In radiation physics, Monte Carlo radiation transport simulations are powerful tools to evaluate the cellular responses after irradiation. When investigating such radiation-induced biological effec...

Boron neutron capture therapy (BNCT) is a type of radiation therapy for eradicating tumor cells through a ¹⁰B(n,α)⁷Li reaction in the presence of ¹⁰B in cancer cells. When delivering a high absorbed dose to cancer cells using BNCT, both the timeline of ¹⁰B concentrations and the relative long dose-delivery time compared to photon therapy must be considered. Changes in radiosensitivity during such a long dose-delivery time can reduce the probability of tumor control; however, such changes have not yet been evaluated. Here, we propose an improved integrated microdosimetric-kinetic model that accounts for changes in microdosimetric quantities and dose rates depending on the ¹⁰B concentration and investigate the cell recovery (dose-rate effects) of melanoma during BNCT irradiation. The integrated microdosimetric–kinetic model used in this study considers both sub-lethal damage repair and changes in microdosimetric quantities during irradiation. The model, coupled with the Monte Carlo track structure simulation code of the Particle and Heavy Ion Transport code System, shows good agreement with in vitro experimental data for acute exposure to ⁶⁰Co γ-rays, thermal neutrons, and BNCT with ¹⁰B concentrations of 10 ppm. This indicates that microdosimetric quantities are important parameters for predicting dose-response curves for cell survival under BNCT irradiations. Furthermore, the model estimation at the endpoint of the mean activation dose exhibits a reduced impact of cell recovery during BNCT irradiations with high linear energy transfer (LET) compared to ⁶⁰Co γ-rays irradiation with low LET. Throughout this study, we discuss the advantages of BNCT for enhancing the killing of cancer cells with a reduced dose-rate dependency. If the neutron spectrum and the timelines for drug and dose delivery are provided, the present model will make it possible to predict radiosensitivity for more realistic dose-delivery schemes in BNCT irradiations.

The particle and heavy ion transport code system (PHITS) is a general-purpose Monte Carlo radiation transport simulation code. It has the ability to handle diverse particle types over a wide range of energy. The latest PHITS development enables the generation of track structure for proton and carbon ions ( ¹ H ⁺ , ¹² C ⁶⁺ ) based on the algorithms in the KURBUC code, which is considered as one of the most verified track-structure codes worldwide. This ion track-structure mode is referred to as the PHITS-KURBUC mode. In this study, the range, radial dose distributions, and microdosimetric distributions were calculated using the PHITS-KURBUC mode. Subsequently, they were compared with the corresponding data obtained from the original KURBUC and from other studies. These comparative studies confirm the successful inclusion of the KURBUC code in the PHITS code. As results of the synergistic effect between the macroscopic and microscopic radiation transport codes, this implementation enabled the detailed calculation of the microdosimetric and nanodosimetric quantities under complex radiation fields, such as proton beam therapy with the spread-out Bragg peak.

Objective. Estimation of the probability density of the microdosimetric quantities in macroscopic matter is indispensable for applying the concept of microdosimetry to medical physics and radiological protection. The Particle and Heavy Ion Transport code System (PHITS) enables estimating the microdosimetric probability densities due to its unique hybrid modality between the Monte Carlo and analytical approaches called the microdosimetric function. It can convert the deposition energies calculated by the macroscopic Monte Carlo radiation transport simulation to microdosimetric probability densities in water using an analytical function based on the track-structure simulations. Approach. In this study, we improved this function using the latest track-structure simulation codes implemented in PHITS. The improved function is capable of calculating the probability densities of not only the conventional microdosimetric quantities such as lineal energy but also the number of ionization events occurring in a target site, the so-called ionization cluster size distribution, for arbitrary site diameters from 3 nm to 1 μm. Main results. The accuracy of the improved function was well verified by comparing the microdosimetric probability densities measured by tissue-equivalent proportional counters with the corresponding data calculated in this study. Test calculations for clonogenic cell survival using the improved function coupled with the modified microdosimetric kinetic model suggested a slight increase of its relative biological effectiveness compared with our previous estimations. As a new application of the improved function, we calculated the relative biological effectiveness of the single-strand break and double-strand break yields for proton irradiations using the updated PHITS coupled with the simplified DNA damage estimation model, and confirmed its equivalence in accuracy and its superiority in computational time compared to our previously proposed method based on the track-structure simulation. Significance. From these features, we concluded that the improved function could expand the application fields of PHITS by bridging the gap between microdosimetry and macrodosimetry.

Complex DNA damage, defined as at least two vicinal lesions within 10–20 base pairs (bp), induced after exposure to ionizing radiation, is recognized as fatal damage to human tissue. Due to the difficulty of directly measuring the aggregation of DNA damage at the nano-meter scale, many cluster analyses of inelastic interactions based on Monte Carlo simulation for radiation track structure in liquid water have been conducted to evaluate DNA damage. Meanwhile, the experimental technique to detect complex DNA damage has evolved in recent decades, so both approaches with simulation and experiment get used for investigating complex DNA damage. During this study, we propose a simplified cluster analysis of ionization and electronic excitation events within 10 bp based on track structure for estimating complex DNA damage yields for electron and X-ray irradiations. We then compare the computational results with the experimental complex DNA damage coupled with base damage (BD) measured by enzymatic cleavage and atomic force microscopy (AFM). The computational results agree well with experimental fractions of complex damage yields, i.e., single and double strand breaks (SSBs, DSBs) and complex BD, when the yield ratio of BD/SSB is assumed to be 1.3. Considering the comparison of complex DSB yields, i.e., DSB + BD and DSB + 2BD, between simulation and experimental data, we find that the aggregation degree of the events along electron tracks reflects the complexity of induced DNA damage, showing 43.5% of DSB induced after 70 kVp X-ray irradiation can be classified as a complex form coupled with BD. The present simulation enables us to quantify the type of complex damage which cannot be measured through in vitro experiments and helps us to interpret the experimental detection efficiency for complex BD measured by AFM. This simple model for estimating complex DNA damage yields contributes to the precise understanding of the DNA damage complexity induced after X-ray and electron irradiations.