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© Oxford University Press 2007.
IN THIS ISSUE
Fruit and Vegetable Intake and Colon Cancer RiskPrevious epidemiologic studies of the association between fruit and and vegetable intake and the risk of colon cancer have been inconsistent. Koushik et al. (p. 1471) analyzed 14 prospective cohort studies and then pooled their results to examine the association between total fruit and/or total vegetable intake and the risk of colon cancer overall, as well as proximal and distal colon cancer separately after adjusting for other colon cancer risk factors. There was little association between intake of fruits and vegetables and the overall risk of colon cancer. However, there was some evidence of an association between high intake of fruits and/or vegetables and lower risk of distal colon cancer.
Alternative Design of Phase II Trials for New Cancer Therapies
Phase II trials of promising cancer therapies have traditionally been single-arm studies in which the primary measure of efficacy is the proportion of patients who achieve a complete or partial response to treatment. Karrison et al. (p. 1455) describe an alternative phase II design that includes a control group whose members receive standard therapy and in which the primary outcome variable is the change in tumor size measured on a continuous scale. The authors argue that by not defining the endpoint as response or no response, this design has the advantage of preserving information on tumor size changes. As a consequence, inclusion of a control arm may not require a prohibitive increase in sample size.
In an editorial, Rubinstein et al. (p. 1422) describe problems with using changes in tumor size to predict whether phase III trials are warranted. They discuss the feasibility of conducting phase II trials that include a control arm and use progression-free survival as an endpoint.
Performance of New Screening Tests for Colorectal Neoplasms
The U.S. Preventive Services Task Force and the Institute of Medicine have recommended the unrehydrated guaiac fecal occult blood test (FOBT) for use in colon cancer screening. However, as a single test it has somewhat low sensitivity for detecting advanced colon neoplasms. Allison et al. (p. 1462) evaluated the performance characteristics of two newer tests—a sensitive guaiac test (sensitive GT) and a fecal immunochemical test (FIT)—and of the combination of both tests in a group of subjects at average risk for colorectal neoplasia. Of the 5,841 participants, 139 were diagnosed with advanced colorectal neoplasms within 2 years after the initial FOBT screening. The FIT was more sensitive than the sensitive GT or the combination test for detecting left-sided colorectal cancer; the FIT and the combination test were more specific than the sensitive GT for left-sided cancers. The authors conclude that the FIT has high sensitivity and specificity for detecting cancers of the left colon, and they suggest that the current test might be replaced by the FIT in screening programs.
In an editorial, Mandel (p. 1424) discusses the use of GT and FIT in colorectal cancer screening. He agrees that the FIT may be superior to the GT, but which FIT is the best is still unclear.
Prostate Cancer Detection on Biopsy: Location vs. Number
The accuracy of detecting prostate cancer from biopsies is unclear because there is often no way to confirm the results—that is, most men who have a negative biopsy do not then have a radical prostatectomy. To assess the prevalence and characteristics of prostate cancer in an autopsy population and to compare the sensitivity of biopsies taken from different anatomic sites, Haas et al. (p. 1484) performed 18-core biopsies—six each from the mid peripheral, lateral peripheral, and central zones of the prostate—on autopsy prostate glands from 147 men who had no history of the disease. Prostate cancer was detected in 47 of the prostate glands; 20 tumors were clinically significant according to histologic criteria. Tumor volume was associated with tumor grade and the man's age. Biopsies from the central zone did not detect any cancer that was not present in biopsies of either the mid or lateral peripheral zone Clinically significant prostate cancer was more often detected in the 12 biopsies of the mid and lateral peripheral zones than in the six biopsies of the mid peripheral zone only. The authors conclude that the anatomic site of a biopsy may be more important than the number of samples taken. More specifically, 12 biopsies predominantly from the mid- and lateral-peripheral zones may capture most clinically significant cancers and limit overdetection of clinically insignificant lesions.
"Cancer Stem Cells" or "Cancer-Initiating Cells"?
Cancer stem cells have been defined as cells in a tumor with the exclusive ability to self-renew and differentiate into the full array of cancer cells found in a tumor. In a commentary, Hill and Perris (p. 1435) write that the term "cancer stem cells" may be misleading because of uncertainties about whether cancer stem cells possess all of the properties of normal stem cells. They suggest a different term: "cancer-initiating cells." Many cancer stem cell properties remain to be clarified, including the stability of their phenotype. The authors conclude that these uncertainties must be considered when compounds targeted against cancer stem cells are developed and tested.
Drug Resistance and the Solid Tumor Microenvironment
For an anticancer drug to kill a high proportion of cancer cells in a solid tumor, it must distribute throughout the tumor vasculature, cross vessel walls, and traverse the tumor tissue. The limited ability of anticancer drugs to penetrate tumor tissue and reach all of the tumor cells in a potentially lethal concentration is an important but little-appreciated cause of drug resistance. In a review, Trédan et al. (p. 1441) describe how heterogeneity within the tumor microenvironment may be involved in solid tumor resistance to chemotherapy and discuss potential strategies to improve the effectiveness of drug treatment by modifying factors relating to the tumor microenvironment.
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J Natl Cancer Inst 2007 99: 1441-1454.
J Natl Cancer Inst 2007 99: 1435-1440.
J Natl Cancer Inst 2007 99: 1462-1470.
J Natl Cancer Inst 2007 99: 1484-1489.
J Natl Cancer Inst 2007 99: 1471-1483.
J Natl Cancer Inst 2007 99: 1455-1461.
J Natl Cancer Inst 2007 99: 1424-1425.
J Natl Cancer Inst 2007 99: 1422-1423.
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