NYP Neuro Template - PDF by JohnKirkpatrick


                                                                                                                                                   Spring 2007

Update: Novel                                   MammoSite’s Results Present
Therapies for                                   New Options, Opportunities
Pancreatic Cancer                               Case Study

                                                                                                                                                                      Photo courtesy of Dattatreyudu Nori, MD
                                                   The advantages of partial-breast radia-

        ancreatic cancer remains among the      tion have long been recognized at
        most lethal cancers in adults, with a   NewYork-Presbyterian Hospital, where
        mortality rate of 90% within the        investigators have been leaders in devel-
first year following diagnosis. Still, new      oping and testing options for its
treatments have provided much hope, and         delivery. Few other cancer centers in the
Columbia and Weill Cornell researchers at       world have comparable experience with
NewYork-Presbyterian Hospital have been         this technique. Weill Cornell oncologists               In the MammoSite procedure, a balloon catheter is
spearheading investigations into new com-       at NewYork-Presbyterian Hospital have                   inserted into the surgical cavity left after removal of
pounds being developed and tested for           a long history of using brachytherapy                   the tumor.
specific molecular targets that may ulti-       with iridium sources implanted at the                   partial-breast radiation and which should
mately contribute to the fund of knowl-         time of surgery.                                        still be treated with external-beam irra-
edge about which elements are critical to          In 2002, a device called MammoSite,                  diation of the whole breast. Rather than
malignant growth.                               with a refined method of delivering                     just 1 or 2 approaches, oncologists at the
   “One agent is a virus that infects and       brachytherapy, was approved by the                      Hospital consider a very broad array of
kills pancreatic cancer cells with the RAS      FDA. Physicians at NewYork-                             options for each patient, including those
mutation, which is the most common              Presbyterian/Weill Cornell began using                  within a clinical trial, which is possible
mutation observed in pancreatic cancer,”        the device soon after FDA approval. Such                at a leading treatment center.
said Allyson J. Ocean, MD, who works            extensive experience with MammoSite                        “Our interest in partial-breast radia-
with coinvestigators Maureen E. Lane,           has led to a clear understanding of which               tion is actually part of an overall
PhD, gastroenterologists Mark Pochapin,         women are the best candidates for this or               approach to minimally invasive treat-
MD, and Felice Schnoll-Sussman, MD;             other forms of adjuvant therapy with                    ments for early-stage breast cancers,”
and oncologist Joseph T. Ruggiero, MD.                                                                                           see MammoSite, page 7
“We have been heavily involved in the
preclinical work in cell lines and animals,
and we are now working on the protocol                    Ovarian Cancer                                    Current Trends in Genitourinary
for a clinical trial. There has already been
some preliminary clinical work in other                   2    Minimally invasive laparoscopy surgery
                                                               may be an option for patients with
                                                          early-stage ovarian carcinoma.
                                                                                                            Malignancies: Third Annual Conference
                                                                                                            October 27, 2007

solid tumors, and we are very excited
about its potential in pancreatic cancer.”                New Hematology/                                   Advances in Colorectal Cancer Therapies
                                                                                                            Web Cast

   NewYork-Presbyterian/Weill Cornell                     Oncology Chief                                    Archived
is part of the Pancreatic Cancer Research
Team (PCRT), a national consortium                        5 EdwardNewYork-Presbyterian Center.
                                                                       P. Gelmann, MD, recently

                                                          Hospital/Columbia University Medical
                                                                                                            “Pure” laparoscopic versus “hand-assisted” laparoscopic
                                                                                                            surgery; new approaches to minimally invasive surgery.
created for both basic research and multi-
center trials under the direction of Daniel               Breast Cancer                                     For more information, please visit
Von Hoff, MD, of the Arizona Health
Sciences Center. The PCRT, with which
                    see Pancreatic, page 4
                                                          6    New research grants expand our
                                                               understanding of breast cancer and
                                                          may lead to new treatments.


                                       Hospital Explores Minimally Invasive                                                                 advances, physicians may one day be
                                                                                                                                            able to utilize laparoscopy for women

                                       Surgery in Ovarian Cancer                                                                            with advanced ovarian cancer.
                                                                                                                                               “We’ve seen tremendous improvement
                                                                                                                                            in minimally invasive surgical technolo-

                                                lthough gynecologic cancers such              more effective adjuvant chemotherapies to     gies,” said Dr. Herzog. For example, cam-
                                                as cervical and uterine are often             treat the remaining disease, noted Dr.        eras and equipment are better, as is the
                                                treated with minimally invasive               Caputo. Better chemotherapies could be        understanding of what physicians see
                                       laparoscopy surgery, the technique                     used to debulk tumors, the remainder of       through the scope, he said.
                                       remains an experimental procedure in                   which could be removed with laparoscopy.         Although debulking late-stage ovarian
                                       selected patients with early-stage ovarian             “Researchers need to be looking for more      cancer may not currently be a widely used
                                       carcinoma, according to oncologists at                 active chemotherapy drugs and com-            option, laparoscopy is sometimes a useful
                                       NewYork-Presbyterian Hospital.                         pounds,” he said.                             tool for staging the disease in select
                                          “Minimally invasive surgery is possible                Although minimally invasive surgery        patients, said Dr. Caputo. For diagnostic
                                       in a subset of carefully selected women,”              is an option for early-stage disease, it is   purposes, the laparoscope allows surgeons
                                       said Thomas Caputo, MD. For example,                   not well established for advanced cancer,     to determine whether patients should pro-
                                       older patients with early-stage disease who            said Thomas Herzog, MD. Most                  ceed with a debulking surgery, followed
                                       cannot tolerate open surgery because of a              advanced cases require extensive surgery      by chemotherapy, or whether the cancer is
                                       higher likelihood of adverse events may be             and debulking, which is performed using       not debulkable, he explained.
                                       candidates for a laparoscopic procedure.               open incisions. Managing advanced ovar-          “With a laparoscope you can look
                                                                                                                                            around and decide how much you can or
                                                                                                                                            cannot do,” he said. However, he empha-
Photo courtesy of Thomas Herzog, MD.

                                                                                                                                            sized that using laparoscopy for staging
                                                                                                                                            patients with ovarian cancer is still
                                                                                                                                               Gynecologic oncologists generally use
                                                                                                                                            laparoscopy to examine pelvic masses up
                                                                                                                                            to 10 cm, said Dr. Herzog. These masses
                                                                                                                                            are removed through laparoscopic ports
                                                                                                                                            and a frozen section examination is per-
                                                                                                                                            formed to determine whether or not the
                                                                                                                                            growth is cancerous, he explained. If
                                                                                                                                            results are malignant, the physician can
                                                                                                                                            determine the extent of the patient’s dis-
                                                                                                                                            ease by using laparoscopy and taking
                                                                                                                                            biopsies of the omentum, peritoneum, and
                                                                                                                                            pelvic lymph nodes.
                                                                                                                                               Minimally invasive laparoscopy sur-
                                       Doctors perform paraaortic lymph node dissection for ovarian cancer using a laparoscope.             gery is more often used to remove
                                                                                                                                            endometrial, uterine, and some cervical
                                          With early-stage disease, it is still pos-          ian tumors through a laparoscope can be       cancers—situations in which the tumor
                                       sible to remove cancerous tissue through               difficult because organs such as the peri-    is not bulky and surrounding lymph
                                       small incisions using a laparoscope if stag-           toneum and bowels need to be stripped,        nodes are small enough to come through
                                       ing has been completed, said Dr. Caputo.               he explained.                                 port sites, said Dr. Caputo.
                                          However, the majority of surgery in                    Other areas of the body to which              Physicians are able to accomplish the
                                       these patients is still performed using an             advanced disease may spread include the       same lymph node yield through mini-
                                       open procedure. “Right now, the goal is to             abdomen, diaphragm, and the pelvic            mally invasive techniques as with open
                                       try and remove as much tumor as possible               region, added Dr. Caputo.                     surgery, said Dr. Herzog. “Laparoscopy
                                       and we recommend being as aggressive as                   Performing debulking of these organs       is usually the first option for many
                                       possible,” he said.                                    often would take too many hours               patients with endometrial and cervical
                                          Increasing the use of minimally inva-               through a laparoscope, said Dr. Herzog.       cancers, and they are often able to go
                                       sive surgery for ovarian cancer may require            However, with future technologic              home the next day,” he added.

2                                      www.nypcancer.org
“How much you really gain                     NewYork-Presbyterian Oncology
                                              is a publication of the Cancer Centers of NewYork-Presbyterian Hospital. The Cancer Centers are at the forefront of
from robotics as compared                     cancer screening and diagnosis, basic science, and clinical research. The Cancer Centers serve more than 6,500 new
                                              cancer patients each year, who receive state-of-the-art multidisciplinary care. The Cancer Centers include the NCI-
to traditional laparoscopic
                                              designated Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University
gynecological surgery needs                   Medical Center and the Weill Cornell Cancer Center at NewYork-Presbyterian Hospital/Weill Cornell Medical Center,
                                              which are respectively comprised of faculty from the Columbia University College of Physicians and Surgeons and
to be evaluated in a scien-                   the Weill Cornell Medical College.
tifically rigorous forum.”
                         Thomas Herzog, MD
                                               NewYork-Presbyterian Oncology Editorial Board
                                              Nasser Altorki, MD                                              John Leonard, MD
                                              Division Chief, Thoracic Surgery                                Associate Attending Physician
                                                NewYork-Presbyterian/Weill Cornell                              NewYork-Presbyterian/Weill Cornell
                                              David B. Skinner Professor of Thoracic Surgery                  Associate Professor of Medicine
   Improvements in treating gynecolog-          Weill Cornell Medical College                                   Weill Cornell Medical College
                                                nkaltork@med.cornell.edu                                        jpleonar@med.cornell.edu
ic cancers with minimally invasive sur-
gery may occur with new developments          Mitchell C. Benson, MD                                          David Nanus, MD
in robotics. In patients with ovarian         Urologist-in-Chief                                              Co-Division Chief, Hematology and Medical Oncology
cancer, minimally invasive robotic sur-         NewYork-Presbyterian/Columbia                                   NewYork-Presbyterian/Weill Cornell
                                              Member                                                          Mark W. Pastmantier Professor of Hematology and Oncology in
gery, “might be used in some cases
                                                Herbert Irving Comprehensive Cancer Center                    Medicine
where precise dissection is required,”                                                                        Professor of Medicine and Urology
                                              George F. Cahill Professor and Chairman of Urology
said Dr. Herzog.                                Columbia University College of Physicians and Surgeons          Weill Cornell Medical College
   Regardless of the cancer type, 1 draw-       mcb2@columbia.edu                                               dnanus@med.cornell.edu
back of robotic laparoscopic surgery is                                                                       Alfred Neugut, MD, PhD
that the physician loses tactical sensa-      Andrew J. Dannenberg, MD
                                                                                                              Co-Director, Cancer Prevention Programs
                                              Co-Director, Cancer Prevention Program
tion, said Dr. Herzog. Benefits include                                                                         NewYork-Presbyterian/Columbia
                                                NewYork-Presbyterian/Weill Cornell
the generation of 3-dimensional com-          Henry R. Erle, MD-Roberts Family Professor of Medicine          Associate Director for Population Sciences
puter images and very little tremor.                                                                            Herbert Irving Comprehensive Cancer Center
                                                Weill Cornell Medical College
                                                                                                              Myron M. Studner Professor of Cancer Research
   “How much you really gain from               ajdannen@med.cornell.edu
                                                                                                                Columbia University College of Physicians and Surgeons
robotics as compared to traditional                                                                             ain1@columbia.edu
laparoscopic gynecological surgery needs      Edward P. Gelmann, MD
                                              Chief, Division of Hematology/Oncology                          Dattatreyudu Nori, MD, FACR
to be evaluated in a scientifically rigor-       NewYork-Presbyterian/Columbia
ous forum,” said Dr. Herzog.                                                                                  Radiation Oncologist-in-Chief, Department of Radiation
                                              Deputy Director for Clinical Research
   This type of study has already                Herbert Irving Comprehensive Cancer Center                     NewYork-Presbyterian/Weill Cornell
occurred in prostate cancer, and              Clyde Wu Professor of Hematology/Oncology                       Professor of Clinical Radiology
researchers found that robotics had              Columbia University College of Physicians and Surgeons         Weill Cornell Medical School
                                                 gelmanne@columbia.edu                                          dnori@nyp.org
advantages over traditional laparoscopy
in certain cases, he said.                    Howard Kaufman, MD                                              Alexander J. Swistel, MD
   Ultimately, the type of surgery cho-       Chief, Division of Surgical Oncology                            Director, Weill Cornell Breast Center
sen for gynecologic cancers, whether            NewYork-Presbyterian/Columbia                                   NewYork-Presbyterian/Weill Cornell
open or minimally invasive, is based on       Member                                                          Associate Professor of Clinical Surgery
each patient’s individual needs, conclud-       Herbert Irving Comprehensive Cancer Center                      Weill Cornell Medical College
                                              Edwin C. and Anne K. Weiskopf Associate Professor of Clinical     aswistel@med.cornell.edu
ed Drs. Caputo and Herzog.                    Surgery Oncology
                                                Columbia University College of Physicians and Surgeons        Michael Weiner, MD
Thomas Caputo, MD, is Director of the           hlk2003@columbia.edu                                          Chief, Pediatric Oncology
Division of Gynecologic Oncology at                                                                             Herbert Irving Child and Adolescent Oncology Center at
NewYork-Presbyterian Hospital/Weill Cornell                                                                     Morgan Stanley Children’s Hospital of NewYork-
Medical Center, and is Vice Chairman of                                                                         Presbyterian/Columbia
Obstetrics and Gynecology at Weill Cornell                                                                    Hettinger Professor of Clinical Pediatrics
Medical College.                                                                                                Columbia University College of Physicians and Surgeons
                                                     NewYork-Presbyterian Hospital’s                            mw216@columbia.edu
E-mail: tac2001@med.cornell.edu.                  Cancer Prevention Newsletter and
                                                  Web site offer information for
Thomas Herzog, MD, is Director of the             professionals on the latest
Division of Gynecologic Oncology at               developments in the field of cancer
NewYork-Presbyterian Hospital/Columbia            prevention and screening. Visit
University Medical Center, and is Professor       www.nypcancerprevention.org.
of Clinical Medicine at Columbia University
College of Physicians and Surgeons.
E-mail: th2135@columbia.edu.

                                                                                                       “We have recently been working to
                                                                                                    combine chemotherapy with therapeutic
                                                                                                    radiation in the neoadjuvant setting to
                                                                                                    increase the number of pancreatic cancers
    Pancreatic                                      Dr. Fine added. “Close collaborations of        that can be made resectable,” Dr. Ocean
    continued from page 1                           our cancer center scientists under the lead-    noted. Her team works in collaboration
    Robert L. Fine, MD and his team at              ership of Ricardo Della-Favora, MD, facil-      with radiation oncologist David Sherr,
    NewYork-Presbyterian/Columbia also col-         itates the development of novel therapeu-       MD. “The question we are attempting to
    laborate, provides access to a tumor bank       tics at Columbia.”                              address is what is the best sequence and
    that will increase resources for tissue sam-                                                    combination of modalities to achieve a
    ples; it also leads in studies of the broad                                                     maximum reduction in tumor size.”
    array of agents that are coming forward in      “The list of targeted agents with                  Understanding the pathophysiology
    clinical development.                           promise in pancreatic cancer is                 and the vulnerabilities of pancreatic cancer
       “The list of targeted agents with prom-                                                      is a recurring theme. At NewYork-
    ise in pancreatic cancer is long and get-       long and getting longer.”                       Presbyterian/Weill Cornell, through col-
    ting longer. In the PCRT, some of the                                 —Allyson J. Ocean, MD     laboration with clinical investigators at
    agents in clinical development include                                                          the Jay Monahan Center for Gastro-
    aurora kinase inhibitors, polo-like-kinase-        The regimen providing the greatest           intestinal Health, there is a project to
    1 inhibitors, imidazoline small molecule        activity so far observed is known as GTX        study pancreatic cystic neoplasms, which
    compounds, Rav-12 monoclonal antibod-           (gemcitabine, docetaxel, and capecitabine),     are premalignant lesions that may provide
    ies, angiogenesis inhibitors, and Src kinase    which demonstrated synergistic in vitro         insight into the pathogenesis of pancreatic
    inhibitors,” Dr. Ocean said.                    and substantial antitumor effects clinically    cancer. At NewYork-Presbyterian/
       “We have developed 6 new regimens            in late-stage metastatic pancreatic cancers     Columbia, new mouse models for pancre-
    for pancreatic and neuroendocrine cancers       and is now being studied for earlier use in     atic cancer as well as cystic neoplasms of
    that have been or will be translated to the     shrinking nonresectable tumors. The             the pancreas developed by Dr. Su and the
    clinic, and several are very promising,”        GTX work was presented at this year’s           molecular and biochemical studies in pan-
    added Dr. Fine. “In studies that were           annual meeting of the American Society of       creatic cancer have been fundamental to
    recently completed with a new regimen,          Clinical Oncology and the American              the progress in bringing new lab-based
    we anticipate the highest rates of response     Association of Cancer Researchers, but          treatments to the clinic.
    and survival ever achieved in patients with     there are other exciting new therapies             “This research provides a platform for a
    metastatic and inoperable non-metastatic        being developed and patented in Dr.             very novel and directed approach in which
    pancreatic cancer.” Although he cautioned       Fine’s lab. These include a new specific        we hope that our therapies will be increas-
    results must be duplicated in large, Phase      gene therapy that only kills cells with         ingly capable of killing malignant cells
    III studies, “the most encouraging aspect       mutant ras/mutant p53; a peptide that           with minimal effects on normal tissues,”
    of this research is that it was conceived in    only kills cancer cells with mutant p53;        noted Dr. Fine. “We are firmly dedicated
    our lab, so we understand the molecular         and a new form of chemotherapy that does        to eradicating this formidable disease. The
    and biochemical mechanisms, and this            not utilize the conventional toxic agents.      close collaboration between the scientists
    provides us with insight for modifying          Importantly, the gene therapy and the           and clinicians at the Hospital will help us
    regimens for greater activity or safety.        peptide also kill premalignant pancreatic,      remain at the forefront of translational
                                                                                                    research in pancreatic cancer. The lessons
       “This work heavily depends upon              breast, and colon cells before they become
                                                                                                    learned will also be applicable to other
    experts in many fields,” said Dr. Fine.         cancers. All are moving forward toward
                                                                                                    malignancies with similar genetic defects
    According to Dr. Fine, surgeons John            clinical development.                           such as lung, breast, and colon cancers.”
    Chabot, MD; John D. Allendorf, MD; and             At NewYork-Presbyterian Hospital,
    Beth Shrope, MD; gastroenterologists            interdisciplinary collaboration is consid-      Robert L. Fine, MD, is Director of the
    Peter D. Stevens, MD; Harold Frucht,            ered essential to the efforts to increase the   Experimental Therapeutics Program, Herbert
    MD; and Stravos N. Stravopoulos, MD;            ratio of cures to transient remissions. The     Irving Comprehensive Cancer Center at
    pathologist Helen Remotti, MD; scien-           primary goal of this collaboration is to        NewYork–Presbyterian Hospital/Columbia
    tists Paul Brandt-Rauf, MD, PhD, ScD,           increase the number of tumors that can be       University Medical Center, and is Herbert
    and Gloria Su, PhD; and medical oncolo-         resected, which is the only treatment asso-     Irving Associate Professor of Medicine,
                                                                                                    Columbia University College of Physicians and
    gists William H. Sherman, MD, and               ciated with significant rates of relapse-free   Surgeons. E-mail: rlf20@columbia.edu.
    Michael J. Hall, MD; and other multidis-        survival. At NewYork-Presbyterian/
    ciplinary research scientists have made         Columbia, Dr. Fine works closely with Dr.       Allyson J. Ocean, MD, is Medical Oncologist,
                                                                                                    The Jay Monahan Center for Gastrointestinal
    vital contributions to this research.           Chabot, who has worked to expand the
                                                                                                    Health at NewYork-Presbyterian
       “Without our laboratory scientists and       definitions of resectability. At NewYork-       Hospital/Weill Cornell Medical Center, and is
    the clinical expertise of my peers, the suc-    Presbyterian/Weill Cornell, Michael D.          Assistant Professor of Medicine at Weill
    cess of the translational research and clini-   Lieberman, MD, has also been actively           Cornell Medical College.
    cal achievements would not be possible,”        involved in collaborative efforts.              E-mail: ajo9001@med.cornell.edu.

4   www.nypcancer.org
New Hematology/Oncology Chief Encourages
Bi-Campus Collaboration at NewYork-Presbyterian

       dward P. Gelmann, MD, recently                                                              Dr. Gelmann’s laboratory studies the
       joined NewYork-Presbyterian               “Some of the more recent                       prostate-specific homeodomain protein
       Hospital/Columbia University              dramatic developments in                       NKX3.1, a tumor suppressor that is com-
Medical Center as the new Chief of the                                                          monly downregulated in prostate cancer
Division of Hematology and Oncology              cancer therapy have been                       in humans. In a recent publication, Dr.
and the Deputy Director for Clinical             based on findings in basic                     Gelmann and colleagues reported their
Research of the Herbert Irving                                                                  finding that NKX3.1 can modify the
Comprehensive Cancer Center (HICCC).             science.”                                      activity of the DNA-resolving enzyme
   Part of Dr. Gelmann’s responsibilities is                     —Edward P. Gelmann, MD         topoisomerase I, which may have implica-
to facilitate collaboration between                                                             tions for organ-specific DNA replication,
NewYork-Presbyterian/Columbia and                                                               transcription, or repair (Cancer Res
NewYork-Presbyterian Hospital/Weill              clinical trial review is faster and the        2007;67:455-467).
Cornell Medical Center. He is working            process is more transparent,” he said.            Another research interest is the andro-
with the Co-Chiefs of NewYork-                      Dr. Gelmann also has several objectives     gen receptor gene. In the Journal of
Presbyterian/Weill Cornell’s                     in mind for his role as Chief of               Biological Chemistry (2005;280:37853-
Hematology/Oncology Department,                  Hematology/Oncology. For example, the          37867), Dr. Gelmann and a colleague
Barbara L. Hempstead, MD, and David              division needs to develop clinical research    recently proposed that the multifunction-
M. Nanus, MD.                                    programs that interface with and take          al oncoprotein β-catenin “may play an
   “The working relationship between the         advantage of the already high academic         integral role in formation of the andro-
2 campuses is a big priority,” said Dr.          standards and accomplishments of               gen-receptor transcriptional complex.”
Gelmann. As part of this relationship,           NewYork-Presbyterian/Columbia, he said.           Dr. Gelmann received his medical
both Hematology/Oncology Departments                Specifically, Dr. Gelmann plans to          degree from Stanford University School of
are working together to conduct joint            establish a developmental therapeutics         Medicine in Palo Alto, Calif, in 1976 and
clinical trials and to provide Web-based         program, that will test new cancer agents      completed his internship and residency in
clinical trial information for patients and      at the earliest phases of clinical trials in   the Department of Internal Medicine at
referring physicians. In addition, the           humans. New cancer drugs and treat-            the University of Chicago Hospitals and
HICCC is working to develop more inter-          ments are increasingly based on cancer         Clinics in 1978. He pursued a clinical fel-
active relationships with satellite research     genetics. Scientists are identifying specif-   lowship in oncology at the Medicine
institutions and private practices.              ic genetic errors that cause a normal cell     Branch of the National Cancer Institute
   Dr. Gelmann also has a number of goals        to become cancerous and then can devel-        (NCI), which he completed in 1980. He
in mind for the HICCC. “We plan to               op drugs that block the function of the        was a medical staff fellow in the Institute’s
build a centralized infrastructure to sup-       cancer-causing proteins. “Some of the          laboratory of tumor cell biology from
port the conduct of clinical trials,” he said.   more recent dramatic developments in           1979 to 1983.
   This includes development of a com-           cancer therapy have been based on find-           In the years since, some of Dr.
prehensive staff with uniform training,          ings in basic science,” said Dr. Gelmann.      Gelmann’s many academic appointments
establishment of institutional guidelines,       “Developing new therapies will take a lot      have included Senior Investigator in the
and use of information technology to             of astute experimentation because each         Medicine Branch at the NCI; Professor of
make the clinical trial process more con-        type of cancer is unique.”                     Medicine and Professor of Cell Biology at
sistent throughout the Center.                      Dr. Gelmann will also continue to           Georgetown University School of
   Also on the agenda is expanding the           pursue his own research interests. His         Medicine; and Director of the Lombardi
HICCC’s relationship with sponsors of            laboratory at Georgetown University            Cancer Center Growth Regulation of
clinical trials. “Sponsors need to know          School of Medicine, in Washington, DC          Cancer Program at Georgetown
that the Center is responsive and a fertile      where he was most recently Chief of the        University.
ground for conducting research,” Dr.             Division of Clinical Sciences in the
Gelmann said. “They need to know that            Department of Oncology, will be moving         Edward P. Gelmann, MD, is Chief, Division
trials can be done expeditiously.”               to NewYork-Presbyterian/Columbia. In           of Hematology/Oncology at NewYork-
   The HICCC is developing a more                this new location, he will collaborate         Presbyterian Hospital/Columbia University
user-friendly interface with sponsors,           with other leaders in genitourinary            Medical Center, Deputy Director for Clinical
                                                                                                Research, Herbert Irving Comprehensive
various review agencies, and the                 malignancies such as NewYork-                  Cancer Center, and is Clyde Wu Professor of
Institutional Review Board (IRB).                Presbyterian’s Daniel P. Petrylak, MD,         Hematology/Oncology at Columbia University
“Agencies and the IRB can be made                Mitchell C. Benson, MD, and Carlos             College of Physicians and Surgeons.
more responsive, so turnaround time on           Cordon-Cardo, MD, PhD.                         E-mail: gelmanne@columbia.edu.


    Investigators Awarded Breast                                                             increase our understanding of how

    Cancer Research Grants
                                                                                             NSAIDs reduce the risk of breast cancer
                                                                                             and provide insights into approaches for
                                                                                             both preventing and treating breast can-

           he Breast Cancer Research             cancer, she explained.                      cer,” said Dr. Dannenberg.
           Foundation (BCRF) and the Susan          An important part of their research         NSAIDs may impact breast cancer
           G. Komen for the Cure                 involves looking at patterns of mammo-      because they inhibit cyclooxygenase
    Foundation have awarded research             graphic density and how these are asso-     (COX) enzymes—COX-1 and
    grants to study breast cancer to several     ciated with various tumor characteris-      COX–2—said Dr. Dannenberg. COX
    Columbia and Weill Cornell investiga-        tics, said Dr. Terry.                       enzymes contribute to the production of
    tors from NewYork-Presbyterian                  “We currently don’t fully understand     prostaglandins that increase aromatase
    Hospital.                                    how density is associated with clinical     activity, thereby stimulating estrogen
       Four researchers from NewYork-            and pathological factors,” she said.        synthesis. Inhibitors of COX proteins
    Presbyterian were among 115 distin-             Over the next year, the researchers      block prostaglandin production and
    guished investigators from around the        will use biospecimens and data from         thereby reduce estrogen synthesis. This
    world selected to receive the 2006-2007      more than 500 women with breast can-        effect may contribute to the reduction
    BCRF grants, which generally range           cer, in addition to more than 500 sisters   in breast cancer incidence in women
    from $225,000 to $250,000. A record-         who do not have the disease. They will      who take NSAIDs, but other anti-breast
    breaking $24.3 million in grants were        expand research on how the ability to       cancer effects are likely, said Dr.
    awarded at the Foundation’s annual           repair damaged DNA impacts breast           Dannenberg.
    symposium and                                cancer risk by investigating a repair          One of the goals of the 2006-2007
    luncheon                                     pathway that fixes double-strand breaks     research project is to evaluate the rela-
                                                 in DNA.                                     tive importance of COX-1 and COX-2

                                                  “This research should both increase our understanding of
                                                   how NSAIDs reduce the risk of breast cancer and provide
                                                  insights into approaches for both preventing and treating
                                                  breast cancer.”
                                                                                                               —Andrew Dannenberg, MD

    held at the Waldorf                             Another part of this research will be    as determinants of aromatase activity, he
    Astoria in New York City in October.         to investigate the role of DNA methyla-     said. Inhibition of either enzyme results
       The Foundation awarded 3 co-investi-      tion and its impact on breast cancer        in a significant reduction in aromatase
    gators, Regina Santella, PhD, Ruby           risk, and whether environmental expo-       activity in cultured cells.
    Senie, PhD, and Mary Beth Terry, PhD,        sures are associated with epigenetic           Consequently, NSAIDs that inhibit
    a grant to study environmental expo-         changes.                                    both COX enzymes, such as aspirin or
    sures and genetic susceptibility to breast      The Foundation also awarded a BCRF       ibuprofen, may be more effective than
    cancer.                                      2006-2007 grant to Andrew Dannenberg,       selective COX-2 inhibitors in suppress-
       “We’re finding that women who are         MD, who is co-investigating with Cliff      ing estrogen production, explained Dr.
    unable to properly repair DNA damage         Hudis, MD, of Memorial Sloan-               Dannenberg. He and his co-investigator
    have an increased risk of developing the     Kettering Cancer Center. The doctors are    are comparing aspirin with COX-2
    disease,” said Dr. Santella.                 studying the effect of nonsteroidal anti-   inhibitors to examine its ability to delay
       Genotyping has revealed that genes        inflammatory drugs (NSAIDs) on estro-       the development of experimental breast
    that remove bulky DNA adducts and            gen, a cause and promoter of growth of      cancer.
    damage from oxidative stress influence       hormone-receptor–positive breast cancer.       Another research goal is to explore the
    how diet and smoking impact breast              “Ultimately, this research should both                  see Breast Cancer, page 8

6   www.nypcancer.org
MammoSite                                          “There must be at least 5 mm to 7 mm        basis, a computerized radiation machine is
continued from page 1                           between the surface of the balloon and the     used to insert a radioactive seed into the
                                                skin,” said Dattatreyudu Nori, MD. “We         inflated balloon, providing a precise dose
noted Alexander J. Swistel, MD. “The            also have very firm criteria for defining      of radiation to the target tissue for a short
movement toward lumpectomy, which               the conformation volume of the inflated        period, after which it is removed. This
provides a similar degree of protection         balloon on CT scan at the time of treat-       treatment is repeated each day for up to 5
from recurrence when compared to mas-           ment relative to the conformation report-      days. When node-negative women with
tectomy in node-negative tumors, was an         ed intraoperatively. We have performed         breast cancer who undergo lumpectomy
early event to preserving quality of life.      more than 2,000 MammoSite treatments,          are given their options for adjuvant radia-
We have seen the same concept extend to         and we have used our expertise to create       tion, they generally prefer MammoSite,
lymph node dissection and now adjuvant          guidelines to identify the optimal candi-      according to Dr. Nori. “Working women
radiation. The question arose, ‘Why radi-       dates for this procedure. We also offer        are especially enthusiastic because they
ate the whole breast if partial-breast radia-   patients 3-dimensional conformal radia-        can continue in their jobs due to the fact
tion can produce the same outcome of            tion, which, like MammoSite, is delivered      that treatment is so convenient and well
lowering recurrences?’”                         twice per day over 5 days. This is also a      tolerated,” he added. “There is minimal to
   In appropriate candidates, MammoSite         partial-breast radiation approach, but it is   no pain or discomfort associated with the
and other partial-breast radiation strate-      not as localized as MammoSite.”                procedure.”
gies offer advantages over external-beam
radiation to the whole breast. Primarily,       The Case                                       Result
the duration of therapy is shorter.                A 63-year-old high school principal            In this case, the treatment was indeed
Whereas a course of external-beam radia-        with an abnormal result on mammogra-           effective, and to date, the patient’s cancer
tion to the whole breast is administered        phy was diagnosed with a 0.5-cm invasive       has not recurred.
over 7 weeks on a daily basis, MammoSite        ductal carcinoma in the upper outer quad-         Because of successes such as these, the
therapy is administered over 5 days. The        rant of her left breast. The patient was       MammoSite procedure is becoming more
device is essentially a small balloon           considered an excellent candidate for          widely available. The American College of
catheter inserted by the surgeon at the         breast conservation and sentinel node dis-     Radiology and the Radiation Oncology
time of lumpectomy. Because MammoSite           section. When margins of the lumpecto-         Treatment Group have opened a prospec-
delivers radiation to the interior of the       my specimen prove negative and the node        tive randomized study to examine the effi-
breast at the site where the tumor was          is clear, the next step to minimize the risk   cacy of the methods used to deliver par-
resected, the risk for skin reactions or dis-   for recurrence is adjuvant whole-breast        tial-breast irradiation. NewYork-
coloration, often associated with external-     irradiation. Recently, in cases in which the   Prebyterian/Weill Cornell was previously
beam radiation, is reduced. Other               tumor size is relatively small and the dis-    1 of only 10 centers in the country that
approaches to partial-breast irradiation        ease is diagnosed early, the concept of        successfully completed a trial in which
have been tested, each with advantages          whole-breast irradiation has come under        MammoSite was used to treat patients
and disadvantages. One approach is to           question, especially because local recur-      with ductal carcinoma in situ. Results
deliver radiation to the tumor site at the      rence appears to arise within the same area    continue to be encouraging, and this tech-
time of resection. A risk of intraoperative     of the breast as the original tumor.           nique may eventually become the standard
treatment, however, is that it is delivered        In this case, the patient had heard         of care for patients with breast cancer who
before the pathology report is completed.       about partial-breast radiation and             require adjuvant radiation therapy.
If the patient has positive margins, intra-     expressed a preference for this treatment
                                                                                               Mary Katherine Hayes, MD, is Associate
operative treatment may complicate sub-         over whole-breast treatment; however, she      Attending Radiologist at NewYork-
sequent re-excision of the radiated             wanted to know her options. Based on her       Presbyterian Hospital/Weill Cornell Medical
lumpectomy bed.                                 pathology report, she was a candidate for      Center, and is Associate Professor of Clinical
   “MammoSite is ideal for small tumors,        partial-breast irradiation, which not only     Radiology at Weill Cornell Medical College.
and it is well tolerated,” Dr. Swistel          reduces the duration of treatment but is       E-mail: mkh2001@med.cornell.edu.
noted. “It can be used in much older            likely to achieve a better cosmetic result.    Dattatreyudu Nori, MD, is Radiation
women with good results. It avoids a lot           In the procedure, a balloon catheter is     Oncologist-in-Chief, Department of Radiation
of the side effects, such as fatigue, associ-   inserted into the surgical cavity left after   Oncology at NewYork-Presbyterian
ated with higher doses of radiation over        removal of the tumor. The catheter can be      Hospital/Weill Cornell Medical Center, and is
longer periods.”                                placed at the time of resection or in a sep-   Professor of Clinical Radiology at Weill
                                                                                               Cornell Medical College.
   Appropriate candidates for the tech-         arate procedure. Before radiation is deliv-
                                                                                               E-mail: dnori@nyp.org.
nique are selected in consultation with         ered, the balloon is inflated with saline
Mary Katherine Hayes, MD. Among the             and a contrast agent. This allows the tis-     Alexander J. Swistel, MD, is Director, Weill
                                                                                               Cornell Breast Center at NewYork-
criteria used are distance from the lesion      sue to conform to the balloon and permits
                                                                                               Presbyterian Hospital/Weill Cornell Medical
to the skin, symmetry of the balloon with-      more consistent irradiation to the target      Center, and is Associate Professor of Clinical
in the lesion cavity, and distance from the     tissue. When the patient returns for treat-    Surgery at Weill Cornell Medical College.
balloon to the chest wall.                      ment, which is delivered on an outpatient      E-mail: aswistel@med.cornell.edu.

                                   Breast Cancer                                                                                               women to take a copper-depletion pill
                                   continued from page 6                               “We’re hoping to understand                             as part of their overall treatment plan,
                                                                                       factors that contribute to                              when they are diagnosed with breast
                                   connections between the several growth-                                                                     cancer and keep the tumor dormant and
                                   promoting pathways contributing to                  the breast tumor being                                  occult forever,” concluded Dr. Vahdat.
                                   breast cancer. For example, the researchers         dormant and occult for up to
                                   have shown that the receptor HER-2                                                                          Andrew Dannenberg, MD, is Director of
                                   causes increased amounts of aromatase               15 to 20 years and then, all                            Cancer Prevention at NewYork-Presbyterian
                                   activity and that this can be prevented                                                                     Hospital/Weill Cornell Medical Center, and
                                                                                       of a sudden, becoming                                   is Henry R. Erle, MD-Roberts Family
                                   with a COX inhibitor.
                                      Similar work is being conducted to               active again.”                                          Professor of Medicine at Weill Cornell
                                                                                                                                               Medical College.
                                   explore the link between COX enzyme                                                                         E-mail: ajdannen@med.cornell.edu.
                                   activity and angiogenesis. Inhibiting                                          —Linda Vahdat, MD
                                   COX can help reduce the formation of                                                                        Regina Santella, PhD, is Director of the
                                   new blood vessels in experimental breast               In the study, patients will orally ingest            Epidemiology Program at the Herbert
                                                                                                                                               Irving Comprehensive Cancer Center at
                                   cancer, explained Dr. Dannenberg.                   tetrathiomolybdate daily for 2 years. They              NewYork-Presbyterian Hospital/Columbia
                                      In addition to the BCRF grants, the              will be evaluated with physical examina-                University Medical Center, and is Professor
                                   Susan G. Komen for the Cure                         tions and routine laboratory studies on a               of Environmental Health Sciences at
                                   Foundation awarded Linda Vahdat, MD,                monthly basis, while imaging studies will               Columbia University Mailman School of
                                   $250,000 during its 2005-2006 fund-                 be performed every 4 months.                            Public Health. E-mail: rps1@columbia.edu.
                                   ing cycle.                                             Researchers will also evaluate circu-                Ruby Senie, PhD, is Professor of Clinical
                                      Dr. Vahdat and her colleagues will               lating surrogate markers of angiogenesis                Sociomedical Sciences and Clinical
                                   conduct a Phase II study of a copper-               at baseline, 1 month, and every 6                       Epidemiology at Columbia University
                                   depletion compound called                           months for the trial duration.                          Mailman School of Public Health.
                                   tetrathiomolybdate, an antiangiogenic                  Plasma angiogenic activity will be                   E-mail: rts15@columbia.edu.
                                   agent, in 50 patients at high risk for              evaluated using an angiogenic assay and                 Mary Beth Terry, PhD, is Associate
                                   breast cancer recurrence.                           assessment and quantification of circulat-              Professor of Epidemiology, Columbia
                                      “We’re hoping to understand factors              ing endothelial and pro-angiogenic                      University Mailman School of Public
                                   that contribute to the breast tumor                 hematopoietic progenitor cells by flow                  Health. E-mail: mt146@columbia.edu.
                                   being dormant and occult for up to 15               cytometry and TUNEL assay. Researchers
                                                                                                                                               Linda Vahdat, MD, is Associate Attending
                                   to 20 years and then, all of a sudden,              will also evaluate plasma vascular                      Physician at NewYork-Presbyterian
                                   becoming active again,” said Dr.                    endothelial growth factor (VEGF)-A,                     Hospital/Weill Cornell Medical Center, and
                                   Vahdat. Researchers also hope to discov-            VEGF-C, VEGF-D, thrombospondin-1,                       is Associate Professor of Clinical Medicine at
                                   er whether they can interrupt this acti-            and histidine-rich glycoprotein.                        Weill Cornell Medical College.
                                   vation process with tetrathiomolybdate.                “One day it may be possible for                      E-mail: ltv2001@med.cornell.edu.

                                NewYork-Presbyterian Hospital • Columbia University College of Physicians and Surgeons • Weill Cornell Medical College

                                               Important news from the Cancer Centers of NewYork-Presbyterian Hospital, at the
N E W Y O R K –P R E S B Y T E R I A N

                                               forefront of cancer prevention and screening, diagnosis, treatment, basic science, and

                                               clinical research.

                                            Spring 2007
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