Modeling the impact of tissue oxygen profiles and oxygen depletion parameter uncertainties on biological response and therapeutic benefit of FLASH

• DOI: 10.1002/mp.16366
• Publication Date: 2023-03-20T14:08:37Z
• Authors: Hongyu Zhu; Jan Schuemann; Qixian Zhang; Leo E. Gerweck
• Keywords: Radiosensitivity; Oxygen enhancement ratio; Limiting oxygen concentration

Abstract Background Ultra‐high dose rate (FLASH) radiation has been reported to efficiently suppress tumor growth while sparing normal tissue; however, the mechanism of differential tissue effect is still not known. Oxygen long known profoundly impact radiobiological responses, and radiolytic oxygen depletion considered be a possible cause or contributor FLASH phenomenon. Purpose This work investigates pO 2 profiles, per unit ( g ), concentration yielding half‐maximum radiosensitization (the average its maximum value one) k ) in tissue. Methods We developed model that considers dependent relationship between change radiosensitivity by irradiation. The assumed irradiation depletes intracellular more rapidly than it diffuses into cell from extracellular environment. Cell survival was calculated based on linear quadratic‐linear related parameters were adjusted 1 Gy increments administered dose. reproduced published experimental data obtained with different lines concentrations, used analyze parameter uncertainties responses. study expands analysis human clinically determined aggregate individual patient profiles. Results results show profile most essential factor affects biological response analyses median rather full can unreliable misleading. Additionally, presence small fraction cells threshold radiobiologic hypoxia substantially alters due depletion. found an increment generally protective higher frequency lower values tumors. Variation at which impacts response, but does alter dose‐dependent trends, if identical both Conclusions therapeutic efficacy likely tissue‐dependent. For breast cancer, beneficial minority cases; subset well oxygenated tumors, gain may realized induced hypoxia.