Clinical Linear Accelerator-Based Electron FLASH: Pathway for Practical Translation to FLASH Clinical Trials

No, H.J.; Wu, Yufan; Dworkin, Michael Louis; Manjappa, Rakesh; Skinner, Lawrie; Ashraf, M.Ramish; Lau, Brianna; Melemenidis, Stavros; Viswanathan, Vignesh; Yu, Amy Shu-Jung; Sürücü, Murat; Schüler, Emil; Graves, Edward Elliot; Maxim, Peter Gregor; Loo, Bill W.

doi:10.1016/j.ijrobp.2023.04.011

Cited by 3 publications

(1 citation statement)

References 41 publications

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“…In their latest configuration ( Fig. 4B ), SSD has been significantly increased allowing sufficient working distance to apply the ultra-high dose-rate radiation therapy (UHDR RT) to human patients in the clinical setting [ 23 ].…”

Section: Flash Radiotherapy: What Is It and Why Is It So Different?mentioning

confidence: 99%

FLASH Radiotherapy: A FLASHing Idea to Preserve Neurocognitive Function

Jo,

Oh,

Lee

et al. 2023

Brain Tumor Res Treat

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FLASH radiotherapy (FLASH RT) is a technique to deliver ultra-high dose rate in a fraction of a second. Evidence from experimental animal models suggest that FLASH RT spares various normal tissues including the lung, gastrointestinal track, and brain from radiation-induced toxicity (a phenomenon known as FLASH effect), which is otherwise commonly observed with conventional dose rate RT. However, it is not simply the ultra-high dose rate alone that brings the FLASH effect. Multiple parameters such as instantaneous dose rate, pulse size, pulse repetition frequency, and the total duration of exposure all need to be carefully optimized simultaneously. Furthermore it is critical to validate FLASH effects in an in vivo experimental model system. The exact molecular mechanism responsible for this FLASH effect is not yet understood although a number of hypotheses have been proposed including oxygen depletion and less reactive oxygen species (ROS) production by FLASH RT, and enhanced ability of normal tissues to handle ROS and labile iron pool compared to tumors. In this review, we briefly overview the process of ionization event and history of radiotherapy and fractionation of ionizing radiation. We also highlight some of the latest FLASH RT reviews and results with a special interest to neurocognitive protection in rodent model with whole brain irradiation. Lastly we discuss some of the issues remain to be answered with FLASH RT including undefined molecular mechanism, lack of standardized parameters, low penetration depth for electron beam, and tumor hypoxia still being a major hurdle for local control. Nevertheless, researchers are close to having all answers to the issues that we have raised, hence we believe that advancement of FLASH RT will be made more quickly than one can anticipate.

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Section: Flash Radiotherapy: What Is It and Why Is It So Different?mentioning

confidence: 99%

FLASH Radiotherapy: A FLASHing Idea to Preserve Neurocognitive Function

Jo,

Oh,

Lee

et al. 2023

Brain Tumor Res Treat

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The effect of electron backscatter and charge build up in media on beam current transformer signal for ultra-high dose rate (FLASH) electron beam monitoring

Pageot,

Zerouali,

Guillet

et al. 2024

Phys. Med. Biol.

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Objective: Beam current transformers (BCT) are promising detectors for real-time beam monitoring in ultra-high dose rate (UHDR) electron radiotherapy. However, previous studies have reported a significant sensitivity of the BCT signal to changes in source-to-surface distance (SSD), field size, and phantom material which have until now been attributed to the fluctuating levels of electrons backscattered within the BCT. The purpose of this study is to evaluate this hypothesis, with the goal of understanding and mitigating the variations in BCT signal due to changes in irradiation Approach: Monte Carlo simulations and experimental measurements were conducted with a UHDR-capable intra-operative electron linear accelerator to analyze the impact of backscattered electrons on BCT signal. The potential influence of charge accumulation in media as a mechanism affecting BCT signal perturbation was further investigated by examining the effects phantom conductivity and electrical grounding. Finally, the effectiveness of Faraday shielding to mitigate BCT signal variations is evaluated. Main Results: Monte Carlo simulations indicated that the fraction of electrons backscattered in water and on the collimator plastic at 6 and 9 MeV is lower than 1%, suggesting that backscattered electrons alone cannot account for the observed BCT signal variations. However, our experimental measurements confirmed previous findings of BCT response variation up to 15% for different field diameters. A significant impact of phantom type on BCT response was also observed, with variations in BCT signal as high as 14.1% when comparing measurements in water and solid water. The introduction of a Faraday shield to our applicators effectively mitigated the dependencies of BCT signal on SSD, field size, and phantom material.Significance: Our results indicate that variations in BCT signal as a function of SSD, field size, and phantom material are likely driven by an electric field originating in dielectric materials exposed to the UHDR electron beam. Strategies such as Faraday shielding were shown to effectively prevent these electric fields from affecting BCT signal, enabling reliable BCT-based electron UHDR beam monitoring.

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Impact of Scattering Foil Composition on Electron Energy Distribution in a Clinical Linear Accelerator Modified for FLASH Radiotherapy: A Monte Carlo Study

Chow,

Ruda

2024

Materials

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This study investigates how scattering foil materials and sampling holder placement affect electron energy distribution in electron beams from a modified medical linear accelerator for FLASH radiotherapy. We analyze electron energy spectra at various positions—ionization chamber, mirror, and jaw—to evaluate the impact of Cu, Pb-Cu, Pb, and Ta foils. Our findings show that close proximity to the source intensifies the dependence of electron energy distribution on foil material, enabling precise beam control through material selection. Monte Carlo simulations are effective for designing foils to achieve desired energy distributions. Moving the sampling holder farther from the source reduces foil material influence, promoting more uniform energy spreads, particularly in the 0.5–10 MeV range for 12 MeV electron beams. These insights emphasize the critical role of tailored material selection and sampling holder positioning in optimizing electron energy distribution and fluence intensity for FLASH radiotherapy research, benefiting both experimental design and clinical applications.

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Clinical Linear Accelerator-Based Electron FLASH: Pathway for Practical Translation to FLASH Clinical Trials

Cited by 3 publications

References 41 publications

FLASH Radiotherapy: A FLASHing Idea to Preserve Neurocognitive Function

FLASH Radiotherapy: A FLASHing Idea to Preserve Neurocognitive Function

The effect of electron backscatter and charge build up in media on beam current transformer signal for ultra-high dose rate (FLASH) electron beam monitoring

Impact of Scattering Foil Composition on Electron Energy Distribution in a Clinical Linear Accelerator Modified for FLASH Radiotherapy: A Monte Carlo Study

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