Impact of the Lorentz force on electron track structure and early DNA damage yields in magnetic resonance-guided radiotherapy.

Magnetic resonance-guided radiotherapy (MRgRT) has been developed and installed in recent decades for external radiotherapy in several clinical facilities. Lorentz forces modulate dose distribution by charged particles in MRgRT; however, the impact of Lorentz forces on low-energy electron track structure and early DNA damage induction remain unclear. In this study, we estimated features of electron track structure and biological effects in a static magnetic field (SMF) using a general-purpose Monte Carlo code, particle and heavy ion transport code system (PHITS) that enables us to simulate low-energy electrons down to 1 meV by track-structure mode. The macroscopic dose distributions by electrons above approximately 300 keV initial energy in liquid water are changed by both perpendicular and parallel SMFs against the incident direction, indicating that the Lorentz force plays an important role in calculating dose within tumours. Meanwhile, DNA damage estimation based on the spatial patterns of atomic interactions indicates that the initial yield of DNA double-strand breaks (DSBs) is independent of the SMF intensity. The DSB induction is predominantly attributed to the secondary electrons below a few tens of eV, of which energy deposition patterns are not considerably affected by the Lorentz force. Our simulation study suggests that treatment planning for MRgRT can be made with consideration of only changed dose distribution.

A Model for Estimating Dose-Rate Effects on Cell-Killing of Human Melanoma after Boron Neutron Capture Therapy.

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.

Estimation of the radiation-induced DNA double-strand breaks number by considering cell cycle and absorbed dose per cell nucleus.

DNA double-strand breaks (DSBs) are thought to be the main cause of cell death after irradiation. In this study, we estimated the probability distribution of the number of DSBs per cell nucleus by considering the DNA amount in a cell nucleus (which depends on the cell cycle) and the statistical variation in the energy imparted to the cell nucleus by X-ray irradiation. The probability estimation of DSB induction was made following these procedures: (i) making use of the Chinese Hamster Ovary (CHO)-K1 cell line as the target example, the amounts of DNA per nucleus in the logarithmic and the plateau phases of the growth curve were measured by flow cytometry with propidium iodide (PI) dyeing; (ii) the probability distribution of the DSB number per cell nucleus for each phase after irradiation with 1.0 Gy of 200 kVp X-rays was measured by means of γ-H2AX immunofluorescent staining; (iii) the distribution of the cell-specific energy deposition via secondary electrons produced by the incident X-rays was calculated by WLTrack (in-house Monte Carlo code); (iv) according to a mathematical model for estimating the DSB number per nucleus, we deduced the induction probability density of DSBs based on the measured DNA amount (depending on the cell cycle) and the calculated dose per nucleus. The model exhibited DSB induction probabilities in good agreement with the experimental results for the two phases, suggesting that the DNA amount (depending on the cell cycle) and the statistical variation in the local energy deposition are essential for estimating the DSB induction probability after X-ray exposure.

Markov chain Monte Carlo analysis for the selection of a cell-killing model under high-dose-rate irradiation.

PURPOSE: High-dose-rate irradiation with 6 MV linac x rays is a wide-spread means to treat cancer tissue in radiotherapy. The treatment planning relies on a mathematical description of surviving fraction (SF), such as the linear-quadratic model (LQM) formula. However, even in the case of high-dose-rate treatment, the repair kinetics of DNA damage during dose-delivery time plays a function in predicting the dose-SF relation. This may call the SF model selection into question when considering the dose-delivery time or dose-rate effects (DREs) in radiotherapy and in vitro cell experiments. In this study, we demonstrate the importance of dose-delivery time at high-dose-rate irradiations used in radiotherapy by means of Bayesian estimation. METHODS: To evaluate the model selection for SF, three types of models, the LQM and two microdosimetric-kinetic models with and without DREs (MKMDR and MKM) were applied to describe in vitroSF data (our work and references). The parameters in each model were evaluated by a Markov chain Monte Carlo (MCMC) simulation. RESULTS: The MCMC analysis shows that the cell survival curve by the MKMDR fits the experimental data the best in terms of the deviance information criterion (DIC). In the fractionated regimen with 30 fractions to a total dose of 60 Gy, the final cell survival estimated by the MKMDR was higher than that by the LQM. This suggests that additional fractions are required for attaining the total dose equivalent to yield the same effect as the conventional regimen using the LQM in fractionated radiotherapy. CONCLUSIONS: Damage repair during dose-delivery time plays a key role in precisely estimating cell survival even at a high dose rate in radiotherapy. Consequently, it was suggested that the cell-killing model without repair factor during a short dose-delivery time may overestimate actual cell killing in fractionated radiotherapy.

Evaluation of Size Correction Factor for Size-specific Dose Estimates (SSDE) Calculation.

American Association of Physicists in Medicine (AAPM) Report No.204 recommends the size-specific dose estimates (SSDE), wherein SSDE=computed tomography dose index-volume (CTDIvol )×size correction factor (SCF), as an index of the CT dose to consider patient thickness. However, the study on SSDE has not been made yet for area detector CT (ADCT) device such as a 320-row CT scanner. The purpose of this study was to evaluate the SCF values for ADCT by means of a simulation technique to look into the differences in SCF values due to beam width. In the simulation, to construct the geometry of the Aquilion ONE X-ray CT system (120 kV), the dose ratio and the effective energies were measured in the cone angle and fan angle directions, and these were incorporated into the simulation code, Electron Gamma Shower Ver.5 (EGS5). By changing the thickness of a PMMA phantom from 8 cm to 40 cm, CTDIvol and SCF were determined. The SCF values for the beam widths in conventional and volume scans were calculated. The differences among the SCF values of conventional, volume scans, and AAPM were up to 23.0%. However, when SCF values were normalized in a phantom of 16 cm diameter, the error tended to decrease for the cases of thin body thickness, such as those of children. It was concluded that even if beam width and device are different, the SCF values recommended by AAPM are useful in clinical situations.

A simulation study of the radiation-induced bystander effect: modeling with stochastically defined signal reemission.

The radiation-induced bystander effect (RIBE) has been experimentally observed for different types of radiation, cell types, and cell culture conditions. However, the behavior of signal transmission between unirradiated and irradiated cells is not well known. In this study, we have developed a new model for RIBE based on the diffusion of soluble factors in cell cultures using a Monte Carlo technique. The model involves the signal emission probability from bystander cells following Poisson statistics. Simulations with this model show that the spatial configuration of the bystander cells agrees well with that of corresponding experiments, where the optimal emission probability is estimated through a large number of simulation runs. It was suggested that the most likely probability falls within 0.63-0.92 for mean number of the emission signals ranging from 1.0 to 2.5.

A parameter study of pencil beam proton dose distributions for the treatment of ocular melanoma utilizing spot scanning.

The results of Monte Carlo calculated dose distributions of proton treatment of ocular melanoma are presented. An efficient spot scanning method utilizing active energy modulation, which also minimizes the number of target spots was developed. We simulated various parameter values for the particle energy spread and the pencil beam diameter in order to determine values suitable for medical treatment. We found that a 2.5-mm-diameter proton beam with a 5% Gaussian energy spread was suitable for treatment of ocular melanoma while preserving vision for the typical case that we simulated. The energy spectra and the required proton current were also calculated and are reported. The results are intended to serve as a guideline for a new class of low-cost, compact accelerators.

Nuclear collision processes around the Bragg peak in proton therapy.

In the physical processes of proton interaction in bio-materials, most of the proton energy is transferred to electrons. Ionization and excitation occur most frequently around the Bragg peak region, where nuclear reactions also exist. In this study, we investigated the processes of energy deposition by considering interactions including the nuclear reactions between protons and water molecules by a Monte Carlo simulation for proton therapy. We estimated the number of particles produced by a variety of nuclear reactions, and we focused on the interaction in the low-energy region (below 1 MeV). Furthermore, we considered the charge-changing processes in the low-energy region (less than a few hundred keV). Finally, we evaluated the total dose and the contribution of primary protons and secondary particles through nuclear reactions to the absorbed dose. The results showed that the protons generate numerous neutrons via nuclear reactions. Particularly, neutrons with relatively low energies produce recoil protons by elastic collisions with the hydrogen atoms. Around the Bragg peak, low-energy primary protons (slowed-down protons) are prevalent, whereas recoil (secondary) protons gradually become dominant behind the distal falloff region of the Bragg peak. Therefore, around the Bragg peak, the main contribution to the absorbed dose is that of the primary protons (from 80 to 90%), whereas secondary protons created by primary proton-induced reactions contribute to the dose from 20 to 5%. Behind the distal endpoint of the Bragg peak, the absorbed dose is mainly due to the protons produced by (1)H(n, p), and the contribution of these is about 70%.