Author:
Levy Karen,Natarajan Suchitra,Wang Jinghui,Chow Stephanie,Eggold Joshua T.,Loo Phoebe E.,Manjappa Rakesh,Melemenidis Stavros,Lartey Frederick M.,Schüler Emil,Skinner Lawrie,Rafat Marjan,Ko Ryan,Kim Anna,H. Al-Rawi Duaa,von Eyben Rie,Dorigo Oliver,Casey Kerriann M.,Graves Edward E.,Bush Karl,Yu Amy S.,Koong Albert C.,Maxim Peter G.,Loo Billy W.,Rankin Erinn B.
Abstract
AbstractRadiation therapy is the most effective cytotoxic therapy for localized tumors. However, normal tissue toxicity limits the radiation dose and the curative potential of radiation therapy when treating larger target volumes. In particular, the highly radiosensitive intestine limits the use of radiation for patients with intra-abdominal tumors. In metastatic ovarian cancer, total abdominal irradiation (TAI) was used as an effective postsurgical adjuvant therapy in the management of abdominal metastases. However, TAI fell out of favor due to high toxicity of the intestine. Here we utilized an innovative preclinical irradiation platform to compare the safety and efficacy of TAI ultra-high dose rate FLASH irradiation to conventional dose rate (CONV) irradiation in mice. We demonstrate that single high dose TAI-FLASH produced less mortality from gastrointestinal syndrome, spared gut function and epithelial integrity, and spared cell death in crypt base columnar cells compared to TAI-CONV irradiation. Importantly, TAI-FLASH and TAI-CONV irradiation had similar efficacy in reducing tumor burden while improving intestinal function in a preclinical model of ovarian cancer metastasis. These findings suggest that FLASH irradiation may be an effective strategy to enhance the therapeutic index of abdominal radiotherapy, with potential application to metastatic ovarian cancer.
Funder
School of Medicine, Stanford University
Department of Defense Ovarian Cancer Research Program
Publisher
Springer Science and Business Media LLC