Design and progress of a trial of selenium to prevent prostate cancer among men with high-grade prostatic intraepithelial neoplasia.

High-grade prostatic intraepithelial neoplasia (HGPIN) is generally regarded as a premalignant lesion that progresses toward prostate cancer. In light of the significant sequelae of prostate cancer treatment, prevention is desirable, and men with HGPIN would be suitable, high-risk subjects. There is in vitro, in vivo, epidemiologic, and human experimental evidence that selenium supplementation may protect against prostate cancer. This article introduces the rationale for, and progress to date, of a double-blind, randomized, placebo-controlled trial of selenium supplementation (200 mug/d in the form of selenomethionine), to prevent the development of prostate cancer among men with HGPIN. The trial, Southwest Oncology Group Protocol 9917, funded by a National Cancer Institute program supporting pivotal prevention trials has registered 537 patients and has randomized >380 to date. Subject accrual is expected to be completed by the fall of 2006, with trial completion in 2009.

Standardization of nuclear morphometry-based biomarkers.

Nuclear morphometry is used to address subtleties of carcinogenesis; it has been proposed for evaluating chemoprevention. An important issue for morphometry concerns control for extraneous sources of variation: fixation, slide cutting and staining. A common strategy has been to standardize the morphometric measures. Morphometric variables--such features as mean nuclear size and staining intensity--are often combined into multivariate indices. In this paper, we consider these variables one by one; any index is to a significant degree dependent on the individual indicators. This paper considers the extent to which statistical adjustment adds to the informational utility of individual indicators. We consider 14 features of 934 prostatic nuclei diagnosed by a single pathologist (Rodolfo Montironi) within a region of either normal tissue or high-grade prostatic intraepithelial neoplasia (HGPIN). HGPIN, a precursor to prostate cancer (PC), has been suggested as a target for PC chemoprevention. We consider a range of adjustment methods: transforming variables into deviations from means or from expected values generated by regression analysis. Our major test of standardization utility is the ability of the variables to deemphasize interindividual differences within diagnostic categories but to distinguish between diagnostic categories.

Measuring dietary change in a diet intervention trial: comparing food frequency questionnaire and dietary recalls.

Measurement of dietary change was assessed in a systematic quota subsample (n = 397) of women recruited into the Women's Healthy Eating and Living Study between 1996 and 1998, a multicenter, randomized dietary intervention trial among breast cancer survivors. Women from the intervention and comparison arms completed the Arizona Food Frequency Questionnaire (AFFQ) and 24-hour dietary recalls at baseline (prerandomization) and at year 1 (postrandomization). Both dietary measurement methods demonstrated significant changes in intake of key intervention-associated nutrients at year 1 in the intervention group subjects compared with minimal or no change in the comparison group subjects. The reliability of the AFFQ and recalls was measured in the comparison group and showed correlations of 0.63 and 0.43, respectively. Both instruments captured differences in dietary intake associated with the diet intervention. These results demonstrate the utility of using a multimode, multimethod approach (AFFQ and 24-hour dietary recalls) to measure differences in self-reported dietary intake over time as shown in this dietary intervention trial being conducted among breast cancer survivors.