ESTRO 2025 - Abstract Book

S3919

Radiobiology - Normal tissue radiobiology

ESTRO 2025

References: 1 Common Terminology Criteria for Adverse Events (CTCAE) Version 5. Published: November 27. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute.

2108

Proffered Paper Single-pulse FLASH radiotherapy reduces acute skin and soft tissue toxicity compared to conventional radiotherapy in a mouse hindlimb model Elise Konradsson 1 , Lucy Whitmore 1 , Nolan Esplen 1 , Safee Baig 1 , Luke Connell 1 , Edgardo Aguilar 1 , Denae Neill 1 , Devarati Mitra 2 , Emil Schüler 1 1 Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, USA. 2 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA Purpose/Objective: Ultra-high dose rate (FLASH) radiotherapy (RT) has been shown to elicit differential biological responses compared to conventional (CONV) RT, including reduced acute normal tissue damage. Beam parameters such as dose-per pulse (DPP) and mean dose rate have been identified as key factors influencing this sparing effect. This study aims to evaluate and compare the skin and soft tissue toxicity profiles of CONV-RT and single-pulse high-DPP electron FLASH-RT across various dose levels, with an emphasis on acute toxicity and tissue injury. Material/Methods: The right hindlimb of female C57Bl/6 mice was irradiated with either CONV-RT or FLASH-RT using a 16 MeV electron beam from a FLASH-capable converted clinical linear accelerator, with a 2-cm diameter field size. FLASH-RT was delivered as a single pulse (4 µs), achieving mean dose rates of 7-10 MGy/s. Doses ranged from 27.5 Gy to 40 Gy, with individual dose verification via in vivo film dosimetry for each mouse. Animals were monitored weekly for up to 9 weeks post-RT. Skin toxicity was scored visually on a 5-point scale based on acquired weekly photographs, and loss of hindlimb contractility was measured and calculated using the unirradiated left hindlimb as control. Results: At doses ≤35 Gy, both FLASH-RT and CONV-RT induced only mild skin toxicity, characterized by subtle fur color changes, and minor hindlimb contractility loss. However, at higher doses, FLASH-RT caused significantly less skin toxicity and tissue injury compared to CONV-RT. At peak toxicity (5 weeks post-RT), 37.5 Gy induced a mean toxicity score of 4.0 for CONV-RT (n=4), while none of the FLASH-RT irradiated animals (n=5) exhibited any damage (p=0.011). Similarly, at 40 Gy, CONV-RT (n=4) and FLASH-RT (n=5) induced mean toxicity scores of 4.0 and 1.0, respectively (p=0.045). Additionally, FLASH-RT resulted in significantly less soft tissue injury at 37.5 Gy, with a mean contractility loss of 4.1% compared to 28.2% for CONV-RT (p=0.022) at 5 weeks post-RT. At 40 Gy, FLASH-RT also caused less hindlimb contractility loss than CONV-RT (16.9% vs. 29.3%), though this difference was not statistically significant (p=0.358). Conclusion: This study demonstrates that single-pulse high-DPP FLASH-RT significantly reduces acute skin and soft tissue toxicity compared to conventional radiotherapy at high doses ( ˃ 35 Gy) in the hindlimb of female C57Bl/6 mice. These results suggest that FLASH-RT could provide a clinical advantage in minimizing superficial tissue injury, a critical consideration for the potential clinical application of electron FLASH-RT in treating superficial tumors.

Keywords: FLASH, ultra-high dose rate, skin toxicity,