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Radiation 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.

The multidisciplinary Medication Safety and Contraceptive Counseling for Reproductive Aged Women with Psychiatric Conditions (MSRP) study conducted between the UCSD Department of Reproductive Medicine, the Gifford Clinic in the Department of Psychiatry at UCSD and the MotherToBaby California teratogen counseling service by UCSD Pediatrics seeks to better understand the feasibility of a novel individualized 1-on-1 counseling session that will help women in this population better understand: 1) which of their medications are safe to use in pregnancy, 2) provide education regarding the importance of using contraception and which contraceptive choices are available to them, and 3) raise awareness of any drug-drug interactions that may exist between their medications and their chosen method of contraception. If this study demonstrates a significant benefit to these patients, this counseling service may lead to a long-term relationship between the MotherToBaby California Project and the Gifford Psychiatric Clinic in which women seen in this clinic are routinely offered this specialized counseling.