S2511
Radiobiology - Biology of novel irradiation techniques
ESTRO 2026
Keywords: FLASH, dose rate parameters, skin toxicity
radiotherapy (FLASH-RT) has been demonstrated in preclinical studies1, 2; however, systematic optimization of dose and dose rate parameters is necessary for its clinical translation3. Material/Methods: In this study, electron conventional radiotherapy (CONV-RT, 0.1 Gy/s) served as the control group for all experiments. The dose threshold was evaluated by comparing FLASH-RT (250 Gy/s) with CONV-RT across a single dose range (18-24 Gy). The dose-rate threshold and optimize parameters were systematic assessed between FLASH-RT (40-400 Gy/s) and CONV-RT at a single fixed dose (20 Gy). Acute skin toxicity in male C57BL/6 mice was assessed through visual analyses and histopathological. Tumor response(20 Gy) was evaluated in B16-F10 melanoma models irradiated at either FLASH (300 Gy/s) or CONV rates. Reirradiation response was assessed following prior hypofractionated CONV-RT (9 Gy × 4 fractions), with subsequent delivery of either FLASH-RT (400 Gy/s) or CONV-RT at 20 Gy. Results: ElectronFLASH-RT significantly reduced acute skin toxicities (e.g.,moist desquamation, necrosis,ulcer) versus CONV-RT at dose( ≤ 22 Gy, P < 0.001), though this protective effect was absent at higher dose( ≥ 24 Gy). Dose-rate optimization demonstrated significant radioprotection exclusively at dose rate(> 200 Gy/s, P < 0.001), with no incremental benefit observed between 300 Gy/s and 400 Gy/s. While 250 Gy/s conferred protection (P < 0.01), 300 Gy/s proved superior sparing effect in skin. In melanoma models, FLASH-RT achieved tumor control equivalent to CONV-RT while significantly reducing lung metastases and mitigating skin toxicity during reirradiation (P < 0.001). Conclusion: A dual-threshold framework for the electron FLASH effect in skin was established: a dose threshold (<24 Gy) and a dose rate threshold (>200 Gy/s), with optimal radioprotection achieved at dose rates exceeding 250 Gy/s. FLASH-RT mitigated acute skin toxicity while maintaining comparable tumor control efficacy to conventional radiotherapy, notably, FLASH- RT may reduce distant metastases, thereby supporting its clinical adoption. References: Soto LA, Casey KM, Wang J, et al. FLASH Irradiation Results in Reduced Severe Skin Toxicity Compared to Conventional-Dose-Rate Irradiation. Radiat Res. 2020;194(6):618-24.2. Duval KEA, Aulwes E, Zhang R, et al. Comparison of Tumor Control and Skin Damage in a Mouse Model after Ultra-High Dose Rate Irradiation and Conventional Irradiation. Radiat Res. 2023;200(3):223-31.3. Brown KH, Ghita-Pettigrew M, Mcivor MP, et al. Dose, dose rate and split dose impacts murine skin responses following photon FLASH irradiation. Radiother Oncol. 2025;212:111125.
Digital Poster 3127
Combining ultra-high dose rate radiotherapy and minibeam radiotherapy opens new rays of hope for enhancing antitumor and mitigate skin toxicity Shun Lu, Jie Zhou, Dongliang Li Precision Radiation in Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China Purpose/Objective: Aim to evaluate the underlying biological effect of the combination of ultra-high dose rate radiotherapy (FLASH-RT) and minibeam radiotherapy (MBRT) . Material/Methods: The combination of FLASH-RT and MBRT was performed on a lead shielding plate (500 μ m aperture, 1000 μ m center-to-center distance), which allowed electron ultra-high dose rate radiation to go through and form a peak and valley dose distribution. C57 mice with average 200 mm3 volume of KPC pancreatic cancer were randomly divided into 5 groups, including control (tumor-bearing only), CONV-RT (0.5 Gy/s, EUD ≈ 5.4 Gy), FLASH-RT (400 Gy/s, EUD ≈ 5.4 Gy), MBRT (0.5 Gy/s, EUD ≈ 5.4 Gy), and FLASH-RT combined with SFRT (F-MBRT) (400 Gy/s, EUD ≈ 5.4 Gy). After irradiation, the tumor volume and dissected tumor weight were determined for within 1 week. The irradiated toxicity of skin and femur were evaluated by Masson staining, HE, Immunofluorescence, and Western blot. Results: Ultra-high dose rate radiation passed through the lead shielding plate, and formed an area of 12 Gy peak dose and 3.5 Gy valley dose (peak-to-valley dose ratio ≈ 3.5, EUD ≈ 5.4 Gy). On the 7th day after irradiation, the tumor volume in each radiation group was lower than that in control group (p<0.001), and the tumor volume inMBRT and F-MBRTgroups was significantly lower than the CONV-RT and FLASH- RT on the 7th day (p<0.01). Similarly, the dissected tumor weight in SFRT and F-MBRT groups was also significantly lower than that in CONV-RT and FLASH-RT group (p<0.05). Under this dosimetry parameters, no obvious toxicity was observed in skin and femur for each radiation group. Notably, after 3 weeks of 20 Gy irradiation, the collagen volume fraction of skin tissue in F-MBRT group was significantly lower than either FLASH-RT or MBRT group (p<0.05). However, there was no significant difference in the expression levels of γ -H2AX in the femur among the F- MBRT, FLASH-RT, and MBRT groups, but all were lower than those in the CONV-RT group. (p<0.05).
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