The methods described herein allow for the classification of patients into groups for receiving optimized radiation treatment based on patient specific biomarker signature. The biomarker signature includes markers that have been shown to correlate with TGF-β expression and to be associated with tumor aggressiveness, radioresistance and poor prognosis. The markers play a key role in the epithelial-mesenchymal transition. The methods described herein provide the dual benefits of anti-tumor efficacy plus normal tissue protection when combining TGF-β inhibitors with ionizing radiation to treat cancer patients.