Generalized cross-entropy methods with applications to rare-event simulation and optimization

The cross-entropy and minimum cross-entropy methods are well-known Monte Carlo simulation techniques for rare-event probability estimation and optimization. In this paper, we investigate how these methods can be eXtended to provide a general non-parametric cross-entropy framework based on φ-divergence distance measures. We show how the χ distance, in particular, yields a viable alternative to the Kullback—Leibler distance. The theory is illustrated with various eXamples from density estimation, rare-event simulation and continuous multi-eXtremal optimization

Validation of a radiosensitivity molecular signature in breast cancer

Purpose: Previously, we developed a radiosensitivity molecular signature [radiosensitivity index (RSI)] that was clinically validated in 3 independent datasets (rectal, esophageal, and head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT)-treated breast cancer patients. Experimental Design: RSI was tested in 2 previously published breast cancer datasets. Patients were treated at the Karolinska University Hospital (n = 159) and Erasmus Medical Center (n = 344). RSI was applied as previously described. Results: We tested RSI in RT-treated patients (Karolinska). Patients predicted to be radiosensitive (RS) had an improved 5-year relapse-free survival when compared with radioresistant (RR) patients (95% vs. 75%, P = 0.0212), but there was no difference between RS/RR patients treated without RT (71% vs. 77%, P = 0.6744), consistent with RSI being RT-specific (interaction term RSI - RT, P = 0.05). Similarly, in the Erasmus dataset, RT-treated RS patients had an improved 5-year distant metastasis-free survival over RR patients (77% vs. 64%, P = 0.0409), but no difference was observed in patients treated without RT (RS vs. RR, 80% vs. 81%, P = 0.9425). Multivariable analysis showed RSI is the strongest variable in RT-treated patients (Karolinska, H