S2509
Radiobiology - Biology of novel irradiation techniques
ESTRO 2026
Digital Poster Highlight 2971 Impact of Dose Fractionation and Pulse Splitting on the FLASH Effect in Ultra-High Dose-Rate Electron Irradiation Amina JOUDAT 1,2 , Aashini RAJPAL 1,2 , Yann SAYOUS 1 , Johan LEYGONIE 1,2 , Elena AGOSTONI 1,2 , Liu SHI 1 , Charlotte ROBERT 1 , Eric DEUTSCH 1 , Lydia MEZIANI 1 1 INSERM U1030 Département d'Oncologie- Radiothérapie, Gustave Roussy, Villejuif, France. 2 Innovation & technologie, Theryq, Paris, France Purpose/Objective: FLASH radiotherapy (RT) has shown a remarkable ability to spare normal tissue while maintaining tumour control compared to conventional dose-rate RT. Despite extensive research, the physical conditions required to induce and sustain the FLASH effect remain only partially characterized. The influence of key parameters, such as dose fractionation and pulse splitting, on the preservation or loss of the effect still needs clarification. This study investigates how variations in these parameters modulate the FLASH effect in ultra-high dose-rate (UHDR) electron irradiation using preclinical models, and aims to better characterize the temporal and dosimetric boundaries that define and sustain the FLASH effect. Material/Methods: B16F10 melanoma cells were injected subcutaneously into the shaved dorsal region of female C57BL/6 mice.
and control embryos. The use of GFP-labeled cells allowed for clear identification of metastatic foci on the upper CAM, validating this approach for in vivo monitoring of tumor spread.
Conclusion: FLASH RT effectively controls pancreatic tumor growth while reducing toxicity, supporting its therapeutic advantage. No significant differences in metastatic dissemination were observed, although this analysis may be limited by the late endpoint (EDD17), which could have underestimated early metastatic events. This is also suggested by the survival analysis showing higher mortality in the CONV group.The CAM model proved to be a versatile preclinical platform for studying tumor response and metastatic behavior, providing a foundation for future investigations of FLASH radiotherapy. References: We thank Fondazione Pisa for funding CPFR with the grant “prog. n. 134/2021”This work was supported by the Italian Ministry of University and Research (MUR) under the Piano Nazionale di Ripresa e Resilienza (PNRR), Mission 4, Component 2, Ecosistemi dell’Innovazione – Tuscany Health Ecosystem (THE), Spoke 1 “Advanced Radiotherapies and Diagnostics in Oncology” (CUP I53C22000780001), and by the PRIN 2022 project “Increasing the therapeutic index of Radiotherapy through temporal (Flash) and spatial (mini-beam) beam modulation” (Code 2022PLNN4F, CUP I53C24002700006). Keywords: FLASH RT, CAM model, metastasis
Irradiations were performed either with a conventional linear accelerator (CONV, 9MeV
electrons, 0.125Gy/s, Clinac 2300C/D, Varian) or an UHDR system (FLASH, 10Mev, ~300Gy/s, 100Hz, FLASHKNiFE, Theryq). Mice were randomized into non- irradiated (NIR), CONV or UHDR groups. The total dose of 30Gy was delivered either as a single fraction or as three daily fractions of 10Gy (3 × 10Gy). For pulse- splitting experiments, mice received 30Gy UHDR irradiation without (one-shot) or with two inter-pulse pauses of 40 seconds(s), 80s, or 120s. Tumor volume and skin toxicity were assessed three times per week. Results: Mice treated with 30Gy UHDR or 30Gy CONV irradiation showed comparable tumor control, indicating similar antitumor efficacy. Likewise, fractionated UHDR irradiation (3 × 10Gy) achieved tumor growth inhibition equivalent to single 30Gy UHDR exposure. Skin toxicity appeared from day 14 post-irradiation in the CONV group, whereas no toxicity was observed in either the single-dose (30Gy) or fractionated UHDR (3x10Gy) group. For mice irradiated with two inter-pulse pauses of 40s, 80s, or 120s, tumor control remained similar across the treatment groups; however, as observed in the CONV 30Gy group and in contrast to single-shot UHDR irradiation, all pulse-splitting groups developed skin
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