ESTRO 2025 - Abstract Book

S2821

Physics - Dose prediction, optimisation and applications of photon and electron planning

ESTRO 2025

2553

Mini-Oral The Therapeutic Potential of FLASH Radiotherapy Filip Hörberger 1 , Kristoffer Petersson 2,3 , Sofie Ceberg 1 , Sven Bäck 2 , Crister Ceberg 1

1 Department of Clinical Sciences, Medical Radiation Physics, Lund University, Lund, Sweden. 2 Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden. 3 Department of Oncology, University of Oxford, Oxford, United Kingdom Purpose/Objective: Ultra-high dose-rate irradiation or “FLASH”-RT has emerged as a promising approach for enhancing normal tissue (NT) sparing, particularly for larger fraction doses (>5 Gy). However, implementing FLASH-RT in clinical settings may increase toxicity for late-reacting NT as transitioning from a conventional- to a hypo-fractionated regimen would require the magnitude of the FLASH-sparing effect to outweigh the elevated toxicity. Assuming treatment-plans (TP) with standard of care dose-conformity, this study examines whether potential FLASH-sparing can yield substantial netsparing for organs at risk (OARs) and for NT within PTV. This analysis contrasts the increased toxicity from higher fraction doses with the NT-sparing effects from FLASH-RT. Material/Methods: Five patients per tumor site (breast, head-and-neck, prostate and glioblastoma) were included in this study. The biological effective dose definition, derived from the Linear-Quadratic (LQ) model, was used to assess tumor control probability and NT toxicity across treatment schedules. Hypofractionated dose-distributions were derived from conventional ones with n fractions to have the same anti-tumor efficacy for a given hypofractionated treatment regime (fractions ranging from 1 to n) . FLASH-modified hypofractionated dose-distributions were then simulated using a voxel-by-voxel analysis applying a FLASH-modifying-factor derived from a polynomial regression as a function of dose, based on available preclinical data [1]. These TPs were then converted into their conventional fractionated equivalents for direct radiobiological comparisons of NT damage in OARs and PTV between the plans. Netsparing was quantified as the difference in OAR-specific dose-volume histrograme value between the conventional and hypofractionated FLASH-simulated treatment plan, normalized with the prescribed dose. Generic α/β-ratios for tumors and late-reacting NT were applied. Results: Netsparing for OARs and PTV varied strongly by tumor location. Breast and prostate cases demonstrated positive netsparing effects, indicating that the FLASH-effect counterbalanced the increased toxicity from transitioning towards more hypofractionated treatments (fig1). Even under conservative scenarios (significantly higher α/β T compared to α/β NT ), a positive netsparing was observed for most OARs in these cases. Conversely, glioblastoma and head-and-neck cancer sites exhibited increased toxicity (negative netsparing) with hypofractionated treatment regimens, despite NT-sparing effects from FLASH-RT (fig1). This outcome persisted across fraction number. Using more favorable tumor α/β-ratios (lower α/β T ) improved netsparing but remained predominantly negative across all OARs.