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Background and Purpose: Dose-response modification of FLASH has previously been established for acute skin toxicity in protons. This study used a similar experimental setup to quantify the dose-response modification of electron FLASH irradiation for acute skin- and late fibrotic toxicity in mice. The setup similarity enabled quantitative comparison of the acute skin response for electrons to protons., Method: Female unanaesthetised C3D2F1 mice were restrained with the right hindleg fixated and submerged in a water bath for horizontal electron irradiation at 16 MeV. Mice were randomised in groups of varying single doses (19.4-57.6 Gy) and irradiated with either 0.162 Gy/s conventional (CONV) or 233 Gy/s FLASH dose rate using 8-10 mice per group. Acute skin toxicity was assessed daily from the 8th to the 28th day post-irradiation. The same mice were kept for a fibrotic assay of leg extension assessment done biweekly until 52 weeks post-irradiation. The dose-modifying factor (DMF) of FLASH was quantified from dose-response curves., Results and Discussion: Electron FLASH irradiated mice showed a considerable skin-sparing effect with a DMF of 1.45-1.54 and a smaller fibrotic-sparing effect with a DMF of 1.15. The development of acute skin toxicity was similar between CONV and FLASH groups with biological equivalent doses based on the DMF. The acute response of the electron irradiations was similar to previous reports on protons., Conclusion: Despite apparent differences, e.g. average and instantaneous dose rates, the acute skin toxicity of electron beams and previously published proton beams were remarkably similar regarding both biological response and quantified acute skin DMFs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The study presented in this manuscript was supported by Varian, a Siemens Healthineers Company. BS and PP are co-inventors on a patent-application (application number 63257211 and EFS ID 44064136). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective. The clinical advantage of proton therapy, compared to other types of irradiations, lies in its reduced dose to normal tissue. Still, proton therapy faces challenges of normal tissue toxicity and radioresistant tumors. To combat these challenges, proton boron capture therapy (PBCT) and neutron capture enhanced particle therapy (NCEPT) were proposed to introduce high-LET radiation in the target volume. Approach . In this work, we performed in-vitro experiments with a V79 cell line to validate PBCT and introduced a novel approach to use NCEPT in proton therapy. We quantified the effectiveness of PBCT and NCEPT with microdosimetric measurements, Monte-Carlo simulations and microdosimetric kinetic RBE model (MKM). Main results . No RBE increase was observed for PBCT. With the use of a tungsten spallation source, enough neutrons were generated in the incoming proton beam to measure significant neutron capture in the microdosimeter. However, no significant increase of RBE was detected when conventional in vitro protocol was followed. The resulting cell deactivation based RBE for NCEPT was found to be heavily dependent on which criteria was used to determine surviving colonies. Significance . PBCT and NCEPT are two proposed treatment modalities that may have the potential to expand the cases in which proton therapy can be beneficial. Understanding the scope of these treatment methods and developing measurement protocols to evaluate and understand their RBE impact are the first step to quantify their potential in clinical context., (Creative Commons Attribution license.)

Background and Purpose: In proton therapy, a relative biological effectiveness (RBE) of 1.1 is used toreach an isoeffective biological response between photon and proton doses. However, the RBE varies with biological endpoints and linear energy transfer (LET), two key parameters in radiotherapy. Few in vivo studies have investigated the increasing RBE with increasing LET. This study aims to test the hypothesis that the RBE varies between endpoints and has a distal edge effect in vivo., Materials and Methods: Unanesthetized micewere restrainedin jigs where their right hind legs were irradiated with a single dose of protons at the center (LET, all  = 5.3 keV/μm) and distal edge (LET, all  = 7.6 keV/μm) of a spread-out Bragg peak (SOBP). 6 MV photons were used as reference. The acute damage and skin toxicity were scored daily until day 30, and the late damage was evaluated using a joint contracture assay for one year after treatment., Results: An acute damage RBE of 1.06 ± 0.02(1.02-1.10) and late damage RBE of 1.16 ± 0.08(1.00-1.32) were found, displaying an enhanced RBE for late damage in the center SOBP. The distal edge RBE for acute and late damage was 1.15 ± 0.02(1.10-1.19) and 1.26 ± 0.09(1.07-1.43), showing a similar center-to-distal edge RBE enhancement of 8 % and 9 % for acute and late damage., Conclusion: The findings demonstrate an increased RBE for late damage than acute damage and the distal edge effect is evident with increased RBE at the distal end of the proton SOBP in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)