Abstract A23: Ultrarapid total abdominal FLASH irradiation in a preclinical model of ovarian cancer

Abstract

Abstract Introduction: Ultrahigh dose-rate irradiation (FLASH RT) is rapidly emerging as new strategy to enhance the therapeutic index of radiotherapy by protecting normal tissues from radiation-induced toxicity while maintaining tumor control. In mice, FLASH has been shown to protect the lung, skin, and brain against radiation-induced toxicity. A recent study has utilized FLASH radiotherapy in preclinical models of lung cancer to demonstrate that FLASH RT radiotherapy achieves similar tumor control to conventional RT. While these findings identify an important role for FLASH RT in the protection of multiple tissues, the role of FLASH in enhancing the therapeutic index of abdominal and pelvic tumors located near the highly radiosensitive intestine is not known. For this purpose, we have developed an experimental platform using a clinical linear accelerator that enables total abdominal FLASH RT where rapid delivery of a single fraction of high-dose radiotherapy is performed in less than one second (200 Gy/sec). Methods: For the tumor model, ID8 cells were injected intraperitoneally into female mice. Radiation was delivered 10 days post-ID8 injection. Tumor burden was assessed at 28 days following tumor injection. Flow cytometry was used to profile infiltrating immune cells. Normal tissue toxicity was assessed through survival, total body weight, solid stool production, complete blood count, and histologic analysis. Results: In ID8 tumor-bearing mice, 14 Gy FLASH promotes GI function with a 2-fold increase in solid stool production at 5 days post-TAI. Both modalities extended median overall survival in the ID8 model by 5 days and reduced tumor burden by 50% relative to unirradiated controls. Irradiated cohorts also demonstrated an increase in the number of proliferating CD8+ and CD4+ T cells present in the ascites. Conclusion: We demonstrate that FLASH RT protects the gastrointestinal (GI) tract from lethal radiation-induced toxicity, improves epithelial integrity and GI function, enhances crypt survival, and provides efficient tumor control in a preclinical model of ovarian peritoneal metastasis. Here we present the first data supporting the potential for tumor control and GI protection using FLASH-TAI in a syngeneic orthotopic preclinical model of ovarian cancer. Citation Format: Karen Levy, Jinghui Wang, Joshua Eggold, Suchitra Natarajan, Peter Maxim, Bill Loo, Erinn Rankin. Ultrarapid total abdominal FLASH irradiation in a preclinical model of ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A23.