Review of chemical models and applications in Geant4-DNA: Report from the ESA BioRad III Project.

A chemistry module has been implemented in Geant4-DNA since Geant4 version 10.1 to simulate the radiolysis of water after irradiation. It has been used in a number of applications, including the calculation of G-values and early DNA damage, allowing the comparison with experimental data. Since the first version, numerous modifications have been made to the module to improve the computational efficiency and extend the simulation to homogeneous kinetics in bulk solution. With these new developments, new applications have been proposed and released as Geant4 examples, showing how to use chemical processes and models. This work reviews the models implemented and application developments for modeling water radiolysis in Geant4-DNA as reported in the ESA BioRad III Project.

Dose and DNA damage modelling of diffusing alpha-emitters radiation therapy using Geant4.

PURPOSE: Diffusing alpha-emitters radiation therapy (DaRT) is a brachytherapy technique using α-particles to treat solid tumours. The high linear energy transfer (LET) and short range of α-particles make them good candidates for the targeted treatment of cancer. Treatment planning of DaRT requires a good understanding of the dose from α-particles and the other particles released in the 224Ra decay chain. METHODS: The Geant4 Monte Carlo toolkit has been used to simulate a DaRT seed to better understand the dose contribution from all particles and simulate the DNA damage due to this treatment. RESULTS: Close to the seed α-particles deliver the majority of dose, however at radial distances greater than 4 mm, the contribution of ß-particles is greater. The RBE has been estimated as a function of number of double strand breaks (DSBs) and complex DSBs. A maximum seed spacing of 5.5 mm and 6.5 mm was found to deliver at least 20 Gy RBE weighted dose between the seeds for RBEDSB and RBEcDSB respectively. CONCLUSIONS: The DNA damage changes with radial distance from the seed and has been found to become less complex with distance, which is potentially easier for the cell to repair. Close to the seed α-particles contribute the majority of dose, however the contribution from other particles cannot be neglected and may influence the choice of seed spacing.

Monte Carlo-calculated beam quality and perturbation correction factors validated against experiments for Farmer and Markus type ionization chambers in therapeutic carbon-ion beams.

Objective. In current dosimetry protocols, the estimated uncertainty of the measured absorbed dose to waterDwin carbon-ion beams is approximately 3%. This large uncertainty is mainly contributed by the standard uncertainty of the beam quality correction factorkQ. In this study, thekQvalues in four cylindrical chambers and two plane-parallel chambers were calculated using Monte Carlo (MC) simulations in the plateau region. The chamber-specific perturbation correction factorPof each chamber was also determined through MC simulations.Approach.kQfor each chamber was calculated using MC code Geant4. The simulatedkQratios in subjected chambers and reference chambers were validated through comparisons against our measured values. In the measurements in Heavy-Ion Medical Accelerator in Chiba,kQratios were obtained fromDwvalues of60Co, 290- and 400 MeV u-1carbon-ion beams that were measured with the subjected ionization chamber and the reference chamber. In the simulations,fQ(the product of the water-to-air stopping power ratio andP) was acquired fromDwand the absorbed dose to air calculated in the sensitive volume of each chamber.kQvalues were then calculated from the simulatedfQand the literature-extractedWairand compared with previous publications.Main results. The calculatedkQratios in the subjected chambers to the reference chamber agreed well with the measuredkQratios. ThekQuncertainty was reduced from the current recommendation of approximately 3% to 1.7%. ThePvalues were close to unity in the cylindrical chambers and nearly 1% above unity in the plane-parallel chambers.Significance. ThekQvalues of carbon-ion beams were accurately calculated in MC simulations and thekQratios were validated through ionization chamber measurements. The results indicate a need for updating the current recommendations, which assume a constantPof unity in carbon-ion beams, to recommendations that consider chamber-induced differences.

In-silico calculations of DNA damage induced by α-particles in the 224Ra DaRT decay chain for a better understanding of the radiobiological effectiveness of this treatment.

Diffusing alpha-emitters radiation Therapy (DaRT) is an interstitial brachytherapy technique using 224Ra seeds. For accurate treatment planning a good understanding of the early DNA damage due to α-particles is required. Geant4-DNA was used to calculate the initial DNA damage and radiobiological effectiveness due to α-particles with linear energy transfer (LET) values in the range 57.5-225.9 keV/µm from the 224Ra decay chain. The impact of DNA base pair density on DNA damage has been modelled, as this parameter varies between human cell lines. Results show that the quantity and complexity of DNA damage changes with LET as expected. Indirect damage, due to water radical reactions with the DNA, decreases and becomes less significant at higher LET values as shown in previous studies. As expected, the yield of complex double strand breaks (DSBs), which are harder for a cell to repair, increases approximately linearly with LET. The level of complexity of DSBs and radiobiological effectiveness have been found to increase with LET as expected. The quantity of DNA damage has been shown to increase for increased DNA density in the expected base pair density range of human cells. The change in damage yield as a function of base pair density is largest for higher LET α-particles, an increase of over 50% for individual strand breaks between 62.7 and 127.4 keV/µm. This change in yield shows that the DNA base pair density is an important parameter for modelling DNA damage particularly at higher LET where the DNA damage is greatest and most complex.

Geant4-DNA simulation of human cancer cells irradiation with helium ion beams.

PURPOSE: This study aimed to develop a computational environment for the accurate simulation of human cancer cell irradiation using Geant4-DNA. New cell geometrical models were developed and irradiated by alpha particle beams to induce DNA damage. The proposed approach may help further investigation of the benefits of external alpha irradiation therapy. METHODS: The Geant4-DNA Monte Carlo (MC) toolkit allows the simulation of cancer cell geometries that can be combined with accurate modelling of physical, physicochemical and chemical stages of liquid water irradiation, including radiolytic processes. Geant4-DNA is used to calculate direct and non-direct DNA damage yields, such as single and double strand breaks, produced by the deposition of energy or by the interaction of DNA with free radicals. RESULTS: In this study, the "molecularDNA" example application of Geant4-DNA was used to quantify early DNA damage in human cancer cells upon irradiation with alpha particle beams, as a function of linear energy transfer (LET). The MC simulation results are compared to experimental data, as well as previously published simulation data. The simulation results agree well with the experimental data on DSB yields in the lower LET range, while the experimental data on DSB yields are lower than the results obtained with the "molecularDNA" example in the higher LET range. CONCLUSION: This study explored and demonstrated the possibilities of the Geant4-DNA toolkit together with the "molecularDNA" example to simulate the helium beam irradiation of cancer cell lines, to quantify the early DNA damage, or even the following DNA damage response.

Prediction of DNA rejoining kinetics and cell survival after proton irradiation for V79 cells using Geant4-DNA.

PURPOSE: Track structure Monte Carlo (MC) codes have achieved successful outcomes in the quantitative investigation of radiation-induced initial DNA damage. The aim of the present study is to extend a Geant4-DNA radiobiological application by incorporating a feature allowing for the prediction of DNA rejoining kinetics and corresponding cell surviving fraction along time after irradiation, for a Chinese hamster V79 cell line, which is one of the most popular and widely investigated cell lines in radiobiology. METHODS: We implemented the Two-Lesion Kinetics (TLK) model, originally proposed by Stewart, which allows for simulations to calculate residual DNA damage and surviving fraction along time via the number of initial DNA damage and its complexity as inputs. RESULTS: By optimizing the model parameters of the TLK model in accordance to the experimental data on V79, we were able to predict both DNA rejoining kinetics at low linear energy transfers (LET) and cell surviving fraction. CONCLUSION: This is the first study to demonstrate the implementation of both the cell surviving fraction and the DNA rejoining kinetics with the estimated initial DNA damage, in a realistic cell geometrical model simulated by full track structure MC simulations at DNA level and for various LET. These simulation and model make the link between mechanistic physical/chemical damage processes and these two specific biological endpoints.

Development of a more accurate Geant4 quantum molecular dynamics model for hadron therapy.

Objective. Although in heavy-ion therapy, the quantum molecular dynamics (QMD) model is one of the most fundamental physics models providing an accurate daughter-ion production yield in the final state, there are still non-negligible differences with the experimental results. The aim of this study is to improve fragment production in water phantoms by developing a more accurate QMD model in Geant4.Approach. A QMD model was developed by implementing modern Skyrme interaction parameter sets, as well as by incorporating with an ad hocα-cluster model in the initial nuclear state. Two adjusting parameters were selected that can significantly affect the fragment productions in the QMD model: the radius to discriminate a cluster to which nucleons belong after the nucleus-nucleus reaction, denoted byR, and the squared standard deviation of the Gaussian packet, denoted byL. Squared Mahalanobis's distance of fragment yields and angular distributions with 1, 2, and the higher atomic number for the produced fragments were employed as objective functions, and multi-objective optimization (MOO), which make it possible to compare quantitatively the simulated production yields with the reference experimental data, was performed.Main results. The MOO analysis showed that the QMD model with modern Skyrme parameters coupled with the proposedα-cluster model, denoted as SkM*α, can drastically improve light fragments yields in water. In addition, the proposed model reproduced the kinetic energy distribution of the fragments accurately. The optimizedLin SkM*αwas confirmed to be realistic by the charge radii analysis in the ground state formation.Significance. The proposed framework using MOO was demonstrated to be very useful in judging the superiority of the proposed nuclear model. The optimized QMD model is expected to improve the accuracy of heavy-ion therapy dosimetry.

Microdosimetric investigation for multi-ion therapy by means of silicon on insulator (SOI) microdosimeter.

Objective.Ion radiotherapy with protons or carbon ions is one of the most advanced clinical methods for cancer treatment. To further improve the local tumor control, ion radiotherapy using multiple ion species has been investigated. Due to complexity of dose distributions delivered by multi-ion therapy in a tumor, a validation strategy for the planned treatment efficacy must be established that can be potentially used in the quality assurance (QA) protocol for the multi-ion treatment plans. In previous work, we demonstrated that the microdosimetric approach using the silicon on insulator (SOI) microdosimeter is practical for validating cell surviving fraction (SF) of MIA PaCa-2 cells in the independent fields of helium, carbon, oxygen, and neon ion beams.Approach.This paper extends the previous study, and we demonstrate a microdosimetry based approach as a pilot study to build the QA protocol in the multi-ion therapy predicting the cell SF along the spread-out Bragg peak obtained by combined irradiations of He+O and C+Ne ions. Across the study, the SOI microdosimeter system MicroPlus was used for measurement of the lineal energy in individual ion fields followed by deriving the lineal energy of combined ion fields delivered by a pencil beam scanning system at HIMAC.Main results.The predicted cell SF based on derived lineal energy and dose in the combined fields was in good agreement with the planned cell SF by our in-house treatment planning system.Significance.The presented results indicated the potential benefit of the SOI microdosimeter system MicroPlus as the QA system in the multi-ion radiotherapy.

Performance Evaluation for Repair of HSGc-C5 Carcinoma Cell Using Geant4-DNA.

Track-structure Monte Carlo simulations are useful tools to evaluate initial DNA damage induced by irradiation. In the previous study, we have developed a Gean4-DNA-based application to estimate the cell surviving fraction of V79 cells after irradiation, bridging the gap between the initial DNA damage and the DNA rejoining kinetics by means of the two-lesion kinetics (TLK) model. However, since the DNA repair performance depends on cell line, the same model parameters cannot be used for different cell lines. Thus, we extended the Geant4-DNA application with a TLK model for the evaluation of DNA damage repair performance in HSGc-C5 carcinoma cells which are typically used for evaluating proton/carbon radiation treatment effects. For this evaluation, we also performed experimental measurements for cell surviving fractions and DNA rejoining kinetics of the HSGc-C5 cells irradiated by 70 MeV protons at the cyclotron facility at the National Institutes for Quantum and Radiological Science and Technology (QST). Concerning fast- and slow-DNA rejoining, the TLK model parameters were adequately optimized with the simulated initial DNA damage. The optimized DNA rejoining speeds were reasonably agreed with the experimental DNA rejoining speeds. Using the optimized TLK model, the Geant4-DNA simulation is now able to predict cell survival and DNA-rejoining kinetics for HSGc-C5 cells.

A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast.

Accurately modeling the radiobiological mechanisms responsible for the induction of DNA damage remains a major scientific challenge, particularly for understanding the effects of low doses of ionizing radiation on living beings, such as the induction of carcinogenesis. A computational approach based on the Monte Carlo technique to simulate track structures in a biological medium is currently the most reliable method for calculating the early effects induced by ionizing radiation on DNA, the primary cellular target of such effects. The Geant4-DNA Monte Carlo toolkit can simulate not only the physical, but also the physico-chemical and chemical stages of water radiolysis. These stages can be combined with simplified geometric models of biological targets, such as DNA, to assess direct and indirect early DNA damage. In this study, DNA damage induced in a human fibroblast cell was evaluated using Geant4-DNA as a function of incident particle type (gammas, protons, and alphas) and energy. The resulting double-strand break yields as a function of linear energy transfer closely reproduced recent experimental data. Other quantities, such as fragment length distribution, scavengeable damage fraction, and time evolution of damage within an analytical repair model also supported the plausibility of predicting DNA damage using Geant4-DNA.The complete simulation chain application "molecularDNA", an example for users of Geant4-DNA, will soon be distributed through Geant4.

Effects of loading a magnetic field longitudinal to the linear particle-beam track on yields of reactive oxygen species in water.

The effects of a magnetic field longitudinal to the ion beam track on the generation of hydroxyl radicals (•OH) and hydrogen peroxide (H2O2) in water were investigated. A longitudinal magnetic field was reported to enhance the biological effects of the ion beam. However, the mechanism of the increased cell death by a longitudinal magnetic field has not been clarified. The local density of •OH generation was estimated by a method based on the EPR spin-trapping. A series of reaction mixtures containing varying concentrations (0.76‒2278 mM) of DMPO was irradiated by 16 Gy of carbon- or iron-ion beams at the Heavy-Ion Medical Accelerator in Chiba (HIMAC, NIRS/QST, Chiba, Japan) with or without a longitudinal magnetic field (0.0, 0.3, or 0.6 T). The DMPO-OH yield in the sample solutions was measured by X-band EPR and plotted versus DMPO density. O2-dependent and O2-independent H2O2 yields were measured. An aliquot of ultra-pure water was irradiated by carbon-ion beams with or without a longitudinal magnetic field. Irradiation experiments were performed under air or hypoxic conditions. H2O2 generation in irradiated water samples was quantified by an EPR spin-trapping, which measures •OH synthesized from H2O2 by UVB irradiation. Relatively sparse •OH generation caused by particle beams in water were not affected by loading a magnetic field on the beam track. O2-dependent H2O2 generation decreased and oxygen-independent H2O2 generation increased after loading a magnetic field parallel to the beam track. Loading a magnetic field to the beam track made •OH generation denser or made dense •OH more reactive.

Computational modeling for the evaluation of suppressed scintillation yields in plastic scintillators using Geant4.

The yield of scintillation photons emitted from scintillators is considered to be proportional to the LET (linear energy transfer) which is energy distribution per unit length, in the low-LET domain, but not proportional in the high LET domain due to the suppression yield from the so-called quenching effect. Ogawa et al. proposed a computational method to estimate scintillation yield using Monte Carlo simulations considering the principle of the FRET (fluorescence resonance energy transfer) process, which is a phenomenon of energy transfer between fluorescent molecules. In their study, the track structure simulations could reproduce measured yields of scintillation. However, Ogawa et al.'s model was not suitable for estimating the scintillation yields when the particle energy was low when using condensed history simulations. Therefore, we propose a new method for estimating scintillation yields more accurately using Geant4 to improve the model calculations based on condensed history simulations. We simulated the local energy deposition pattern in a NE102A plastic scintillator to calculate the number of excitors in the microscopic volume for various nuclides (helium to argon ions). The suppressed scintillation yields were estimated using the model calculations of sequential FRET processes while considering the inactivation of the excitors selected as donors of the FRET process. The model calculations successfully reproduced the experimental scintillation yields within 10% error for the lighter ions up to neon. However, when the analysis was repeated for silicon and argon, the maximum error in the scintillation yields increased up to 27%. The proposed computational model for the evaluation of the suppressed scintillation yields emitted from NE102A scintillator irradiated with heavy ions using sequential FRET calculations with condensed history method returned simulated scintillation yields.

DNA double-strand breaks in cancer cells as a function of proton linear energy transfer and its variation in time.

PURPOSE: The complex relationship between linear energy transfer (LET) and cellular response to radiation is not yet fully elucidated. To better characterize DNA damage after irradiations with therapeutic protons, we monitored formation and disappearance of DNA double-strand breaks (DNA DSB) as a function of LET and time. Comparisons with conventional γ-rays and high LET carbon ions were also performed. MATERIALS AND METHODS: In the present work, we performed immunofluorescence-based assay to determine the amount of DNA DSB induced by different LET values along the 62 MeV therapeutic proton Spread out Bragg peak (SOBP) in three cancer cell lines, i.e. HTB140 melanoma, MCF-7 breast adenocarcinoma and HTB177 non-small lung cancer cells. Time dependence of foci formation was followed as well. To determine irradiation positions, corresponding to the desired LET values, numerical simulations were carried out using Geant4 toolkit. We compared γ-H2AX foci persistence after irradiations with protons to that of γ-rays and carbon ions. RESULTS: With the rise of LET values along the therapeutic proton SOBP, the increase of γ-H2AX foci number is detected in the three cell lines up to the distal end of the SOBP, while there is a decrease on its distal fall-off part. With the prolonged incubation time, the number of foci gradually drops tending to attain the residual level. For the maximum number of DNA DSB, irradiation with protons attain higher level than that of γ-rays. Carbon ions produce more DNA DSB than protons but not substantially. The number of residual foci produced by γ-rays is significantly lower than that of protons and particularly carbon ions. Carbon ions do not produce considerably higher number of foci than protons, as it could be expected due to their physical properties. CONCLUSIONS: In situ visualization of γ-H2AX foci reveal creation of more lesions in the three cell lines by clinically relevant proton SOBP than γ-rays. The lack of significant differences in the number of γ-H2AX foci between the proton and carbon ion-irradiated samples suggests an increased complexity of DNA lesions and slower repair kinetics after carbon ions compared to protons. For all three irradiation types, there is no major difference between the three cell lines shortly after irradiations, while later on, the formation of residual foci starts to express the inherent nature of tested cells, therefore increasing discrepancy between them.

Application of lung substitute material as ripple filter for multi-ion therapy with helium-, carbon-, oxygen-, and neon-ion beams.

A development project for hypo-fractionated multi-ion therapy has been initiated at the National Institute of Radiological Sciences in Japan. In the treatment, helium, carbon, oxygen, and neon ions will be used as primary beams with pencil beam scanning. A ripple filter (RiFi), consisting of a thin plastic or aluminum plate with a fine periodic ridge and groove structure, has been used to broaden the Bragg peak of heavy-ion beams in the beam direction. To sufficiently broaden the Bragg peak of helium-, carbon-, oxygen-, and neon-ion beams with suppressed lateral scattering and surface dose inhomogeneity, in this study, we tested a plate made of a lung substitute material, Gammex LN300, as the RiFi. The planar integrated dose distribution of a 183.5 MeV u-1neon-ion beam was measured behind a 3 cm thick LN300 plate in water. The Bragg peak of the pristine beam was broadened following the normal distribution with the standard deviationσvalue of 1.29 mm, while the range of the beam was reduced by 8.8 mm by the plate. To verify the LN300 performance as the RiFi in multi-ion therapy, we measured the pencil beam data of helium-, carbon-, oxygen- and neon-ion beams penetrating the 3 cm thick LN300 plate. The data were then modeled and used in a treatment planning system to achieve a uniform 10% survival of human undifferentiated carcinoma cells within a cuboid target by the beam for each of the different ion species. The measured survival fractions were reasonably reproduced by the planned ones for all the ion species. No surface dose inhomogeneity was observed for any ion species even when the plate was placed close to the phantom surface. The plate made of lung substitute material, Gammex LN300, is applicable as the RiFi in multi-ion therapy with helium-, carbon-, oxygen- and neon-ion beams.

Review of the Geant4-DNA Simulation Toolkit for Radiobiological Applications at the Cellular and DNA Level.

The Geant4-DNA low energy extension of the Geant4 Monte Carlo (MC) toolkit is a continuously evolving MC simulation code permitting mechanistic studies of cellular radiobiological effects. Geant4-DNA considers the physical, chemical, and biological stages of the action of ionizing radiation (in the form of x- and γ-ray photons, electrons and ß±-rays, hadrons, α-particles, and a set of heavier ions) in living cells towards a variety of applications ranging from predicting radiotherapy outcomes to radiation protection both on earth and in space. In this work, we provide a brief, yet concise, overview of the progress that has been achieved so far concerning the different physical, physicochemical, chemical, and biological models implemented into Geant4-DNA, highlighting the latest developments. Specifically, the "dnadamage1" and "molecularDNA" applications which enable, for the first time within an open-source platform, quantitative predictions of early DNA damage in terms of single-strand-breaks (SSBs), double-strand-breaks (DSBs), and more complex clustered lesions for different DNA structures ranging from the nucleotide level to the entire genome. These developments are critically presented and discussed along with key benchmarking results. The Geant4-DNA toolkit, through its different set of models and functionalities, offers unique capabilities for elucidating the problem of radiation quality or the relative biological effectiveness (RBE) of different ionizing radiations which underlines nearly the whole spectrum of radiotherapeutic modalities, from external high-energy hadron beams to internal low-energy gamma and beta emitters that are used in brachytherapy sources and radiopharmaceuticals, respectively.

Fully integrated Monte Carlo simulation for evaluating radiation induced DNA damage and subsequent repair using Geant4-DNA.

Ionising radiation induced DNA damage and subsequent biological responses to it depend on the radiation's track-structure and its energy loss distribution pattern. To investigate the underlying biological mechanisms involved in such complex system, there is need of predicting biological response by integrated Monte Carlo (MC) simulations across physics, chemistry and biology. Hence, in this work, we have developed an application using the open source Geant4-DNA toolkit to propose a realistic "fully integrated" MC simulation to calculate both early DNA damage and subsequent biological responses with time. We had previously developed an application allowing simulations of radiation induced early DNA damage on a naked cell nucleus model. In the new version presented in this work, we have developed three additional important features: (1) modeling of a realistic cell geometry, (2) inclusion of a biological repair model, (3) refinement of DNA damage parameters for direct damage and indirect damage scoring. The simulation results are validated with experimental data in terms of Single Strand Break (SSB) yields for plasmid and Double Strand Break (DSB) yields for plasmid/human cell. In addition, the yields of indirect DSBs are compatible with the experimental scavengeable damage fraction. The simulation application also demonstrates agreement with experimental data of [Formula: see text]-H2AX yields for gamma ray irradiation. Using this application, it is now possible to predict biological response along time through track-structure MC simulations.

Advances in modelling gold nanoparticle radiosensitization using new Geant4-DNA physics models.

Gold nanoparticles have demonstrated significant radiosensitization of cancer treatment with x-ray radiotherapy. To understand the mechanisms at the basis of nanoparticle radiosensitization, Monte Carlo simulations are used to investigate the dose enhancement, given a certain nanoparticle concentration and distribution in the biological medium. Earlier studies have ordinarily used condensed history physics models to predict nanoscale dose enhancement with nanoparticles. This study uses Geant4-DNA complemented with novel track structure physics models to accurately describe electron interactions in gold and to calculate the dose surrounding gold nanoparticle structures at nanoscale level. The computed dose in silico due to a clinical kilovoltage beam and the presence of gold nanoparticles was related to in vitro brain cancer cell survival using the local effect model. The comparison of the simulation results with radiobiological experimental measurements shows that Geant4-DNA and local effect model can be used to predict cell survival in silico in the case of x-ray kilovoltage beams.

Nuclear-interaction correction for patient dose calculations in treatment planning of helium-, carbon-, oxygen-, and neon-ion beams.

In charged-particle therapy treatment planning, the patient is conventionally modeled as variable-density water, i.e. stopping effective density ρ S, and the planar integrated dose distribution measured in water (PID) is applied for patient dose calculation based on path length scaling with the ρ S. This approximation assures the range accuracy of charged-particle beams. However, it causes dose calculation errors due to water nonequivalence of body tissues in nuclear interactions originating from compositional differences. We had previously proposed and validated a PID correction method for the errors in carbon-ion radiotherapy. In the present study, we verify the PID correction method for helium-, oxygen-, and neon-ion beams. The one-to-one relationships between ρ S and the nuclear effective density ρ N of body tissues were constructed for helium-, carbon-, oxygen-, and neon-ion beams, and were used to correct the PIDs to account for the dose calculation errors in patient. The correction method was tested for non-water materials with un-scanned and scanned ion beams. In un-scanned beams penetrating the materials, the dose calculation errors of up to 5.9% were observed at the Bragg peak region, while they were reduced to ⩽0.9% by the PID correction method. In scanned beams penetrating olive oil, the dose calculation errors of up to 2.7% averaged over the spread-out Bragg peak were observed, while they were reduced to ⩽0.4% by the correction method. To investigate the influence of water nonequivalence of body tissues on tumor dose, we carried out a treatment planning study for prostate and uterine cases. The tumor over-doses of 0.9%, 1.8%, 2.0%, and 2.2% were observed in the uterine case for the helium-, carbon-, oxygen-, and neon-ion beams, respectively. These dose errors could be diminished by the PID correction method. The present results verify that the PID correction method is simple, practical, and accurate for treatment planning of these four ion species.

Electron track structure simulations in a gold nanoparticle using Geant4-DNA.

Gold Nanoparticles (GNPs) have recently gained a lot of attention due to their potential benefit to improve the efficacy of X-ray radiotherapy. Owing to their high atomic number, GNPs are able to absorb higher quantities of incident radiation with respect to the surrounding tissue, producing, in particular, photoelectrons and low energy Auger electrons. These additional low energy electrons increase the local energy deposition in the region surrounding the GNP. Monte Carlo simulations play a key role in the investigation of GNP radio-enhancement and it is widely recognised that track structure physics models are the state-of-the-art for nano-scale studies. In 2016, we have developed track structure physics models for the Geant4-DNA toolkit allowing electron transport for microscopic bulk gold (Geant4_DNA_AU_2016) and we have recently improved them in the low energy domain (Geant4_DNA_AU_2018). In this paper, we report the benchmarking of these newly developed physics models when calculating the physical dose and the Dose Enhancement Factor (DEF) around a GNP. We demonstrate that Geant4_DNA_AU_2018 models give similar azimuthal distribution of two dimensional absorbed dose around a single GNP, but result in larger absorbed dose and DEF than Geant4_DNA_AU_2016 models. In parallel, we investigated the performance of a newly developed multiple scattering model in Geant4 based on the Goudsmit-Saunderson (GS) model, when used together with the electromagnetic physics models with the Geant4 Livermore condensed-history approach. Our results show that the GS model does not affect the results of the simulations when studying GNP radio-enhancement with a condensed-history approach.