greatly
for biomarker discovery, particularly   with others to leverage resources,     aided by a recent report from
protein biomarkers, much like the       and build synergy.” Most of the        National Research Council and
SNP Consortium.                         goals in the NCI Strategic Plan        Institute of Medicine (NRC / IoM)
                                        require large-scale collaboration      titled “Large-Scale Biomedical
Survivorship                            across two or more entities.           Science.” This report is strongly
Research requires longitudinal                                                 recommended for a much greater
studies, multiple sites of care, or                                            depth of consideration of these
                                        Current Knowledge,
studies at multiple institutions to                                            topics than can be provide here.
obtain sufficient samples sizes. The    issues, and Problems
lack of uniformity or standardiza-      There are many potential arenas        emerging therapeutic
tion of quality control can impede      for collaboration for NCI-desig-
combining data from different           nated Cancer Centers. Moreover,
                                                                               and interventional
sources. Provisions of the Health       these collaborations extend from       Strategies
Information Privacy and Account-        a micro-scale – involving indi-
ability Act (HIPAA) inhibit the                                                The NCI Strategic Plan for 2006
                                        viduals within a Cancer Center
ability to track and collect data                                              lays out a large number of strate-
                                        collaborating with individuals or
for research.                                                                  gic aims, many of which are big
                                        organizations outside the Center
                                                                               science projects requiring collabo-
                                        – to the macro-scale involving
Action item: A consortium of                                                   ration across many sectors of the
                                        institution to institution collabo-
Cancer Centers should be formed                                                discovery, commercialization, and
                                        ration and consortia of institu-
to coordinate research efforts                                                 implementation pipeline. As part of
                                        tions. In general, micro-scale
and funding strategies in order to                                             the academic medical community,
                                        collaborations are frequent and
facilitate the conduct of multi-in-                                            Cancer Centers have had limited
                                        productive and depend more upon
stitutional studies and the creation                                           success with these larger scale col-
                                        the initiative of the individual
of a comprehensive research infra-                                             laborations. Four areas described
                                        than the leadership of the institu-
structure.                                                                     below– prevention, diagnostics,
                                        tion. A survey was taken of the
                                                                               therapeutics, and survivorship
                                        NCI-designated Cancer Centers
                                                                               – might benefit from more effective
introduction                            to identify core resources that
                                                                               large-scale collaboration.
                                        could be shared among centers
The NCI goal as expressed in the
                                        (Appendix F). We will focus our
2006 Strategic Plan is to “Reduce
                                        consideration for this report in the
the burden and eliminate the ad-
                                        macro-scale collaborations.



                                                                                       Accelerating Successes Against Cancer 
identification and                         agents, and a consortium of research     A set of initiatives supported by
                                           centers for conducting chemopre-         NCI’s National Cancer Advisory
Prioritization of                          vention trials.                          Board (NCAB) for revamping the
opportunities for                                                                   NCI clinical trials system is address-
                                           At present, there are focused            ing the need for enhanced scientific
Advancement                                programs within NCI’s Division of        quality and clinical trial prioritiza-
Prevention                                 Cancer Prevent (DCP) that support        tion, including increased collabora-
Focus on Collaborations in Chemopre-       collaborative work on chemopre-          tion with the broad oncology com-
vention Trials During the past decade      vention agents and Phase I clinical      munity. The plan is to investigate
several prominent task forces of           trial development, including:            expansion of these initiatives in
national experts have identified             • The Rapid Access to                  the future to include studies of new
chemoprevention as a major area                 Preventive Intervention             preventive agents.
of cancer prevention research that              Development (RAPID)
                                                program provides contract
could have a significant impact on                                                  Key Challenges
the cancer burden. Studies have                 resources to the research
shown that chemopreventive agents               community for preclinical and       requiring large-Scale
can be effective in preventing can-             early clinical drug development     Collaborations
cer in a high-risk population (e.g.,            of potential chemopreventive
the Breast Cancer Prevention Trial,             agents. This facilitates the        Chemoprevention
testing tamoxifen in women at high              process of bringing discoveries     While there has been significant
risk for breast cancer that showed              from the laboratory to clinical     progress and promising outcomes in
a 49% reduction in incidence of                 trials, potentially enhancing       the developing chemoprevention
invasive breast cancer).                        the attractiveness of licensing     field, it faces some significant chal-
                                                candidates for industry.            lenges and an overarching need for
Currently, NCI has about 400                 • The Early Detection                  large-scale collaborations:
compounds under study and has                   Research Network (EDRN)
identified five classes of promising            is a national network and           Size, expense, and timeframe Large-
chemopreventive agents that are                 scientific consortium for the       scale Phase III clinical trials,
considered priority. Because the                development, evaluation,            involving hundreds to thousands of
chemoprevention research pipeline               and validation of biomarkers        high-risk and healthy populations,
is complex and involves large, long-            for early detection and risk        and multi-institutional participa-
term, expensive studies of high-risk            assessment for cancer. With         tion, are required to test whether
and healthy populations, the col-               relatively small funding, experts   cancer risk can be reduced by che-
laborations required – among NCI,               note that this mechanism has        moprevention interventions as well
Cancer Centers, research networks,              done a “commendable job”            as to provide opportunities to vali-
and industry – are substantial to               developing collaborations across    date potential biomarkers. These
continue to advance this area of                Cancer Centers, SPORES, and         trials are expensive and require a
cancer prevention.                              Program Projects.                   long timeframe for completion (10
                                                                                    years or more).
NCI’s Chemoprevention Program              Clinical trials for chemoprevention
Among the cancer prevention                agents are currently coordinated         Clinical trial infrastructure Within
initiatives, the NCI Strategic Plan        through consortium groups of             individual Cancer Centers, the
has identified strategies to advance       research centers conducting ongo-        infrastructure for supporting large
chemoprevention research that will         ing Phase I and II trials, Cancer        Phase II and Phase III chemopre-
require broad-scale collaborations         Centers, and cooperative groups,         vention trials is viewed by many
within the cancer research commu-          with additional participation of         experts as “gravely lacking” and
nity, including supporting a robust        community physicians through the         a key research barrier. Cancer
cancer prevention agent develop-           Community Clinical Oncology              Center clinical trials offices and
ment program, large-scale clinical         Program (CCOP).                          data management support are
trials to evaluate cancer prevention                                                primarily focused on therapeutic


 Accelerating Successes Against Cancer
trials involving cancer patients         vitamin A supplements in persons         imaging agents to improve moni-
rather than population-based trials      at high risk for lung cancer, showed     toring of treatment response; and
requiring specialized support (i.e.,     a 28% increase in lung cancers and       developing molecularly-targeted
data management, statistical, trial      17% higher death rate compared to        agents with fewer toxicities. The
recruitment, etc.). Only institutions    the placebo group. This has raised       Plan emphasizes the importance of
with large Program Project grants        concerns about the safety of using       integrating preclinical and clinical
– which have been an effective           chemopreventive agents in other-         research and recognizes that col-
mechanism for advancing cancer           wise healthy subjects and the need       laboration among clinical scien-
prevention translational research,       for scientific collaboration to ensure   tists, cancer modelers, and imaging
although such funding is declining       that long-term benefits outweigh         researchers through public/private
– have been able to develop the          major side effects.                      partnerships will be an important
capacity for Phase IIB or Phase III                                               implementation strategy.
chemoprevention trials. However,         Concerns have also been raised
individual Cancer Centers generally      about past chemoprevention               However, NCI’s Strategy does not
do not have the ability to accrue        agents moving into Phase III             address how these collaborations
large patient volumes for Phase III      studies without adequate justifica-      and partnerships can be facilitated
trials or to coordinate and conduct      tion. These concerns have been           so they are more effective than
large-scale intermediate biomarker       attributed to issues such as ap-         past NCI efforts to foster partner-
endpoints required for translational     propriate dose scheduling; single-       ships among these groups. Recent
research success.                        versus multiple-agent regimens;          examples include the NCI Cancer
                                         and inadequate underlying animal         Genome Anatomy Project (CGAP)
The lack of infrastructure within        pharmacology/mechanistic studies,        program for development of early
Cancer Centers – coupled with            Phase I and early Phase II studies,      drugs in clinical trials, SPORE
declining Program Project fund-          and intermediate biomarker end-          grants, and the AP4 initiative,
ing and the size, complexity, and        points. Some of these concerns are       all of which are popular with the
expense of these trials – mandates       beginning to be addressed through        participating institutions, but
a need for collaborations between        DCP’s Phase I/II chemoprevention         which have not yet demonstrated
Cancer Centers to conduct large          consortium effort.                       their value through promising new
chemoprevention trials. Mecha-                                                    therapeutic targets.
nisms need to be considered –            Additional challenges include
potentially centralized or through       engaging the interest and in-            A challenge of all of these types of
a consortium arrangement– that           volvement of pharmaceutical and          initiatives is the long time frame
most effectively address infrastruc-     biotechnology companies. To date,        required to take a therapeutic
ture deficiencies for large-scale        they have had a lack of interest in      agent from concept to practice.
trials. Collaborations will also be      the cancer chemoprevention field,        Therefore, collaboration models
needed with cooperative groups           in contrast to embracing cardio-         must be measured over a 10-15
and research networks, which will        vascular chemoprevention. This           year time horizon, and it is difficult
likely benefit from consortium           has been in part due to safety and       for partnerships to remain intact
arrangements comprised of orga-          liability concerns and the alleged       for such a long period. Cancer
nizations that are best suited for,      lack of profitability of chemopre-       Center directors were surveyed
and interested in, population-based      vention agents.                          about successful inter-institutional
chemoprevention trials.                                                           partnerships at their organiza-
                                         Treatment                                tions. Two interesting models that
Safety and trial design The results of   As discussed in the NCI’s 2006           were presented for further analy-
some recent large chemopreventive        Strategic Plan, the most important       sis were: the State of California,
studies have varied significantly        scientific strategies for advancing      the University of California and
from expectations. For example,          cancer treatment are: understanding      various industry groups; and the
the Beta-Carotene and Retinol            the fundamental differences between      Immune Tolerance Network,
Efficacy Trial (CARET), testing a        metastatic and non-metastatic can-       which is a nonprofit organization
combination of beta carotene and         cers; developing biomarkers and          that provides funding, clinical


                                                                                           Accelerating Successes Against Cancer 
trials support, and access to assays,      There are two working groups with-       Biomarkers and Imaging
agents, and equipment.                     in the NCI that are endeavoring to       The NCI Strategic Plan relies
                                           understand how barriers to partner-      heavily on advances in biomarkers
Interviews with academic and               ship in therapeutics can be over-        and targeted imaging for improv-
industry scientists revealed many in-      come. The first is the Translational     ing the diagnosis, treatment, and
herent difficulties with academic/in-      Research Working Group (TRWG)            prevention of cancer. The pipeline
dustry partnerships that will require      and the second is the Clinical Trials    for both biomarkers and targeted
significant leadership in the field to     Working Group (CTWG). Both               imaging agents involves a series
overcome. Although academic in-            have representation from most            of steps from discovery to valida-
stitutions bring a wealth of expertise     of the key stakeholders and their        tion, commercialization, regulatory
to the table, most industry partners       recommendations will help shape          approval, and implementation.
have become extraordinarily wary           the changes that need to be made to      For both there is a continuum of
about dealing with the legal, tech-        create an environment more favor-        partnerships needed involving
nology licensing, and contracting          able to partnership. Both groups         research funding from the NIH or
offices of these institutions. Agree-      must assure that their recommenda-       foundations, discovery in aca-
ments can take months or years to          tions are reviewed by economists         demic or commercial laboratories,
negotiate, and many institutional          because, in the end, development         commercialization by companies,
review boards are unsophisticated          of translational discoveries must be     approval by FDA and implemen-
and cumbersome. Most industry              funded by the financial markets and      tation by CMS and other insur-
representatives have abandoned             the health care payers. NCI’s ability    ers, and adoption by health care
academic institutions as a clinical        to fund this development effort is       agencies and patients. Incentives
trials venue and try to eliminate          extremely limited and Cancer Cen-        and bottlenecks along this pipe-
them from the drug development             ters must look to industry partners      line were considered, and points
process at the earliest possible time.     for this effort.                         at which innovative solutions are
                                                                                    needed are identified below.
It is ironic that community hospitals,     In addition, several Cancer Centers
community oncology groups and              are willing to partner with other        Need for Protein Biomarkers Many
overseas health systems are easier to      Centers and with industry to bring       applications of DNA-based bio-
work with than organizations that          together the strengths of each orga-     markers require direct biopsy of
were created and structured for this       nization. However, many of them          diseased tissue, which requires that
very purpose. Furthermore, many            will need help to overcome admin-        the tumor be identified, localized,
of the new technologies that show          istrative barriers that transcend the    and accessible, and hence are only
promise toward shortening the long-        creative skills of academic officials.   applicable between the stages of
term costs of clinical trials – such as    NCI should consider taking some of       tumor localization and removal.
biomarkers and new imaging modali-         the key resources that the NIH has       Biomarkers that can be accessed
ties – are very expensive on a cost-       invested in – such as the San Diego      noninvasively are needed at all
per-case basis. Much work remains          Center for Chemical Genomics,            stages of disease management,
to be done to communicate the cost         Harvard’s Initiative for Chemical        from risk assessment to treatment.
effectiveness of these studies to pay-     Genetics, the Mouse Model Con-           The most informative biomarkers
ers and industry representatives.          sortium – and hiring top-tiered in-      are likely to be proteins because
                                           tellectual property lawyers to work      of their diversity and proximity to
A discipline that receives little          with the institutions involved on        function. They are also likely can-
mention in the therapeutics section        a shared licensing agreement that        didates for imaging targets.
of the NCI Strategic Plan is health        reduces the burden of individual
economics. Nonetheless, in these           contract negotiations with each          Diagnostics Work in a System Our
difficult times in the Federal budget,     partner. Industry groups and founda-     goals in applying biomarkers to
the therapies with the highest like-       tions have found ways to manage          disease management are: to identify
lihood of adoption by Medicare and         these licensing issues and nonprofit     persons with potentially life-threat-
other payers are those that reduce         and governmental organizations           ening cancers at the earliest stage
the total cost of cancer care.             must adopt their best practices.         possible; to avoid false-positive


 Accelerating Successes Against Cancer
tests and unnecessary treatments;         without an academic partner. Few           different entities own IP rights to
and to minimize the overall cost of       protein biomarkers are currently in        different markers.
the program. Since no single test         the validation stage. The bottleneck
performs perfectly, sensitivity, speci-   at discovery means that valida-            The total market for a successful
ficity, and cost become tradeoffs in      tion studies are often limited to a        diagnostic may be $50-100 million
the application of diagnostics to         single biomarker at a time. If the         per year but the cost of develop-
disease management. Ultimately,           bottleneck to discovery were solved,       ment can be more than $100
the goal will be to optimize overall      biomarkers could be multiplexed by         million. As a consequence, there is
performance of a system of tests and      the hundreds in validation studies,        not enough economic incentive to
interventions. The advantage of a         dramatically decreasing the cost per       develop diagnostic tests that will
systems approach is that biomarkers       marker and increasing the probabil-        only be used once regardless of their
whose performance may be inad-            ity that some would be validated.          importance in health care. The
equate when considered at a single        At the other end of the pipeline,          opportunity for early detection and
stage of the disease continuum may        the perception of low reimburse-           risk assessment is very poor due to
actually be of great value when in-       ment and thus insignificant profits        the lack of reimbursement by CMS
tegrated into a disease management        to cover development cost inhibits         for disease prevention practices.
continuum.                                companies from undertaking valida-
                                          tion studies unless the biomarker          Approval of Biomarkers Both the
Discovery of Protein Biomarkers           is necessary for a drug therapy            FDA and CMS regulate diagnostic
Although there have been signifi-         that will yield significant financial      tests. FDA regulates tests that are
cant advances in proteomics, the          return. One major challenge to the         sold as kits or systems in interstate
discovery of new protein biomark-         use of surrogate markers in clinical       commerce while CMS oversees
ers appears to be stalled. NCI has        trials is the difficulty of establishing   laboratory testing services com-
recently moved to accelerate the          a predictive relationship between          mercially offered at single sites,
field with programs that foster dis-      the surrogate and mortality.               in-house or “home-brew” or sold
covery in mouse models of cancer,                                                    commercially to CLIA-approved
provide for informatics support, re-      Commercialization of Biomarkers            laboratories as analyte-specific
agents, and large grants for centers      Commercialization of biomarkers            reagents. Several hurdles frequently
for technology development. Tech-         for diagnostic tests usually involves      thwart the FDA approval process.
nology advancements are acutely           a commercial entity to provide the         As a result, the CLIA home-brew
needed in the rapid development           necessary investment and quality           policy is an easier route to approval
of assays for proteins in blood and       control, and an academic partner           and may obtain higher reimburse-
other body fluids that are inexpen-       to provide biological insight, as-         ment by dealing directly with the
sive, sensitive, and quantitative. In     says, and tissues. Industry scientists     user. There is concern in some
the area of collaborations, most of       complain of an inadequate source of        quarters that the home-brew pro-
the effort is currently being made        well-annotated human samples for           cedures for approval do not assure
between NIH and academic labora-          marker validation. Obtaining such          enough patient protection and that
tories. A consortium of companies         samples is the single most expensive       this option should be eliminated.
that would invest in discovery tech-      aspect of diagnostic test develop-         This recommendation would be a
nology as a precompetitive activity,      ment. New health privacy regula-           disaster for the implementation of
much like the SNP consortium,             tions (HIPAA) and differences in           biomarkers in cancer.
could be highly effective in moving       interpretation of what constitutes
the field forward.                        informed consent further exacerbate        Given the likelihood that many
                                          this problem.                              biomarker tests will be developed
Validation of Biomarkers Protein                                                     for use in guiding molecularly-tar-
biomarker validation is currently         Another serious impediment to              geted therapeutic interventions,
conducted either via collabora-           biomarker commercialization stems          there are not currently procedures
tions between NCI and academia            from intellectual property (IP)            for co-review or co-approval by
(for example, the EDRN program)           issues. Use of panels of biomarkers        FDA and CMS, although these are
or as a commercial activity with or       in the future will be very difficult if    under consideration.


                                                                                              Accelerating Successes Against Cancer 
Implementation of Biomarkers The           three large companies that produce       and should address the appropriate
economic incentive for diagnostic          imaging instrumentation. The             use of new imaging procedures in
tests is low because most tests will       NCI has established a series of          early clinical trials of experimental
be performed infrequently on a             such imaging centers. While these        therapies. New imaging agents for
patient. Reimbursement is calcu-           provide a strong focus for collabo-      targeted therapy cannot be devel-
lated based on the cost of doing the       ration, progress is often less than      oped and validated independent of
test rather than considering value         optimal because of the difficulty of     the treatment protocols.
added by the test or the costs of its      collaborating across disciplines. In
development. This is entirely differ-      many academic institutions these         Implementation of Imaging Agents
ent than reimbursement for thera-          collaborations are not effective.        Since most new imaging agents
peutics. There is a need for more                                                   will be designed to be used in one
understanding of the value added by        Validation of Imaging Agents Fast-       of a half dozen instruments that are
a good diagnostic test. Two govern-        track FDA approval for new               widely available in health care set-
ment commissioned reports have             agents only works for drugs with         tings, and since diagnostic imaging
recommended a re-evaluation of             known toxicities that are adapted        tests are well reimbursed, there are
reimbursement rates for diagnostics.       to imaging strategies. Completely        both the technical platforms and
                                           new drugs do not fare as well. The       trained personnel to implement
Three diagnostic companies                 preclinical burdens hamper devel-        new imaging agents.
compete for control of clinical            opment in terms of cost and time.
laboratory testing. Tests are stan-        Medical ethics committees do not         However, one of the most impor-
dardized utilizing primarily antibody      understand the low risks imaging         tant applications of imaging agents
tests and polymerase chain reac-           studies pose to subjects, and are of-    – to inform therapeutic outcomes
tion (PCR) technology. Any new             ten overly restrictive in their appli-   in clinical trials – has not been
technology platform for diagnostics        cation of vague safety and consent       effectively implemented. More
would be difficult to introduce.           requirements that are designed for       than 80% of drugs entering clinical
                                           therapy trials.                          development do not receive FDA
The promise of biomarkers for re-                                                   approval, with many failing late in
ducing mortality by early detection        Commercialization of Imaging             development, often after prolonged
of cancer is completely undermined         Agents The major instrumenta-            Phase III trials, because of unex-
by the fact that Medicare does not         tion providers will be the likely        pected safety issues or difficulties in
reimburse for screening tests unless       entities to commercialize new            determining efficacy. This contrib-
mandated by Congress, as is the            imaging markers that achieve the         utes to the high costs of oncology
case for colonoscopy.                      necessary validation and approval.       drug development and highlights
                                           Reimbursement is good for imag-          the need for tools to identify prom-
Recommendations for Biomarkers A           ing used in clinical diagnosis and       ising candidates early in develop-
specific statement from NCI as to          treatment so there is both sufficient    ment. To that end, NCI, FDA, aca-
the clinical problems for which            resources for commercialization          demic researchers, and industry are
tests are needed, what performance         and incentive to do so.                  discussing ways to collaborate with
standards need to be met, and funds                                                 the goal of identifying biomarkers
to support their development might         Approval of Imaging Agents Pre-          that will provide a clear and timely
provide motivation for development         clinical and validation components       picture of a patient’s cancer and its
of new biomarker tests.                    for imaging studies should focus on      response to therapy.
                                           optimally defining the initial human
Discovery of Imaging Agents Dis-           trial. The rules of evidence for prog-   In oncology, the gold standard
covery of new imaging agents               nostic studies are not nearly as well    clinical trial endpoint is overall sur-
seems to be most productive in             defined as they are for treatment        vival, which may require long-term
academic centers that involve              trials or for simple diagnostic mea-     studies and may be confounded by
collaboration across academic              sures. These need to be developed        a patient’s death from causes other
departments and disciplines, with          through a dialogue involving FDA,        than cancer. Over the years, the
funding from NIH and one of the            NCI, academia, and industry groups       oncology community and the FDA


0 Accelerating Successes Against Cancer
have come to rely on endpoints          biomarkers based on newer imag-         • Delivery
that are regarded as correlates of      ing technologies for use in oncol-            n Ensuring the delivery
clinical benefit or surrogate end-      ogy drug development, particularly              of new information,
points (SEP). However, the mea-         evaluation of therapeutic response.             interventions, and best
surements of SEPs using standard        Ultimately, the outcome of these                practices in collaboration
anatomic imaging techniques are         studies will inform the development             with other Federal,
often inadequate, especially for        FDA guidance and best practices in              professional, and nonprofit
monitoring the effects of drugs that    oncology.                                       organizations.
do not cause tumor shrinkage or                                                 •   Development
for cancers that progress slowly or     Survivorship                                  n Accelerating intervention

metastasize diffusely.                  Advances in the ability to detect,              research in order to reduce
                                        treat, and support cancer patients              cancer-related chronic
Newer imaging modalities, includ-       have turned cancer into a chronic               or late morbidity and
ing volumetric and functional           or readily managed disease for many.            mortality.
imaging, show high promise as           There are 10 million Americans
additional biomarkers in cancer.        alive today with a personal history    Key Challenges The majority of
For example, clinical trials in         of cancer and as of 1997 there were    survivors (62%) are 5 years or more
breast cancer and other settings        270,000 survivors of childhood         post-treatment. Thus research to
(e.g., non-small cell lung can-         cancer.                                understand the multiple factors
cer and esophageal cancer) have                                                influencing the health of survi-
demonstrated that FDG-PET – a           Recently, task forces of national      vors requires longitudinal studies,
physiologic imaging modality – may      experts have evaluated and identi-     multiple sites of care, or studies at
provide an early indication of ther-    fied the requirements for a com-       multiple institutions to obtain suf-
apeutic response that is well-corre-    prehensive approach to addressing      ficient samples sizes.
lated with clinical outcome. If the     the needs of cancer survivors and
use of FDG-PET can be confirmed         patients diagnosed or treated for      Funding Strategies Funding for
as a biomarker in such settings,        cancer. In accordance with those       research has traditionally been
unnecessary chemotherapy may            task force recommendations, the        based on shorter-term projects
be avoided for some patients and        NCI Strategic Plan focuses on the      rather than the longitudinal ap-
the costs of unnecessary long-term      following areas:                       proach required for the long-term
follow up reduced. The FDG-PET            • Discovery                          studies fundamental to survivorship
imaging modality has the potential             n Expanding research            research.
to facilitate oncologic drug devel-              efforts to understand
opment by shortening Phase II                    the biological, physical,     Complexities of Conducting Multi-
trials and detecting clinical benefit            psychological, and social     Institutional Studies and Long-term
earlier in Phase III investigations.             mechanisms, and their         Studies Multi-institutional studies
                                                 interactions, that affect a   may require data from a variety
Current obstacles to including cor-              cancer patient’s response     of sources and the lack of unifor-
relative imaging studies in clinical             to disease, treatment, and    mity or standardization of quality
trials are: cost; the perception that            recovery.                     control can impede combining data
adding a correlative imaging study             n Expanding the                 from different sources. Data collect-
will make the trial more difficult to            development and use of        ed in large-scale projects is often
implement and may hamper accru-                  tools to assess the health-   placed in publicly accessible data-
al; and the investigators’ concerns              related quality of life and   bases, giving rise to issues of patient
that the imaging study will not add              quality of care of cancer     confidentiality and consent. The
value in terms of yielding pub-                  survivors and their family    provision of HIPAA may inhibit
lishable findings or as a validated              members, and tracking         the ability to track and collect data
endpoint that can be used in trial               outcomes for these            for research. Obtaining appropriate
design. Collaborations are needed                populations.                  patient consent can be challenging
to define and develop imaging                                                  for longitudinal studies and studies


                                                                                          Accelerating Successes Against Cancer 
conducted on data collected over a         funding the development of cancer      NCI Strategic Plan. http://strategic-
long period of time.                       survivorship programs in multiple      plan.nci.nih.gov. January 2006.
                                           sites. Coordination of these efforts
Coordination Among Health Care             with NCI can provide efficiencies      NCI meeting minutes related to
Providers Given that the majority          and contribute to a more compre-       recommendations and develop-
of follow-up care for survivors is         hensive approach.                      ments from the Chemoprevention
provided in the community, coor-                                                  Implementation Group: NCI/
dination between health specialists                                               NCAB September 1997 meeting
                                           references
at Cancer Centers and commu-                                                      minutes and NCI Board of Scien-
nity-based providers is critical but       Chemoprevention                        tific Advisors 11/08/99 meeting
underdeveloped.                            Interviews with and email commu-       minutes.
                                           nications:
Infrastructure for a Comprehensive            - David Alberts MD, Director of     Restructuring the National Cancer
Database on Cancer Survivorship                 Arizona Cancer Center             Clinical Trials Enterprise. Report of
While the NCI has provided statisti-          - John Baron MD, Dartmouth          the Clinical Trials Working Group
cal information on cancer survivors             Medical School                    of the National Cancer Advisory
in the United States, further work            - John Crowley PhD, Southwest       Board. June 2005.
is required to improve coordination             Oncology Group Statistical
between existing resources [e.g., the           Center                            Report of the NCI Cancer Preven-
Surveillance, Epidemiology, and End           - John Potter MD, PhD, Fred         tion Program Review Group.
Results (SEER) program], and to                 Hutchinson Cancer Research        June 1997.
develop the infrastructure for large-           Center
scale studies.                                - Ross Prentice PhD, Fred           Report from THE MARCH Re-
                                                Hutchinson Cancer Research        search Task Force, September 1998.
Successes and Opportunities There               Center/Coordinating Center
are opportunities for further coor-             for Woman’s Health Initiative     Sporn MB, Libey KT. Cancer che-
dination between the NCI, Cancer           Alberts DS, et al. What happened       moprevention: scientific promise,
Centers, foundations, community            to the coxibs on the way to the car-   clinical uncertainty. Nature Clini-
groups, and advocacy organizations.        diologist? Can Epid Bio Prev, March    cal Practice Oncology 2005; 2(10):
NCI is successfully partnering with        2005 14(3): 555-556.                   518-525.
local and national organizations
including the American Cancer              Exploring the Role of Cancer           Therapy
Society, the Intercultural Cancer          Centers for Integrating Aging          Interviews:
Council, and the Lance Armstrong           and Cancer Research. Report of            Mac Cheever, MD
Foundation to provide informational        “Working Group 4: Prevention,             John Crowley, MD
resources on cancer survivorship           Risk Assessment, and Screening”,          Ben Shapiro, PhD
to patients, family members and            from the NIA/NCI workshop June            Spencer Lemons
medical providers. These collabora-        13-15, 2001.                           Communications:
tions are ideal for the dissemination                                                Kristiina Vuori, MD, PhD
of educational materials including         Greenwald P, McDonald SS.                 Ronald Herberman, MD
statistical information about cancer       Cancer prevention: the roles of diet      Bruce Stillman, PhD
survivors, survivors’ second malig-        and chemoprevention. Can Contr J       Catalyzing Team Science. Report
nancies, quality of life, and other        1997; 4(2).                            from the 2003 BECON Symposium
information such as current research
grants and post-treatment resources.       Jankowski JA, Hawk ET. A meth-         DTP-NCI Academic Public-Pri-
                                           odologic analysis of chemopreven-      vate Partnership Program (AP4)
Future collaborations to consider          tion and cancer prevention studies     http://dtp.nci.nih.gov/docs/ap4/ap4-
include coordination of efforts and        for gastrointestinal cancer. Nature    index.jsp.
funding strategies. For example, the       Clin Prac Gastro & Hep 2006; 3(2):
Lance Armstrong Foundation is              101-111.


 Accelerating Successes Against Cancer
Hon ML. Can anyone make money           and validation. Nature Rev Can        Janet Eary / University of
from biomarkers? Start-Up Septem-       2004; 4(4):309-314.                   Washington
ber 2005.
                                        Medicare Laboratory Payment           Ralph Weissleder / MGH
NCI Strategic Plan. http://strategic-   Policy Now and in the Future.
plan.nci.nih.gov. January 2006.         Report from the Institute of          Bob Day / Fred Hutchinson Cancer
                                        Medicine http://www.nap.edu/          Research Center
Policy issues in the evaluation of      books/0309072662/html.
clinical genetic testing for complex                                          Tim Yeatman / Moffitt Cancer
conditions. A University of Cam-        Peter Corr / Pfizer                   Center
bridge/Wellcome Trust Research
Project.                                Steve Gutman / Director of the Of-    Les Robinson / St. Jude
                                        fice of InVitro Diagnostics, Center
Restructuring the National Cancer       for Devices & Radiologic Health       Dan Sullivan / NCI
Clinical Trials Enterprise. Report of
the Clinical Trials Working Group       Arthur Holden, Chairman and           Survivorship
of the National Cancer Advisory         Executive Director, DMD Trans-        Childhood Cancer Survivorship:
Board. June 2005.                       lational Research Consortium /        Improving Care and Quality of Life.
                                        Chairman and Founder, Pharmaceu-      Report of a committee established
Simon JA, et al. Accelerating           tical Biomedical Research Consor-     by the Institute of Medicine, 2003.
cancer drug discovery and develop-      tium, Ltd
ment: leveraging the Nation’s aca-                                            From Cancer Patient to Cancer
demic cancer centers. Unpublished       Bob Zivin / Johnson & Johnson         Survivor: Lost in Translation. Re-
manuscript.                                                                   port of a committee established by
                                        Jean-Luc Vanderheyden / GE            the Institute of Medicine, 2006.
Biomarkers and Imaging                  Healthcare
Gutman S, Kessler L. The Food and                                             A National Action Plan for Cancer
Drug Administration perspective         Steven Seelig / VP, Abbott-Vysis      Survivorship: Advancing Public
on development of biomarkers for                                              Health Strategies. Report sponsored
cancer. (submitted for publication).    Kathryn Phillips / School of Phar-    by Centers for Disease Control and
                                        macology / UCSF                       Prevention and the Lance Arm-
Large-Scale Biomedical Science:                                               strong Foundation, 2004.
Exploring Strategies for Future         Kenneth Hillan, VP of Develop-
Research. Report of the Institute       ment / Genentech & Bill Pignato       Living Beyond Cancer: Finding
of Medicine / National Research         (contractor for Genentech)            a New Balance. Report of the
Council. 2003.                                                                President’s Cancer Panel, 2003-
                                        Alessandra Cesano / Amgen             2004 Annual Report.
Phillips KA, et al. Diagnostics and
biomarker development: priming          Greg Rossi / Amgen                    National Cancer Institute web site
the pipeline. Nat Rev Drug Dis (in                                            www.cancer.gov
press).                                 Judith Yost / Div of Lab Svcs (gov)
                                                                              Interviews with Drs. Debra Fried-
Phillips KA. A marriage made in         Lucy Lu, VP Technology Manage-        man, Jean Sanders, Stephanie Lee,
heaven? Health policy implications      ment, Head of US Chief Tech Of-       Paul Martin
of the integration of biotechnology     fice and Linda McAllister / Roche
and pharmacogenomics. (submitted
for publication).                       Sam Gambhir / Stanford

Ransohoff DF. Rules of evidence for     Ken Krohn / University of
cancer molecular-marker discovery       Washington


                                                                                       Accelerating Successes Against Cancer 
                                            Summary

                                            A
                                                   dvances in diagnostic tests and treatments for cancer usually
                                                   are made available to patients rapidly by Cancer Centers,
                                                   academic medical centers, and major health care provid-
                                            ers. However, reaching all patients with cancer, and their health
                                            care providers, is a goal obtainable only through concerted efforts
                                            in education and widespread adoption of best practices, especially
                                            by physicians for underserved populations. The NCI-designated
                                            Cancer Centers should ensure that opportunities to participate in
                                            clinical trials of new cancer treatments, preventative strategies,
                                            and early detection tests are made available to greater numbers of
                                            individuals, including underserved and diverse populations.

DisseminaTion
                                            Highest Priority Strategies
                                                                                    introduction
                                             • The Federal government needs
                                                 to designate a lead agency         In order to fulfill as quickly as
                                                 within the Department of           possible NCI’s Challenge Goal to
                                                 Health and Human Services          eliminate the death and suffering
                                                 (HHS) to coordinate funding        from cancer – and to realize the
                                                 and dissemination of cancer        potential for known best practices
                                                 control efforts to the entire      and research advances – it is es-
                                                 U.S. population, by bringing       sential to extend the expertise and
                                                 together the fragmented efforts    infrastructure that has been ex-
                                                 of NCI, CDC, CMS, and other        traordinarily well developed at the
                                                 HHS agencies.                      NCI-designated Cancer Centers to
                                             •   Cancer Centers should take the     all the relevant populations in the
                                                 lead in disseminating cancer       United States that are currently
                                                 care guidelines throughout         beyond the areas and communities
                                                 their states, in collaboration     that are traditionally serviced by
                                                 with state health departments      the Cancer Centers.
                                                 and state cancer plans.
                                             •   Cancer Centers should work         There is ample evidence that even
                                                 with state cancer registries to    when advances are made in cancer
                                                 convert them into outcomes         treatment, early detection, and
                                                 registries, and should use them    prevention, the overall populations
                                                 to identify populations with       that can and should benefit have
                                                 disproportionate needs for         insufficient knowledge of and access
                                                 cancer prevention and care.        to these advances and evidence-
                                             •   Demonstration projects on the      based best practices.
                                                 medical and financial benefits
                                                 of best cancer control practices
                                                 should be initiated in regions
                                                 served by Cancer Centers,
                                                 funded by CMS and led by the
                                                 Cancer Centers.



  Accelerating Successes Against Cancer
                                                                               research studies of cancer preven-
Current Knowledge,                     adequate dissemination of clinical
                                       research access to these populations    tion or early detection. A major
barriers and                           will require culturally-sensitive       bottleneck and rate-limiting issue
opportunities                          approaches.                             is the low participation in the
                                                                               large number of translational and
The main focus of the Cancer           It is widely recognized that par-       innovative early phase investiga-
Centers and NCI support for them       ticipation in cancer therapeutic        tor-initiated trials, which are now
has been on basic, translational and   trials only involves 3-5% of can-       performed almost entirely at the
clinical research. Participation of    cer patients in the United States.      Cancer Centers. There currently
Cancer Centers in education and        There are considerable efforts being    is little access to such studies by
outreach activities has generally      made to reduce barriers to participa-   the overall appropriate population.
not been encouraged, or has taken      tion in the Phase III clinical trials   Effective linkages to community
the form of unfunded mandates.         conducted under the auspices of         hospitals and to clinical oncolo-
Dissemination of research advances     the cooperative groups, CCOPs,          gists and primary care physicians in
to all appropriate populations         and other multicenter collaborative     the regions served by the Cancer
– including ethnic minorities and      consortia supported by NCI and by       Centers could provide much wider
the underserved, uninsured and         the pharmaceutical and biotechnol-      access and also substantially accel-
uninformed – has been suboptimal.      ogy industries.                         erate accrual to such studies.
There are well known barriers to
enlisting various populations into     Similarly, only a very small pro-       There is striking heterogeneity in
clinical research studies, including   portion of individuals at high risk     the United States in the knowledge
cultural and language issues, and      for cancer participate in clinical      of best practices or evidence-based


                                                                                       Accelerating Successes Against Cancer 
approaches to cancer therapy, early        Cancer Centers, which often have            disseminate to those states that
detection, prevention, and survivor-       this expertise, is not supported.           lack NCI-designated Cancer
ship issues, and also in their imple-                                                  Centers.
mentation by health care providers.        Another major current barrier to        •   Designation by the Federal
To address these disparities, most         effective dissemination of best             government of a lead agency
of the NCI-designated Cancer               practices for cancer control is the         within the Department of
Centers have – in addition to their        limited reimbursement by CMS or             Health and Human Services
research excellence – developed            private payers for cancer preven-           (HHS) for dissemination of
the expertise, and needed faculty          tion, early cancer detection screen-        cancer control programs to the
and well-trained staff, to provide to      ing, or survivorship issues.                entire population of the United
the populations that they serve the                                                    States and to coordinate
best practices and evidence-based                                                      what are currently relatively
                                           emerging Dissemination
approaches for cancer (see sidebar,                                                    fragmented efforts by various
“UPMC Cancer Centers Network:              Strategies                                  HHS agencies, including NCI
Dissemination Beyond NCI-desig-            The important problems summa-               and CDC. An appropriate
nated Cancer Centers”). However,           rized above are clearly multifaceted        level of resources needs to be
there have been relatively little          and will require enhanced collab-           provided to the designated lead
attention, processes, or resources di-     orative efforts among many organi-          agency in order to effectively
rected toward the capability of these      zations and sectors, including the          promote dissemination of
Cancer Centers to disseminate their        Federal government – not just NCI           cancer control throughout the
knowledge and expertise to most            and other relevant NIH institutes,          country.
of the communities in the United           but even more importantly, CMS,         •   Provide leadership by the HHS
States, especially those that are not      CDC, AHRQ and HRSA – along                  lead agency for cancer control
directly proximal to or traditionally      with state governments, local gov-          dissemination to forge effective
linked to the Cancer Centers.              ernments, academic cancer centers,          linkages between NCI-
                                           community-based cancer centers,             designated Cancer Centers
It is very encouraging that national       and other health care providers, pri-       and state governments, CDC
organizations such as the CDC,             vate insurers, and the business com-        and CMS to implement action
American Cancer Society, and               munity, especially the pharmaceuti-         plans to address the areas of
C-Change – and also a substan-             cal and biotechnology industries.           greatest need.
tial number of the state governors                                                 •   Added support for NCI’s
– have promoted the development            There is a real opportunity for the         Cancer Centers program to
and implementation of cancer con-          network of NCI-designated Cancer            allow substantive involvement
trol plans in all of the states in the     Centers across the United States to         in, and leadership role for,
country. Many of the state plans           play a major role in linking together       cancer control plans in states
are very well conceived, compre-           these key stakeholders in order to          that have one or more Cancer
hensive, and feasible. However,            mount effective dissemination of            Centers, for working together
these plans have largely remained          both research advances and best             and with other health care
only on paper, due to lack of suf-         practices for addressing cancer pre-        providers in their state. Various
ficient and effective infrastructure       vention, early detection, treatment         mechanisms and processes
and resources for implementation.          and improved survivorship.                  might be implemented to
Implementation of the cancer                                                           facilitate a central role by
control plans is the responsibility        The following specific recommenda-          the NCI-designated Cancer
of the departments of health in            tions are proposed:                         Centers in dissemination.
each state, which often lack the             • Strengthening of current            •   Development of effective
needed cancer-relevant expertise to            overall infrastructure for              processes for substantive
implement the best practices and               dissemination of research and           involvement of the Cancer
evidence-based approaches encom-               best practices by clinical and          Centers in the CDC-funded
passed in the plans. Linkage of the            comprehensive Cancer Centers            cancer control efforts in
state plans to the NCI-designated              to their region, and also to            the states, with the CDC


 Accelerating Successes Against Cancer
UPMC Cancer Centers Network
Dissemination beyond nCi-Designated Cancer Centers

The University of Pittsburgh Medical Center (UPMC) Cancer Centers, one of the largest clinical cancer networks in the United
States, provides highly specialized cancer care to patients within their own communities. This truly multifunctional cancer
care network is economically integrated and uniformly managed and operated across multiple settings.

In a regional “hub and satellite” structure, inpatients and specialized treatment are provided at UPMC’s central hub facility,
the Hillman Cancer Center in Pittsburgh. Outpatient care in medical oncology, radiation therapy, and surgery is offered at
more than 40 UPMC Cancer Centers’ regional satellite sites across western Pennsylvania, eastern Ohio, and northern West
Virginia.

UPMC Cancer Centers works in tandem with the University of Pittsburgh Cancer Institute (UPCI), western Pennsylvania’s only
NCI-designed Comprehensive Cancer Center. As the academic and research partner, UPCI is nationally and internationally
renowned for its translational, clinical, cancer control and population sciences research programs, thus providing a strong
scientific base for the dissemination of knowledge and best practices to the community network of UPMC Cancer Centers.

UPMC Cancer Centers’ integrated cancer care delivery network treats more than 36,000 new patients each year for hema-
tologic and oncologic disorders. This translates to more than 285,000 patient visits annually. The working partnership with
UPCI allows for the expedited implementation of new, more efficient ways of delivering cancer care by:

  •   Translating research discoveries to clinical therapeutic, early detection and prevention applications which are available at
      both the academic medical center and community satellite centers
  •   Providing cutting-edge treatments and technologies, including access to more than 150 clinical trials
  •   Developing and implementing clinical pathways for major types of cancer, to provide standardized approaches and best
      practices for care, to improve patient outcomes and efficiencies while decreasing operating costs
  •   Offering access to cancer control and ancillary support services such as symptom and side effect management, nutrition
      advice, family counseling, psychological care, stress management, close follow-up of cancer survivors, and cancer
      education resources

In addition to these activities in western Pennsylvania, UPCI is also playing a key role in implementation of the Pennsylva-
nia Comprehensive Cancer Control Plan, that includes the establishment of the Coordinating Center for the Pennsylvania
Cancer Control Consortium(PAC3) at UPCI, a statewide biorepository and clinical and tissue informatics network, as well as
a statewide clinical trials network to facilitate the completion of innovative, investigator-initiated clinical trials originating in
the academic cancer centers.




                                                                                                         Accelerating Successes Against Cancer 
      promoting partnerships                   for wider implementation of            of disproportionate need for
      between the NCI-designated               early phase studies on new             focusing outreach efforts.
      Cancer Centers and the state             treatments, early cancer           •   Leveraging of Federal
      health departments for maximal           detection, risk assessment,            support and leadership to
      collaboration and utilization of         prevention, and improved               obtain needed corporate
      the expertise and capabilities           survivorship.                          and philanthropic support
      of the Cancer Centers in             •   Support telemedicine                   for effective dissemination
      implementing the state cancer            approaches as important                of cancer control, including
      control plans.                           infrastructure for the Cancer          facilitation of close cooperation
  •   Provide funding by CDC                   Centers to effectively and             between Cancer Centers,
      for demonstration projects               conveniently communicate               community hospitals, and other
      in some regions or states,               with other organizations               health care providers in each
      particularly those led by NCI-           and health care providers in           region of the United States.
      designated Cancer Centers, for           the region, as well as to link     •   Support for Cancer Centers,
      implementation of population-            the Cancer Centers with                by CMS and private payers,
      based cancer control efforts,            community hospitals, clinical          to develop specific clinical
      especially those focused on              oncologists, and primary care          pathways for best practices for
      cancer prevention and early              physicians.                            treatment of patients at each
      detection of cancer.                 •   Support should be provided for         stage of each type of cancer,
      In states without an NCI-desig-          developing a mechanism for             and similarly for early detection
      nated cancer center, a mecha-            Cancer Centers to effectively          approaches for the major types
      nism should be developed for             partner with state cancer              of cancer.
      some cancer centers, especially          registries to convert these        •   Support, perhaps as
      those in the same region of              registries from what are now           supplements to CCSGs, for
      the country, to partner with             mainly incidence registries, to        research studies of behavioral
      academic medical centers and             outcomes registries.                   barriers to compliance by the
      community hospitals, in order            These converted registries             relevant populations, with
      to play a significant role in dis-       would include detailed data            recommended best practices
      semination. It is proposed that          on stage of disease, treat-            for cancer prevention, early
      10 such demonstration projects           ments administered, response           detection, treatment, and
      be implemented, each with an             to treatments, recurrence or           improved survival, and ways
      annual cost of $2.5 million.             development of metastatic              to overcome the identified
  •   NCI-designated Cancer                    disease, as well as deaths from        barriers.
      Centers, which generate                  cancer, development of a               Defining and overcoming
      most of the innovative early             second primary cancer, side            barriers to screening and early
      phase investigator-initiated             effects of therapy, and persis-        detection is a priority because
      clinical research studies, could         tence of known environmental           after primary prevention, the
      disseminate these studies more           risk factors that may modify           greatest improvements in
      widely by various mechanisms             prognosis. It is estimated that        outcomes will be realized by
      and processes.                           such conversions would entail          identifying cancers early, when
      Supplements to NCI’s Cancer              a one-time cost of $50 million,        treatments are most effective.
      Center grants (CCSGs)                    with maintenance then borne        •   Support from CMS should
      could be used to develop and             by the states and individual           be sought for demonstration
      implement infrastructure to              medical institutions.                  projects, led by the Cancer
      effectively link together Cancer     •   Supplements to CCSGs should            Centers, to evaluate and
      Centers in a region and to link          be provided for use of state           demonstrate effectiveness of
      those Centers with community             cancer registries and SEER data,       various dissemination efforts
      hospitals, clinical oncologists,         coupled with GIS mapping, to           for maximal implementation
      and primary care physicians              identify areas and populations         of best practices in a region,



 Accelerating Successes Against Cancer
     and for compliance with the             education on best practices,
     recommended practices.                  including electronic tumor
 •   Education of relevant                   boards conducted by the NCI-
     populations about the                   designated Cancer Center.
     importance of availing
     themselves of dissemination         It will be important not only to im-
     programs, and education of          plement programs for dissemination
     health care providers about         beyond the Cancer Centers, but
     the value and importance            also to objectively evaluate the ef-
     of promoting and utilizing          ficacy of the various efforts, e.g., the
     the relevant dissemination          degrees of increased access to pre-
     programs for their patients.        vention, screening, clinical trials,
                                         and survivor services. Evaluation
                                         should also include monitoring the
Anticipated outcomes                     key outcomes in the regions served,
and Potential impact                     e.g., cancer incidence, disease-free
The NCI-designated Cancer Cen-           interval, morbidity, quality of life,
ters can play a major role in educa-     and survival. National outcomes
tion of various key groups about         studies also should be planned and
dissemination if the Centers are         supported.
provided with needed support from
the Federal and state governments        The economic benefits of dis-
and from philanthropic and busi-         semination can also be measured
ness sources. This would support         and support should be provided to
education programs for:                  NCI-designated Cancer Centers for
                                         this activity.
 • Cancer patient populations
     about the importance of             Together with the evaluation of the
     seeking out clinical oncologists    effects of the new program, there is
     and centers with cancer             a need for benchmarking to assess
     experts, about innovative           if quality of care is maintained and
     clinical research programs, and     improved. This can be obtained
     utilization of best practices.      through a national cancer data
 •   General population and, most        system working in connection with
     importantly, those at increased     SEER and the National Cancer
     risk for cancer, about best         Data Base (NCDB).
     practices for cancer prevention,
     risk assessment, and early          references
     detection of cancer.
                                         Ensuring Quality Cancer Care.
 •   Health care providers about
                                         Report by the Institute of Medi-
     the value of clinical cancer
                                         cine. 1999.
     research studies, best practices,
     and the technology needed
                                         Translating Research into Cancer
     for effective treatment,
                                         Care: Delivering on the Promise.
     diagnosis, early detection, and
                                         Annual Report of the President’s
     prevention of cancer. Such
                                         Cancer Panel. 2005.
     educational programs could
     include various approaches for
     continuing medical and nursing



                                                                                    Accelerating Successes Against Cancer 
Appendix A
Selected positive phase III chemoprevention and dietary intervention trials funded by the National
Cancer Institute and/or pharmaceutical industry
            Site
                                    Reference              Trial Design             Major Result                        Comments
         Trial Name
 Breast Cancer
  Breast Cancer                 Fisher et al. (1998)   13,388 women at           50% reduction in the      Equivalent effect of tamoxifen
   Prevention Trial                                    intermediate to high      risk of invasive breast   on DCIS; increased incidence of
   (BCPT)                                              risk; tamoxifen vs        cancer                    endometrial cancer and pulmonary
                                                       placebo for up to 5                                 embolism
                                                       years
     Study of Raloxifene        Wickerham et al.       19,747 women at           Approximately 50%         Raloxifene was associated with
     and Tamoxifen in           (2006)                 intermediate to high      reduction in the risk     a lower incidence of endometrial
     Postmenopausal                                    risk; raloxifene versus   of invasive breast        cancer, pulmonary embolism and
     Women (STAR)                                      tamoxifen for up to 5     cancer by both agents     deep vein thrombosis
                                                       years
     Women’s                    Chlebowski et al.      2,437 women at high       24% reduction             In contrast to low fat diet of up to
     Interventional             (2005)                 risk for developing       in breast cancer          31% calories from fat at end of
     Nutrition Study                                   second primary            recurrence risk           WHI trial, low fat diet in WINS was
     (WINS)                                            cancer (stage I and II    associated with low       maintained
                                                       breast cancer, within     fat diet
                                                       1 yr of dx): low fat
                                                       (<20% calories) vs
                                                       standard diet
 Cervix Cancer
   HPV-16 L1 virus-             Koutsky et al.         2,392 women (age          100% efficacy against     Trial led to recent FDA approval of
   like–particle                (2002)                 16-23), HPV negative,     HPV 16 infection          Merck HPV 16/18 vaccine in June,
   vaccine study                                       randomized to                                       2006
                                                       placebo or vaccine
     Quadrivalent HPV           Villa et al. (2005)    1,158 women (age          90% efficacy (95% CI      Trial led to recent FDA approval of
     6, 11, 16, 18                                     16-23), randomized        71–97) against HPV-       Merck bivalent HPV 16/18 vaccine in
     vaccine study                                     to one of three           specific infection/       June, 2006
                                                       vaccine preparations      disease in the treated
                                                       or placebo                versus placebo
                                                                                 groups
     Bivalent HPV 16/18         Harper et al.          1,113 women (age          95.1% efficacy (CI:       GSK vaccine continues in
     vaccine                    (2004); Harper et      15–25), randomized        63.5–99.3) against        development for future submission
                                al. (2006)             to placebo or vaccine     persistent cervical       to FDA
                                                                                 infection with HPV-
                                                                                 16/18 at close of
                                                                                 study.
                                                                                 significant vaccine
                                                                                 efficacy against
                                                                                 HPV-16 and HPV-18
                                                                                 endpoints at 4.5 year
                                                                                 follow up: persistent
                                                                                 infection: 6 month
                                                                                 definition, 94.3 (CI:
                                                                                 63.2–99.9); 12 month
                                                                                 definition, 100% (CI:
                                                                                 33.6–100)




70 Accelerating Successes Against Cancer
        Site
                           Reference             Trial Design             Major Result                       Comments
     Trial Name
Colon Cancer
  Dartmouth             Baron et al. (1999)   930 polyp patients       Significant 19%          Significant 25% reduction in risk of
  Calcium Polyp                               randomized to            reduction in risk of     the largest recurrent adenoma being
  Prevention Study                            calcium carbonate        polyp recurrence at      > 5mm (unadjusted risk ratio)
                                              versus placebo for 3+    endpoint colonoscopy
                                              years                    (adjusted risk ratio)
  Dartmouth Aspirin     Baron et al. (2003)   1121 polyp patients      Significant 19%          81 mg, but not 325 mg ASA dose
  Polyp Prevention                            randomized to ASA        reduction in polyp       effective; unadjusted risk ratio for
  Study                                       81 mg or 325 mg/day      recurrence in 81 mg      advanced lesions 0.59 (CI: 0.38-0.92)
                                              for 3+ years             group
  CALGB Aspirin Trial   Sandler et al.        635 patients with        Signficant 35%           No significant difference in advanced
                        (2003)                previous colorectal      reduced risk of          adenomas
                                              cancer randomized        new adenoma with
                                              to 325 mg ASA or         ASA (CI: 0.46-0.91),
                                              placebo                  adjusted relative risk
  NCI/Pfizer            Bertagnolli et al.    2,035 polyp patients     45% and 33%              Significant reduction in advanced
  Adenoma               (2006)                randomized to            reduction in risk of     adenoma (p<0.0001), but increased
  Prevention with                             200 mg or 400 mg         polyp recurrence         cardiovascular events, especially in
  Celecoxib Trial                             celecoxib BID or         at 3-5 years, more       400 mg group
  (APC)                                       placebo                  pronounced in 400
                                                                       mg group
  Pfizer American/      Arbor et al. (2006)   1,561 polyp patients     36% reduction in risk    Increased risk of cardiovascular
  Israeli Celecoxib                           randomized to 400        of polyp recurrence at   events seen only in those with
  Polyp Prevention                            mg QD or placebo for     3-5 years                preexisting CV disease (1.3%)
  Trial (PreSAP)                              up to 5 years
Prostate Cancer
  Prostate Cancer       Thompson et al.       18,882 men (age          Significant 25%          Increase in sexual dysfunction
  Prevention Trial      (2003)                55 or over) with         reduction in risk        (p<0.001) and increased incidence
  (PCPT)                                      normal DRE and PSA       of biopsy-proven         of advanced Gleason grade cancers
                                              < 3 randomized to        prostate cancer          associated with finasteride (6.4% vs
                                              finasteride or placebo                            5.1% for placebo)
                                              for 7 years
Skin Cancer
  Vitamin A             Moon et al. (1997)    2,290 patients with      Significant 26%          No effect of basal cell cancer risk;
  Prevention Trial                            evidence of moderate     reduction in risk of     little or no Vitamin A toxicity
                                              to severe actinic        squamous cell cancer
                                              keratosis randomized     of the skin
                                              to Vitamin A 25,000
                                              IU/day for up to 5 yrs
                                              vs placebo
  Nutritional           Clark et al. (1996)   1,303 patients           No effect on risk        49% reduction in risk of prostate
  Prevention Study                            with resected non-       of developing new        cancer as a secondary analysis
  with Selenium                               melanoma skin            primary skin cancers     (Duffield-Lillico, et al. 2003)
                                              cancers randomized
                                              to selenium 300 mcg
                                              QD vs placebo for up
                                              to 5 yrs




                                                                                                       Accelerating Successes Against Cancer 71
Appendix B




72 Accelerating Successes Against Cancer
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Appendix C




88 Accelerating Successes Against Cancer
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90 Accelerating Successes Against Cancer
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Appendix D




             Survivorship Activities
             at Cancer Centers
             Due to the amount of information available,
             this appendix can be viewed at the following website:


             www.cancer.gov/cancercenters/




                                                     Accelerating Successes Against Cancer 99
Appendix E

                                            Survivorship Activities at NCI Cancer Centers
        Cancer Center                                Survivorship Activity                        Research   Clinical Care   Education *   Community
                                                                                                                                            Outreach

 Siteman Cancer Center Survivorship Activity
  Psychosocial Clinical Service
                              Medical care and counseling                                                         X
                              Psychiatric and psychological services                                              X
                              Support groups for patients and family members                                      X
                              Nutritional counseling                                                              X
                              Quality of life assessment and activities (institutional and NCI/      X            X
                              NIH-funded clinical studies)
  Help Us Give Support (HUGS) program in breast cancer (Deshields Komen local funding)
                              Education and support activities for children related to breast                                    X            X
                              cancer patients (Deshields Komen local funding)
                              Support groups for children related to breast cancer patients                                      X            X
                              (Deshields Komen local funding)
  Young Women’s Breast Cancer Program (Ivanovich Komen local funding)
                              Genetic counseling for young women (Ivanovich Komen local                           X              X            X
                              funding)
                              Risk assessment for young women (Ivanovich Komen local                              X              X            X
                              funding)
  Witness Program (Mathews Komen local funding)
                              Support groups for breast cancer patients/survivors (Mathews                                                    X
                              Komen local funding)
                              Educational and support materials for breast cancer patients/                                                   X
                              survivors (Mathews Komen local funding)
                              Relationships with local organizations, such as the Breakfast                                                   X
                              Club (Mathews Komen local funding)
  Cancer Center Support Grant (CCSG) Shared Resources (Eberlein NCI P30)
                              Hereditary Cancer Core (Eberlein NCI P30)                              X
                              Health Behavior and Outreach Core (Eberlein NCI P30)                   X                           X            X
  Community Education and Screening Activities
                              Community education events (prevention, care, and survivor-                                        X            X
                              ship) touching more than 28,000 people annually
                              Screening activities across the spectrum of cancers                                                X            X
  Clinical Support Services
                              Siteman Cancer Center at Barnes-Jewish Hospital - St. Peters:                       X              X
                              AWARE Program (guided imagery and relaxation); Conquer
                              program (general support group); KIDScope (support group for
                              children 4-13 whose parent or caregiver has cancer/adults
                              meet at the some time to discuss parenting); Massage Therapy
                              (offered weekly to patients and caregivers); DHHS/CDC skin
                              cancer programs; and ACS programs (Look Good, Feel Better;
                              Daffodil Days, ACS Days)
                              Siteman Cancer Center at Barnes-Jewish Hospital - West Co.                          X              X
                              Bone Marrow Transplant                                                              X              X
  Palliative Care Service
                              Routine medical follow-up and surveillance                                          X
                              Pain and symptom management                                                         X
                              Medical management and counseling                                                   X
                              Hospice management                                                                  X              X




* Education may be student, patient or community education

100 Accelerating Successes Against Cancer
       Cancer Center                                   Survivorship Activity                            Research   Clinical Care   Education *      Community
                                                                                                                                                     Outreach

 Barnard Health and Cancer Information Center (BHCIC)
                               Print educational materials on cancer survivorship                                                        X
                               Aduiovisual educational materials and kiosks on cancer survi-                                             X
                               vorship
                               Information about websites related to cancer survivorship                                                 X
  Program for the Elimination of Cancer Disparities (PECaD) Community Networks Program                     X                             X                X
  (Farria NCI U01)
                               Research projects focused on reducing cancer-related disparities            X                             X                X
                               Educational programs focused on reducing cancer-related                                                   X                X
                               disparities
                               Community (disease-oriented) action teams (community-based                  X                             X                X
                               participatory research and education)
                               Training programs for investigators and communities                         X                             X                X
  Prevention and Control Research Program (Eberlein NCI P30)
                               Quality of life over time: DCIS vs early breast cancer (Jeffe NCI R01)      X
                               Geographic variation of breast cancer survival (Schootman NCI R01)          X                                              X
                               Neighborhood effects on quality of life in breast cancer (Schoot-           X                                              X
                               man NCI R01)
                               Comorbidity prognostic impact in elderly cancer patients (Pic-              X
                               cirillo NCI R01)
                               Centers of Excellence in Cancer Communications Research                     X                                              X
                               (CECCR) (Kreuter NCI P50)
                               Minority pre-doctoral education to reduce disparities (Kreuter R25)         X
                               Health promotion and disease prevention research center                     X                             X                X
                               (Brownson U48)
                               Predictors of Relapse to Smoking in Lung Cancer (Walker NCI R01)            X
                               Mental Health History and Survival Among Breast Cancer                      X
                               Patients (Walker Longer Life Foundation funding)
  Translational and Clinical Research Program
                               Phase 2 Trial of Estradiol Therapy for Advanced Breast Cancer               X
                               (Ellis NCI/Avon P30 supplement)
                               Impact of Neodadjuvant Chemotherapy With or Without Zometa                  X
                               on Occult Micrometastases and Bone Density in Women with
                               Locally Advanced Breast Cancer (Aft Novartis and Pfizer funding)
                               Overcoming Barriers to Early Phase Clinical Trials: Coaching                X                                              X
                               Promotion for Minority Recruitment (Fracasso NCI R21)
                               Estimating the probability of death from prostate cancer or other           X
                               competing risk factors (Yan Longer Life Foundation funding)
  Siteman Clinical Research Affiliates
                               Affiliates for clinical studies (two satellite/affiliate Siteman            X                                              X
                               Cancer Centers, other study affiliates)
                               Prevention and control affiliate (Columbia, MO)                             X                                              X
                               Member of Mayo Phase II Consortium (NCI funded)                             X                                              X
                               Member of Northwestern Phase II Chemoprevention Consortium                  X                                              X
                               (NCI funded)




* Education may be student, patient or community education

                                                                                                                       Accelerating Successes Against Cancer 101
        Cancer Center                                  Survivorship Activity                   Research   Clinical Care   Education *   Community
                                                                                                                                         Outreach

 Abramson Cancer Center Survivorship Activities
  The Lance Armstrong Foundation Living Well After Cancer Program:
                           Consultative Programs:                                                 x                           x         TBA Penn
                                                                                                                                         Network
                                                                                                                                        Hospitals
                                  Breast Cancer Survivors
                                  Lymphoma Survivors
                                  BMT Survivors

                                  Clinical Programs: (TBA Penn Network Hospitals)                 x            x              x         TBA Penn
                                                                                                                                         Network
                                                                                                                                        Hospitals
                           Testicular Cancer Survivors
                           Transition program-Young Adult Survivors of Childhood Cancers
                                (CHOP-PENN Model)
   The Abramson Cancer Center Patient and Family Services Program:
                           Psychosocial Counseling                                                             x              x
                           Nutrition Counseling                                                                x              x
                           Patient & Family Services                                                           x              x

                                  Genetic Risk Evaluation Program:
                                  Breast Cancer                                                   x            x              x             x
                                  Testicular Cancer                                               x            x              x             x


                                  Consultations:
                                  Breast Ca Survivors
                                  Lymphoma Survivors
                                  BMT Survivors
                                  Nutrition Counseling
                                  Patient & Family Services
                                  Psychosocial Counseling
                                  Breast Cancer Genetic Risk Evaluation Program
                                  Testicular Cancer Genetic Risk Evaluation Program

                                  Databases:
                                  Consultative Programs (Breast, Lymphoma, BMT)
                                  Clinical Programs (Testicular, Young Adult)
                                  Psychosocial Counseling
                                  Breast Cancer Genetic Risk Evaluation Program
                                  Testicular Cancer Genetic Risk Evaluation Program

                                  Survivorship focused: Presentations (poster & podium),
                                  Consultations, Educational Programs, National working
                                  groups

                                  ACC support groups for survivors of breast, prostate, head
                                  & neck, GI cancers & their families




* Education may be student, patient or community education

102 Accelerating Successes Against Cancer
       Cancer Center                              Survivorship Activity               Research   Clinical Care   Education *      Community
                                                                                                                                   Outreach

 Robert H. Lurie Comprehensive Cancer Center of Northwestern University
                            Cancer Survivors’ Celebration and Walk                                                                      X
                            Cancer Therapy Cutaneous Adverse Reaction Clinic             X            X
                            Community education programs                                                               X                X
                            EndLink                                                                                    X                X
                            EPEC-O Project                                                                             X
                            Fertility Preservation Program                                                             X
                            Geriatric Oncology Consultation Services                                  X                X                X
                            Health Learning Center Satellite                                                           X                X
                            Hospice/Palliative Medicine Program                                       X                X                X
                            Lunchtime Lectures: Cancer Prevention/Control                                              X                X
                            Lynn Sage Breast Cancer Symposium                                                          X                X
                            Lynn Sage Breast Cancer Town Hall Meeting                                                  X                X
                            Office of Special Population Initiatives                                                   x                X
                            Ovarian Cancer Survivor Course                                                             X                X
                            Patient Advisory Board                                                                     X                X
                            Patient Navigator Program                                                 X                X                X
                            Patient Support Groups                                                                     X                X
                            Psychosocial Oncology Program                                X            X                X                X
                            STAR (Survivors Taking Action and Responsibility)                         X                X                X
                            Survivors’ Day with the Chicago White Sox                                                                   X

 Norris Cotton Cancer Center Survivorship Activities
                             Community Outreach and Education
                             Cancer Help Line                                                                          X                X
                             Cancer Support and Information Groups                                                     X                X
                             Patient and Family Libraries                                                              X                X
                             The Women’s Health Resource Center                                                        X                X
                             Community Information and Education: Conferences, etc.                                    X                X
                             Charting Your Course: Breast Cancer                                                       X                X
                             Programmatic Development at the State Level                                               X
                             American Cancer Society                                                                   X
                             Survivorship Research
                              Cancer Prevention and Risk Reduction
                                Chemoprevention Research                                 X
                                SunSafe                                                  X                             X                X
                                Tobacco Control                                          X                             X
                                Cervical Cancer Prevention                               X            X
                                The Familial Cancer Program                              X            X                X
                              Screening and Early Detection
                                Breast Imaging                                           X            X
                                The New Hampshire Mammography Network                    X                             X
                                The National Lung Screening Trial (NLST)                 X            X
                                Interdisciplinary Prostate Cancer Risk Clinic            X            X
                                Primary Care Colon Cancer Screening Consortium           X
                              Quality of Life/Quality of Care
                                Psycho-Oncology                                          X            X                X



* Education may be student, patient or community education

                                                                                                     Accelerating Successes Against Cancer 103
        Cancer Center                                 Survivorship Activity                     Research   Clinical Care   Education *   Community
                                                                                                                                          Outreach

                                  Clinical Care/Supportive Services for Cancer Survivors
                                  Multidisciplinary Second Opinions                                             X              X
                                  The Palliative Care Program                                      X            X              X
                                  The Haelan Program of Complementary Therapies                                 X
                                  Peer Mentorship                                                               X                           X
                                  Programs for Pediatric Cancer Survivors                                       X              X
                                  The Center for Shared Decision Making                            X            X              X
                                  Chaplaincy Services                                                           X
                                  Rehabilitation                                                                X
                                  Case Management and Financial Planning Consultation                           X              X

 M. D. Anderson Cancer Center Survivorship Program
  Follow-up/Surveillance
                            Life After Cancer Care (LACC) - Evaluates medical sequelae                          X
                            for survivors of any malignancy
                            Long-term Follow-up Clinics
                            Breast Survivorship Clinic                                                          X              X            X
                            Life After Cancer Care (LACC)                                                       X
                            Melanoma                                                                            X
                            Pediatrics and the Children’s Cancer Hospital (Childhood Cancer                     X
                            Survivors Study)
                            Prostate                                                                            X
                            Surveillance of Secondary Cancer
                            Cancer and Screening Prevention Clinic - surveillance of early         X
                            cancer including 2nd malignancies
                            Melanoma and Skin Center - monitoring skin for changes in                           X
                            lesions
                            Prognostic risk characteristics for secondary primary cancers          X
                            (Epidemiology research)
  Cancer/Treatment Effects
                            Fatigue
                            Fatigue Clinic - evaluates and treats cancer or cancer related         X
                            fatigue
                            Fatigue and other symptoms in ovarian cancer patients (Behav-
                            ioral Science research)
                            Co-morbidities
                            Chemotherapy Treatment Complications Clinic                                         X
                            General Internal Medicine Clinic - evaluates and treats survivors                   X
                            co-morbidities
                            Inpatient Service - survivors need acute mgt co-morbidity and                       X
                            symptoms
                            Blood sugar control to prevent steroid-induced hyperglycemia           X
                            (Diabetes research)
                            Cognitive functioning
                            Behavior Interventions Clinic - addresses and remediate’s                           X              X
                            cognitive dysfunction
                            Cognitive and vocational rehabilitation (Neuro-oncology)                            X




* Education may be student, patient or community education

104 Accelerating Successes Against Cancer
       Cancer Center                               Survivorship Activity                        Research   Clinical Care   Education *      Community
                                                                                                                                             Outreach

                             Neuro-cognitive function hematological and testicular cancer          X
                             (Cancer Medicine Research)
                             Pain Management and Palliative Care
                             Integrative Medicine Program
                             Complementary/Integrative Medicine Education Resources                                              X
                             (CIMER) - website health information
                             Place...of wellness - complementary therapies to manage                            X
                             symptoms, relief stress & improve QOL
                             Research examining intervention programs to improve quality of        X
                             life and clinical outcomes
                             Physical and Occupational Rehabilitation
                             Lymphedema                                                                         X
                             Treatment Effects
                             Cardiology - Post chemo CHF/cardiomyopathy (Cardiology                X
                             Research)
                             GvHD - Late toxicities of GvHD (Pulmonary Research)                   X
                             Neuropathy - defining mechanisms of chemotherapy induced              X
                             peripheral neuropathy (Anes research)
                             Osteoporosis/Bone Disease
                                 Bone Disease Program of Texas                                                  X
                                 Bisphosphonates relationship to osteonecrosis of the jaw          X
                                 (BDPT research)
                                 Bone health among breast cancer survivors (Breast research)
                             Radiation and chemotherapy damage to the lung (Pulmonary              X
                             research)
                             Pulmonary Rehabilitation to restore/enhance pulmonary func-                        X
                             tion (Pulmonary)
                             Radiation - long term effects of radiation emphasis on pediatric      X
                             patients (Radiation Physics research)
                             Fertility
                             Cancer related fertility - Parenthood after Cancer Conference         X
                             (Research Behavioral Science )
                             Sexual dysfunction/early menopause
                             Sexual dysfunction research (Behavioral Science Research)             X
  Family/Caregiver Issues
                             Individual and family counseling (Social Work)                                     X
                             Psychiatric services (Behavioral Medicine)                                         X
                             Support groups (Social Work)                                                       X
                             Breast Cancer Survivors, Physical Activity and Quality of Life        X
                             (Behavioral Science research)
                             Predicting exercise among endometrial cancer survivors (Be-           X
                             havioral Science research)
                             Psychological & relationship functioning of lung patients &           X
                             spouses (Behavioral Science Research)
                             Prostate cancer survivors (psychosocial status & physical activ-      X
                             ity) (Behavioral Science Research)
                             Weight gain prevention for breast cancer survivors (Behavioral        X
                             Science Research)




* Education may be student, patient or community education

                                                                                                               Accelerating Successes Against Cancer 105
        Cancer Center                                    Survivorship Activity                           Research   Clinical Care   Education *   Community
                                                                                                                                                   Outreach

                                  Testicular cancer survivors quality of life and health behavior
                                  (Behavioral Science research)
                                  Male breast cancer survivors (psychosocial status) (Cancer                X
                                  Medicine Research)
                                  Quality of life and health behaviors (testicular, prostate and anal)      X
                                  (Cancer Medicine Research)
                                  Providing cancer survivor services for follow-up and early                X
                                  detection (Caner Prevention research)
                                  Exercise studies (Epidemiology Research)                                  X
                                  Survivorship issues and rare cancers (Epidemiology)                       X
                                  Biology, anatomy and management grief in cancer survivors and             X
                                  caregivers (GI Med Onc research)
                                  Psychosocial and neuro-cognitive aspects of pediatric cancer              X
                                  survivorship (Pediatrics research)
                                  Quality of life (Neuro-oncology research)                                 X
                                  Fear of recurrence or second malignancy (Symptom Research )               X
   Economic Effects
                                  Short-term & long-term labor market performance among                     X
                                  cancer survivors (Health Services research)
                                  Retaining/returning to previous employment, vocational rehab, &           X
                                  insurability (Symptom Research)
   Health Disparities
                                  Health Disparities Research - disparities in health care of minor-        X
                                  ity groups
                                  Asian Americans/Hepatitis and relationship hepatocellular                 X
                                  cancer (research)
   Instrument Development
                                  System assessment tools (Symptom Research)                                X
                                  Development of Chronic Graft Versus Host Disease Symptom                  X
                                  Inventory) (Symptom Research)
                                  World Health Organization Collaborating Center for Supportive             X
                                  Care (Symptom Research)
   Health Promotion
                                  Screening and follow-up care - Cancer Screening Prevention                             X
                                  Clinic
                                  Risk factors/susceptibility- prognostic risk characteristics for          X
                                  second cancers (Epidemiology research)
                                  Melanoma risk-reduction practices (Behavioral Science Re-                 X
                                  search)
                                  Tobacco cessation and control (Behavioral Science Research)               X
   Education
                                  The Learning Center - 3 consumer health libraries                                                     X            X
                                  Texas Medical Association - faculty work with TMA to develop                                          X            X
                                  programs for primary physicians to address needs of cancer
                                  survivors
   Community Outreach
                                  Anderson Network
                                    Volunteer patient and survivor support group that shares                                            X            X
                                    information and support
                                  Living Fully with Cancer - annual patient/caregiver conference                                        X            X
                                  (in its 10th year)
                                    Young Breast Cancer Survivors workshop to take place in 2006                                        X            X

* Education may be student, patient or community education

106 Accelerating Successes Against Cancer
       Cancer Center                              Survivorship Activity                      Research   Clinical Care   Education *      Community
                                                                                                                                          Outreach

                             Brain Tumor Conference for patients and family (biannual                                         X                X
                             conference planned with National Brain Tumor)
                             Gynecologic Awareness Month at Houston Astros                                                    X                X
                             Sprint for Life 5K (annual ovarian cancer fundraiser and com-                                    X                X
                             munity awareness event)
                             Skin cancer screening (annual)                                                                   X                X
                             Tobacco Outreach and Education Program (TOEP)

 Holden Comprehensive Cancer Center Iowa Survivorship Activities
  Clinical Components Adults
   Routine Follow-Up and Surveillance                                                                        x
   Pain and symptom management                                                                               x
   Emg. Housing Fund & Guest House                                                                           x
   Sexual Rehabilitation                                                                                     x
   CAM Clinic                                                                                                x
   Support Groups for pts & family                                                                           x                x
   Financial Counseling        Counseling                                                                    x
   Lymphedema Therapy                                                                                        x
   Mindfulness Based Stress Reduction                                                                        x                x
   Nutrition therapy                                                                                         x
   Speech, occupational, physical ther.                                                                      x
   Psychiatric & psychological services                                                                      x
   Palliative Care/Spiritual Support                                                                         x
   Coming Soon: ACS Hope Lodge                                                                               x
  Clinical Components-Pediatrics
   Routine Follow-up & Surveillance
   Room accomodations for parents                                                                            x
   Child development activities                                                                              x
   Procedure support                                                                                         x
   Diversional activities                                                                                    x
   Emotional support                                                                                         x
   Support group-siblings                                                                                    x
   Music Therapy                                                                                             x
   New Do Head Covers                                                                                        x
   Hospital teacher                                                                                          x
   Sperm banking costs covered                                                                               x
   Amenities for parents
       Massage/spa for parents                                                                               x
       Breakfasts                                                                                            x
      Vouchers: gas, food, hotels                                                                            x
       $500.00 per family for co-pays                                                                        x
       Ronald McDonald House                                                                                 x
  Research Components
   Iowa Cancer Registry                                                                         x
   Cancer and Aging Program                                                                     x
   Quality of Life and Breast Cancer                                                            x
   Healing Touch and Breast Cancer                                                              x
   Quality of Life & Gynecologic Cancer                                                         x


* Education may be student, patient or community education

                                                                                                            Accelerating Successes Against Cancer 107
        Cancer Center                             Survivorship Activity             Research   Clinical Care   Education *   Community
                                                                                                                              Outreach

    Neurobehavior Outcomes in Children                                                 x
    Adverse Events After Childhood Cancer                                              x
   Education and Outreach Components
    IA Consortium Comp. Ca Control                                                                                 x             x
    Holden Cancer Information Service                                                                              x             x
    NCI-CIS/ICCCC Partnership Position                                                                             x             x
    Health for Your Lifetime                                                                                       x             x
    Cancer Survivor’s Day                                                                                                        x
    BM Transplant Reunion                                                                                                        x
    Palliative Care Conference                                                                                     x
    Prof. Psychosocial Oncology Conf.                                                                              x
    Scofield Adv. Oncology Nurse Conf.                                                                             x
   Holden Networks
    Iowa City Cancer Care                                                                           x                            x
    Outreach Services                                                                               x                            x

 Huntsman Cancer Center Survivorship Activity
                           Wellness/Survivorship Program                                            X              X            X
                           Family Cancer Registries                                    X            X              X            X
                           Pain Medicine and Palliative Care                           X            X              X            X
                           Social Work Services                                                     X              X            X
                           Department of Patient and Public Education                               X              X            X

 Hawaii Cancer Center Survivorship Activity
  Prevention and Control Program (current active projects only)
                             Quality of life in breast cancer survivors                x
                             CAM use in cancer survivors                               x
                             Pilot writing progam                                      x
                             Quality of life in testicular cancer                      x
                             Massage in cancer survivors and partners                  x
                             Reflexology in cancer survivors                           x
                             Internet-based health promotion for cancer survivors      x
  Epidemiology Program
                             SEER Registry                                             x
                             Mulitethnic Cohort                                        x
                             Colorectal Family Registry                                x
  Clinical Trials Unit
                             Minority-Based Community Clinical Oncology Program        x            x              x             x
                             Clinical Trials Update                                                                x             x
  Cancer Information Service                                                           x                           x             x
  Community Networks
                             Imi Hale                                                  x                           x             x
                             AANCART                                                   x                           x             x
  Cancer Research Center of Hawaii
                             Cancer Research Day                                                                   x             x




* Education may be student, patient or community education

108 Accelerating Successes Against Cancer
       Cancer Center                                Survivorship Activity                     Research   Clinical Care   Education *      Community
                                                                                                                                           Outreach

 Fred Hutchinson Cancer Center Survivorship Activity
                            Transplant LTFU                                                      X            X                X                X
                            ACCESS                                                               X            X                X                X
                              Prostate Cancer Research                                           X            X                X                X
                              Womens Wellness Center                                             X            X                X                X
                              LIVESTRONG Survivorship Center of Excellence                       X            X                X                X
                              This incorporates the above programs and will add a
                              survivorship program for all medical oncology patients

 Albert Einstein Cancer Center Survivorship Activity
                              Psychosocial Oncology Program                                                   x                x                x
                              Yoga-based Cancer Rehabilitation Pgm                               x
                              Mind-Body Cancer Research Program                                  x
                              Quit Smoking Program                                               x            x                x                x
                              Psychosocial Onc / QoL Volunteer Pgm                                                             x                x
                              H.O.P.E. Program                                                                x                x                x
                              Psychosocial Oncology Fellows Seminar                              x                             x
                              Psycho-oncology externship/internship                                           x                x

 Duke Cancer Center Survivorship Activity
  Prevention, Detection & Control Research Program                                               X
                             Physical Activity/Diet in Breast and Prostate Cancer Patients       X
                             RENEW: improving physical function in elderly                       X
                             STRENGTH: Survivor Training for Enhancing Total Health              X
                             Preoperative exercise program for lung cancer patients              X
                             Value of cardiopulmonary exercise in breast/lung patients           X
                             Endurance training in early stage lung cancer patients              X
                             Endurance training in early stage breast cancer patients            X
                             Efficacy of caregiver-assisted copying skills training              X
                             Coping skills of African American cancer patients                   X
                             Efficacy of partner-assisted emotional disclosure intervention      X
                             Efficacy of couple-based cognitive behavioral intervention          X
                             Studying communication in oncologist-patient encounters             X
                             Smoking relatives of lung cancer patients                           X
  Clinical Intervention
                             Hereditary Cancer Clinic offers risk assessment for survivors                    X                                 X
                             Integrative Oncology Program focuses on care for survivors                       X
                             Pathfinder, patient support program within a research project                    X
                             Childhood Cancer Survivor Follow-up Program                                      X
  Patient Support and Education
                             Center for Cancer Survivorship                                                                    X                X
                             Cancer Patient Support Program                                                                    X                X
                             Cancer Patient Education Program                                                                  X                X
                             Oncology Recreation Program                                                                       X                X
                              Survivorship Patient Focus Group                                                                 X
                              Survivorship Advisory Council                                                                    X




* Education may be student, patient or community education

                                                                                                             Accelerating Successes Against Cancer 109
        Cancer Center                                  Survivorship Activity                     Research   Clinical Care   Education *   Community
                                                                                                                                           Outreach

   Outreach
                                  Power of Knowledge Seminar                                                                    X            X
                                  Melanoma Consortium                                                                           X            X
                                  Rainbow of Heroes - Pediatric Bone Marrow survivor event                                                   X
                                  Cancer Survivors Day Celebration                                                                           X
                                  Cancer Information Service                                                                    X            X
                                  Cancer Center Notes newsletter                                                                X            X
                                  cancer.dukehealth.org website                                                                 X            X
                                  Brain Tumor Action Week                                                                       X            X
                                  Gynecologic Seminar Series                                                                    X            X

 Dana-Farber Cancer Institute Survivorship Activity
 Lance Armstrong Foundation Adult Survivorship Clinic                                               X            X
 David B Perini, Jr., Quality of Life Clinic for Childhood Cancer Survivors                         X            X
                               Transitioning to Survivorship: What Every Parent Should Know         X            X              X
                               Health Lifestyles                                                                                X
                               Facing Forward for Childhood Cancer Survivors                                     X              X
                               Weekend Retreat for Childhood Cancer Survivors                                                   X            X
 Stop & Shop Family Pediatric Neuro-Oncology Outcomes Clinic                                        X            X
 Perini Family Survivors’ Center
                               Living Proof: Celebrating Survivorship                                                           X            X
                               Survivorship Education Series (for patients)                                                     X
                               Improving Life After Cancer Treatment (IMPACT) (for patients)                                    X
                               May 2006 Symposium (collaboration with Breast Oncology)
                               Nursing Education CEU Course (collaboration with Nursing ed)                                     X
                               Workshop for Psychosocial Oncology Researchers                                                   X
                               Visiting Scholar Program                                             X                           X
                               Survivorship Research Symposium (Oct. 2006)                          X                           X
                               Community Outreach Consortium                                        X            X              X            X
                               A Group Educational Intervention for Female Hodgkin’s Disease        X
                               Survivors at Increased Risk for Breast Cancer
                               Calculation of cardiac valve irradiation in lymphoma patients
                               treated with mantle radiation
                               Neuroendocrine Function in Survivors of Childhood Leukemia           X
                               Detection of microalbuminuria in survivors of childhood cancer:      X
                               A pilot study.
                               Cardiac Screening in Survivors of Hodgkin’s disease treated          X
                               with mediastinal irradiation
                               Breast MRI Screening in Women Treated with Mediastinal Ir-           X
                               radiation for Hodgkin’s Disease
  Department of Care Coordination
                               Facing Forward After Breast Cancer Treatment                                      X              X
                               Stepping Stones                                                                                  X
                               Young Survivors Support Group                                                                    X




* Education may be student, patient or community education

110 Accelerating Successes Against Cancer
       Cancer Center                               Survivorship Activity                        Research   Clinical Care   Education *      Community
                                                                                                                                             Outreach

  Center for Community Based Research
                           Exploring the Healthcare Needs of Low Income Cancer Survivors           X                                              X
                           A Web-based smoking cessation intervention for Cancer                   X                             X                X
                           Survivors
                           Proxy Information Agents Focus Groups                                   X                                              X
                           Survivor Care after Cancer Survey                                       X
                           Coping After Breast Cancer                                              X

 Chicago Cancer Center Survivorship Activity
 Quality of Life Studies                                                                           X
                              Conflict of Interest Interview of Advanced Cancer Patients           X
                              Factors Related to and Influencing the Disclosure of Prognostic      X
                              Information in the Advanced Cancer Setting
                              Improving Patient Understanding of EarlyPhase Clinical Trials        X
                              Quality of Life in Children Who Survived Neuroblastoma               X
                              Cognitve and Functional Outcomes of Cancer Treatment in              X
                              Elderly Patients
                              Observational Cohort Study of Chemotherapy Decisions &               X
                              Outcomes in Women Ages 55 or Older
                              A Study of Parental Disclosure of Genetic Test Results to Young      X
                              Adolescents
                              Quality of Life in African American Cancer Survivors                 X
                              Perceptions of Chemotherapy Between African Americans and            X
                              Whites
                              Functional Impact of Breast Cancer Treatment in Older Women          X
                              Impact of Comorbidity and Functional Status on Outcome for           X
                              Older Recipients of Allogeneic Transplant
                              Health Related Quality of Life for Hodgkin’s Disease Survivors       X
                              Are the Elderly Capable of Informed Consent for Research             X
                              Participation?
                              Comprehensive Geriatric Assessment to Examine Geriatric              X
                              Domains in Older Prostate Cancer Patients
  Cancer Registry
                              The University of Chicago Cancer Research Center Clinical and        X
                              Research Registry Protocol
                              Children’s Oncology Group Registry                                   X
                              Cancer Registry Data Quality Subcommittee                                                          X
                              Commission on Cancer - Cancer Liaison Committee                                                                     X
                              Transplatation Registry Protocol                                     X
  Cancer Genetics
                              The Center for Clinical Cancer Genetics                                           X
                              University of Chicago Cancer Risk Clinic                                          X
                              Cancer Risk Assessment and Genetic Screening in Cancer Prone         X
                              Families
                              Genetic Counseling and Testing
                              A Review of Preganancy Associated Breast Cancer at the Uni-
                              versity of Chicago Hospitals
  Patient and Family Services
                              University of Chicago Cancer Resouce Center                                                        X
                              Facing the Mirror                                                                                  X
                              Smoking Cessation                                                                 X
* Education may be student, patient or community education

                                                                                                               Accelerating Successes Against Cancer 111
        Cancer Center                                   Survivorship Activity                     Research   Clinical Care   Education *   Community
                                                                                                                                            Outreach

                                  Massage Therapy                                                                 X
                                  Look Good Feel Better                                                           X
                                  The Herbert T. Abelson Family Learning Center                                                  X
                                  Living a Healthy Life: How To Balance Good Eating, Exercise,                                                X
                                  Relaxation & Everything Else in Your Life
                                  Head and Neck Cancer Support Group                                                             X
                                  Lung Cancer Support Group                                                                      X
                                  Family Nutrition Education Classes                                                             X
                                  University of Chicago Blood Bank                                                X
                                  Crochet Classes for Cancer Survivors                                                           X
                                  Straight Talk for Teens                                                         X              X            X
   Departments
                                  University of Chicago School of Social Service Administration      X                           X            X
                                  Center for Interdiscipinary Health Diparities Research             X            X              X            X
   Community Programs
                                  Community Fitness                                                                                           X
                                  Community Empowerment Forum                                                                                 X
                                  University of Chicago Hospitals Office of Community Affairs                                    X            X

 UNC Lineberger Cancer Center Survivorship Activities
  Behavioral Interventions
                             NC STRIDES                                                              x
                             Managing uncertainty in prostate cancer                                 x
                             Managing uncertainty in breast cancer                                   x
                             Health eCommunities                                                     x
                             Can Thrive                                                              x
                             NC BEAUTY                                                               x
  Epidemiological Studies
                             LIBCSP                                                                  x
                             Follow-up of African-American survivors
                             Head & neck cancer follow-up study
                             CanCORS                                                                 x
 Patient Family Resouce Center                                                                                                   x             x

 Arizona Cancer Center Survivorship Activity
  Health Outcomes and Behavior
                              The Effect of Moderate Physical Activity on the Physical and           x
                              Emotional Recovery of Patients with a History of Colon Cancer
                              Assessing the Needs of Long-term Breast Cancer Survivors               x
                              HR-QOL for colorectal cancer long-term survivors                       x
                              Neurological Effects of Chemotherapy and Radiation Treatment:          x
                              Colon Cancer
                              Green Tea Intervention for Weight Gain Prevention among
                              Women with Breast Cancer
                              Women’s Healthy Eating and Living (WHEL) Study                         x
                              Longitudinal Effects of Intimate Partner Relationship Quality in       x
                              Newly Diagnosed Breast Cancer Patients
  Psychosocial and Palliative Care
                              Routine medical follow-up and surveillance                                          x

* Education may be student, patient or community education

112 Accelerating Successes Against Cancer
       Cancer Center                                 Survivorship Activity                         Research   Clinical Care   Education *      Community
                                                                                                                                                Outreach

                            Pain and symptom management                                               x            x                x
                            Sexual rehabilitation                                                                  x                x
                            Cognitive evaluation                                                      x            x
                            Psychiatric and psychological services                                                                                   x
                            Support groups for patients and family members                                         x                x                x
                            Speech, occupational and physical therapy                                                               x                x
                            Telephone counseling for breast cancer patients                                                         x                x
                            Nutritional counseling                                                                 x                x                x
                            End-of-Life Care Curriculum                                               x                             x
  Patient Education and Resource
                            Print and video educational material on cancer survivorship                                             x                x
                            Monthly supportive care class for Patients and Survivors, family                       x                x                x
                            members
                            Information about websites for cancer survivors                                                         x                x
  Community and Outreach Services
                            Sunstone Healing Center                                                   x                             x                x
                            Referral to/from other cancer resources/centers (local and regional)                                    x                x

 Vanderbilt-Ingram Cancer Center
  Health Outcomes and Behavior Program
                               Cognitive evaluation in pediatric oncology patients                    x
                               Cognitive function in breast cancer survivors                          x
                               Fatigue in cancer survivors                                            x
  Psychosocial and Palliative Care Program
                               Routine medical follow-up and surveillance                                          x
                               Pain and symptom management                                                         x                x
                               Integrative Medicine                                                                x
                               Cognitive evaluation                                                                x
                               Psychiatric and psychological services                                 x            x
                               Support groups for patients and family members                                      x                x
                               Speech, occupational and physical therapy                              x            x
                               Nutritional counseling                                                 x            x
 Patient Education and Resource Center
                               Education and Community Outreach                                                                     x
                               Cancer Information Program (CT referrel service)                       x            x                x
                               Print and audiovisual educational material on cancer survivor-                                       x
                               ship
                               Full-time Patient Education Coordinator and Advocacy Manager                                         x
                               Survivorship Educational Programs                                                                    x
                               Wellness Community Cancer Survivor Program Grant                                                     x
                               CancerHelp Touch Screen Monitor/Computer Education                                                   x
                               Annual cancer survivor conference                                                                    x
                               Clinical Trials Mentor Program (pt advocacy)                                                         x
                               Patient Navigation Conference                                                                        x
  Cancer Survivors Clinic (to be implemented Summer 2006)                                                          x                x
  Minority Affairs Office
                               Southern Community Cohort Study                                        x                             x
                               Educational programs focused on reducing cancer-related                             x                x                x
                               disparities

* Education may be student, patient or community education

                                                                                                                  Accelerating Successes Against Cancer 113
        Cancer Center                                   Survivorship Activity       Research   Clinical Care   Education *   Community
                                                                                                                              Outreach

   VICC Affiliate Network
                                  Resource for conducting community-based studies      x            x                            x
   VICC Family Cancer Clinic
                                  Family Risk Service

 Memorial Sloan Kettering Cancer Center
 Sexual Health Program                                                                 X            X              X
 Clinical Genetics                                                                     X            X
   Long-Term Follow-Up
                             Pediatrics                                                X            X              X
                             Young Adults                                              X            X              X
                             Adults                                                    X            X              X
   BMT Program
                             Pediatrics                                                X            X
                             Adults                                                    X            X
 Queens Cancer Center                                                                  X            X                           X
 Post-Treatment Resource                                                                            X                           X
 Program
 Integrative Medicine                                                                  X            X
 Counseling Center                                                                     X            X
 Smoking Cessation                                                                     X            X
 Program
 Physical Rehabilitation                                                               X            X
 Program
 Behavioral Research                                                                   X
 Late Effects Research                                                                 X
   Patient Education Program
                             Patient Library                                                                       X
                             Survivorship Website                                                                  X
                             MSKCC Medical Library                                                                 X

 Jonsson Comprehensive Cancer Center UCLA
   Patients and Survivors CCSG Program
                              Breast, lung, CRC, Prostate                              x
                              Pediatric young adult                                    x
                              Geriatrics                                               x
 Revlon Breast Center                                                                               x
 Breast CA
                              Follow-up Program
 Prostate Cancer IMPACT                                                                                                          x
 program
 UCLA Family Cancer                                                                    x            x                            x
 Registry
 School of Medicine R-25                                                                                           x
 on Cancer Survivors
 Young adult survivors/                                                                x            x
 transition clinic
 Ted Mann Family Re-                                                                                x              x             x
 source Center
 Pediatric Pain Program                                                                x            x              x             x
 East-West Medicine                                                                                 x
 Program

114 Accelerating Successes Against Cancer
 LAF Center of Excellence                                                                               x
      Cancer Center                                   Survivorship Activity                          Research   Clinical Care   Education *      Community
                                                                                                                                                  Outreach

 Moffitt Cancer Center Survivorship Activity
  Health Outcomes and Behavior Program
                               Fatigue in Breast Cancer Survivors                                       x
                               Cognitive Function in Prostate Cancer Survivors                          x
                               Sexual Fuctioning in Cervical Cancer Survivors                           x
                               Cognitive Function in BMT Survivors                                      x
                               Mindfulness Meditation for Breast Cancer Survivors                       x            x
                               Exercise Training for Prostate Cancer Survivors                          x            x
                               Barriers to Fertility Preservation in Cancer Patients                    x
  Psychosocial and Palliative Care Program
                               Routine medical follow-up and surveillance                                            x
                               Pain and symptom management                                                           x
                               Sexual rehabilitation                                                                 x
                               Cognitive evaluation                                                                  x
                               Psychiatric and psychological services                                                x
                               Support groups for patients and family members                                        x
                               Speech, occupational and physical therapy                                             x
                               Nutritional counseling                                                                x
  Patient Education and Resource Center
                               Print and audiovisual educational material on cancer survivorship                                      x
                               Information about websites for cancer survivors                                                        x
  Skillbuilding in Psychosocial and Palliative Care
                               Annual professional education conference                                                               x
  Community and Outreach Services
                               Support group for Latina breast cancer survivors in Central Florida                   x                                 x
  Tampa Bay Community Cancer Network
                               Projects focused on reducing cancer-related disparities                               x                x                x
  Moffitt Affiliate Network
                               Resource for conducting community-based studies                          x            x                                 x




* Education may be student, patient or community education

                                                                                                                    Accelerating Successes Against Cancer 115
                                                Appendix F

                                                                                                               Shared Resources Survey
                                                                                                                                                                   Do you have              If these services
                                                                                            Which of these          Which of            Would you be
                                                                                                                                                               adequate capacity /        were available from
                                                                                             services do         these are you        willing to provide
                                                   Services                                                                                                    could you expand to           another cancer
                                                                                            you currently         particularly      this service for a fee
                                                                                                                                                                address expanded           center, would you
                                                                                              provide?             strong in?         to other centers?
                                                                                                                                                                     usage?                  be a customer?
                                                                                                                                                                                          Y: JHU, USC, JAX, FH,
                                                                                                                                    Y: UVA, RP, NW, NE, IA,    Y: UVA, RP, NW, NE, IA,
                                                                                        UVA, RP, NW, NE, IA,                                                                              SJ, OH, WT, NM, DV,
                                                                                                                UVA, RP, FH, CH,    MD, CH, DF, FC, CO, WT,    MD, CH, DF, FC, CO, WT,
                                                                                        MD, FH, CH, DF, AE,                                                                               BI, DM
                                                   Antibody Development                                         DF, AE, FC, CO,     MI, DM, MSK                MI, DM
                                                                                        FC, PA, CO, WT, MI,
                                                                                                                WT, MI
                                                                                        DM, MSK                                                                                           N: RP, NW, IA, MD, CH,
                                                                                                                                    N: JAX, FH, PA             N: FH, PA
                                                                                                                                                                                          FC, PA, CO, MI
                                                                                                                                                                                          Y: UVA, RP, WF, NE, IA,
                                                                                        RP (GLP only),
                                                                                                                                    Y: RP, FH, CH, WU, NY,     Y: RP, FH, CH, WU, NY      OH, WT, GT, NM, DM
                                                                                        JHU, FH, CH, WU,
                                                                                                                RP, JHU, FH, CH,    COH, MSK
                                                   Biologics Production – GMP           PA, SJ, OH-cellular
                                                                                                                WU, PA, COH                                    N: JHU, PA                 N: JHU, NW, JAX, MD,
                                                                                        and viral, NY, COH,
                                                                                                                                    N: JHU, JAX, PA, SJ                                   FH, CH, WU, PA, CO, NY,
                                                                                        MSK
                                                                                                                                                                                          BI, COH
                                                                                                                                                                                          Y: RP, NW, NE, OH, WT,
                                                                                                                                    Y: RP, IA, MI              Y: RP, IA, MI
                                                                                        RP, IA, FH, CH, PA,                                                                               GT
                                                   Biologics Production
                                                                                        SJ, WT, COH, MI,        RP, PA, COH
                                                   – Research                                                                       N: JAX, FH, CH, PA, SJ,    N: FH, PA, WT
                                                                                        DM, MSK                                                                                           N: JHU, JAX, IA, MD, FH,
                                                                                                                                    WT, COH
                                                                                                                                                                                          PA, CO, BI, MI
                                                                                                                                    Y: RP, USC, NW, NE, IA,                               Y:
                                                                                        RP, JHU, USC, NW,       RP, JHU, USC,
                                                                                                                                    MD, CH, WU, FC, CO,        Y: RP, USC, NW , NE, IA,
                                                                                        JAX, NE, IA, MD, FH,    NW, IA, MD, FH,
                                                                                                                                    SF, WT, NY, VT, NM, DV,    MD, CH, WU, FC, CO, SF,    N: RP, JHU, USC, NW,
                                                                                        CH, WU, FC, CO, SJ,     CH, WU, FC, CO,
Cell Biology, Immunology & Pathology Services




                                                   Cell Analysis                                                                    MI, MSK                    WT, VT, NM, DV, MI, IN     JAX, IA, MD, FH, CH,
                                                                                        OH, SF, WT, GT, NY,     SF, WT, NY, VT,
                                                                                                                                                                                          WU, FC, CO, SF, WT, NY,
                                                                                        VT, NM, DV, BI, COH,    NM, DV, COH, MI,
                                                                                                                                    N: JAX, FH, SJ, COH, OR,   N: JHU, FH, NY, OR, DM     VT, NM, DV, BI, MI, OR,
                                                                                        MI, OR, DM, IN, MSK     DM, IN
                                                                                                                                    DM, IN                                                DM, IN
                                                                                        UVA, RP, JHU, USC,                          Y: UVA, RP, JHU, USC,      Y: UVA, RP, JHU, USC,
                                                                                                                UVA, RP, JHU,                                                             Y: NE
                                                                                        NW, JAX, WF, IA,                            NW, IA, MD, CH, WU,        NW, JAX, IA, MD, CH,
                                                                                                                USC, NW, JAX, IA,
                                                                                        MD, FH, CH, AE, WU,                         FC, PA, UT, CO, SF, WT,    WU, FC, PA, CO, SF, WT,
                                                                                                                MD, FH, CH, AE,                                                           N: RP, JHU, USC, NW,
                                                                                        FC, PA, UT, CO, SJ,                         SA, GT, NY, NM, DV, BI,    SA , GT, NM, DV, BI, MI,
                                                   Cell Sorting                                                 WU, FC, PA, CO,                                                           JAX, WF, IA, MD, FH, CH,
                                                                                        OH, SF, WT, SA, GT,                         MI, MSK                    OR, IN
                                                                                                                SF, WT, GT, NY,                                                           WU, FC, PA, CO, SF, WT,
                                                                                        NY, VT, NM, DV, BI,
                                                                                                                NM, DV, BI, COH,                                                          SA, GT, NY, VT, NM, DV,
                                                                                        COH, MI, OR, DM,                            N: JAX, WF, FH, AE, SJ,    N: WF, FH, AE, NY, VT,
                                                                                                                MI, OR, DM, IN                                                            BI, MI, OR, DM, IN
                                                                                        IN, MSK                                     VT, COH, OR, DM, IN        DM
                                                                                                                                                                                          Y: NW, NE, IA, WU, WT,
                                                                                                                                    Y: RP, USC, MD, CH, CO,    Y: RP, MD, CH, CO, MI,
                                                                                        RP, USC, JAX, MD,                                                                                 GT, NM
                                                                                                                RP, MD, CH, CO,     MI, DM                     DM
                                                   Cellular Immunoassays                FH, CH, CO, SJ, DV,
                                                                                                                COH, MI
                                                                                        COH, MI, DM                                                                                       N: RP, JHU, USC, JAX,
                                                                                                                                    N: JAX, FH, SJ, COH        N: USC, FH
                                                                                                                                                                                          FH, CH, CO, BI, MI, DM
                                                                                                                                    Y: UVA, RP, USC, NW,                                  Y: RP, NE, IA, WT, GT, NM
                                                                                        UVA, RP, USC, NW,                                                      Y: UVA, RP, USC, NW,
                                                                                                                                    MD, FH, CH, WU, CO,
                                                                                        JAX, MD, FH, CH,        RP, USC, NW, MD,                               MD, FH, CH, WU, CO, MI
                                                   Cytokine Analysis                                                                MI, DM                                                N: JHU, USC, NW, JAX,
                                                                                        WU, PA, CO, DV,         FH, CH, COH, MI
                                                                                                                                                                                          FH, CH, PA, CO, BI, MI,
                                                                                        COH, MI, DM                                                            N: PA
                                                                                                                                    N: JAX, PA, COH                                       DM
                                                                                                                                                                                          Y: RP, NE, IA, WU, WT,
                                                                                                                                    Y: RP, NW , MD, CH, DV,
                                                                                        RP, NW, JAX, MD,                                                       Y: RP, NW, MD, DV, MI      GT, NM
                                                                                                                RP, NW, MD, CH,     MI, DM
                                                   ELISA                                FH, CH, PA, DV, MI,
                                                                                                                DV, MI
                                                                                        DM, MSK                                                                N: FH                      N: JHU, NW, JAX, FH,
                                                                                                                                    N: JAX, FH, PA
                                                                                                                                                                                          CO, BI, MI, DM
                                                                                                                                                                                          Y: RP, NE, IA, WT, NM
                                                                                                                                    Y: CH, WU, OH              Y: WU, CO, OH
                                                                                        MD, FH, CH, DF, WU,     MD, CH, DF, WU,
                                                   Hematopoetic Cell Production
                                                                                        PA, CO, OH              OH                                                                        N: NW, JAX, FH, WU,
                                                                                                                                    N: JAX, MD, FH, DF, CO     N: MD, FH, DF
                                                                                                                                                                                          CO, BI
                                                                                                                                    Y: CH, OH
                                                                                                                                                               Y: CO, OH                  Y: RP, IA, NM
                                                   Hematopoetic Transplantation         MD, FH, CH, DF, PA,
                                                                                                                MD, CH, DF, OH
                                                   Analysis & Production                CO, SJ, OH                                  N: JAX, MD, FH, DF,
                                                                                                                                                               N: MD, FH, DF              N: NW, JAX, FH, CO, BI
                                                                                                                                    CO, SJ




                                                116 Accelerating Successes Against Cancer
                                                                                                                                                    Do you have                 If these services
                                                                           Which of these           Which of             Would you be
                                                                                                                                                adequate capacity /           were available from
                                                                            services do          these are you         willing to provide
                                                Services                                                                                        could you expand to              another cancer
                                                                           you currently          particularly       this service for a fee
                                                                                                                                                 address expanded              center, would you
                                                                             provide?              strong in?          to other centers?
                                                                                                                                                      usage?                     be a customer?
                                                                                                                                                                             Y: RP, IA, WT, NM
                                                                                                                     Y: RP, CH, WU              Y: RP, WU
                                                Immuno-competent Cell     RP, MD, FH, CH, DF,    RP, MD, CH, DF,
                                                Production                WU, PA                 WU, PA                                                                      N: NW, JAX, FH, WU,
                                                                                                                     N: JAX, MD, FH, DF         N: MD, FH, DF
                                                                                                                                                                             CO, BI
                                                                                                                     Y: UVA, RP, USC, NW,
                                                                                                                                                Y: RP, USC, NW, JAX,         Y: JHU, IA, OH
                                                                          UVA, RP, USC, NW,                          JAX, NE, IV, MD, CH,
                                                                                                 RP, USC, NW,                                   NE, IV, MD, DF, AE, CO,
                                                                          JAX, NE, IV, MD, FH,                       DF, AE, CO, SF, GT, NY,
                                                                                                 JAX, IV, MD, FH,                               GT, NM                       N: RP, NW, JAX, IV, FH,
                                                                          CH, DF, AE, FC, PA,                        NM, OR
                                                Immunohistochemistry                             CH, DF, AE, FC,                                                             FC, CO, SF, GT, NY, NM,
                                                                          UT, CO, SJ, SF, GT,
                                                                                                 SF, GT, NM, MI,                                N: FH, FC, SF, NY, MI,       BI, MI, OR, DM
                                                                          NY, NM, COH, MI,                           N: FH, FC, SJ, COH, MI,
                                                                                                 OR                                             OR, DM
                                                                          OR, DM, IN, MSK                            DM, IN
                                                                                                                                                                             Maybe: USC
Cell Biology, Immunology & Pathology Services




                                                                                                                     Y: RP, USC, NM                                          Y: JHU, NE, IA
                                                                                                                                                Y: RP, USC, CO, NM
                                                                          RP, USC, JAX, MD,
                                                Immunotyping              FH, CO, SJ, NM,        RP, JAX, NM         N: JAX, MD, FH, CO, SJ,                                 N: RP, USC, NW, JAX, FH,
                                                                                                                                                N: MD, FH, DM
                                                                          COH, DM, MSK                               COH, DM                                                 CH, CO, NM, BI, DM

                                                                                                                                                                             Y: RP, JAX, NE, IA, FH,
                                                                          RP (purchased,
                                                                                                                     Y: RP, USC, MD, FH         Y: RP, USC, MD               CH, OH, WT
                                                                          service to strain,
                                                MHC Tetramers             analyze), USC, JAX,    USC, FH
                                                                                                                     N: JAX, PA, SJ, COH, DM    N: FH, PA, DM                N: JHU, USC, NW, PA,
                                                                          MD, FH, PA, SJ,
                                                                                                                                                                             CO, BI, DM
                                                                          COH, DM, MSK

                                                                                                                     Y: RP, JAX*, DV, MI        Y: RP, JAX, CO, DV, MI       Y: NE, IA, CH, WU, WT
                                                                          RP, JAX*, MD, FH,
                                                Necropsy                  AE, CO, SJ, DV,        RP, JAX, DV, MI
                                                                                                                     N: MD, FH, CO, SJ, COH     N: MD, FH                    N: RP, JHU, NW, JAX, FH,
                                                                          COH, MI
                                                                                                                                                                             CO, DV, BI, MI
                                                                                                                                                                             Y: NE, IA , WT
                                                                                                                     Y: RP, MD, WU              Y: RP, MD, WU
                                                TCR Analysis              RP, MD, FH, WU, SJ     RP, WU                                                                      N: RP, JHU, NW, JAX, FH,
                                                                                                                     N: JAX, SJ                 N:
                                                                                                                                                                             CH, WU, CO, BI

                                                                                                                                                                             Y: RP, NE, IA, IV, CH, WU,
                                                                                                                     Y: MD, FC, NY, DV, MI,
                                                                          NW, JAX, IV-soon,                                                                                  WT, NM, BI, MI
                                                                                                                     MSK                        Y: MD, FC, CO, DV, MI
                                                                          MD, FH, AE, FC, CO,
                                                Veterinary Pathology                             MD, FC, DV, MI
                                                                          SJ, OH, GT, NY, DV,                                                                                N: JHU, NW, JAX, FH, FC,
                                                                                                                     N: NW, JAX, FH, CO,        N: NW, FH, NY, OR
                                                                          MI, OR, MSK                                                                                        CO, NY, DV, OR
                                                                                                                     SJ, OR

                                                                          UVA, RP, JHU, NW,                          Y: UVA, RP, JAX, WF, IA,
                                                                                                                                                Y: UVA, RP, JAX*, WF, IA,    Y: RP, IV, MI
                                                                          JAX, WF, NE, IA, IV,                       IV, MD, WU, FC, CO, GT,
                                                                                                 UVA, RP, WF, IA,                               IV, MD, WU, FC, CO, GT,
                                                                          MD, FH, CH, AE, WU,                        NY, NM, DV, BI, MI, IN,
                                                                                                 IV, MD, WU, FC,                                NM, DV, BI, MI, IN           N: JHU, NW, JAX, WF, IA,
                                                Animal Imaging            FC, PA, CO, SJ, OH,                        MSK
                                                                                                 PA, GT, NY, NM,                                                             FH, WU, FC, PA, CO, WT,
                                                                          SF, GT, NY, NM, DV,
                                                                                                 DV, COH, MI, IN                                N: JHU, NW, NE, FH,          GT, NY, NM, DV, BI, IN
                                                                          BI, COH, MI, DM, IN,                       N: JHU, NW, NE, FH, PA,
                                                                                                                                                PA, NY
Molecular & Imaging Services




                                                                          MSK                                        SJ, COH
                                                                          UVA, RP, JHU, NW,                          Y: NW, JAX, NE, IV, WU,    Y: NW, JAX, NE, IV, WU,
                                                                                                                                                                             Y: IA, WU, WT, HI
                                                                          JAX, WF, NE, IV, MD,   RP, JHU, NW,        CO, WT, GT, NM, DV,        FC, PA, CO, WT, GT, NM,
                                                                          FH, CH, AE, WU, FC,    JAX, IV, MD, WU,    COH, MI, OR, MSK           MI, OR
                                                                                                                                                                             N: RP, JHU, NW, JAX, WF,
                                                Bioinformatics Analysis   PA, CO, SJ, OH, SF,    FC, PA, WT, GT,
                                                                                                                                                                             IV, FH, FC, PA, CO, SF, VT,
                                                                          WT, GT, HI, VT, NM,    VT, NM, DV, COH,    N: RP, JHU, WF, MD, FH,    N: RP, JHU, WF, FH, SF,
                                                                                                                                                                             NM, DV, BI, MI, OR
                                                                          DV, BI, COH, MI, OR,   MI, OR              FC, PA, SJ, SF, HI, VT     HI, VT, DV, COH
                                                                          DM, MSK
                                                                          UVA, RP, JHU, JAX,                         Y: UVA, RP, IA, MD, CH,    Y: UVA, RP, IA, MD, CH,      Y: WT
                                                                          NE, IA, MD, FH, CH,    UVA, RP, JHU, IA,   WU, UT, CO, SF, WT, NY,    WU, FC, UT, CO, SF, WT,
                                                                          WU, FC, PA, UT, CO,    MD, FH, CH, WU,     NM, DV, MI                 NM, DV, MI, IN               N: RP, JHU, NW, JAX,
                                                Cell Analysis             SJ, OH, SF, WT, GT,    FC, CO, SF, WT,                                                             IA, FH, CH, WU, FC, CO,
                                                                          NY, NM, DV, BI, MI,    NY, NM, DV, MI,     N: JHU, JAX, NE, FH, FC,   N: JHU, JAX, NE, FH, NY,     SF, NY, NM, BI, MI, OR,
                                                                          OR, PD, DM, IN,        DM, IN              SJ, OR, DM, IN             OR, DM                       DM, IN
                                                                          MSK


                                                                                                                                                            Accelerating Successes Against Cancer 117
                                                                                                                                                       Do you have               If these services
                                                                            Which of these           Which of               Would you be
                                                                                                                                                   adequate capacity /         were available from
                                                                             services do          these are you           willing to provide
                                  Services                                                                                                         could you expand to            another cancer
                                                                            you currently          particularly         this service for a fee
                                                                                                                                                    address expanded            center, would you
                                                                              provide?              strong in?            to other centers?
                                                                                                                                                         usage?                   be a customer?
                                                                           UVA, RP, JHU, JAX,     UVA, RP, JHU,         Y: RP, JHU, IA, MD, CH,                                Y: NE
                                                                                                                                                   Y: RP, JHU, JAX, IA, MD,
                                                                           WF, IA, MD, FH, CH,    JAX, IA, MD, FH,      WU, PA, UT, CO, SF, WT,
                                                                                                                                                   CH, WU, FC, PA, UT, CO,
                                                                           AE, WU, FC, PA, UT,    CH, AE, WU, FC,       GT, NY, NM, MI                                         N: RP, JHU, NW, JAX, WF,
                                                                                                                                                   SF, WT, GT, NM, MI, IN
                                  Cell Sorting                             CO, SJ, OH, SF, WT,    PA, CO, SF, WT,                                                              IA, FH, CH, WU, FC, PA,
                                                                           GT, NY, NM, DV, BI,    GT, NY, NM, BI,       N: JAX, WF, FH, FC, SJ,                                CO, SF, WT, NY, NM, BI,
                                                                                                                                                   N: WF, FH, NY, OR, DM
                                                                           COH, MI, OR, PD,       COH, MI, OR,          BI, COH, OR, DM, IN                                    MI, OR, DM, IN
                                                                           DM, IN, MSK            DM, IN
                                                                                                                        Y: UVA, RP, USC, NW,       Y: UVA, RP, USC, NW,
                                                                           UVA, RP, JHU, USC,     UVA, RP, JHU,                                                                Y: WU, SA
                                                                                                                        JAX, IA, MD, CH, FC, UT,   JAX, IA, MD, CH, FC,
                                                                           NW, JAX, WF, NE, IA,   USC, NW, JAX,
                                                                                                                        SF, WT, GT, NM, BI, MI,    UT, SF, WT, GT, NM , BI,
                                                                           IV, MD, FH, CH, AE,    IA, IV, MD, FH,                                                              N: RP, JHU, USC, NW,
                                                                                                                        MSK                        MI, IN
                                  Confocal Microscopy                      FC, PA, UT, SJ, OH,    CH, AE, FC, UT,                                                              JAX, WF, IA, IV, FH, CH,
                                                                           SF, WT, SA, GT, VT,    SF, WT, GT, VT,                                                              FC, PA, CO, SF, WT, VT,
                                                                                                                        N: JHU, WF, NE, IV, FH,    N: JHU, WF, NE, IV, FH,
                                                                           NM, BI, COH, MI, PD,   NM, BI, COH, MI,                                                             NM, BI, MI, DM, IN
                                                                                                                        PA, CO, SJ, SA, VT, COH,   PA, SA, VT, DM
                                                                           DM, IN, MSK            DM, IN
                                                                                                                        DM, IN
                                                                                                                                                                               Y: RP, MD, WU, WT
                                                                           NW, JAX, IA, FH, CH,                         Y: NW, JAX, CH, FC, UT,    Y: NW, JAX, CH, FC, UT,
                                                                           AE, FC, UT, SA, GT,    CH, AE, FC, UT,       SA, NM, MI, MSK            SA, NM, MI, IN
                                  Deconvolution Microscopy                                                                                                                     N: JHU, NW, JAX, IA, FH,
                                                                           NM, COH, MI, IN,       NM, COH, MI, IN
                                                                                                                                                                               CH, FC, CO, SA, NM, BI,
                                                                           MSK                                          N: FH, CO, COH, IN         N: FH
                                                                                                                                                                               MI, IN
                                                                           UVA, RP, USC, NW,                            Y: RP, USC, NW , JAX,      Y: UVA, RP, USC, NW,        Y: WU, SF, WT
                                                                                                  UVA, RP, USC,
                                                                           JAX, WF, NE, IA, IV,                         WF, NE, IA, IV, MD, FH,    JAX, WF, NE, IA, MD, FH,
                                                                                                  NW, JAX, IA, MD,
                                                                           MD, FH, CH, AE, WU,                          CH, AE, WU, FC, PA, UT,    CH, AE, WU, FC, PA, UT,     N: RP, JHU, USC, NW,
                                                                                                  FH, CH, AE, WU,
                                  DNA Sequencing                           FC, PA, UT, CO, SJ,                          CO, SF, WT, GT, VT, NM,    CO, WT, GT, VT, NM, BI,     JAX, WF, IA, FH, CH, FC,
                                                                                                  FC, PA, CO, SF,
                                                                           OH, SF, WT, GT, VT,                          BI, COH, MI, DM            MI, DM                      PA, CO, GT, VT, NM, BI,
                                                                                                  WT, VT, NM, COH,
Molecular & Imaging Services




                                                                           NM, DV, BI, COH, MI,                                                                                MI, DM
                                                                                                  MI, DM
                                                                           PD, DM, MSK                                  N: SJ                      N:
                                                                           UVA, RP, JHU, USC,                           Y: RP, USC, NW, IA, MD,
                                                                                                  UVA, RP, JHU,                                    Y: RP, USC, NW, IA, MD,     Y:
                                                                           NW, JAX, WF, NE, IA,                         CH, DF, FC, UT, WT, GT,
                                                                                                  USC, NW, IA, IV,                                 CH, DF, FC, UT, WT, GT,
                                                                           IV, MD, FH, CH, DF,                          VT, NM, DV, MI, MSK
                                                                                                  MD, CH, DF, AE,                                  NM, MI, IN                  N: RP, JHU, USC, NW,
                                  Fluorescence Microscopy                  AE, FC, PA, UT, SJ,
                                                                                                  FC, UT, WT, GT,                                                              JAX, WF, IA, IV, FH, CH,
                                                                           SF, WT, GT, VT, NM,                          N: JHU, JAX, WF, NE, IV,
                                                                                                  VT, NM, COH,                                     N: JHU, JAX, WF, NE, IV,    FC, PA, CO, SF, WT, VT,
                                                                           DV, BI, COH, MI, PD,                         FH, PA, CO, SJ, COH,
                                                                                                  MI, IN                                           FH, PA, VT, DM              NM, BI, MI, DM, IN
                                                                           DM, IN, MSK                                  DM, IN
                                                                                                                        Y: UVA, RP, IV, FH, WU,    Y: UVA, RP, FH, WU, NM,     Y: IA
                                                                           UVA, RP, JHU, NW,
                                                                                                                        NM, MI, DM                 MI, DM
                                                                           JAX, NE, IV, FH, AE,   UVA, RP, FH, AE,
                                  Gel and Blot Imaging                                                                                                                         N: RP, JHU, NW, JAX, IV,
                                                                           WU, GT, VT, NM, BI,    WU, VT, NM, MI
                                                                                                                        N: JHU, NW, JAX, NE,       N: JHU, NW, JAX, NE, IV,    MD, FH, CH, WT, VT, NM,
                                                                           MI, OR, PD, DM
                                                                                                                        CO, VT, OR                 VT, OR                      BI, MI, OR, DM
                                                                           UVA, RP, USC, NW,                            Y: UVA, RP, NW, IV, MD,    Y: UVA, RP, NW, JAX, IV,    Y: NE, IA, IV, FH, SF, WT
                                                                                                  UVA, RP, USC,
                                                                           JAX, IV, MD, FH, CH,                         FH, CH, DF, WU, FC, PA,    MD, FH, CH, DF, WU, FC,
                                                                                                  JAX, IV, FH, CH,
                                  Genotyping (SNP and                      DF, AE, WU, FC, PA,                          UT, CO, SF, GT, HI, NM,    PA, UT, CO, GT, HI , NM ,   N: RP, JHU, USC, NW,
                                                                                                  DF, WU, FC, PA,
                                  microsatellite)                          UT, CO, SJ, SF, GT,                          DV, COH, MI, OR, MSK       DV, MI , OR, IN             JAX, CH, WU, FC, PA,
                                                                                                  UT, CO, SF, GT, HI,
                                                                           HI, VT, NM, DV, COH,                                                                                CO, HI, VT, NM, DV, BI,
                                                                                                  NM, DV, COH, MI
                                                                           MI, OR, IN, MSK                              N: USC, JAX, SJ, VT, IN    N: USC, VT                  MI, OR, IN
                                                                                                                                                                               Y: NE, WT
                                                                           UVA, RP, USC, JAX,                           Y: RP, USC, IV, MD, FC,    Y: RP, USC, IV, MD, FC,
                                                                           IA, IV, MD, FH, CH,    UVA, RP, USC, IV,     HI, NM, COH, MI, MSK       HI, NM , MI
                                                                                                                                                                               N: RP, JHU, USC, NW,
                                  HPLC                                     AE, FC, PA, SJ, GT,    MD, FH, FC, HI,
                                                                                                                                                                               JAX, IA, IV, FH, WU, FC,
                                                                           HI, NM, COH, MI,       NM, COH, MI           N: JAX, FH, CO, SJ         N: JAX, FH
                                                                                                                                                                               CO, HI, NM, BI, MI
                                                                           PD, MSK

                                                                           UVA, RP, JHU, USC,                           Y: UVA, RP, USC, WF, NE,
                                                                                                                                                   Y: UVA, RP, USC, WF, NE,    Y: JAX , CO
                                                                           WF, NE, IA, IV, MD,    UVA, RP, JHU,         IV, MD, FH, DF, AE, FC,
                                                                                                                                                   IV, MD, FH, DF, AE, FC,
                                                                           FH, CH, DF, AE, FC,    USC, WF, IV, MD,      UT, CO, OH, WT, SA, HI,
                                                                                                                                                   UT, OH, WT, SA, HI , NY,    N: RP, JHU, USC, NW,
                                                                           PA, UT, CO, SJ, OH,    FH, DF, AE, PA,       NY, BI, COH, MI, PD, IN
                                  Mass Spectrometry                                                                                                BI, MI, PD, IN              WF, IA, IV, FH, FC, PA,
                                                                           WT, SA, GT, HI, NY,    UT, OH, WT, HI,
                                                                                                                                                                               WT, SA, HI, NY, NM, BI,
                                                                           NM, BI, COH, MI,       NY, NM, COH, MI,      N: JHU, JAX, PA, SJ,
                                                                                                                                                   N: JHU, PA, CO, NM, OR      MI, OR, IN
                                                                           OR, PD, DM, IN,        OR, PD, IN            NM, OR
                                                                           MSK


                               118 Accelerating Successes Against Cancer
                                                                                                                                         Do you have                     If these services
                                                               Which of these           Which of             Would you be
                                                                                                                                     adequate capacity /               were available from
                                                                services do          these are you         willing to provide
                               Services                                                                                              could you expand to                  another cancer
                                                               you currently          particularly       this service for a fee
                                                                                                                                      address expanded                  center, would you
                                                                 provide?              strong in?          to other centers?
                                                                                                                                           usage?                         be a customer?
                                                              UVA, RP, JHU, NW,                          Y: UVA, RP, JHU, NW,        Y: UVA, RP, JHU, NW,
                                                                                                                                                                      Y: WU, WT, VT, DM
                                                              JAX, WF, NE, IA, IV,   UVA, RP, JHU,       JAX, NE, IA , IV, MD, FH,   JAX, NE, IA, IV, MD, FH,
                                                              MD, FH, CH, AE, FC,    JAX, IA, IV, MD,    CH, AE, FC, PA, UT, CO,     CH, AE, FC, PA, UT, CO,
                                                                                                                                                                      N: RP, JHU, NW, JAX, WF,
                                                              PA, UT, CO, SJ, OH,    FH, CH, AE, FC,     OH, SF, WT, SA , NY, NM,    OH, SF, WT, SA, NM, DV,
                               Microarray                                                                                                                             IA, IV, FH, CH, FC, PA,
                                                              SF, WT, SA, GT, NY,    PA, UT, OH, SF,     DV, BI, MI, OR, DM, MSK     BI, MI, OR, DM
                                                                                                                                                                      CO, SF, SA, NY, NM, DV,
                                                              VT, NM, DV, BI, COH,   WT, NM, DV, BI,
                                                                                                                                                                      BI, MI, OR
                                                              MI, OR, PD, DM,        COH, MI, OR         N: WF, SJ, VT, COH          N: WF, NY, VT
                                                              MSK
                                                                                                                                                                      Y: JAX, NE, IA, FH, WT,
                                                                                                         Y: UVA, RP, USC, WF, MD,    Y: UVA, RP, USC, WF,             GT, NM
                                                              UVA, RP, JHU, USC,
                                                                                                         UT, COH, MSK                MD, UT
                                                              WF, MD, CH, AE,        UVA, RP, MD, UT,
                               Peptide Synthesis                                                                                                                      N: RP, JHU, NW, WF,
                                                              PA, UT, SJ, BI, COH,   COH
                                                                                                         N: JAX, CO, SJ              N: CO                            CO, BI
                                                              MSK
                                                                                                                                                                      Maybe: USC
                                                                                                         Y: UVA, RP, USC, WF, NE,                                     Y: JAX, IA , CO, NM
                                                              UVA, RP, JHU, USC,
Molecular & Imaging Services




                                                                                                         IV, MD, FH, DF, UT, OH,     Y: UVA, RP, USC, WF, IV,
                                                              JAX, WF, NE, IV, MD,   UVA, RP, JHU, IV,
                                                                                                         SF, WT, NY, COH, MI, IN,    MD, FH, DF, UT, OH, SF,          N: RP, JHU, NW, WF, IV,
                               Protein Identification /       FH, CH, DF, AE, PA,    MD, FH, DF, PA,
                                                                                                         MSK                         WT, NY, MI, IN                   FH, PA, SF, WT, NY, BI,
                               characterization               UT, CO, SJ, OH, SF,    UT, OH, WT, NY,
                                                                                                                                                                      MI, OR, IN
                                                              WT, GT, NY, BI, COH,   COH, MI, IN
                                                                                                         N: JHU, JAX, PA, CO,        N: JHU, PA, CO, OR
                                                              MI, OR, IN, MSK
                                                                                                         SJ, OR                                                       Maybe: USC
                                                              UVA, RP, JHU, NW,                          Y: UVA, RP, NW, IA, MD,     Y: UVA, RP, NW, IA, MD,
                                                                                                                                                                      Y:
                                                              JAX, NE, IA, IV, MD,   UVA, RP, JAX, IA,   CH, FC, UT, OH, SF, WT,     CH, WU, FC, UT, CO,
                                                              FH, CH, AE, WU, FC,    MD, FH, CH, FC,     NY, NM, DV, MI, DM,         OH, SF, WT, NM, DV, MI,
                                                                                                                                                                      N: RP, JHU, NW, JAX, IA,
                               Real-time PCR                  PA, UT, CO, OH, SF,    UT, CO, OH, SF,     MSK                         DM, IN
                                                                                                                                                                      IV, FH, CH, WU, FC, CO,
                                                              WT, SA, GT, NY, VT,    NY, VT, NM, DV,
                                                                                                                                                                      SF, WT, SA, NY, VT, NM,
                                                              NM, DV, BI, COH, MI,   COH, MI             N: JHU, JAX, NE, IV, FH,    N: JHU, JAX, NE, IV, FH,
                                                                                                                                                                      DV, BI, MI, DM, IN
                                                              DM, IN, MSK                                WU, CO, SA, VT, COH, IN     SA, NY, VT
                                                                                                         Y: UVA, RP, USC, JAX
                                                              UVA, RP, USC, JAX,                                                     Y: UVA, RP, USC, JAX,            Y: USC, NW, MD, WU, WT
                                                                                     UVA, RP, USC,       , WF, NE, IA, MD, FH,
                                                              WF, NE, IA, IV, MD,                                                    WF, IA, MD, FH, AE, FC,
                                                                                     JAX, WF, IA, MD,    AE, FC, PA, UT, GT, NM,
                               Scanning Electron Microscopy   FH, CH, AE, FC, PA,                                                    UT, GT, NM, MI                   N: RP, JHU, JAX, WF, IA,
                                                                                     FH, AE, PA, VT,     COH, MI
                                                              UT, SJ, GT, VT, NM,                                                                                     IV, FH, FC, PA, CO, VT,
                                                                                     NM, COH, MI
                                                              COH, MI, MSK                                                           N: NE, IV, PA, CO, VT            NM, BI, MI
                                                                                                         N: IV, CO, SJ, VT
                                                                                                         Y: UVA, RP, USC, NW,        Y: UVA, RP, USC, NW,
                                                              UVA, RP, USC, NW,                                                                                       Y: MD, WU, WT
                                                                                     UVA, RP, USC,       JAX, WF, IA, MD, FH, CH,    JAX, WF, IA, MD, FH,
                                                              JAX, WF, IA, IV, MD,
                                                                                     JAX, WF, IA, MD,    AE, FC, UT, WT, GT, NM,     CH, AE, FC, UT, WT, GT,
                               Transmission Electron          FH, CH, AE, FC, PA,                                                                                     N: RP, JHU, USC, NW,
                                                                                     FH, CH, AE, FC,     COH, MI                     NM, MI
                               Microscopy                     UT, SJ, WT, GT, VT,                                                                                     JAX, WF, IA, IV, FH, CH,
                                                                                     WT, VT, NM, COH,
                                                              NM, BI, COH, MI,                                                                                        FC, CO, VT, NM, BI, MI
                                                                                     MI                  N: IV, CO, SJ, VT           N: IV, CO, VT
                                                              MSK

                                                                                                         Y: NE, FH, WU, UT, CO,
                                                              UVA, RP, JHU, USC,                                                     Y: NE, FH, WU, FC, UT,           Y: RP (excluding clinical
                                                                                                         NM, DV, COH, MI
                                                              NW, WF, NE, IA, IV,                                                    CO, HI, NM, DV, MI, IN           research services), DV
                                                                                     RP, USC, NW, IV,
                                                              MD, FH, CH, DF, AE,
                               Data Collection and                                   FH, WU, FC, UT,     N: UVA, RP, JHU, USC,
Human Subject Study Services




                                                              WU, FC, PA, UT, CO,                                                    N: UVA, RP, JHU, USC,            N: JHU, USC, NW, WF, IA,
                               Management                                            CO, VT, NM, DV,     NW, WF, IA, IV, MD, DF,
                                                              SJ, GT, HI, NY, VT,                                                    NW, WF, IA, IV, MD, DF,          IV, FH, WU, FC, PA, CO,
                                                                                     COH, MI, OR, IN     FC, PA, SJ, HI, NY, VT,
                                                              NM, DV, COH, MI,                                                       PA, NY, VT, OR                   HI, NY, VT, NM, BI, MI,
                                                                                                         OR, IN
                                                              OR, DM, IN                                                                                              OR, IN

                                                                                                                                                                      Y: WF, NE, IA, FC
                                                                                                         Y: RP, FH, HI, MI           Y: RP, FH, HI, MI
                               Dietary Assessment             RP, FH, SJ, HI, MI     RP, FH, HI                                                                       N: RP, NW, MD, FH, CO,
                                                                                                         N: CO, SJ                   N: CO
                                                                                                                                                                      HI, BI, MI

                                                                                                                                                                      Y: IA, FC
                                                                                                         Y: MI                       Y: MI
                               Exercise Studies               FH, MI                 FH
                                                                                                                                                                      N: NW, MD, FH, CO,
                                                                                                         N: FH, CO                   N: FH, CO
                                                                                                                                                                      BI, MI


                                                                                                                                                     Accelerating Successes Against Cancer 119
                                                                                                                                                     Do you have              If these services
                                                                           Which of these        Which of               Would you be
                                                                                                                                                 adequate capacity /        were available from
                                                                            services do       these are you           willing to provide
                                  Services                                                                                                       could you expand to           another cancer
                                                                           you currently       particularly         this service for a fee
                                                                                                                                                  address expanded           center, would you
                                                                             provide?           strong in?            to other centers?
                                                                                                                                                       usage?                  be a customer?
                                                                                                                                                                            Y: IA, FC
                                                                                                                    Y:                           Y:
                                  Feeding Studies                      RP, FH                 RP, FH
                                                                                                                                                                            N: RP, NW, MD, FH,
                                                                                                                    N: RP, FH, CO                N: RP, FH, CO
                                                                                                                                                                            CO, BI
                                                                       UVA, RP, JHU, USC,                                                        Y: RP, USC, NE, WU, FC,    Y: DV
                                                                                                                    Y: RP, USC, NE, WU, UT,
                                                                       NW, WF, NE, IA, IV,    RP, JHU, USC,                                      CO, GT, HI, DV, IN
                                                                                                                    GT, DV, COH, MI
                                                                       MD, FH, CH, DF, AE,    NW, IV, MD, FH,                                                               N: RP, JHU, NW, IA, IV,
                                  Oncology Clinical Trials
                                                                       WU, FC, PA, UT, CO,    CH, FC, UT, CO,                                    N: UVA, JHU, NW, IA, IV,   FH, CH, WU, FC, PA, CO,
                                  Support                                                                           N: JHU, NW, IA, IV, MD,
                                                                       SJ, OH, SF, GT, HI,    GT, VT, NM, DV,                                    MD, FH, CH, DF, PA, SF,    SF, HI, NY, VT, NM, BI, MI,
                                                                                                                    FH, CH, DF, FC, PA, SJ,
                                                                       NY, VT, NM, DV, COH,   COH, MI, OR, IN                                    NY, VT, NM, MI, OR         OR, IN
                                                                                                                    SF, HI, NY, VT, NM, OR, IN
                                                                       MI, OR, DM, IN
                                                                                                                                                 Y: UT, CO, DV, MI          Y: NE, IA
                                                                                                                    Y: UT, CO, DV, MI
                                  Prevention Center – Research         RP, MD, FH, UT, CO,    MD, UT, CO, NM,
                                  Clinic                               GT, NM, DV, MI         DV, MI                                             N: RP, MD, FH, NM          N: RP, USC, NW, FH, CO,
                                                                                                                    N: MD, FH, NM
                                                                                                                                                                            NM, DV, BI, MI
                                                                       RP, JHU, NW, IV, MD,                         Y: FH, UT, GT, NM, DV,       Y: FH, WU, FC, UT, GT,     Y: NE, IA, IV, MI
                                                                                              RP, NW, IV, MD,
                                                                       FH, CH, AE, WU, FC,                          COH, MI                      NM, DV, MI, IN
Human Subject Study Services




                                  Programming, Database                                       FH, WU, FC, PA,
                                                                       PA, UT, CO, SJ, SF,                                                                                  N: RP, JHU, NW, FH, CH,
                                  Design and Development                                      UT, GT, NM, DV,
                                                                       GT, NM, DV, COH,                             N: RP, JHU, NW, IV, MD,      N: RP, JHU, NW, IV, MD,    WU, FC, PA, CO, NM, DV,
                                                                                              COH, MI
                                                                       MI, IN                                       WU, FC, PA, CO, SJ, IN       PA, CO                     BI, IN
                                                                                                                    Y: WU, UT                    Y: WU, UT                  Y: IA
                                  Technology & Scientific              RP, JHU, IV, MD, FH,   IV, MD, WU, UT,
                                                                                                                    N: RP, JHU, IV, MD, FH,      N: RP, JHU, IV, MD, FH,    N: RP, JHU, NW, IV, FH,
                                  Project Management                   CH, WU, UT, NM, MI     NM, MI
                                                                                                                    CH, CO, NM, MI               CH, CO, NM, MI             CH, WU, CO, NM, BI, MI

                                                                                                                                                                            Y: NE, IA, CH, FC, SF
                                                                                                                    Y: RP, FH, CO                Y: RP, FH, CO, IN
                                                                       RP, JHU, IV, FH, CO,
                                  Telephone Interviewing                                      RP, FH, CO, NM
                                                                       SJ, NM                                                                                               N: RP, JHU, NW, IV, MD,
                                                                                                                    N: JHU, IV, SJ, NM, IN       N: JHU, IV, NM
                                                                                                                                                                            FH, CO, NM, BI, IN
                                                                                                                    Y: UVA, RP, USC, NE, IA,
                                                                       UVA, RP, JHU, USC,                                                        Y: RP, USC-limited
                                                                                                                    IV, CH, WU, UT, CO, OH,                                 Y: UVA, WT, VT, DV, BI
                                                                       NW, WF, NE, IA, IV,    RP, USC, NW, IV,                                   space, NE, IA, IV, CH,
                                                                                                                    NY, NM, DV, MI, OR
                                                                       MD, CH, AE, WU,        MD, CH, WU, FC,                                    WU, FC, UT, CO, OH, NM,
                                  Tissue Procurement and                                                                                                                    N: RP, JHU, USC, NW,
                                                                       FC, UT, CO, SJ, OH,    UT, CO, OH, SF,                                    DV, OR, IN
                                  Banking                                                                           N: JHU, NW, WF, MD, FC,                                 WF, IA, IV, FH, WU, FC,
                                                                       SF, GT, NY, VT, NM,    NM, DV, COH,
                                                                                                                    SJ, SF, VT, COH                                         CO, SF, NY, NM, MI,
                                                                       DV, COH, MI, OR, IN,   MI, OR                                             N: UVA, JHU, NW, WF,
                                                                                                                                                                            OR, IN
                                                                       MSK                                                                       MD, SF, NY, VT, MI
                                                                                                                    Maybe: IN
                                                                                                                    Y: RP, IV, FH, UT, CO,       Y: RP, IV, FH, UT, CO,     Y: FC
                                                                       RP, JHU, USC, WF,
                                                                                                                    DV, MI                       DV, IN
                                                                       IA, IV, MD, FH, DF,
                                                                                              RP, IV, FH, DF, UT,                                                           N: RP, JHU, USC, NW,
                                  Tracking Subjects                    WU, UT, CO, SJ, GT,
                                                                                              CO, NM, COH, MI       N: JHU, USC, WF, MD,         N: JHU, USC, WF, MD,       WF, IA, IV, FH, WU, CO,
                                                                       NY, NM, DV, COH,
                                                                                                                    DF, WU, SJ, NY, NM,          DF, WU, NY, NM, MI         NY, NM, DV, BI, MI, IN
                                                                       MI, DM
                                                                                                                    COH, MI, IN
                                                                       UVA, RP, JHU, NW,                            Y: UVA, RP, JAX, WF, IA,     Y: UVA, JAX, WF, IA,       Y: RP, MI
Laboratory Support Services




                                                                       JAX**, WF, NE, IA,                           MD, WU, FC, CO, OH, NY,      MD, WU, FC, CO, OH, DV,
                                                                                              UVA, RP, JAX, WF,
                                                                       MD, FH, CH, AE, WU,                          DV, BI, MI, DM, IN           BI, MI, DM, IN             N: UVA, JHU, NW, JAX,
                                  Animal Imaging                                              IA, MD, WU, FC,
                                                                       FC, PA, CO, SJ, OH,                                                                                  WF, IA, IV, FH, WU, FC,
                                                                                              PA, DV, MI, IN
                                                                       WT, NY, DV, BI, MI,                          N: JHU, NW, NE, FH, PA,      N: RP, JHU, NW, NE, FH,    PA, CO, WT, NY, DV, BI,
                                                                       DM, IN, MSK                                  SJ, WT                       PA, WT, NY                 DM, IN
                                                                       RP, JHU, NW, JAX,                            Y: RP, JAX , IV, CH, OH,     Y: RP, JAX, CH, CO, OH,    Y:
                                                                       IV, MD, FH, CH, AE,    RP, JAX, IV, MD,      WT, DV, MI                   WT, DV, MI
                                  Animal Husbandry and
                                                                       FC, CO, SJ, OH, WT,    FH, CH, FC, WT,                                                               N: RP, NW, JAX, IA, IV,
                                  Veterinary Services
                                                                       VT, DV, BI, COH, MI,   DV, COH, MI           N: JHU, NW, IA, MD, FH,      N: JHU, NW, IA, IV, MD,    FH, CH, FC, CO, WT, VT,
                                                                       MSK                                          FC, CO, SJ, VT, COH, IN      FH, FC, VT, IN             DV, BI, MI, IN




                               120 Accelerating Successes Against Cancer
                                                                                                                                                  Do you have                  If these services
                                                                         Which of these           Which of            Would you be
                                                                                                                                              adequate capacity /            were available from
                                                                          services do          these are you        willing to provide
                                          Services                                                                                            could you expand to               another cancer
                                                                         you currently          particularly      this service for a fee
                                                                                                                                               address expanded               center, would you
                                                                           provide?              strong in?         to other centers?
                                                                                                                                                    usage?                      be a customer?
                                                                        UVA, RP, USC, NW,                         Y: UVA, RP, USC, JAX,       Y UVA, RP, USC, JAX,
                                                                                                                                                                            Y: FH, VT, DM
                                                                        JAX, NE, IV, MD, FH,   RP, USC, JAX,      NE, IV, MD, CH, FC, UT,     NE, MD, CH, FC, UT, CO,
                                                                        CH, AE, FC, PA, UT,    IV, MD, CH, FC,    CO, OH, WT, SA, NY, DV,     OH, WT, SA, DV, MI, PD,
                                                                                                                                                                            N: RP, USC, NW, JAX, IA,
                                          Transgenic / Knockout Mice    CO, SJ, OH, WT, SA,    PA, UT, WT, VT,    COH, MI, OR, PD, DM,        DM, IN
                                                                                                                                                                            IV, CH, FC, PA, CO, WT,
                                                                        NY, VT, DV, BI, COH,   DV, COH, MI, OR,   IN, MSK
                                                                                                                                                                            SA, NY, DV, BI, MI, OR, IN
                                                                        MI, OR, PD, DM, IN,    PD, IN                                         N: NW, IA, IV, FH, PA, NY,
Laboratory Support Services




                                                                        MSK                                       N: NW, IA, FH, PA, SJ, VT   VT, OR
                                                                        RP, NW, JAX, MD,                          Y: RP, JAX, MD, CO,         Y: RP, JAX, MD, CO, OH,       Y: IA, IV, FH, WT
                                                                        FH, CH, AE, FC, CO,                       OH, WT                      WT, IN
                                          NOD / SCID Mice                                      RP, JAX, FC, IN
                                                                        SJ, OH, WT, BI, IN,                                                                                 N: RP, NW, JAX, FC, CO,
                                                                        MSK                                       N: NW, IA, FH, FC, SJ, IN   N: NW, IA, FH, FC             BI, IN
                                                                        UVA, RP, JHU, NW,                         Y: UVA, RP, JAX, UT, CO,    Y: RP, JAX , CO, WT,          Y: IV
                                                                        JAX, MD, FH, CH,                          WT, DV, MI, MSK             DV, MI
                                          Research Animal Technical                            RP, JAX, MD, FH,
                                                                        AE, FC, UT, CO, SJ,                                                                                 N: RP, JHU, NW, JAX, IA,
                                          Services                                             FC, WT, DV, MI
                                                                        WT, VT, DV, BI, MI,                       N: JHU, NW, IA, MD, FH,     N: JHU, NW, IA, MD, FH,       FH, FC, CO, WT, VT, DV,
                                                                        MSK                                       FC, SJ, VT, IN              FC, VT, IN                    BI, MI, IN
                                                                        UVA, RP, USC, JAX,                        Y: RP, USC, IA, IV , PA,    Y: RP, USC, IA, IV, FC,       Y: USC, IV
                                                                        WF, IA, IV, MD, FH,                       UT, CO                      CO, IN
                                                                                               RP, USC, IA, MD,
                                          Tissue Culture Supplies       AE, FC, PA, UT,                                                                                     N: RP, JHU, NW, JAX, WF,
                                                                                               FC, WT, OR
                                                                        CO, WT, OR, MSK                           N: JAX, WF, MD, FH, FC,     N: JAX, WF, MD, FH, PA,       IA, FH, FC, PA, CO, WT,
                                                                        (media)                                   WT, OR, IN                  WT, OR                        BI, OR, IN
                                                                                                                                                                            Y: WF, IA, MD, FH, OH,
                                                                        RP, JAX, FH, CH, AE,                      Y: JAX, WU, WT, MI, OR      Y: JAX, WU, FC, MI            WT, VT, MI
                                                                                               RP, JAX, WU, FC,
                                          Analytical Software           WU, FC, WT, VT, BI,
                                                                                               WT, MI, OR
                                                                        MI, OR, MSK                               N: RP, FH, CH, FC, CO, VT   N: RP, FH, CH, WT, VT, OR     N: RP, NW, JAX, CH, WU,
                                                                                                                                                                            FC, CO, BI, OR
                                                                        UVA, RP, USC, NW,                         Y: UVA, JAX, NE , CH, UT,
                                                                                                                                              Y: USC, JAX, NE, CH, FC,      Y: UVA, OH, WT, BI
                                                                        JAX, WF, NE, IA, IV,   RP, USC, NW,       MI, OR
                                                                                                                                              UT, HI, DV, MI, OR, IN
                                                                        MD, FH, CH, DF, AE,    JAX, WF, FH, CH,
                                                                                                                                                                            N: RP, USC, NW, JAX,
                                          Biostatistics                 FC, UT, CO, SJ, OH,    DF, FC, UT, CO,    N: RP, USC, NW, WF, IA,
                                                                                                                                              N: RP, NW, WF, IA, MD,        WF, IA, FH, CH, FC, CO,
                                                                        SF, WT, HI, VT, DV,    OH, HI, VT, DV,    MD, FH, DF, FC, CO, SJ,
                                                                                                                                              FH, DF, CO, SF, WT, VT,       SF, HI, VT, DV, MI, OR,
                                                                        COH, MI, OR, DM,       COH, MI, OR, DM    SF, WT, HI, VT, DV, COH,
                                                                                                                                              DM                            DM, IN
                                                                        IN, MSK                                   DM, IN
Library, Computing and Graphic Services




                                                                                                                                                                            Y: IA, OH
                                                                                                                  Y: RP, WT, MI               Y: RP, FC, WT, MI
                                                                        RP, JAX, MD, FH, AE,   RP, FH, FC, WT,
                                          Computing Lab
                                                                        FC, WT, BI, MI, MSK    MI                                                                           N: RP, NW, JAX, FH, FC,
                                                                                                                  N: JAX, MD, FH, FC, CO      N: JAX, MD, FH
                                                                                                                                                                            CO, WT, BI, MI
                                                                                                                  Y: NE, FC, BI, MI                                         Y: IV, OH, WT
                                                                        RP, JAX, NE, MD,                                                      Y: RP, FC, BI, MI, IN
                                                                                               RP, JAX, DF,
                                          Graphic Design and Posters    FH, DF, FC, SJ, BI,
                                                                                               FC, MI             N: RP, JAX, MD, FH, DF,                                   N: RP, NW, JAX, IA, FH,
                                                                        MI, MSK                                                               N: JAX, NE, MD, FH, DF
                                                                                                                  CO, SJ, IN                                                FC, CO, BI, MI, IN
                                                                                                                                                                            Y: JAX, IA, IV, MD, OH,
                                                                                                                  Y: RP, UT, WT
                                                                        RP, JAX, FH, AE, WU,                                                  Y: RP, JAX, WU, FC, WT        WT, VT
                                                                                               RP, FH, WU, FC,
                                          High Performance Computing    FC, UT, SJ, WT, VT,
                                                                                               UT, VT             N: JAX, MD, FH, WU, FC,
                                                                        BI, MI, MSK                                                           N: FH, VT, MI                 N: RP, NW, FH, WU, FC,
                                                                                                                  CO, SJ, VT, MI
                                                                                                                                                                            CO, BI, MI
                                                                                                                                                                            Y: JAX, IV, FH, OH, WT
                                                                        RP, JAX, NE, MD,                          Y: JAX, CH, FC, WT          Y: JAX, CH, FC, WT
                                          Interlibrary Loan             FH, CH, FC, UT, WT,    JAX, CH, FC, WT
                                                                                                                                                                            N: RP, NW, IA, CH, FC,
                                                                        BI, MSK                                   N: RP, NE, MD, CO           N: RP, MD, FH
                                                                                                                                                                            CO, BI
                                                                        UVA, RP, JAX, NE,                         Y: JAX, CH, FC, WT                                        Y: RP, JAX, IV, OH
                                                                                                                                              Y: JAX, MD, CH, FC, WT
                                                                        MD, FH, CH, FC, UT,    JAX, FH, CH,
                                          Online Databases & Journals
                                                                        SJ, WT, BI, COH,       FC, BI             N: RP, NE, MD, FH, CO,                                    N: NW, IA, FH, CH, FC,
                                                                                                                                              N: RP, FH
                                                                        MSK                                       SJ, BI, COH                                               CO, WT, BI
                                                                                                                  Y: USC, FC, WT, MI          Y: RP, USC, JAX, FC,          Y: IV, OH
                                                                        RP, USC, JAX, MD,
                                          Photography and Digital                                                                             WT, MI
                                                                        FH, AE, FC, SJ, WT,    RP, USC, FC, WT
                                          Imaging                                                                 N: RP, JAX, MD, FH,                                       N: RP, USC, NW, JAX, IA,
                                                                        BI, MI, MSK
                                                                                                                  CO, SJ                      N: MD, FH                     FH, FC, CO, WT, BI, MI


                                                                                                                                                           Accelerating Successes Against Cancer 121
                                                                                                                                                            Do you have               If these services
                                                                                      Which of these        Which of            Would you be
                                                                                                                                                        adequate capacity /         were available from
                                                                                       services do       these are you        willing to provide
                                             Services                                                                                                   could you expand to            another cancer
                                                                                      you currently       particularly      this service for a fee
                                                                                                                                                         address expanded            center, would you
                                                                                        provide?           strong in?         to other centers?
                                                                                                                                                              usage?                   be a customer?
                                                                                                                            Y: RP, FH, WU, UT, WT, MI                               Y: RP, IA, IV, FH, OH, WT
Library, Computing and Graphic Services




                                                                                  RP, NW, JAX, IV, MD,   RP, NW, JAX, IV,                               Y: RP, WU, FC, UT, WT, MI
                                             Programming, Database
                                                                                  FH, CH, WU, FC, UT,    FH, WU, FC, UT,
                                             Design and Development                                                         N: NW, JAX, IV, MD,                                     N: NW, JAX, WU, FC, CO,
                                                                                  WT, BI, MI, MSK        WT, MI                                         N: NW, JAX, IV, MD, FH
                                                                                                                            FC, CO                                                  BI, MI

                                                                                                                                                                                    Y: JAX, IV, MD, OH, WT
                                                                                                                            Y: RP, UT, WT, MI           Y: RP, FC, UT, WT, MI
                                                                                  RP, JAX, MD, FH, FC,
                                             Scientific Application Hosting                              FC, UT, WT, MI
                                                                                  UT, WT, BI, MI                                                                                    N: RP, NW, IA, FH, FC,
                                                                                                                            N: JAX, FH, FC, CO          N: JAX, FH
                                                                                                                                                                                    CO, BI, MI

                                                                                                                                                                                    Y: IV, WT
                                                                                                                            Y:                          Y: RP
                                                                                  RP, JAX, MD, FH, BI,
                                             Slide Production                                            RP, JAX
                                                                                  MSK                                                                                               N: RP, NW, JAX, IA, FH,
                                                                                                                            N: RP, JAX, MD, FH, CO      N: JAX, MD, FH
                                                                                                                                                                                    CO, BI



                                          *The Jackson Laboratory could more easily provide necropsy services (on mice only) for animals available from their
                                          production services—other animals would have to be shipped and possibly imported and bred depending on the specific
                                          research needs.

                                          **The Jackson Laboratory could more easily provide imaging services (on mice only) for animals available from their
                                          production services—other animals would have to be imported and bred before the specific research service could be
                                          carried out.

                                          Key                     Cancer Center                                              Key                     Cancer Center
                                          UVA                     University of Virginia                                     SJ                      St. Jude Children’s Research Hospital
                                          RP                      Roswell Park                                               OH                      Ohio State University
                                          JHU                     Johns Hopkins University                                   SF                      University of California, San Francisco
                                          USC                     University of Southern California                          WT                      Wistar Institute
                                          NW                      Northwestern University                                    SA                      Salk Institute
                                          JAX                     Jackson Laboratory                                         GT                      Georgetown University
                                          WF                      Wake Forest University                                     HI                      University of Hawaii
                                          NE                      University of Nebraska                                     NY                      New York University
                                          IA                      University of Iowa                                         VT                      Vermont Cancer Center
                                          IV                      University of California-Irvine                            NM                      University of New Mexico
                                          MD                      MD Anderson Cancer Center                                  DV                      University of California, Davis
                                          FH                      Fred Hutchinson Cancer                                     BI                      Burnham Institute
                                                                    Research Center                                          COH                     City of Hope National
                                          CH                      University of Chicago                                                                Medical Center
                                          DF                      Dana Farber/Harvard Cancer Center                          MI                      University of Michigan
                                          AE                      Albert Einstein College of                                 OR                      Oregon Cancer Institute
                                          WU                      Washington University-St. Louis                            PD                      Perdue University Cancer Center
                                          FC                      Fox Chase Cancer Center                                    DM                      Dartmouth: Norris Cotton
                                          PA                      University of Pennsylvania                                                           Cancer Center
                                          UT                      University of Utah, Huntsman                               IN                      Indiana University Cancer Center
                                                                    Cancer Center                                            MSK                     Memorial Sloan Kettering
                                          CO                      University of Colorado                                                               Cancer Center



                                          122 Accelerating Successes Against Cancer
The Burnham Institute’s Cancer Center in La Jolla, CA, has specialized expertise and high-end technologies that
focuses on various aspects of chemical biology research and early-stage drug discovery. We currently have adequate
capacity and/or could expand the following services to provide them for a fee to other Centers:

(1) Protein Expression for large-scale production and purification of multi-milligram quantities of recombinant protein in
bacterial, yeast, insect and eukaryotic cell systems;

(2) Chemical Library Screening, which provides access to a ~200,000 compound library and fully integrated, robotic
liquid handling systems for HT screening using either biochemical or cell-based assays;

(3) In silico Screening/Computational Modeling, which utilizes a dedicated Linux cluster, and applies docking algorithms
for screening a virtual library of >1 million compounds for hits against protein targets when a high quality 3-dimensional
structure is available;

(4) High-Throughput Microscopy, which houses several HT microscopes for cell-based screens using high-content
imaging, along with supporting software for automated image analysis;

(5) NMR, which includes a 500 MHz instrument equipped with automatic sample changer for applying chemical
compounds to protein targets, in addition to a 300 MHz instrument dedicated for chemical compound structure
determination, and a 600 MHz instrument for protein structure determination, as well as supporting computer
workstations and software for data analysis;

(6) X-ray Crystallography, which provides x-ray diffractometers and supporting computer workstations and software for
determination of protein/chemical compound complexes at atomic resolution;

(7) Medicinal Chemistry, which performs contract-based synthesis and purification of analogs of compounds using
medicinal chemistry approaches, including using structure-based methods for guiding medicinal chemistry efforts;

(8) Functional Genomics, which consists of HTS-formatted siRNA libraries.

                                                         Contact:

                                                Kristiina Vuori, M.D., Ph.D
                                              Acting Director, Cancer Center
                                          Burnham Institute for Medical Research
                                              10901 North Torrey Pines Road
                                                    La Jolla, CA 92037

                                                  Tel (858) 646-3129
                                                  FAX (858) 713-9929
                                               e-mail: kvuori@burnham.org

                                              Senior Administrative Assistant:
                                                       Ms. Trixi Czink
                                                Tel (858) 646-3100, x3343
                                                    FAX (858) 713-6272
                                                e-mail: trixi@burnham.org




                                                                                              Accelerating Successes Against Cancer 123
Notes




124 Accelerating Successes Against Cancer

								
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