C. Wang1, W. Wang2, Z. Gu1, X. Yang2, Z. Zhou3, F. Zhang2, and K. Hu2; 1Department of radiation oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, 2Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China, 3Department of radiation oncology, Peking Union Medical College Hospital. Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China, Beijing, China
Purpose/Objective(s): Previous studies have revealed that ultrahigh dose rates of FLASH radiotherapy (RT) appears to reduce toxicity of normal tissue than conventional dose rate (CONV) RT while maintaining local tumor control. It is generally accepted that the FLASH effect appears only when the dose rate reaches a certain specific level. However, the protective effects of different mean dose rates on various normal tissues remain inconclusive. In the context of pulsed electron beam structure, several interdependent but vital beam parameters, including pulse dose, repetition rate, width and number, have potential impact in biological results which remain unknown. Thus, we conduct research on mouse skin model to elucidate the impact of various mean dose rates and beam parameters on the FLASH effect. Metabolomics analysis, when correlated with skin toxicity and pathological changes, further reveals the characteristics of metabolic alterations within mice following exposure to electron beams at different dose rates. The study provides a direction for further exploration into the physiological and pathological mechanisms underlying the FLASH effect. Materials/
Methods: All procedures were approved by the institutional animal ethics committee. 96 male Balb/c mice were shaven in advance, anesthetized via intraperitoneal injection, immobilized on a specially-designed platform, and then underwent a single fraction of CONV or FLASH irradiation in a 6 MeV beam on self-developed electron beam linear accelerator. Mean dose rate modulation was achieved by adjusting pulse dose, repetition rate, width and number. Dose rate calibration and concurrent dose verification were performed using radiochromic films. Skin toxicity was assessed using a modified Radiation Therapy Oncology Group scoring system. Skin and blood samples were collected, at predetermined time points. A portion of skin tissues was processed for paraffin embedding and stained with hematoxylin and eosin (H&E). The remaining in situ skin and blood samples were sent for metabonomic analysis. Unirradiated mice served as blank controls. Results: The output doses were stable and showed good consistency with the preset doses. The electron FLASH RT demonstrated a protective effect on the mouse skin, consistent with previous findings. The protective effect increased with rising mean dose rates within the range of 30 Gy/s to 900 Gy/s, supported by histopathological evaluation. The FLASH effect is primarily influenced by the mean dose rate, with no significant impact observed from single doses or repetition frequencies. Metabonomic studies are undergoing further analysis, and results will be reported when available. Conclusion: The positive correlation between the FLASH effect and the mean dose rate, emphasizes in-depth analysis of beam structures to fully harness the advantages of FLASH RT. Further study of biological response mechanisms under different FLASH patterns will guide the design and practice of FLASH RT in clinical application.
