Disclosed are biomarkers, methods and assay systems for the identification of cancer patients who are predicted to respond, or not respond to the therapeutic administration of radiation therapy to treat cancer. Thus, the invention provides a diagnostic paradigm to select cancer patients who will benefit from radiation therapy. In particular, the invention provides a novel 41-gene biomarker model associated with clinical outcome following radiotherapy across multiple histological tumor types, including the biomarker Cyclophilin B (PPIB).