Abstract
Radiation therapy is the most effective treatment of localized tumors. However, radiation-induced toxicity to normal tissues limits the radiation dose and therefore the curative potential of radiotherapy. In particular, the highly radiosensitive intestine greatly limits the use of radiation for patients with intra-abdominal tumor diseases. Here we report that ultrahigh dose rate FLASH irradiation causes significantly less radiation-induced intestinal injury in both healthy and tumor-bearing mice compared to conventional dose rate (CONV) irradiation. Using FLASH for total abdominal irradiation of mice, we observed lower mortality from gastrointestinal syndrome, preserved gut function and epithelial integrity, and decreased cell death in crypt base columnar cells. A reduced number of γ-H2AX foci in crypt cells indicates less DNA damage and/or increased DNA repair after FLASH compared to CONV irradiation. Importantly, FLASH and CONV irradiation have similar efficacy in the reduction of ovarian cancer peritoneal metastases. These findings suggest that FLASH irradiation may be an effective strategy to enhance the therapeutic index of radiotherapy for the treatment of abdominal and pelvic tumor disease.