Journal of the National Cancer Institute
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J. Natl. Cancer Inst. · Apr 2013
Renal carcinoma after childhood cancer: a report from the childhood cancer survivor study.
Adult survivors of childhood cancer are known to be at increased risk of subsequent malignancy, but only limited data exist describing the incidence and risk factors for secondary renal carcinoma. Among 14 358 5-year survivors diagnosed between 1970 and 1986, we estimated standardized incidence ratios (SIRs) for subsequent renal carcinoma and identified associations with primary cancer therapy using Poisson regression. ⋯ Highest risk was observed among neuroblastoma survivors (SIR = 85.8, 95% CI = 38.4 to 175.2) and, in multivariable analyses, with renal-directed radiotherapy of 5 Gy or greater (relative risk [RR] = 3.8, 95% CI = 1.6 to 9.3) and platinum-based chemotherapy (RR = 3.5, 95% CI = 1.0 to 11.2). To our knowledge, this is the first report of an association between cisplatin and subsequent renal carcinoma among survivors of childhood cancer.
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J. Natl. Cancer Inst. · Mar 2013
Validation of a breast cancer risk prediction model developed for Black women.
A breast cancer risk prediction model for black women, developed from data in the Women's Contraceptive and Reproductive Experiences (CARE) study, has been validated in women aged 50 years or older but not among younger women or for specific breast cancer subtypes. ⋯ The CARE model underpredicted breast cancer risk in the BWHS, at least in part because of older age at first birth in this cohort, which led to higher breast cancer incidence rates. Our results suggest that inclusion of age at first birth may improve model performance. Discriminatory accuracy was modest and worse for ER-negative breast cancer.
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Surrogate endpoints offer the hope of smaller or shorter cancer trials. It is, however, important to realize they come at the cost of an unverifiable extrapolation that could lead to misleading conclusions. With cancer prevention, the focus is on hypothesis testing in small surrogate endpoint trials before deciding whether to proceed to a large prevention trial. ⋯ Successively leaving out one historical trial and computing the predicted treatment effect in the left-out trial yields a standard error multiplier that summarizes the increased uncertainty in estimation extrapolation. If this increased uncertainty is acceptable, three additional extrapolation issues (biological mechanism, treatment following observation of the surrogate endpoint, and side effects following observation of the surrogate endpoint) need to be considered. In summary, when using surrogate endpoint analyses, an appreciation of the problems of extrapolation is crucial.