The type of pathologic response but not pretreatment parameters was associated with OS and DFS. Efforts to increase the rate of pathologic response and better systemic cancer control are warranted.

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Risk assessment of rare natural hazards, such as large volcanic block and ash or pyroclastic flows, is addressed. Assessment is approached through a combination of computer modeling, statistical modeling, and extreme-event probability computation. A computer model of the natural hazard is used to provide the needed extrapolation to unseen parts of the hazard space. Statistical modeling of the available data is needed to determine the initializing distribution for exercising the computer model. In dealing with rare events, direct simulations involving the computer model are prohibitively expensive. The solution instead requires a combination of adaptive design of computer model approximations (emulators) and rare event simulation. The techniques that are developed for risk assessment are illustrated on a test-bed example involving volcanic flow.

Patients with hyperplastic polyposis have multiple hyperplastic polyps (HPs) and increased risk of colorectal carcinomas. Aberrant crypt foci (ACF) are postulated to be the earliest precursor lesions in colorectal carcinogenesis. We evaluated BRAF mutations by DNA sequencing in 53 ACF from patients with sporadic colorectal carcinomas and familial adenomatous polyposis, in 18 sporadic HPs from patients with resected colorectal cancer, and in 70 HPs, 4 serrated adenomas, 3 admixed hyperplastic-adenomatous polyps, 10 tubular adenomas, and 6 carcinomas from 17 patients with multiple/large HPs and/or hyperplastic polyposis. BRAF mutation status was compared with clinicopathological features and other genetic alterations by marginal logistic regression. BRAF mutation was present in only 2% of ACF and 6% of sporadic HPs. In contrast, BRAF mutation was present in 43% of HPs (P = 0.01 versus sporadic HPs), 75% of serrated adenomas, 33% of admixed hyperplastic-adenomatous polyps, 30% of tubular adenomas, and 33% of carcinomas from patients with multiple/large HPs and/or hyperplastic polyposis. BRAF mutation status in patients with multiple/large HPs and/or hyperplastic polyposis correlated with HPs from the same patient (odds ratio, 5.8; P = 0.0002) but associated with younger age (odds ratio, 0.83; P = 0.006 compared to older age), with a large HP (odds ratio, 22.5; P = 0.01 compared with patients with multiple HPs), with location of HPs in the right colon (odds ratio, 3.0; P = 0.03), and with methylation of the p16 gene and the MINT31 locus [odds ratio, 12.2 (P = 0.0001) and 4.4 (P = 0.02), respectively]. Our study shows that BRAF mutation status is heterogeneous among patients with multiple/large HPs and/or hyperplastic polyposis, suggesting differences in pathogenesis of HPs that indicate subsets within this phenotype.

BACKGROUNDThe value of baseline positron emission tomography (PET) for predicting overall survival (OS) or disease‐free survival (DFS) is unclear in patients with nondistant metastatic (locoregional only) esophageal carcinoma. The authors tested the hypothesis that, in this setting, the number of PET abnormalities (NPA) would correlate with OS and DFS.METHODSThe authors of the current study analyzed patients with localized esophageal carcinoma (Stages II and III) who had a baseline PET and endoscopic ultrasonography (EUS) and were all treated with chemoradiotherapy followed by surgery. The standardized uptake value (SUV) of PET avid lesions were evaluated for: SUV of the primary, NPA, peak SUV, and total SUV. Correlations were performed with baseline EUS results, OS, DFS, and clinical and pathologic response.RESULTSForty‐seven patients who underwent chemoradiotherapy followed by surgery were analyzed. Most patients had clinical Stage III cancer. NPA was significantly associated with OS (Cox model, P = 0.02; log‐rank test, P = 0.04) and DFS (P = 0.04). Patients with NPA > 1 had a death hazard ratio of 4.49 (reference, NPA = 1). In a multivariate analysis, NPA was independently predictive of OS (P = 0.03). Alternatively, SUV of the primary tumor, peak SUV, total SUV, and EUS clinical stage did not correlate with the type of response, OS or DFS.CONCLUSIONSData from the current study suggest that for nondistant metastatic esophageal carcinoma, baseline PET can predict patient outcome. Baseline NPA (> 1), reflecting the regional nodal metastases, is an independent predictor of OS. Baseline PET may become a useful stratification factor in randomized trials and for individualizing therapy. Cancer 2005. © 2005 American Cancer Society.