FLASH irradiation (FLASH-IR) is one of the cutting-edge research directions in the field of tumor radiotherapy. Previous studies have demonstrated that FLASH-IR can effectively eradicate tumors while significantly reducing damage to normal tissues, exhibiting unique biological effects characterized by high efficiency and low toxicity. Monte Carlo simulation at the microscopic scale is a critical method for studying radiobiological effects and has been widely applied in conventional radiotherapy research. In recent years, its application in microscopic reaction analysis and mechanistic exploration of FLASH-IR has grown rapidly. This article systematically reviews the latest advances and key challenges in microscopic Monte Carlo simulation studies of FLASH-IR, aiming to provide theoretical insights and method ological guidance for future research.

FLASH irradiation (FLASH-IR) is one of the cutting-edge research directions in the field of tumor radiotherapy. Previous studies have demonstrated that FLASH-IR can effectively eradicate tumors while significantly reducing damage to normal tissues, exhibiting unique biological effects characterized by high efficiency and low toxicity. Monte Carlo simulation at the microscopic scale is a critical method for studying radiobiological effects and has been widely applied in conventional radiotherapy research. In recent years, its application in microscopic reaction analysis and mechanistic exploration of FLASH-IR has grown rapidly. This article systematically reviews the latest advances and key challenges in microscopic Monte Carlo simulation studies of FLASH-IR, aiming to provide theoretical insights and method ological guidance for future research.

Objective:To develop a simplified DNA model tailored for Monte Carlo track structure simulations and investigate the influence of microstructural variations at the scale of several base pairs on the physical simulation of proton-induced biological effects, providing a novel approach to enhance the efficiency of modeling and computational processes in proton radiotherapy simulations.Methods:A circular double-helix DNA molecule consisting of 4 362 base pairs was constructed based on the pBR322 plasmid structure. These molecules were evenly distributed without overlap within a spherical region at the center of a water phantom, representing the cellular nucleus. Integrated into the GPU-based gMicroMC code framework, the model facilitated simulations to calculate proton-induced double-strand break (DSB) yields across three distinct models with twist angles of 20°, 36°, and 72° between adjacent nucleotide pairs. Comparative analyses were conducted to assess differences among these models.Results:Intra-model analyses revealed a consistent decrease in proton-induced DSB yields with increasing initial energy. Under proton irradiation at different energies, the DSB yields for the three models followed the order 72°>36°>20°, with intergroup relative differences exceeding 34.6%. Comparative RBE calculations suggested that models with twist angles between 36° and 72° may better replicate proton-induced damage observed in V79 cells.Conclusions:By strategically simplifying the separation of macroscopic and microscopic levels of DNA structure, adjustments to microstructural parameters can be effectively implemented to refine the model, thereby enhancing the efficiency of modeling and physical simulations. This methodology shows potential as a model for simulating relative biological effectiveness (RBE) in proton therapy planning.

Objective:To develop a simplified DNA model tailored for Monte Carlo track structure simulations and investigate the influence of microstructural variations at the scale of several base pairs on the physical simulation of proton-induced biological effects, providing a novel approach to enhance the efficiency of modeling and computational processes in proton radiotherapy simulations.Methods:A circular double-helix DNA molecule consisting of 4 362 base pairs was constructed based on the pBR322 plasmid structure. These molecules were evenly distributed without overlap within a spherical region at the center of a water phantom, representing the cellular nucleus. Integrated into the GPU-based gMicroMC code framework, the model facilitated simulations to calculate proton-induced double-strand break (DSB) yields across three distinct models with twist angles of 20°, 36°, and 72° between adjacent nucleotide pairs. Comparative analyses were conducted to assess differences among these models.Results:Intra-model analyses revealed a consistent decrease in proton-induced DSB yields with increasing initial energy. Under proton irradiation at different energies, the DSB yields for the three models followed the order 72°>36°>20°, with intergroup relative differences exceeding 34.6%. Comparative RBE calculations suggested that models with twist angles between 36° and 72° may better replicate proton-induced damage observed in V79 cells.Conclusions:By strategically simplifying the separation of macroscopic and microscopic levels of DNA structure, adjustments to microstructural parameters can be effectively implemented to refine the model, thereby enhancing the efficiency of modeling and physical simulations. This methodology shows potential as a model for simulating relative biological effectiveness (RBE) in proton therapy planning.