Hypofractionated FLASH-RT as an effective treatment against glioblastoma that reduces neurocognitive side effects in mice
(2021) In Clinical Cancer Research 27(3). p.775-784- Abstract
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... (More)
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.
(Less)
- author
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- in
- Clinical Cancer Research
- volume
- 27
- issue
- 3
- pages
- 775 - 784
- publisher
- American Association for Cancer Research
- external identifiers
-
- scopus:85100351070
- pmid:33060122
- ISSN
- 1078-0432
- DOI
- 10.1158/1078-0432.CCR-20-0894
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2020 American Association for Cancer Research.
- id
- c7315133-88ca-4e7a-9147-b998af509ce5
- date added to LUP
- 2021-11-03 18:20:14
- date last changed
- 2024-04-20 15:45:00
@article{c7315133-88ca-4e7a-9147-b998af509ce5,
abstract = {{<p>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.</p>}},
author = {{Montay-Gruel, Pierre and Acharya, Munjal M. and Jorge, Patrik Gonçalves and Petit, Benoît and Petridis, Ioannis G. and Fuchs, Philippe and Leavitt, Ron and Petersson, Kristoffer and Gondre, Maude and Ollivier, Jonathan and Moeckli, Raphael and Bochud, François and Bailat, Claude and Bourhis, Jean and Germond, Jean François and Limoli, Charles L. and Vozenin, Marie Catherine}},
issn = {{1078-0432}},
language = {{eng}},
number = {{3}},
pages = {{775--784}},
publisher = {{American Association for Cancer Research}},
series = {{Clinical Cancer Research}},
title = {{Hypofractionated FLASH-RT as an effective treatment against glioblastoma that reduces neurocognitive side effects in mice}},
url = {{http://dx.doi.org/10.1158/1078-0432.CCR-20-0894}},
doi = {{10.1158/1078-0432.CCR-20-0894}},
volume = {{27}},
year = {{2021}},
}