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8. Hypofractionated FLASH-RT as an Effective Treatment against Glioblastoma that Reduces Neurocognitive Side Effects in Mice.

Author

Montay-Gruel, Pierre, Acharya, Munjal M, Gonçalves Jorge, Patrik, Petit, Benoît, Petridis, Ioannis G, Fuchs, Philippe, Leavitt, Ron, Petersson, Kristoffer, Gondré, Maude, Ollivier, Jonathan, Moeckli, Raphael, Bochud, François, Bailat, Claude, Bourhis, Jean, Germond, Jean-François, Limoli, Charles L, and Vozenin, Marie-Catherine

Subjects
Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract

PurposeRecent 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 designTherefore, 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.ResultsThe 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.ConclusionsThe 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.

Published
2021

15. Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

Author

Montay-Gruel, Pierre, Acharya, Munjal M, Petersson, Kristoffer, Alikhani, Leila, Yakkala, Chakradhar, Allen, Barrett D, Ollivier, Jonathan, Petit, Benoit, Jorge, Patrik Gonçalves, Syage, Amber R, Nguyen, Thuan A, Baddour, Al Anoud D, Lu, Celine, Singh, Paramvir, Moeckli, Raphael, Bochud, François, Germond, Jean-François, Froidevaux, Pascal, Bailat, Claude, Bourhis, Jean, Vozenin, Marie-Catherine, and Limoli, Charles L

Subjects
Mental Health, Behavioral and Social Science, Neurosciences, Animals, Brain, Cognitive Dysfunction, Female, Inflammation, Mice, Mice, Inbred C57BL, Neuroprotection, Radiation Dosage, Radiotherapy, Reactive Oxygen Species, ultra-high dose-rate irradiation, cognitive dysfunction, neuronal morphology, neuroinflammation, reactive oxygen species
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.

Published
2019

20. Comparison of volumetric modulated arc therapy and helical tomotherapy for prostate cancer using Pareto fronts.

Author

Wüthrich, Diana, Wang, Zirun, Zeverino, Michele, Bourhis, Jean, Bochud, François, and Moeckli, Raphaël

Subjects
VOLUMETRIC-modulated arc therapy, RECTUM, PROSTATE cancer, LINEAR accelerators, PROSTATE cancer patients, ELECTRIC arc, FEMUR head
Abstract

Background: Studies comparing different radiotherapy treatment techniques—such as volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT)—typically compare one treatment plan per technique. Often, some dose metrics favor one plan and others favor the other, so the final plan decision involves subjective preferences. Pareto front comparisons provide a more objective framework for comparing different treatment techniques. A Pareto front is the set of all treatment plans where improvement in one criterion is possible only by worsening another criterion. However, different Pareto fronts can be obtained depending on the chosen machine settings. Purpose: To compare VMAT and HT using Pareto fronts and blind expert evaluation, to explain the observed differences, and to illustrate limitations of using Pareto fronts. Methods: We generated Pareto fronts for twenty‐four prostate cancer patients treated at our clinic for VMAT and HT techniques using an in‐house script that controlled a commercial treatment planning system. We varied the PTV under‐coverage (100% ‐ V95%) and the rectum mean dose, and fixed the mean doses to the bladder and femoral heads. In order to ensure a fair comparison, those fixed mean doses were the same for the two treatment techniques and the sets of objective functions were chosen so that the conformity indexes of the two treatment techniques were also the same. We used the same machine settings as are used in our clinic. Then, we compared the VMAT and HT Pareto fronts using a specific metric (clinical distance measure) and validated the comparison using a blinded expert evaluation of treatment plans on these fronts for all patients in the cohort. Furthermore, we investigated the observed differences between VMAT and HT and pointed out limitations of using Pareto fronts. Results: Both clinical distance and blind treatment plan comparison showed that VMAT Pareto fronts were better than HT fronts. VMAT fronts for 10 and 6 MV beam energy were almost identical. HT fronts improved with different machine settings, but were still inferior to VMAT fronts. Conclusions: That VMAT Pareto fronts are better than HT fronts may be explained by the fact that the linear accelerator can rapidly vary the dose rate. This is an advantage in simple geometries that might vanish in more complex geometries. Furthermore, one should be cautious when speaking about Pareto optimal plans as the best possible plans, as their calculation depends on many parameters. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Corrigendum to “Determination of the gamma and X-ray emission intensities of terbium-161” [Appl. Radiat. Isot. 174 (2021) 109770]

Author

Juget, Frédéric, primary, Talip, Zeynep, additional, Buchillier, Thierry, additional, Durán, M. Teresa, additional, Nedjadi, Youcef, additional, Desorgher, Laurent, additional, Bochud, François, additional, Grundler, Pascal, additional, van der Meulen, Nicholas P., additional, and Bailat, Claude, additional

Published
2023
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26. Treatment of a first patient with FLASH-radiotherapy

Author

Bourhis, Jean, Sozzi, Wendy Jeanneret, Jorge, Patrik Gonçalves, Gaide, Olivier, Bailat, Claude, Duclos, Fréderic, Patin, David, Ozsahin, Mahmut, Bochud, François, Germond, Jean-François, Moeckli, Raphaël, and Vozenin, Marie-Catherine

Published
2019
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37. Independent Reproduction of the FLASH Effect on the Gastrointestinal Tract: A Multi-Institutional Comparative Study

Author

Valdés Zayas, Anet, primary, Kumari, Neeraj, additional, Liu, Kevin, additional, Neill, Denae, additional, Delahoussaye, Abagail, additional, Gonçalves Jorge, Patrik, additional, Geyer, Reiner, additional, Lin, Steven H., additional, Bailat, Claude, additional, Bochud, François, additional, Moeckli, Raphael, additional, Koong, Albert C., additional, Bourhis, Jean, additional, Taniguchi, Cullen M., additional, Herrera, Fernanda G., additional, and Schüler, Emil, additional

Published
2023
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45. Figure S1a from The Advantage of FLASH Radiotherapy Confirmed in Mini-pig and Cat-cancer Patients

Author

Vozenin, Marie-Catherine, primary, De Fornel, Pauline, primary, Petersson, Kristoffer, primary, Favaudon, Vincent, primary, Jaccard, Maud, primary, Germond, Jean-François, primary, Petit, Benoit, primary, Burki, Marco, primary, Ferrand, Gisèle, primary, Patin, David, primary, Bouchaab, Hanan, primary, Ozsahin, Mahmut, primary, Bochud, François, primary, Bailat, Claude, primary, Devauchelle, Patrick, primary, and Bourhis, Jean, primary

Published
2023
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46. Supplementary Data from Hypofractionated FLASH-RT as an Effective Treatment against Glioblastoma that Reduces Neurocognitive Side Effects in Mice

Author

Montay-Gruel, Pierre, primary, Acharya, Munjal M., primary, Gonçalves Jorge, Patrik, primary, Petit, Benoît, primary, Petridis, Ioannis G., primary, Fuchs, Philippe, primary, Leavitt, Ron, primary, Petersson, Kristoffer, primary, Gondré, Maude, primary, Ollivier, Jonathan, primary, Moeckli, Raphael, primary, Bochud, François, primary, Bailat, Claude, primary, Bourhis, Jean, primary, Germond, Jean-François, primary, Limoli, Charles L., primary, and Vozenin, Marie-Catherine, primary

Published
2023
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47. Supplementary Data from The Advantage of FLASH Radiotherapy Confirmed in Mini-pig and Cat-cancer Patients

Author

Vozenin, Marie-Catherine, primary, De Fornel, Pauline, primary, Petersson, Kristoffer, primary, Favaudon, Vincent, primary, Jaccard, Maud, primary, Germond, Jean-François, primary, Petit, Benoit, primary, Burki, Marco, primary, Ferrand, Gisèle, primary, Patin, David, primary, Bouchaab, Hanan, primary, Ozsahin, Mahmut, primary, Bochud, François, primary, Bailat, Claude, primary, Devauchelle, Patrick, primary, and Bourhis, Jean, primary

Published
2023
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48. In Reply to Horst et al.

Author

Böhlen, Till Tobias, primary, Germond, Jean-François, additional, Bochud, François, additional, Bailat, Claude, additional, Moeckli, Raphaël, additional, Bourhis, Jean, additional, Vozenin, Marie-Catherine, additional, and Ozsahin, Esat Mahmut, additional

Published
2023
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