Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species.
Pierre Montay-Gruel,Munjal M. Acharya,Kristoffer Petersson,Leila Alikhani,Chakradhar Yakkala,Barrett D. Allen,Jonathan Ollivier,Benoit Petit,Patrik Gonçalves Jorge,Amber R. Syage,Thuan Nguyen,Al Anoud D. Baddour,Celine Lu,Paramvir Singh,Raphaël Moeckli,François Bochud,Jean François Germond,Pascal Froidevaux,Claude Bailat,Jean Bourhis,Marie-Catherine Vozenin,Charles L. Limoli +21 more
TLDR
The remarkable normal tissue sparing afforded by FLASH may someday provide heretofore unrealized opportunities for dose escalation to the tumor bed, capabilities that promise to hasten the translation of this groundbreaking irradiation modality into clinical practice.Abstract:
Here, we highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy⋅s−1). Compared with conventional dose-rate (CONV; 0.07–0.1 Gy⋅s−1) modalities, we showed that FLASH did not cause radiation-induced deficits in learning and memory in mice. Moreover, 6 months after exposure, CONV caused permanent alterations in neurocognitive end points, whereas FLASH did not induce behaviors characteristic of anxiety and depression and did not impair extinction memory. Mechanistic investigations showed that increasing the oxygen tension in the brain through carbogen breathing reversed the neuroprotective effects of FLASH, while radiochemical studies confirmed that FLASH produced lower levels of the toxic reactive oxygen species hydrogen peroxide. In addition, FLASH did not induce neuroinflammation, a process described as oxidative stress-dependent, and was also associated with a marked preservation of neuronal morphology and dendritic spine density. The remarkable normal tissue sparing afforded by FLASH may someday provide heretofore unrealized opportunities for dose escalation to the tumor bed, capabilities that promise to hasten the translation of this groundbreaking irradiation modality into clinical practice.read more
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Journal ArticleDOI
Ultra-High Dose Rate (FLASH) Radiotherapy: Silver Bullet or Fool's Gold?
TL;DR: The tissue response to FLASH radiotherapy is examined, the evidence supporting hypotheses surrounding the biological basis of the FLASH effect is critically evaluated, and the potential for FLash radiotherapy to be translated into clinical contexts is considered.
Journal ArticleDOI
Clinical translation of FLASH radiotherapy: Why and how?
Jean Bourhis,Pierre Montay-Gruel,Patrik Gonçalves Jorge,Claude Bailat,Benoit Petit,Jonathan Ollivier,Wendy Jeanneret-Sozzi,Mahmut Ozsahin,François Bochud,Raphaël Moeckli,Jean-François Germond,Marie-Catherine Vozenin +11 more
TL;DR: The main data supporting the clinical translation of FLASH-RT is summarized, the key irradiation parameters and the potential technologies needed for a successful clinical translation are explored and its feasibility is explored.
Journal ArticleDOI
Design, Implementation, and in Vivo Validation of a Novel Proton FLASH Radiation Therapy System.
Eric S. Diffenderfer,Ioannis I. Verginadis,Michele M. Kim,Khayrullo Shoniyozov,Anastasia Velalopoulou,Denisa Goia,Mary E. Putt,Sarah Hagan,Stephen Avery,K. Teo,Wei Zou,Alexander Lin,Samuel Swisher-McClure,Cameron J. Koch,Ann R. Kennedy,Andy J. Minn,Amit Maity,Theresa M. Busch,Lei Dong,Costas Koumenis,James M Metz,Keith A. Cengel +21 more
TL;DR: Using a novel RT apparatus that delivers FLASH proton RT (PRT) using double scattered protons with computed tomography guidance, it is found that FLASH-PRT decreases acute cell loss and late fibrosis after whole-abdomen and focal intestinal RT, whereas tumor growth inhibition is preserved between the 2 modalities.
Journal ArticleDOI
Reduced cognitive deficits after FLASH irradiation of whole mouse brain are associated with less hippocampal dendritic spine loss and neuroinflammation.
Danielle A. Simmons,Frederick M. Lartey,Emil Schüler,Marjan Rafat,Gregory King,Anna Kim,Ryan B. Ko,Sarah Semaan,Selena Gonzalez,Melissa Jenkins,P. Pradhan,Zion Shih,Jinghui Wang,Rie von Eyben,Edward E. Graves,Peter G. Maxim,Peter G. Maxim,Frank M. Longo,Billy W. Loo +18 more
TL;DR: In this article, the impact of ultra-rapid FLASH mouse whole brain irradiation on hippocampal dendritic spines and neuroinflammation was evaluated with a custom configured clinical linac.
Journal ArticleDOI
The FLASH effect depends on oxygen concentration.
Gabriel Adrian,Elise Konradsson,Michael Lempart,Sven Bäck,Crister Ceberg,Kristoffer Petersson +5 more
TL;DR: In vitro-evidence for the role of oxygen concentration underlying the difference between FLASH and CONV irradiation is shown, and the in vitro FLASH effect depends on oxygen concentration.
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