Hypo-fractionated FLASH-RT as an effective treatment against glioblastoma that reduces neurocognitive side effects in mice

Hypo-fractionated FLASH-RT as an effective treatment against glioblastoma that reduces neurocognitive side effects in mice:

Purpose: Recent data has shown that single fraction irradiation delivered to the whole brain in less than tenths of a second using FLASH radiation therapy (RT), does not elicit neurocognitive deficits in mice. This observation has important clinical implications for the management of invasive and treatment-resistant brain tumors that involves relatively large irradiation volumes with high cytotoxic doses. Experimental design: Therefore, we aimed at simultaneously investigating the anti-tumor efficacy and neuroprotective benefits of FLASH-RT 1-month after exposure, using a well-characterized murine orthotopic glioblastoma model. As fractionated regimens of radiotherapy are the standard of care for glioblastoma treatment, we incorporated dose fractionation to simultaneously validate the neuroprotective effects and optimized tumor treatments with FLASH-RT. Results: The capability of FLASH-RT to minimize the induction of radiation-induced brain toxicities has been attributed to the reduction of reactive oxygen species, casting some concern that this might translate to a possible loss of anti-tumor efficacy. Our study shows that FLASH and CONV-RT are iso-efficient in delaying GBM growth for all tested regimens. Furthermore, only FLASH-RT was found to significantly spare radiation-induced cognitive deficits in learning and memory in tumor bearing animals after the delivery of large neurotoxic single dose or hypo-fractionated regimens. Conclusion: The present results show that FLASH-RT delivered with hypo-fractionated regimens is able to spare the normal brain from radiation-induced toxicities without compromising tumor cure. This exciting capability provides an initial framework for future clinical applications of FLASH-RT.