RT Journal Article
SR Electronic
T1 Hypofractionated FLASH-RT as an Effective Treatment against Glioblastoma that Reduces Neurocognitive Side Effects in Mice
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 775
OP 784
DO 10.1158/1078-0432.CCR-20-0894
VO 27
IS 3
A1 Montay-Gruel, Pierre
A1 Acharya, Munjal M.
A1 Gonçalves Jorge, Patrik
A1 Petit, Benoît
A1 Petridis, Ioannis G.
A1 Fuchs, Philippe
A1 Leavitt, Ron
A1 Petersson, Kristoffer
A1 Gondré, Maude
A1 Ollivier, Jonathan
A1 Moeckli, Raphael
A1 Bochud, François
A1 Bailat, Claude
A1 Bourhis, Jean
A1 Germond, Jean-François
A1 Limoli, Charles L.
A1 Vozenin, Marie-Catherine
YR 2021
UL http://clincancerres.aacrjournals.org/content/27/3/775.abstract
AB Purpose: Recent data have shown that single-fraction irradiation delivered to the whole brain in less than tenths of a second using FLASH radiotherapy (FLASH-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 antitumor 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 antitumor efficacy. Our study shows that FLASH and CONV-RT are isoefficient in delaying glioblastoma 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 hypofractionated regimens.Conclusions: The present results show that FLASH-RT delivered with hypofractionated 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.See related commentary by Huang and Mendonca, p. 662