Radiation Dose-Dependent Skin Toxicity and Therapeutic Advantage of FLASH Radiation Therapy Via Immune Modulation

Background FLASH radiotherapy shows promise in reducing normal tissue toxicity compared to conventional radiotherapy. Although several studies report skin-sparing effects of FLASH, few have quantitatively assessed this effect or explored underlying immunological mechanisms. Methods We quantified the skin-sparing effect of FLASH following single and fractionated hemithorax irradiation in mice. Multiplex gene expression analysis and immune profiling were performed to assess the immune status of irradiated skin. We also investigated the impact of CD8 + T-cell depletion for the different irradiation conditions. Results FLASH irradiation significantly delayed the onset and reduced the severity of skin toxicity compared to conventional irradiation for both single and fractionated irradiation ( p