Disclosed herein are methods for personalized treatment of individual patient tumors. In one embodiment, a method of calculating a personalized radiation therapy dosage for a subject comprises determining expression levels of one or more signature genes from a subject's tumor sample, applying a linear regression model to the gene expression levels and assigning a radiation sensitivity index (RSI) to the subject's tumor sample, calculating a genomic adjusted radiation dose (GARD) value based on RSI, radiation dose and fractionation schedule of the subject, and calculating a personalized radiation dosage (RxRSI) for the subject based on a pre-determined GARD value.