Hypofractionated FLASH-RT as an Effective Treatment against Glioblastoma that Reduces Neurocognitive Side Effects in Mice.
Animals
Brain
/ physiopathology
Brain Neoplasms
/ radiotherapy
Cognitive Dysfunction
/ diagnosis
Electrons
/ therapeutic use
Female
Glioblastoma
/ radiotherapy
Humans
Mice
Organs at Risk
/ physiopathology
Radiation Dose Hypofractionation
Radiation Injuries, Experimental
/ diagnosis
Radiotherapy Dosage
Reactive Oxygen Species
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 02 2021
01 02 2021
Historique:
received:
18
03
2020
revised:
03
09
2020
accepted:
12
10
2020
pubmed:
17
10
2020
medline:
19
1
2022
entrez:
16
10
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 33060122
pii: 1078-0432.CCR-20-0894
doi: 10.1158/1078-0432.CCR-20-0894
pmc: PMC7854480
mid: NIHMS1643102
doi:
Substances chimiques
Reactive Oxygen Species
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
775-784Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR001416
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA244091
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS089575
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
©2020 American Association for Cancer Research.
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