Radiosensitivity Index (RSI) is not fit to be used for dose-adjustments: a pan-cancer analysis

Radiotherapy has been striving to find markers of radiotherapy sensitivity for decades. In recent years the community has spent significant resources on exploring the wide range of omics data-sets to find that elusive perfect biomarker. One such candidate termed the Radiosensitivity Index, RSI for short, has been heavily publicized as a marker suitable for making dose-adjustments in the clinical setting. However, none of the analyses conducted, thus far, has assessed whether RSI explains enough of the outcome variance to elucidate a dose-response empirically. Here we re-analyze a pan-cancer data-set and find that RSI is no better than random chance at explaining outcome variance, overall survival times. For completeness, we then assessed whether RSI captured a sufficient amount of outcome variance to elucidate a dose-response, it did not. These results suggest that like the initial in-vitro analysis 12 years previously RSI is not a marker of radiotherapy sensitivity and is thus not fit to be used in any dose-adjustment algorithms.