Abstract
The Cancer Genome Atlas (TCGA) is a valuable resource for developing and validating gene signatures for personalizing treatments. TCGA samples came from patients who received heterogeneous treatments – dominated by surgery. Improving the biological precision of radiotherapy is hampered by the lack of well annotated cohorts that reflect patient populations relevant for radiation oncologists. We aimed to generate transcriptomic data from needle core biopsies for a large multicenter cohort of high-risk prostate cancer patients and use the data to validate published gene signatures. A total of 478 NCCN classified high-risk patients treated from 2008-2016 were identified: 244 patients received intensity modulated radiotherapy (IMRT) to the prostate only (BEDα/β 1.5-3Gy of 120 – 180 Gy) and 234 patients received IMRT to the prostate and a high dose rate (HDR) brachytherapy boost (BEDα/β 1.5-3Gy 159 – 265 Gy). Androgen deprivation was given to all patients for 3-36 months. Biochemical failure was defined as prostate-specific antigen (PSA) rise of ≥2 ng/ml above nadir post radiotherapy. The primary clinical end-point was 7-year biochemical-relapse free survival (bRFS). Gene expression data were generated from diagnostic needle core biopsies using arrays. Two (28-gene and 32 gene) published hypoxia gene signatures were tested for prognostic significance. Additional non-prostate gene expression signatures were also validated. The median follow-up for the entire cohort was 6.3 years. Both the 28 gene (p = 0.021) and 32-gene (p = 0.033) hypoxia signatures were prognostic for 7-year bRFS. Non-prostate hypoxia signatures were not prognostic. We generated the largest high-risk prostate radiotherapy cohort with full gene expression data and showed its value in validating published gene signatures. Our resource will be a valuable asset for future research generating and validating signatures for personalizing radiotherapy in men with prostate cancer.
Published Version
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