ESTRO 2025 - Abstract Book

S3913

Radiobiology - Normal tissue radiobiology

ESTRO 2025

Keywords: FLASH, Proton

References: Liu K, Titt U, Esplen NM, Connell L, Konradsson EK, Yang M, Wang X, Takaoka T, Li Z, Koong AC, Mitra D. Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation. bioRxiv. 2024:2024-09.

1161

Proffered Paper Unraveling RBE variability: Distal edge effects and dose fractionation effects on acute and late damage in vivo Cathrine Bang Overgaard 1 , Fardous Reaz 2 , Mateusz Sitarz 2 , Per Poulsen 2 , Harald Spejlborg 3 , Jacob Johansen 4 , Jens Overgaard 5 , Cai Grau 2 , Niels Bassler 2 , Brita Singers Sørensen 1,2 1 Experimental Clinical Oncology, Aarhus University Hospital, Aarhus N, Denmark. 2 Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus N, Denmark. 3 Clinical Medicine, Aarhus University, 8200, Denmark. 4 Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark. 5 Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark Purpose/Objective: In clinical proton therapy, a constant relative biological effectiveness (RBE) of 1.1 is commonly used to convert prescribed photon doses into isoeffective proton doses, effectively reducing the proton dose by 10%. However, RBE is not static; it varies with tissue type, biological endpoint, dose fractionation, and linear energy transfer (LET). Despite these dynamics, very few in vivo studies quantify the proton RBE variations using late damage endpoints, fractionated doses, or the distal edge effect, which are highly significant in a clinical setting. Using a murine leg model, this study aimed to determine (1) the RBE of an acute and late damage endpoint, (2) the RBE for single and fractionated doses, and (3) the enhancement from the center to the distal edge of a proton spread-out Bragg peak (SOBP). Material/Methods: The right hindlimb of unanesthetized mice was irradiated with protons or 6 MV photons (reference) using a single fraction of 22-47 Gy or four fractions of 7.5-16.5 Gy per fraction. The legs were positioned in the center (LET,all=5.33 keV/mm) or the distal edge (LET,all=7.63 keV/mm) of a 3 cm wide proton SOBP (Figure 1). The severity of acute skin damage was evaluated daily until day 30 using an arbitrary scoring system. For late damage, radiation-induced fibrosis was assessed using a joint contracture assay, analyzing the extensibility of the ankle joint biweekly up to 12 months post-treatment. The RBE was calculated using the ratio of the ED50 (equivalent dose for 50% of responders) in full dose-response curves between protons and the photon reference beam or between center protons and distal edge protons for enhancement determination.