Effects of the Oxygen depletion in FLASH irradiation investigated through Geant4-DNA toolkit

FLASH radiotherapy (or FLASH-RT) is a novel radiotherapy technology consisting of radiation delivery at dose rates several orders of magnitude higher (> 40 Gy/s) than the currently used in conventional clinical radiotherapy. Many recent in-vivo preclinical studies indicate that FLASH-RT can greatly spare healthy tissues while maintaining unchanged tumour control. The generally acknowledged, though not entirely substantiated, explanation for the FLASH effect relates to the oxygen depletion that occurs after the radiation passage. On the other hand, oxygen depletion or, more in general, oxygen-related effects are still not fully clarified. Different research groups carried out the Monte Carlo simulations of electron and proton irradiations in oxygenated water to evaluate the oxygen-concentration-related effects at the cell-scale level. We analysed and compared the simulation results of the oxygen effect under the FLASH condition (considering the time-dependent G-values and the oxygen enhancement ratio-weighted dose) we obtained with GEANT4-DNA against TRAX-CHEM code results in the literature. Our results indicate that oxygen depletion has a negligible effect on radiosensitivity via oxygen enhancement, showing a close agreement with the TRAX-CHEM code. The conclusion is that the Geant4-DNA toolkit can be a valid instrument to study the FLASH effect.