S2599
Radiobiology - Radiobiological modelling
ESTRO 2026
by maximum diameter size: ≤ 5 mm, 5.1-10 mm, 10.1-20 mm. Kaplan-Meier method was utilized to assess cumulative rate of TOO and Cox regression to analyze the risk of an adverse TOO. Multivariate (MVA) log-rank test was applied to determine TOO distributions stratified by lesion size. Results: We analyzed 1,503 SBMs in 235 patients that received SRS. BEDwas 45.19 Gy10 for 297 (19.8%) lesions, 50.68 Gy10 for 442 (29.4%) lesions, and 56.00 Gy10 for 764 (50.8%) lesions. With a median follow-up of 10 months, on a per-lesion analysis, 138 (9.2%) LF events in 45 patients and 50 (3.5%) radiologic RN events in 37 patients were observed. The actuarial 1-year cumulative rate of TOO was 72.25% with 45.19 Gy10, 89.94% with 50.68 Gy10 and 91.83% with 56.00 Gy10, p<0.001 for all comparisons versus 45.19 Gy10 (Figure 1). Between 50.68 Gy10 and 56.00 Gy10 (p=0.48), there was no statistically significant difference. Compared to 45.19 Gy10, 50.68 Gy10 and 56.00 Gy10 were associated with 59.7% (HR: 0.40; 95% CI: 0.27-0.60; p<0.001) and 63.9% (HR: 0.36; 95% CI: 0.25-0.52; p<0.001) reductions in an adverse TOO. Stratification by lesion size showed a significantly higher impact of the 2 higher dose levels vs. the lowest dose for lesions >5 mm (p<0.001; Table 1). MVA demonstrated that higher BED10 was an independent predictor after accounting for lesion size (HR: 0.34 [95% CI: 0.22-0.51] for 50.68 Gy10, p<0.001; HR: 0.35 [95% CI: 0.22-0.56] for 56.00 Gy10, p<0.001; comparator for both is 45.19 Gy10). Figure 1: Kaplan-Meier curves depicting the cumulative incidence of TOO
Technology, Guangdong Institute of Laser Plasma Accelerator Technology, Guangzhou, China. 6 State Key Laboratory of Heavy Oil Processing, China University of Petroleum, Qingdao, China. 7 State Key Laboratory of Nuclear Physics and Technology and Institute of Heavy Ion Physics, School of Physics, Peking University, Beijing, China Purpose/Objective: To reveal the coupling mechanism of beam temporal profile and tissue oxygen content on radical kinetics, further explain the potential biological basis of the FLASH effect, and provide a reference for beam optimization and treatment planning design of FLASH radiotherapy (FLASH-RT). Material/Methods: TOPAS-nBio v3.0 was used to simulate the physical and chemical processes of electron beams in water, and a full-scale kinetic model covering the generation, diffusion, reaction, and quenching of free radicals such as hydroxyl radical (·OH) and hydrated electrons (eaq-) was established. Under different beam temporal profiles (single pulse, multi-pulses, continuous wave irradiation) and different oxygen concentration conditions, the evolution dynamics of free radicals were systematically simulated. At the same time, the content data of eaq- were obtained by experimental measurement of laser absorption spectroscopy to verify the accuracy of the model prediction. Results: The changing trend of eaq- concentration measured in the experiment was highly consistent with the simulation results, verifying the reliability of the constructed model. The beam time structure had a significant impact on the peak value and duration of free radical concentration. The single-pulse structure can cause the free radicals to rapidly increase and then quickly quench in a short time, while the continuous or long-pulse structure can cause the radical concentration to remain at a high level for a long time. The evolution of ·OH was not sensitive to the oxygen environment, while eaq- are greatly affected by the oxygen environment. The scavenging efficiency of free radicals in a hypoxic environment was significantly decreased, leading to an enhanced accumulation of oxidative damage to biological macromolecules. The lifespan of eaq- in an oxygen-rich environment decreased rapidly. Conclusion: Radical kinetics are regulated by both the beam temporal profile and oxygen content. FLASH-RT can utilize single-pulse or multi- pulses intervals to form periodic windows, reducing normal tissue damage by efficiently scavenging free radicals through antioxidants, while free radicals in tumor tissues continuously accumulate and amplify damage, thus generating a selective protective effect. References: [1] Hu A, Qiu Rui, Li ,Wei Bo, Zhou Wanyi, Wu Zhen Zhang Hui, et al. Radical recombination and antioxidants: a hypothesis on the FLASH effect mechanism. Int J Radiat Biol 2023;99:620–8. [2] Sun J, Kong X, Lv J, Liu X, Wang J, Lin C, et al. Dependence of the Radical Dynamics on the Beam Temporal Profile in FLASH Radiotherapy 2025. [3] Lv J, Wang J, Li Q, Yang G, Gai W, Zhu K, et al. Geometry-optimized electron beam scattering foils enabling dose uniformity and dose rate enhancement for FLASH radiotherapy studies. Phys Med Biol 2025;70:185009. [4] Thompson SJ, Prise KM, McMahon SJ. Investigating the potential contribution of inter-track interactions within ultra-high dose-rate proton therapy. Phys Med Biol 2023;68:055006. Keywords: FLASH-RT, Monte Carlo, Beam temporal structure
Conclusion: Both 50.68-56.00 Gy10 achieved superior TOO compared to 45.00 Gy10 for SBM, particularly in lesions >5 mm. Keywords: SRS, Brain metastases, BED
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Study on the radical kinetics driven by the beam time profile under different oxygen contents in FLASH radiotherapy Jianhan Sun 1,2 , Xianghui Kong 3 , Jianfeng Lv 1,4 , Jinghui Wang 4,5 , Xiaodong Liu 6 , Mengyi Tai 1 , Chen Lin 1,4 , Tian Li 3 , Yibao Zhang 2 , Senlin Huang 7 1 State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing, China. 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China. 3 Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, Hong Kong. 4 Beijing Laser Acceleration Innovation Center, Beijing Laser Acceleration Innovation Center, Beijing, China. 5 Guangdong Institute of Laser Plasma Accelerator
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