Design and validation of a dosimetric comparison scheme tailored for ultra-high dose-rate electron beams to support multicenter FLASH preclinical studies

Jorge, Patrik Gonçalves; Melemenidis, Stavros; Grilj, Veljko; Buchillier, Thierry; Manjappa, Rakesh; Viswanathan, Vignesh; Gondré, Maude; Vozenin, Marie‐Catherine; Germond, Jean‐François; Bochud, F.; Moeckli, R.; Limoli, Charles L.; Skinner, Lawrie; No, H.J.; Wu, Yufan; Sürücü, Murat; Yu, Amy S.; Lau, Brianna; Wang, Jinghui; Schüler, Emil; Bush, Karl; Graves, Edward E.; Maxim, Peter G.; Loo, Billy W.; Bailat, Claude

doi:10.1016/j.radonc.2022.08.023

Cited by 18 publications

(13 citation statements)

References 29 publications

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“…Considering the agreement of all tested detectors within standard uncertainty (k=2), we successfully proved the dosimetric consistency of PSI and IRA/CHUV. Additionally, we showed that the methodology developed by Jorge et al could be extended to proton beams (23).…”

Section: Discussionmentioning

confidence: 83%

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Dosimetric and biologic intercomparison between electron and proton FLASH beams

Almeida

Togno

Ballesteros-Zebadúa

et al. 2023

Preprint

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Background and purpose: The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at a mean dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by e vs. pFLASH has yet been performed and constitutes the aim of the present study. Materials and methods: The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (above 100 Gy/s eFLASH and pFLASH) irradiation. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed with previously validated models. Results: Doses measured at Gantry1 were in agreement (+/- 2.5%) with reference dosimeters calibrated at CHUV/IRA. The neurocognitive capacity of e and pFLASH irradiated mice was indistinguishable from the control while both e and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained with the two beams and was similar between e and pFLASH vs. e and pCONV. Tumor rejection was similar indicating that T-cell memory response is beam-type and dose-rate independent. Conclusion: Despite major differences in the temporal microstructure, this study shows that dosimetric standards can be established. The sparing of brain function and tumor control produced by the two beams were similar, suggesting that the most important physical parameter driving the FLASH effect is the overall time of exposure which should be in the range of hundreds of milliseconds for WBI in mice. In addition, we observed that immunological memory response is similar between electron and proton beams and is independent off the dose rate.

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Section: Discussionmentioning

confidence: 83%

“…ρ = 1.19 g•cm -3 ) and recently described and validated by Jorge et al, was used for this comparison(23). The phantom has a 5 mm (diameter) by 10.4 mm (length) central cylindrical cavity to simultaneously house three TLDs, two alanine pellets, and six laser-cut films.…”

mentioning

confidence: 99%

Dosimetric and biologic intercomparison between electron and proton FLASH beams

Almeida

Togno

Ballesteros-Zebadúa

et al. 2023

Preprint

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“…Irradiation was performed at two institutions, with two different electron linear accelerators (linac) (12). Comparative phantom dosimetry had been conducted as previously published (13).…”

Section: Methodsmentioning

confidence: 99%

A multi-institutional study to investigate the sparing effect after whole brain electron FLASH in mice: Reproducibility and temporal evolution of functional, electrophysiological, and neurogenic endpoints

Drayson,

Melemenidis,

Katila

et al. 2024

Preprint

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Purpose: Ultra-high dose-rate radiotherapy (FLASH) has been shown to mitigate normal tissue toxicities associated with conventional dose rate radiotherapy (CONV) without compromising tumor killing in preclinical models. A prominent challenge in preclinical radiation research, including FLASH, is validating both the physical dosimetry and the biological effects across multiple institutions. Methods: We previously demonstrated dosimetric reproducibility of two different electron FLASH devices at separate institutions using standardized phantoms and dosimeters. In this study, we compared the outcome of FLASH and CONV 10 Gy whole brain irradiation on female adult mice at both institutions to evaluate the reproducibility and temporal evolution of multiple endpoints. Results: FLASH sparing of behavioral performance on novel object recognition (4 months post-irradiation) and electrophysiologic long-term potentiation (LTP, 5-months post-irradiation) was reproduced between institutions. Interestingly, differences between FLASH and CONV on the endpoints of hippocampal neurogenesis (Sox2, doublecortin), neuroinflammation (microglial activation), and electrophysiology (LTP) at late times were not observed at early times. Conclusions: In summary, we demonstrated reproducible FLASH sparing effects between two beams and two institutions with validated dosimetry. FLASH sparing effects on the endpoints evaluated manifested at late but not early time points.

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“…Several TLDs and OSLDs were demonstrated to be dose rate independent in photon (Jursinic 2007, Zorloni et al 2020), electron (Karsch et al 2012, Motta et al 2023a, and proton beams (Christensen et al 2021, Motta et al 2023b, indicating their suitability for UHDR dosimetry. For example, TLDs and OSLDs were used to support radiobiological experiments for FLASH radiotherapy (Jorge et al 2019, Christensen et al 2021, and TLDs were used for cross validation of UHDR beams (Jorge et al 2022). The experimental evidence that such luminescence detectors are dose rate independent is in contrast with theoretical studies that point to the possibility of dose rate effects (Chen and Leung 2001).…”

Section: Introductionmentioning

confidence: 99%

Dosimetry of ultra-high dose rate electron beams using thermoluminescence and optically stimulated luminescence detectors

Motta,

Dal Bello,

Christensen

et al. 2024

Phys. Med. Biol.

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Objective: The aim of this work is to investigate the dose rate dependence of thermoluminescence and optically stimulated luminescence detectors (TLDs and OSLDs) in a wide uniform ultra-high dose rate electron beam and demonstrate the potential use of TLDs and OSLDs to correct the ion recombination in air-filled ionization chambers. This study avoids previously reported complications related to the field size and homogeneity.Approach: Two types of OSLDs (BeO and Al2O3:C) and three types of TLDs (LiF:Mg,Ti, LiF:Mg,Cu,P, CaF2:Tm) were irradiated simultaneously in a uniform 16 MeV electron beam generated by a clinically decommissioned C-Arm LINAC, modified to deliver dose per pulsesbetween 8.3 × 10−4 Gy and 1.255 Gy, corresponding to instantaneous dose rates between 2 ×102 Gy s−1 and 3 × 105 Gy s−1. A prototype ultra-thin parallel plate ionization chamber wasemployed as reference detector.Main results: Reproducible results were achieved both at conventional (standard deviation of the data < 2%) and at the highest dose per pulse (standard deviation of the data < 4%). No trend in the dose rate response of the TLDs and OSLDs was observed in the investigated dose per pulse range. The Al2O3:C OSLD was found to be the most precise detector, with a standard deviation of the data < 2% at all investigated dose rates and dose levels.Significance: The dose rate independence of the investigated TLDs and OSLDs make them good candidates for dosimetry at ultra-high dose rates, at least up to 3 × 105 Gy s−1.A dose rate independent method to measure the dose per pulse is proposed, which can be applied to characterize ultra-high dose rate electron beams and correct for ion recombination in ionization chambers.

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Design and validation of a dosimetric comparison scheme tailored for ultra-high dose-rate electron beams to support multicenter FLASH preclinical studies

Cited by 18 publications

References 29 publications

Dosimetric and biologic intercomparison between electron and proton FLASH beams

Dosimetric and biologic intercomparison between electron and proton FLASH beams

A multi-institutional study to investigate the sparing effect after whole brain electron FLASH in mice: Reproducibility and temporal evolution of functional, electrophysiological, and neurogenic endpoints

Dosimetry of ultra-high dose rate electron beams using thermoluminescence and optically stimulated luminescence detectors

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