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Brain radiation impairs cognition, associated with neuronal degeneration and neuroinflammation. • Ultra-rapid FLASH produced reduced cognitive deficits vs. conventional delivery time. • Loss of hippocampal dendritic spines and neuroinflammation were less evident after FLASH. • These factors may mediate the improved therapeutic index of FLASH brain irradiation.

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.

Purpose To evaluate the prognostic value of metabolic tumor volume measured on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and other clinical factors in patients treated for locally advanced head and neck cancer at a single institution. Materials/Methods From March 2003 to August 2007, 85 patients received PET/CT-guided chemoradiotherapy for HNC. Metabolically active tumor regions were delineated on pretreatment PET scans semi-automatically using custom software. We evaluated the relationship of FDG-PET maximum standardized uptake value (SUV) and total metabolic tumor volume (MTV) with disease-free survival (DFS) and overall survival (OS). Results Mean follow-up for surviving patients was 20.4 months. The estimated 2-year locoregional control, DFS, and OS for the group were 88.0%, 69.5% and 78.4%, respectively. The median time to first failure was 9.8 months among the 16 patients with relapse. An increase in MTV of 17.4 mL (difference between the 75th and 25th percentiles) was significantly associated with an increased hazard of first event (recurrence or death) (1.9-fold, p<0.001), even after controlling for Karnofsky performance status (KPS) (1.8-fold, p=0.001), and of death (2.1-fold, p<0.001). We did not find a significant relationship of maximum SUV, stage, or other clinical factors with DFS or OS. Conclusion Metabolic tumor volume is an adverse prognostic factor for disease recurrence and death in HNC. MTV retained significance after controlling for KPS, the only other significant adverse prognostic factor found in this cohort. MTV is a direct measure of tumor burden and is a potentially valuable tool for risk stratification and guiding treatment in future studies.

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VLS oximetry provides a continuous, noninvasive, and localized measurement of the StO2, sensitive to hypoxemia, regional, and global ischemia. The reproducible and narrow StO2 normal range for oral/enteric mucosa supports use of this site as an accessible and reliable reference point for the VLS monitoring of systemic flow.