In this work, we use the next sub-volume method (NSM) to investigate the possibility of using the compartment-based (“on-lattice”) model to simulate water radiolysis. We, first, start with a brief description of the reaction-diffusion master equation (RDME) in a spatially discretized simulation volume (“mesh”), which is divided into sub-volumes (or “voxels”). We then discuss the choice of voxel size and merging technique of a given mesh, along with the evolution of the system using the hierarchical algorithm for the RDME (“hRDME”). Since the compartment-based model cannot describe high concentration species of early radiation-induced spurs, we propose a combination of the particle-based step-by-step (“SBS”) Brownian dynamics model and the compartment-based model (“SBS-RDME model”) for the simulation. We, finally, use the particle-based SBS Brownian dynamics model of Geant4-DNA as a reference to test the model implementation through several benchmarks. We find that the compartment-based model can efficiently simulate the system with a large number of species and for longer timescales, beyond the microsecond, with a reasonable computing time. Our aim in developing this model is to study the production and evolution of reactive oxygen species generated under irradiation with different dose rate conditions, such as in FLASH and conventional radiotherapy.

This paper presents the capabilities of the Geant4-DNA Monte Carlo toolkit to simulate water radiolysis with scavengers using the step-by-step (SBS) or the independent reaction times (IRT) methods. It features two examples of application areas: (1) computing the escape yield of H₂O₂ following a ⁶⁰Co γ-irradiation and (2) computing the oxygen depletion in water irradiated with 1 MeV electrons. To ease the implementation of the chemical stage in Geant4-DNA, we developed a user interface that helps define the chemical reactions and set the concentration of scavengers. The first application area example required two computational steps to perform water radiolysis using NO₂^- and NO₃^- as scavengers and a ⁶⁰Co irradiation. The oxygen depletion computation technique for the second application area example consisted of simulating track segments of 1 MeV electrons and determining the radio-induced loss and gain of oxygen molecules. The production of H₂O₂ under variable scavenging levels is consistent with the literature; the mean relative difference between the SBS and IRT methods is 7.2 % ± 0.5 %. For the oxygen depletion 1 µs post-irradiation, the mean relative difference between both methods is equal to 9.8 % ± 0.3 %. The results in the microsecond scale depend on the initial partial pressure of oxygen in water. In addition, the computed oxygen depletions agree well with the literature. The Geant4-DNA toolkit makes it possible to simulate water radiolysis in the presence of scavengers. This feature offers perspectives in radiobiology, with the possibility of simulating cell-relevant scavenging mechanisms.

FLASH radiotherapy is a promising approach to cancer treatment that offers several advantages over conventional radiotherapy. With this novel technique, high doses of radiation are delivered in a short period of time, inducing the so-called FLASH effect - a phenomenon characterized by healthy tissue sparing without alteration of tumor control. The mechanisms behind the FLASH effect remain unknown. One way to approach this problem is to gain insight into the initial parameters that can distinguish FLASH from conventional irradiation by simulating particle transport in aqueous media using the general-purpose Geant4 Monte Carlo toolkit and its Geant4-DNA extension. This review article discusses the current status of Geant4 and Geant4-DNA simulations to investigate mechanisms underlying the FLASH effect, as well as the challenges faced in this research field. One of the primary challenges is to accurately simulate the experimental irradiation parameters. Another challenge is the temporal extension of the simulations. This review also focuses on two hypotheses to explain the FLASH effect - namely the oxygen depletion hypothesis and the inter-track interactions hypothesis - and discusses how the Geant4 toolkit can be used to investigate them. The aim of this review is to provide an overview of Geant4 and Geant4-DNA simulations for FLASH radiotherapy and to highlight the challenges that need to be overcome in order to better study the FLASH effect.

Ultra-high dose rate FLASH radiotherapy, a promising cancer treatment approach, offers the potential to reduce healthy tissue damage during radiotherapy. As the mechanisms underlying this process remain unknown, several hypotheses have been proposed, including the altered production of radio-induced species under ultra-high dose rate (UHDR) conditions. This study explores realistic irradiation scenarios with various dose-per-pulse and investigates the role of pulse temporal structure. Using the Geant4 toolkit and its Geant4-DNA extension, we modeled the Oriatron eRT6 linac, a FLASH-validated electron beam, and conducted simulations covering four distinct dose-per-pulse scenarios – 0.17 Gy, 1 Gy, 5 Gy, and 10 Gy – all featuring a 1.8 µs pulse duration. Results show close agreement between simulated and experimental dose profiles in water, validating the eRT6 model for Geant4-DNA simulations. We observed important changes in the temporal evolution of certain species, such as the earlier fall in hydroxyl radicals ( $$^{ \bullet } \text{O}\text{H}$$ ) and reduced production and lifetime of superoxide ( $${\text{O}}_{2}^{{\bullet\:}-}$$ ) with higher dose-per-pulse levels. The pulse temporal structure did not influence the long-term evolution of species. Our findings encourage further investigation into different irradiation types, such as multi-pulse configurations, and emphasize the need to add components in water to account for relevant cellular processes.

The discrete physics models available in the Geant4-DNA Monte Carlo toolkit are a subject of continuous evolution and improvement in order to meet the needs of state-of-the-art radiobiological research for medical and space applications. The current capabilities of Geant4-DNA for event-by-event electron transport extend up to 1 MeV. In this work, Geant4-DNA’s most accurate electron inelastic model for sub-keV energies is improved and extended up to 10 MeV via the Relativistic Plane Wave Born Approximation and other theoretical considerations. Benchmark simulations of the electronic stopping power and range of electrons in liquid water using the new model show almost excellent agreement (at the few % level) with the recommendations of the International Commission on Radiation Units and Measurements (ICRU) up to 10 MeV, offering notable improvement (by a factor of ~2) over the default Geant4-DNA inelastic model and an order-of-magnitude higher electron limit. The present development will allow Geant4-DNA users to perform electron track-structure simulations up to 10 MeV, thus, covering a wider range of radiotherapeutic applications (including FLASH-RT) as well as space applications involving MeV electrons which are not currently reachable.