High-Resolution Computed Tomography Screening for Lung Cancer: Unexpected Findings and New Controversies Regarding Adenocarcinogenesis by ProQuest

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CONTEXT: Recent advances in human imaging technologies reawakened interest in lung cancer screening. Although historic and current preliminary and noncontrolled studies have not shown a decrease in lung cancer mortality in screened populations, many explanations have been proffered while the lung cancer community awaits the results of several large controlled population studies. OBJECTIVE: To critically review the current model of adenocarcinoma development against the background of lung cancer screening results combined with observational pathologic and radiographic studies. DATA SOURCES: Published articles pertaining to lung cancer screening, lung adenocarcinoma pathology, and radiology accessible through PubMed form the basis for this review. CONCLUSIONS: The current adenocarcinogenesis model is probably valid for many but not all lung adenocarcinomas. Screening data combined with radiographic and pathologic studies suggest that not all lung adenocarcinomas are clinically aggressive, and it is uncertain whether all aggressive adenocarcinomas arise from identified precursors.

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									   High-Resolution Computed Tomography Screening for
                      Lung Cancer
   Unexpected Findings and New Controversies Regarding Adenocarcinogenesis
                                           Lucian R. Chirieac, MD; Douglas B. Flieder, MD

● Context.—Recent advances in human imaging technol-                      Data Sources.—Published articles pertaining to lung
ogies reawakened interest in lung cancer screening. Al-                cancer screening, lung adenocarcinoma pathology, and ra-
though historic and current preliminary and noncontrolled              diology accessible through PubMed form the basis for this
studies have not shown a decrease in lung cancer mortality             review.
in screened populations, many explanations have been                      Conclusions.—The current adenocarcinogenesis model
                                                                       is probably valid for many but not all lung adenocarcino-
proffered while the lung cancer community awaits the re-
                                                                       mas. Screening data combined with radiographic and path-
sults of several large controlled population studies.                  ologic studies suggest that not all lung adenocarcinomas
   Objective.—To critically review the current model of ad-            are clinically aggressive, and it is uncertain whether all
enocarcinoma development against the background of lung                aggressive adenocarcinomas arise from identified precur-
cancer screening results combined with observational                   sors.
pathologic and radiographic studies.                                      (Arch Pathol Lab Med. 2010;134:41–48)


G    iven the aggressive nature of lung cancer and the gen-
       eral inability of the world to curtail the abuse of
tobacco products, we now must confront the bitter truth
                                                                       dividuals continues—and its future as a public health pol-
                                                                       icy is unknown—the dialectic has produced an original
                                                                       and thoughtful reexamination of our most basic accepted
that lung cancer is the deadliest human cancer worldwide               notions regarding lung adenocarcinoma. This review aims
and that current treatment options are just not adequate.              to present our evolving understanding or lack of under-
   Recent medical advances in lung cancer care include                 standing of lung adenocarcinoma within the context of
noninvasive and minimally invasive methods of diagnos-                 lung cancer screening.
ing and treating lung cancer and pharmacogenetic ap-
proaches to chemotherapy selection. However, technologic                      ADENOCARCINOMA OF THE LUNG AND
advances have truly reinvigorated lung cancer clinicians                       LUNG CANCER SCREENING FINDINGS
and researchers alike. Although chest x-ray screening for
                                                                          Not unlike cancer models employed in other organ sys-
lung cancer was left for dead following the disappointing
                                                                       tems, the current lung adenocarcinoma model assumes a
results of the Mayo Clinic (Rochester, Minnesota), Johns
                                                                       progression from a few malignant cells to a group of cells
Hopkins (Baltimore, Maryland), and Memorial Sloan-Ket-
                                                                       to a small ‘‘early-stage’’ carcinoma, leading to ‘‘advanced-
tering (New York, New York) studies from the 1970s, high-
                                                                       stage’’ carcinoma and death. This model suggests that all
resolution computed tomography (HRCT) screening has
                                                                       lung adenocarcinomas are stage I before progressing to
forced lung cancer specialists to reconsider their long-held
                                                                       higher stages and causing death.1,2 Thus, early-stage and
assumptions about the disease. The past 10 years have wit-
nessed an accelerated pace in the radiologic characteriza-             late-stage carcinomas are separated only by time and the
tion of lung lesions and the histologic classification of lung          molecular events that occur during this time. This long-
adenocarcinoma.                                                        accepted scheme appears reasonable and provides the
   Although the fierce and often acrimonious debate re-                 framework for much research; however, lung cancer
garding the efficacy of HRCT screening of high-risk in-                 screening data do not convincingly support this general
                                                                       view.3 Lung cancer screening with early detection should
                                                                       lead to an increase in early-stage cancers, a decrease in
   Accepted for publication February 12, 2009.                         late-stage cancers, and lower lung cancer mortality. Yet,
   From the Department of Pathology, Brigham and Women’s Hospital      published data do not show these results and suggest that
and Harvard Medical School, Boston, Massachusetts (Dr Chirieac); and   perhaps not all clinically early lung adenocarcinomas pro-
the Department of Pathology, Fox Chase Cancer Center, Philadelphia,    gress to advanced lung cancers.
Pennsylvania (Dr Flieder).                                                Randomized trials of chest radiography with or without
   The authors have no relevant financial interest in the products or
                                                                       sputum cytology performed in the 1970s noted a large
companies described in this article.
   Reprints: Douglas B. Flieder, MD, Department of Pathology, Fox      increase in early-stage cancers in the screened populations
Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111           but not a meaningful decrease in the number of advanced
(e-mail: Douglas.Flieder@fccc.edu).                                    cancers.4–8 The Mayo Lung Project, London and Czecho-
Arch Pathol Lab Med—Vol 134, January 2010                                       HRCT Screening for Lung Cancer—Chirieac & Flieder 41
slovakian studies, demonstrated a near doubling of the           tically altered our
								
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