Monte Carlo in the mechanistic modelling of the FLASH effect: a review

FLASH radiotherapy employs ultra-high dose rates of > 40 Gy s⁻¹, which may reduce normal tissue complication as compared to conventional dose rate treatments, while still ensuring the same level of tumour control. The potential benefit this can offer to patients has been the cause of great interest within the radiation oncology community, but this has not translated to a direct understanding of the FLASH effect. The oxygen depletion and inter-track interaction hypotheses are currently the leading explanations as to the mechanisms behind FLASH, but these are still not well understood, with many questions remaining about the exact underpinnings of FLASH and the treatment parameters required to optimally induce it. Monte Carlo simulations may hold the key to unlocking the mystery behind FLASH, allowing for analysis of the underpinning mechanisms at a fundamental level, where the interactions between individual radiation particles, DNA strands and chemical species can be studied. Currently, however, there is still a great deal of disagreement in simulation findings and the importance of the different mechanisms they support. This review discusses current studies into the mechanisms of FLASH using the Monte Carlo method. The simulation parameters and results for all major investigations are provided. Discussion primarily revolves around the oxygen depletion and inter-track interactions hypotheses, though other, more novel, theories are also mentioned. A general list of recommendations for future simulations is provided, informed by the articles discussed. This review highlights some of the useful parameters and simulation methodologies that may be required to finally understand the FLASH effect.