Showing papers by "Dale C. Snover published in 2014"

Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer

Abstract: Background As screening methods for colorectal cancer (CRC) are limited by uptake and adherence, further options are sought. A blood test might increase both, but none has yet been tested in a screening setting. Objective We prospectively assessed the accuracy of circulating methylated SEPT9 DNA (mSEPT9) for detecting CRC in a screening population. Design Asymptomatic individuals ≥50 years old scheduled for screening colonoscopy at 32 US and German clinics voluntarily gave blood plasma samples before colon preparation. Using a commercially available assay, three independent blinded laboratories assayed plasma DNA of all CRC cases and a stratified random sample of other subjects in duplicate real time PCRs. The primary outcomes measures were standardised for overall sensitivity and specificity estimates. Results 7941 men (45%) and women (55%), mean age 60 years, enrolled. Results from 53 CRC cases and from 1457 subjects without CRC yielded a standardised sensitivity of 48.2% (95% CI 32.4% to 63.6%; crude rate 50.9%); for CRC stages I–IV, values were 35.0%, 63.0%, 46.0% and 77.4%, respectively. Specificity was 91.5% (95% CI 89.7% to 93.1%; crude rate 91.4%). Sensitivity for advanced adenomas was low (11.2%). Conclusions Our study using the blood based mSEPT9 test showed that CRC signal in blood can be detected in asymptomatic average risk individuals undergoing screening. However, the utility of the test for population screening for CRC will require improved sensitivity for detection of early cancers and advanced adenomas. Clinical Trial Registration Number: NCT00855348

Abstract CT335: A clinical trial of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas

Abstract: Considerable epidemiological and preclinical evidence suggests that high vitamin D status confers a lower risk of colorectal neoplasia. High calcium intake has also been associated with reduced risks, and trials using calcium have shown a reduction in the occurrence of adenomas. To study these issues, we conducted a randomized, double blind, placebo-controlled trial of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas. We hypothesized that subjects receiving Vitamin D supplementation would have a lower risk of metachronous adenomas than those given placebo, that those randomized to calcium would have a lower risk, and that subjects given calcium and vitamin D together would have a lower risk than those given calcium alone. Secondary hypotheses involved effects of study agents on advanced lesions. Methods: In 11 US centers, we recruited subjects recently diagnosed with at least one adenoma; with no known polyps remaining in the bowel; and with no known contraindication to, or need for, the study agents. In a modified 2 x 2 factorial design, 2259 subjects were randomized to vitamin D3 (1000 IU daily), calcium (1200 mg daily), both agents, or neither. Women could elect to be randomized only to vitamin D. Follow-up colonoscopy was planned by the subjects’ clinicians at either 3 or 5 years after the baseline exam. Every 6 months, subjects were queried about endoscopic procedures, major medical events, and compliance with study procedures. Intention to treat risk ratios (RRs) and 95% confidence intervals (CIs) were computed with adjustment for age, sex, study center, number of baseline adenomas, planned follow-up interval (3 or 5 years) and participation in calcium randomization. Results: Treatment arms were well balanced with regard to personal characteristics and risk factors for metachronous neoplasia. Treatment adherence was very good; 90% of subjects reported taking at least half their study tablets during the trial. About 93% of subjects had a follow-up colonoscopy at least 1 year after randomization; nearly all were complete examinations. Baseline 25-OH vitamin D levels were 24.6 ng/ml overall; by the end of study treatment, subjects given vitamin D had levels 7.8 ng/ml higher than those given placebo. Overall, 42% of subjects had one or more adenomas during follow-up (mean size 5 mm). The study treatments had no effect on adenoma outcomes. The RR for vitamin D vs. placebo was 0.97 (95% CI 0.88-1.08); for vitamin D plus calcium vs. calcium alone, 0.99 (95% CI 0.86-1.13); and for calcium alone, 0.95 (95% CI 0.85-1.06). RRs for advanced adenomas were similar. Numbers of subjects with major medical events were low, but study agents had no material effect on risk of cardiovascular endpoints, cancer or kidney stones. Conclusion: Despite previous evidence, we found supplemental vitamin D and calcium to be ineffective in reducing risk of metachronous colorectal adenomas over 3 - 5 years. Citation Format: John A. Baron, Elizabeth L. Barry, Dennis J. Ahnen, Carol A. Burke, Roberd M. Bostick, Robert S. Bresalier, Timothy R. Church, Marcia Cruz-Correa, Michael Goodman, Robert Haile, Anastasia Ivanova, Richard I. Rothstein, Robert S. Sandler, Dale Snover, Robert W. Summers. A clinical trial of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT335. doi:10.1158/1538-7445.AM2014-CT335