Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s

Montay‐Gruel, Pierre; Petersson, Kristoffer; Jaccard, Maud; Boivin, Gaël; Germond, Jean‐François; Petit, Benoît; Doenlen, Raphaël; Favaudon, Vincent; Bochud, François; Bailat, Claude; Bourhis, Jean; Vozenin, Marie-Catherine

doi:10.1016/j.radonc.2017.05.003

Cited by 495 publications

(523 citation statements)

References 25 publications

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“…This enables using the beam monitoring system for documenting the actual dose delivered during each animal exposure. The Oriatron eRT6 linac is nowadays in full operation and preclinical irradiation studies with accurate dosimetry are being performed …”

Section: Discussionmentioning

confidence: 99%

High dose‐per‐pulse electron beam dosimetry: Commissioning of the Oriatron eRT6 prototype linear accelerator for preclinical use

et al. 2018

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Section: Discussionmentioning

confidence: 99%

High dose‐per‐pulse electron beam dosimetry: Commissioning of the Oriatron eRT6 prototype linear accelerator for preclinical use

et al. 2018

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“…Thoracic IR of mice using 15 Gy conventional X-ray (DR 1.8 Gy/min) or 20 Gy Flash RT (DR > 2400 Gy/min; pulse rate < 500 ms) provided comparable lung tumour control, but Flash RT produced fewer fibrotic lesions (Favaudon et al 2014). In a similar study, 10 Gy murine whole brain FLASH RT (DR > 6000 Gy/min; pulse rate 1 µs) preserved spatial memory and hippocampal neurogenesis when compared to conventional RT (6 Gy/min) (Montay-Gruel et al 2017). The effect was absent if DR < 1800 Gy/min were used.…”

Section: Effect Of Radiation Delivery On the Immune Responsementioning

confidence: 90%

Radiation, inflammation and the immune response in cancer

et al. 2018

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Radiation is an important component of cancer treatment with more than half of all patients receive radiotherapy during their cancer experience. While the impact of radiation on tumour morphology is routinely examined in the pre-clinical and clinical setting, the impact of radiation on the tumour microenvironment and more specifically the inflammatory/immune response is less well characterised. Inflammation is a key contributor to short- and long-term cancer eradication, with significant tumour and normal tissue consequences. Therefore, the role of radiation in modulating the inflammatory response is highly topical given the current wave of targeted and immuno-therapeutic treatments for cancer. This review provides a general overview of how radiation modulates the inflammatory and immune response-(i) how radiation induces the inflammatory/immune system, (ii) the cellular changes that take place, (iii) how radiation dose delivery affects the immune response, and (iv) a discussion on research directions to improve patient survival, reduce side effects, improve quality of life, and reduce financial costs in the immediate future. Harnessing the benefits of radiation on the immune response will enhance its maximal therapeutic benefit and reduce radiation-induced toxicity.

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“…The phenomenon of the increased therapeutic index of FLASH compared to conventional dose rate irradiation, or the “FLASH effect,” has now been reported in multiple preclinical models. Normal tissue sparing by FLASH of multiple organ systems including lung, brain, intestinal tract, and skin has been demonstrated in multiple mouse strains and even additional species (cat and mini‐pig), while demonstrating an equivalent (and in some cases superior) tumoricidal effect relative to conventional dose‐rate delivery in multiple in vivo tumor models . Given the nascent state of the field, a large portion of experimental observations to date remain preliminary and unpublished, and many questions remain unanswered particularly with respect to mechanism.…”

Section: For the Proposition: Peter G Maxim Phdmentioning

confidence: 99%

“…The FLASH effect is also incompletely characterized even from a phenomenological standpoint. Evidence to date suggests that a dose rate threshold of approximately 40 Gray/s or higher is needed to produce the FLASH effect . However, the accelerator‐based radiation delivery systems used for FLASH experiments to date produce pulsed radiation, and there are many aspects of delivery speed, for example, total dose and delivery time, dose per pulse, pulse timing structure, etc., that may be critical to the effect and have not been comprehensively evaluated, since an exhaustive study is an experimentally daunting combinatorial problem.…”

Section: For the Proposition: Peter G Maxim Phdmentioning

confidence: 99%