An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer.

Individualization of cancer management requires prognostic markers and therapy-predictive markers. Prognostic markers assess risk of disease progression independent of therapy, whereas therapy-predictive markers identify patients whose disease is sensitive or resistant to treatment. We show that an experimentally derived IFN-related DNA damage resistance signature (IRDS) is associated with resistance to chemotherapy and/or radiation across different cancer cell lines. The IRDS genes STAT1, ISG15, and IFIT1 all mediate experimental resistance. Clinical analyses reveal that IRDS(+) and IRDS(-) states exist among common human cancers. In breast cancer, a seven-gene-pair classifier predicts for efficacy of adjuvant chemotherapy and for local-regional control after radiation. By providing information on treatment sensitivity or resistance, the IRDS improves outcome prediction when combined with standard markers, risk groups, or other genomic classifiers.

Chronic genitourinary and gastrointestinal toxicity of prostate cancer patients undergoing pelvic radiotherapy with intensity-modulated versus 4-field technique.

PURPOSE: To compare chronic GU and GI toxicity of pelvic radiotherapy delivered using intensity-modulated radiotherapy (IMRT) versus conventional 4-field technique. METHODS: The records of consecutive prostate cancer patients receiving RT at a single institution with a minimum follow-up of 120 days were reviewed; 48 of these patients received a prostate boost preceded by pelvic radiotherapy (PRT), 14 with IMRT (IM-PRT), and 34 with 4-field (4F-PRT). Dosimetric endpoints for the bladder, rectum, composite, and target for the PRT plans were compared using the 2-tailed t test. Late RTOG GU and GI toxicity were compared using the chi test. Ordered logit regression analyses were performed using all major patient, disease, and treatment factors as covariates. RESULTS: IM-PRT demonstrated superior bladder and rectum dosimetric endpoints over 4F-PRT for the PRT portion of the treatment and for the composite treatment at the expense of higher target inhomogeneity in the PRT portion of the treatment plan. Late GU toxicity was significantly lower in the IM-PRT group (P < 0.001), whereas late GI toxicity was similar in both groups (P = 0.44). When considering a similar follow-up interval in both groups, however, the difference in GU toxicity only reached a trend (P = 0.10). The regression analyses showed that no factor, including IMRT, reached significance in predicting GU or GI toxicity. CONCLUSION: Use of pelvic IMRT for prostate cancer patients was not associated with reduction of late GI toxicity but was associated with a small reduction of late GU toxicity. This reduction of late GU toxicity warrants further exploration in consortium studies.