The Advantage of FLASH Radiotherapy Confirmed in Mini-pig and Cat-cancer Patients.
Marie-Catherine Vozenin,Pauline de Fornel,Kristoffer Petersson,Vincent Favaudon,Maud Jaccard,Jean François Germond,Benoit Petit,Marco Burki,Gisele Ferrand,David Patin,Hanan Bouchaab,Mahmut Ozsahin,François Bochud,Claude Bailat,Patrick Devauchelle,Jean Bourhis +15 more
TLDR
The results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLash-RT in human patients.Abstract:
Purpose: Previous studies using FLASH radiotherapy (RT) in mice showed a marked increase of the differential effect between normal tissue and tumors. To stimulate clinical transfer, we evaluated whether this effect could also occur in higher mammals. Experimental Design: Pig skin was used to investigate a potential difference in toxicity between irradiation delivered at an ultrahigh dose rate called “FLASH-RT” and irradiation delivered at a conventional dose rate called “Conv-RT.” A clinical, phase I, single-dose escalation trial (25–41 Gy) was performed in 6 cat patients with locally advanced T2/T3N0M0 squamous cell carcinoma of the nasal planum to determine the maximal tolerated dose and progression-free survival (PFS) of single-dose FLASH-RT. Results: Using, respectively, depilation and fibronecrosis as acute and late endpoints, a protective effect of FLASH-RT was observed (≥20% dose-equivalent difference vs. Conv-RT). Three cats experienced no acute toxicity, whereas 3 exhibited moderate/mild transient mucositis, and all cats had depilation. With a median follow-up of 13.5 months, the PFS at 16 months was 84%. Conclusions: Our results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLASH-RT in human patients. See related commentary by Harrington, p. 3read more
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Treatment of a first patient with FLASH-radiotherapy.
Jean Bourhis,Wendy Jeanneret Sozzi,Patrik Gonçalves Jorge,Olivier Gaide,Claude Bailat,F. Duclos,David Patin,Mahmut Ozsahin,François Bochud,Jean-François Germond,Raphaël Moeckli,Marie-Catherine Vozenin +11 more
TL;DR: This first FLash-RT treatment was feasible and safe with a favorable outcome both on normal skin and the tumor, and prompt to further clinical evaluation of FLASH-RT.
Journal ArticleDOI
Biological Benefits of Ultra-high Dose Rate FLASH Radiotherapy: Sleeping Beauty Awoken.
TL;DR: The current knowledge about the FLASH effect is summarized and a synthesis of the observations that have been reported on various experimental animal models, various organs, and by various groups across 40 years of research are provided.
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
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
TL;DR: 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.
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.
References
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Epidermal stem cells of the skin.
Cédric Blanpain,Elaine Fuchs +1 more
TL;DR: This work discusses the fundamental characteristics of epidermal SCs of the adult skin, the methods recently designed to isolate these cells, the genes preferentially expressed in the multipotent SC niche, and the signaling pathways involved in SC niche formation, SC maintenance, and activation.
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Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice
Vincent Favaudon,Vincent Favaudon,Laura Caplier,Virginie Monceau,Virginie Monceau,Frederic Pouzoulet,Frederic Pouzoulet,Mano Sayarath,Mano Sayarath,Charles Fouillade,Charles Fouillade,Marie-France Poupon,Marie-France Poupon,Isabel Brito,Isabel Brito,Philippe Hupé,Jean Bourhis,Jean Bourhis,Jean Bourhis,Janet Hall,Janet Hall,Jean-Jacques Fontaine,Marie-Catherine Vozenin +22 more
TL;DR: The results suggest that FLASH radiation may be a viable option for treating lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.
Journal ArticleDOI
Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s
Pierre Montay-Gruel,Pierre Montay-Gruel,Kristoffer Petersson,Maud Jaccard,Gael Boivin,Jean-François Germond,Benoit Petit,Raphael Doenlen,Vincent Favaudon,François Bochud,Claude Bailat,Jean Bourhis,Marie-Catherine Vozenin +12 more
TL;DR: This study shows for the first time that normal brain tissue toxicities after WBI can be reduced with increased dose rate.
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
Experimental Platform for Ultra-high Dose Rate FLASH Irradiation of Small Animals Using a Clinical Linear Accelerator.
Emil Schüler,S. Trovati,Gregory King,Frederick M. Lartey,Marjan Rafat,Manuel Villegas,A. Joe Praxel,Billy W. Loo,Peter G. Maxim +8 more
TL;DR: A simple methodologic approach for using a clinical LINAC for FLASH irradiation with a clinically available linear accelerator (LINAC) achieves dose rates exceeding 200 Gy/s after simple tuning of the LINAC, with excellent dosimetric properties for small animal experiments.
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Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species.
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