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To evaluate the clinical relative biological effectiveness (RBE) of carbon-ion radiotherapy (C-ion RT) for prostate cancer.The records of 262 patients with low-risk prostate cancer (median age, 65 [47-80] years) treated with C-ion RT at QST Hospital, National Institutes for Quantum Science and Technology in Japan during 2000-2018 were reviewed retrospectively. Four different protocol outcomes and prostate-specific antigen (PSA) responses were evaluated. The median follow-up was 8.4 years. The Kaplan-Meier method was used to estimate the biochemical or clinical failure-free rate (BCFFR). Clinical RBE was calculated using the tumor control probability model.The 5-, 7-, and 10-year BCFFRs were 91.7%, 83.8%, and 73.2%, respectively. The 10-year BCFFRs of patients who received C-ion RT at 66 Gy (RBE) in 20 fractions, 63 Gy (RBE) in 20 fractions, and 57.6 Gy (RBE) in 16 fractions were 81.4%, 70.9%, and 68.9%, respectively. The PSA level and density during follow-up were better in the patients treated with the lower fraction size. A higher PSA nadir and shorter time to PSA nadir were risk factors for biochemical or clinical failure by multivariate Cox regression. The tumor control probability analysis showed that the estimated clinical RBE values to achieve an 80% BCFFR at 10 years for 20, 16, and 12 fractions were 2.19 (2.18-2.24), 2.16 (2.14-2.23), and 2.12 (2.09-2.21), respectively.Using clinical data from low-risk prostate cancer patients, we showed the clinical RBE of C-ion RT decreased with increasing dose per fraction.

Carbon-ions are charged particles with a high linear energy transfer, and therefore, they make a better dose distribution with greater biological effects on the tumors compared with photons and protons. Since prostate cancer, renal cell carcinoma, and retroperitoneal sarcomas such as liposarcoma and leiomyosarcoma are known to be radioresistant tumors, carbon-ion radiotherapy, which provides the advantageous radiobiological properties such as an increasing relative biological effectiveness toward the Bragg peak, a reduced oxygen enhancement ratio, and a reduced dependence on fractionation and cell-cycle stage, has been tested for these urological tumors at the National Institute for Radiological Sciences since 1994. To promote carbon-ion radiotherapy as a standard cancer therapy, the Japan Carbon-ion Radiation Oncology Study Group was established in 2015 to create a registry of all treated patients and conduct multi-institutional prospective studies in cooperation with all the Japanese institutes. Based on accumulating evidence of the efficacy and feasibility of carbon-ion therapy for prostate cancer and retroperitoneal sarcoma, it is now covered by the Japanese health insurance system. On the other hand, carbon-ion radiotherapy for renal cell cancer is not still covered by the insurance system, although the two previous studies showed the efficacy. In this review, we introduce the characteristics, clinical outcomes, and perspectives of carbon-ion radiotherapy and our efforts to disseminate the use of this new technology worldwide.

Radiation monitoring in space radiation is complex due to galactic cosmic rays (GCRs), solar particle events (SPEs), and albedo particles. Thermal neutrons are an important component in the Moon radiation albedo field which can cause single event upset (SEU) in electronics when they interact with the 10B present in electronic components. In this work, we studied an application of silicon on insulator (SOI) microdosimeters for neutron monitoring in various mixed radiation field environments. A 10-µm SOI microdosimeter was utilized in conjunction with a 10B4C thin-film converter to successfully measure the thermal neutron contribution out of field of a therapeutic proton beam as well as an 18-MV X-ray linear accelerator (LINAC). The microdosimeter was placed downstream of the Bragg peak (BP) as well as laterally out of field of the proton beam and at two positions along the treatment couch of the 18-MV LINAC. It was demonstrated that the 10-µm SOI microdosimeter with 10B4C converter is suitable for detection of thermal neutrons with excellent discrimination of gamma, fast and thermal neutron components in the presence of a gamma-neutron pulsed field of an 18-MV LINAC. To reduce the gamma contribution and further improve detection of neutrons in mixed radiation fields, a new 2 µm Mushroom-planar microdosimeter was fabricated and characterized in detail using an ion beam induced charge collection (IBIC) technique with 1.78 MeV He2+ ions. It was demonstrated that this 2 µm SOI microdosimeter can be operated in a passive mode. The SOI microdosimeter with the 10B4C converter can be recommended for the detection of thermal neutrons for SEU prediction in the mixed gamma-neutron fields during space missions, especially for the Moon mission.

In this study, the stopping-power ratios (SPRs) of mouthpiece materials were measured and the errors in the predicted SPRs based on conversion table values were further investigated. The SPRs of the five mouthpiece materials were predicted from their computed tomography (CT) numbers using a calibrated conversion table. Independently, the SPRs of the materials were measured from the Bragg peak shift of a carbon-ion beam passing through the materials. The errors in the SPRs of the materials were determined as the difference between the predicted and measured values. The measured SPRs (errors) of the Nipoflex 710™ and Bioplast™ ethylene-vinyl acetate copolymers (EVAs) were 0.997 (0.023) and 0.982 (0.007), respectively. The SPRs of the vinyl silicon impression material, light-curable resin, and bis-acrylic resin were 1.517 (0.134), 1.161 (0.068), and 1.26 (0.101), respectively. Among the five tested materials, the EVAs had the lowest SPR errors, indicating the highest human-tissue equivalency.

We developed a human-scale single-ring OpenPET (SROP) system, which had an open space allowing us access to the subject during measurement. The SROP system consisted of 160 4-layer depth-of-interaction detectors. The open space with the axial width of 430 mm was achieved with the ring axial width of 214 mm and the ring inner diameter of 660 mm. The detectors were axially shifted to each other so that the detector ring was aligned along a plane horizontally tilted by 45° against the axial direction. The system was developed as a mobile scanner to be used not only in clinical positron emission tomography (PET) rooms but also in charged-particle therapy treatment rooms as well as animal experiment rooms. Almost uniform spatial resolution better than 3 mm throughout the entire field of view (FOV) was realized with an iterative image reconstruction method. Peak absolute sensitivity was 3.1%, and there was a region with sensitivity better than 0.8% for a length of more than 700 mm. An in-beam imaging experiment conducted at the heavy ion medical accelerator in Chiba showed that the system was operable even at the highest beam intensity available for heavy-ion therapy. In addition, we conducted entire-body monkey dynamic imaging utilizing the long region inside the gantry by positioning a monkey along the direction having the longest FOV tilted by 45° against the axial direction. We concluded the developed system has a capability to realize versatile PET applications by utilizing its wide-open space and mobility in addition to high spatial resolution with sufficiently good sensitivity. -9mm]Please consider rephrasing the sentence “We concluded the developed system” for clarity.

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.

PURPOSE The stochastic microdosimetric kinetic (SMK) model is one of the most sophisticated and precise models used in the estimation of the relative biological effectiveness of carbon-ion radiotherapy (CRT) and boron neutron capture therapy (BNCT). However, because of its complicated and time-consuming calculation procedures, it is nearly impractical to directly incorporate this model into a radiation treatment-planning system. MATERIALS AND METHODS Through the introduction of Taylor expansion (TE) or fast Fourier transform (FFT), we developed two simplified SMK models and implemented them into the Particle and Heavy Ion Transport code System (PHITS). To verify the implementation, we calculated the photon isoeffective doses in a cylindrical phantom placed in the radiation fields of passive CRT and accelerator-based BNCT. RESULTS AND DISCUSSION Our calculation suggested that both TE-based and FFT-based SMK models can reproduce the data obtained from the original SMK model very well for absorbed doses approximately below 5 Gy, whereas the TE-based SMK model overestimates the original data at higher doses. In terms of computational efficiency, the TE-based SMK model is much faster than the FFT-based SMK model. CONCLUSION This study enables the instantaneous calculation of the photo isoeffective dose for CRT and BNCT, considering their cellular-scale dose heterogeneities. Treatment-planning systems that use the improved PHITS as a dose-calculation engine are under development.

It has been observed that healthy tissues are spared at ultra-high dose rate (UHDR:40 Gy/s), so called FLASH effect. To elucidate the mechanism of FLASH effect, we evaluate changes in radiation chemical yield (G value) of 7-hydroxy-coumarin-3-carboxylic acid (7OH-C3CA), which is formed by the reaction of hydroxyl radicals with coumarin-3-carboxylic acid (C3CA), under carbon ions (140 MeV/u) and protons (27.5 and 55 MeV) in a wide-dose-rate range up to 100 Gy/s. The relative G value, which is the G value at each dose rate normalized by that at the conventional dose (CONV: 0.1 Gy/s), 140 MeV/u carbon-ion beam is almost equivalent to 27.5 and 55 MeV proton beams. This finding implies that UHDR irradiations using carbon-ion beams have a potential to spare healthy tissues. Furthermore, we evaluate the G value of 7OH-C3CA under the de-oxygenated condition to investigate roles of oxygen to the generation of 7OH-C3CA effect. The G value of 7OH-C3CA under the de-oxygenated condition is lower than that under the oxygenated condition. The G value of 7OH-C3CA under the de-oxygenated condition is higher than those under UHDR irradiations. By direct measurements of the oxygen concentration during 55 MeV proton irradiations, the oxygen concentration drops by 0.1%/Gy, which is independent of the dose rate. When the oxygen concentration directly affects to yields of 7OH-C3CA, the rate of decrease in the oxygen concentration may be correlated with that of decrease in the G value of 7OH-C3CA. However, the reduction rate of G value under UHDR is significantly higher than the oxygen consumption. This finding implied that the influence of the reaction between water radiolysis species formed by neighborhood tracks could be strongly related to the mechanisms of UHDR effect.

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 fiel...

Despite the low contribution of heavy ions to the total fluence in the space radiation environment, their radiobiological effect on the human body is extremely high. In this article, we investigated the radiation field which resulted from the interaction of galactic cosmic rays (GCRs), specifically some heavy ions and energies, typically encountered in space with a realistic multilayer sample of the International Space Station (ISS) Columbus module’s shielding wall. The quality factor, Q, and the normalized dose equivalent, H, derived from microdosimetric measurements for C, Ne, and Si ions behind different spacecraft wall configurations and materials are presented in this article. Particularly, carbon fiber, polyoxymethylene, and perspex with same areal density compared to currently used aluminum were investigated.

Background and purpose Several studies have focused on increasing the linear energy transfer (LET) within tumours to achieve higher biological effects in carbon-ion radiotherapy (C-ion RT). However, it remains unclear whether LET affects late complications. We assessed whether physical dose and LET distribution can be specific factors for late rectal complications in C-ion RT. Materials and methods Overall, 134 patients with uterine carcinomas were registered and retrospectively analysed. Of 134 patients, 132 who were followed up for >6 months were enrolled. The correlations between the relative biological effectiveness (RBE)-weighted dose based on the Kanai model (the ostensible “clinical dose”), dose-averaged LET (LETd), or physical dose and rectal complications were evaluated. Rectal complications were graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results Nine patients developed grade 3 or 4 late rectal complications. Linear regression analysis found that D2cc in clinical dose was the sole risk factor for ≥grade 3 late rectal complications (p = 0.012). The receiver operating characteristic analysis found that D2cc of 60.2 Gy (RBE) was a suitable cut-off value for predicting ≥grade 3 late rectal complications. Among 35 patients whose rectal D2cc was ≥60.2 Gy (RBE), no correlations were found between severe rectal toxicities and LETd alone or physical dose per se. Conclusion We demonstrated that severe rectal toxicities were related to the rectal D2cc of the clinical dose in C-ion RT. However, no correlations were found between severe rectal toxicities and LETd alone or physical dose per se.

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.

The Centre for Medical Radiation Physics introduced the concept of Silicon On Insulator (SOI) microdosimeters with 3-Dimensional (3D) cylindrical sensitive volumes (SVs) mimicking the dimensions of cells in an array. Several designs of high-definition 3D SVs fabricated using 3D MEMS technology were implemented. 3D SVs were fabricated in different sizes and configurations with diameters between 18 and 30 µm, thicknesses of 2–50 µm and at a pitch of 50 µm in matrices with volumes of 20 × 20 and 50 × 50. SVs were segmented into sub-arrays to reduce capacitance and avoid pile up in high-dose rate pencil beam scanning applications. Detailed TCAD simulations and charge collection studies in individual SVs have been performed. The microdosimetry probe (MicroPlus) is composed of the silicon microdosimeter and low-noise front–end readout electronics housed in a PMMA waterproof sheath that allows measurements of lineal energies as low as 0.4 keV/µm in water or PMMA. Microdosimetric quantities measured with SOI microdosimeters and the MicroPlus probe were used to evaluate the relative biological effectiveness (RBE) of heavy ions and protons delivered by pencil-beam scanning and passive scattering systems in different particle therapy centres. The 3D detectors and MicroPlus probe developed for microdosimetry have the potential to provide confidence in the delivery of RBE optimized particle therapy when introduced into routine clinical practice

Background/Aim: The local control rate of chondrosarcomas treated with carbon-ion radiotherapy (CIRT) worsens as tumour size increases, possibly because of the intra-tumoural linear energy transfer (LET) distribution. This study aimed to evaluate the relationship between local recurrence and intra-tumoural LET distribution in chondrosarcomas treated with CIRT. Patients and Methods: Thirty patients treated with CIRT for grade 2 chondrosarcoma were included. Dose-averaged LET (LETd) distribution was calculated by the treatment planning system, and the relationship between LETd distribution in the planning tumour volume (PTV) and local control was evaluated. Results: The mean LETd value in PTV was similar between cases with and without recurrence. Recurrence was not observed in cases where the effective minimum LETd value exceeded 40 keV/μm. Conclusion: LETd distribution in PTV is associated with local control in chondrosarcomas and patients treated with ion beams of higher LETd may have an improved local control rate for unresectable chondrosarcomas.

Background and purpose: Several studies have focused on increasing the linear energy transfer (LET) within tumours to achieve higher biological effects in carbon-ion radiotherapy (C-ion RT). However, it remains unclear whether LET affects late complications. We assessed whether physical dose and LET distribution can be specific factors for late rectal complications in C-ion RT. Materials and methods: Overall, 134 patients with uterine carcinomas were registered and retrospectively analysed. Of 134 patients, 132 who were followed up for >6 months were enrolled. The correlations between the relative biological effectiveness (RBE)-weighted dose based on the Kanai model (the ostensible "clinical dose"), dose-averaged LET (LETd), or physical dose and rectal complications were evaluated. Rectal complications were graded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: Nine patients developed grade 3 or 4 late rectal complications. Linear regression analysis found that D2cc in clinical dose was the sole risk factor for ≥grade 3 late rectal complications (p = 0.012). The receiver operating characteristic analysis found that D2cc of 60.2 Gy (RBE) was a suitable cut-off value for predicting ≥grade 3 late rectal complications. Among 35 patients whose rectal D2cc was ≥60.2 Gy (RBE), no correlations were found between severe rectal toxicities and LETd alone or physical dose per se. Conclusion: We demonstrated that severe rectal toxicities were related to the rectal D2cc of the clinical dose in C-ion RT. However, no correlations were found between severe rectal toxicities and LETd alone or physical dose per se.

Carbon-ion radiotherapy using the Heavy-Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences (NIRS) has been conducted on more than 12,000 patients since 1994. We started the heavy-ion radiotherapy with a 3D scanning irradiation system in 2011 and using a superconducting rotating gantry in 2017, at a new treatment research facility in NIRS. We have continued some R&Ds on HIMAC to enhance the treatment quality and to improve the treatment results. From 2016, we have started developments of a compact superconducting rotating gantry and synchrotron to be applied for a newly started project of a “quantum scalpel” that is a next generation of the heavy-ion radiotherapy machine. This paper outlines those R&Ds as well as the present status of HIMAC facility.

Purpose The purpose is to verify experimentally whether application of magnetic fields longitudinal and perpendicular to a proton beam alters the biological effectiveness of the radiation. Methods and Materials Proton beams with linear energy transfer of 1.1 and 3.3 keV/μm irradiated human cancer and normal cells under a longitudinal (perpendicular) magnetic field of BL (BP) = 0, 0.3, or 0.6 T. Cell survival curves were constructed to evaluate the effects of the magnetic fields on the biological effectiveness. The ratio of dose that would result in a survival fraction of 10% without the magnetic field Dwo to the dose with the magnetic field Dw, R10 = Dwo/Dw, was determined for each cell line and magnetic field. Results For cancer cells exposed to the 1.1- (3.3-) keV/μm proton beams, R10s were increased to 1.10 ± 0.07 (1.11 ± 0.07) and 1.11 ± 0.07 (1.12 ± 0.07) by the longitudinal magnetic fields of BL = 0.3 and 0.6 T, respectively. For normal cells, R10s were increased to 1.13 ± 0.06 (1.17 ± 0.06) and 1.17 ± 0.06 (1.30 ± 0.06) by the BLs. In contrast, R10s were not changed significantly from 1 by the perpendicular magnetic fields of BP = 0.3 and 0.6 T for both cancer and normal cells exposed to 1.1- and 3.3-keV/μm proton beams. Conclusions The biological effectiveness of proton beams was significantly enhanced by longitudinal magnetic fields of BL = 0.3 and 0.6 T, whereas the biological effectiveness was not altered by perpendicular magnetic fields of the same strengths. This enhancement effect should be taken into account in magnetic resonance imaging guided proton therapy with a longitudinal magnetic field.

Background and Purpose The purpose is to verify experimentally whether application of magnetic fields longitudinal and perpendicular to a proton beam alters the biological effectiveness of the radiation. Methods and Materials Proton beams with linear energy transfer (LET) of 1.1 and 3.3 keV/μm were irradiated onto human cancer and normal cells under the longitudinal (perpendicular) magnetic field of BL (BP) = 0, 0.3, or 0.6 T. Cell survival curves were constructed to evaluate the effects of the magnetic fields on the biological effectiveness. The ratio of dose that would result in a survival fraction of 10% without the magnetic field Dwo to the dose with the magnetic field Dw, R10 = Dwo / Dw, was determined for each cell line and magnetic field. Results For cancer cells exposed to the 1.1- (3.3-) keV/μm proton beams, R10s were increased to 1.10±0.07 (1.11±0.07) and 1.11±0.07 (1.12±0.07) by the longitudinal magnetic fields of BL = 0.3 and 0.6 T, respectively. For normal cells, R10s were increased to 1.13±0.06 (1.17±0.06) and 1.17±0.06 (1.30±0.06) by the BLs. In contrast, R10s were not changed significantly from 1 by the perpendicular magnetic fields of BP = 0.3 and 0.6 T for both cancer and normal cells exposed to 1.1- and 3.3-keV/μm proton beams. Conclusions The biological effectiveness of proton beams was significantly enhanced by the longitudinal magnetic fields of BL = 0.3 and 0.6 T, while the biological effectiveness was not altered by the perpendicular magnetic fields of the same strengths. This enhancement effect should be taken into account in MRI guided proton therapy with a longitudinal magnetic field.

Heavy ion radiotherapy with the Heavy-Ion Medical Accelerator in Chiba (HIMAC) has been carried out more than 13000 patients since 1994. In 2010, a new particle therapy research facility connected to HIMAC was built, and we started heavy-ion radiotherapy using a 3D scanning irradiation system in 2011 and using a superconducting rotating gantry in 2017 at the new facility. In 2016, we began a project of "quantum scalpel", a next-generation heavy-ion radiotherapy machine that applies a compact superconducting synchrotron and rotating gantry currently under development. This paper outlines R&Ds for a new project and current facility as well as the present status of HIMAC.

Previous studies have revealed application of a magnetic field longitudinal to a carbon-ion beam enhances its biological effectiveness. This communication investigated how timing of the magnetic field application with respect to beam irradiation influenced this effect. Human cancer cells were exposed to carbon-ion beams with linear energy transfer (LET) of 12 and 50 keV/μm. The longitudinal magnetic field of 0.3 T was applied to the cells just before, during, or right after the beam irradiation. The effects of the timing on the biological effectiveness were evaluated by cell survival. The biological effectiveness increased only if the magnetic field was applied during beam irradiation for both LET beams.

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.

The multi-ion radiotherapy with dose distribution and Liner Energy Transfer optimization is being studied at QST. Helium, carbon, oxygen and neon ions are considered as ion species for multi-ion therapy. A basic experiment using these ion beams has been carried out at the HIMAC. For heavy-ion radiotherapy facility, it is desirable to operate with only one ECR ion source. We considered the operating method with only one ion source for multi-ion radiotherapy. Ionization gases were helium, methane, oxygen, and neon to produce He2+, C4+, O6+ and Ne7+ ions. Requirement values of beam current were 940 µA correspond to He2+, 290 µA to C4+, 330 µA to O6+, and 245 µA to Ne7+, respectively. This value was obtained from the number of particles required for the cancer treatment and the transmission efficiency of the accelerator in the HIMAC. We performed some beam tests for design of a new compact ion source with the existing 18 GHz ECR ion source (NIRS-HEC). From the results of the beam tests, we estimate the mirror magnetic field of NIRS-HEC by using POISSON/SUPERFISH code. Then, the structure of the permanent magnets for new ECR ion source is determined so that they reproduce the values of the upstream mirror peak (Binj), B minimum (Bmin) and the downstream mirror peak (Bext) at the NIRS-HEC. The magnetic field of Binj, Bmin and Bext at NIRS-HEC were 1.14 T, 0.475 T and 0.9 T, respectively. We will describe about the beam tests with the NIRS-HEC and design of the new compact ECR ion source.

For hypo-fractionated multi-ion therapy (HFMIT), the stochastic microdosimetric kinetic (SMK) model had been developed to estimate the biological effectiveness of radiation beams with wide linear energy transfer (LET) and dose ranges. The HFMIT will be applied to radioresistant tumors with oxygen-deficient regions. The response of cells to radiation is strongly dependent on the oxygen condition in addition to radiation type, LET and absorbed dose. This study presents an adaptation of the SMK model to account for oxygen-pressure dependent cell responses, and develops the oxygen-effect-incorporated stochastic microdosimetric kinetic (OSMK) model. In the model, following assumptions were made: the numbers of radiation-induced sublethal lesions (double-strand breaks) are reduced due to lack of oxygen, and the numbers of oxygen-mediated lesions are reduced for radiation with high LET. The model parameters were determined by fitting survival data under aerobic and anoxic conditions for human salivary gland tumor cells and V79 cells exposed to helium-, carbon-, and neon-ion beams over the LET range of 18.5-654.0 keVμm-1. The OSMK model provided good agreement with the experimental survival data of the cells with determination coefficients >0.9. In terms of oxygen enhancement ratio, the OSMK model reproduced the experimental data behavior, including slight dependence on particle type at the same LET. The OSMK model was then implemented into the in-house treatment planning software for the HFMIT to validate its applicability in clinical practice. A treatment plan with helium- and neon-ion beams was made for a pancreatic cancer case assuming an oxygen-deficient region within the tumor. The biological optimization based on the OSMK model preferentially placed the neon-ion beam to the hypoxic region, while it placed both helium- and neon-ion beams to the surrounding normoxic region. The OSMK model offered the accuracy and usability required for hypoxia-based biological optimization in HFMIT treatment planning.

The National Institute of Radiological Sciences in Japan started clinical studies of carbon-ion radiotherapy (CIRT) in 1994. Due to the high linear energy transfer (LET) of highly charged particles, carbon-ion beams show high relative biological effectiveness in cell killing, especially at the Bragg peak of dose near the beam range, which is controlled to conform to a tumor. Recent technological developments for CIRT include fast pencil-beam scanning, fluoroscopic respiratory motion management, advanced beam modeling for treatment planning, and a superconducting rotating gantry, which have contributed to accuracy, precision, and conformation of dose, operational efficiency, and patient comfort. With technological maturity, CIRT facilities are rapidly increasing in Asia and Europe. Ongoing developments include extension to multiple ion species and facility downsizing to raise the quality and availability of ion-beam therapy in medical care.

Purpose: Our previous study revealed that the application of a magnetic field longitudinal to a carbon-ion beam of 0.1 ≤ B//≤ 0.6 T enhances the biological effectiveness of the radiation. T...

For safe and effective proton therapy, the proton range in a patient’s body is characterized by the water equivalent length (WEL), and must be accurately determined. Current treatment planning is based on X-ray computed tomography images, which might cause uncertainty because of the different energy loss processes between protons and X-rays. We develop a simple, novel, and real-time proton CT system. The system uses a CCD camera and scintillator , which is thin enough for protons to penetrate. Since protons lose energy when they pass through a phantom, different emissions corresponding to the proton energy loss are acquired in the scintillator. Images of the scintillator were gathered by the CCD camera with 70 MeV and 200 MeV proton beams . Since blurring due to proton reactions such as multiple Coulomb scattering and nuclear reactions significantly degrades the obtained images in both beams, we developed two kinds of effective correction methods. One method is applied to broad beam systems, while the other is applied to narrow beam systems. We successfully obtain clear images with minor proton reaction effects by applying these correction methods. Moreover, we confirm that the WEL values estimated from the acquired CT images agree well with the theoretical values for materials such as polymethyl methacrylate (PMMA) and isopropyl alcohol, within 1- σ uncertainty. Through simulations, we found that nuclear reactions significantly contribute to the uncertainty of WEL values.

Purpose: A magnetic field longitudinal to an ion beam will potentially affect the biological effectiveness of the radiation. The purpose of this study is to experimentally verify the significance o...

Physics in medicine and biology 67(15), 15TR02 (2022). doi:10.1088/1361-6560/ac65d3, Published by IOP Publ., Bristol

Objective. In charged-particle therapy, a ripple filter (RiFi) is used for broadening the Bragg peak in the beam direction. A conventional RiFi consists of plates with a fine ridge and groove structure. The construction of the RiFi has been a time-consuming and costly task. In this study, we developed a simple RiFi made of multi-layered metal mesh (mRiFi), with which the Bragg peak is broadened due to structural randomness, similar to what occurs for the already proposed RiFi with porous material. Approach. The mRiFi was constructed by stacking commercially available metal meshes at random positions and angles. The mRiFi was inexpensive to fabricate due to its high availability and low machining accuracy. The Bragg peak width modulated by the mRiFi can be uniquely determined by the wire material, wire diameter, wire-to-wire spacing of the metal mesh, and the number of mesh sheets. We fabricated four mRiFis consisting of 10, 20, 30, and 40 layers of stainless steel meshes with a wire diameter of 0.1 mm and a wire-to-wire spacing of 0.508 mm. Main results. Using the mRiFis consisting of 10, 20, 30, and 40 mesh sheets, we succeeded in broadening the Bragg peak following the normal distribution with the respective standard deviation σ values of 0.83, 1.15, 1.41, and 1.56 mm in water in experimental planar-integrated depth dose measurements with 140.3 MeV u−1 carbon-ion beams. The effect of range broadening with the mRiFi was independent of its lateral position, and the measurement of the surface dose using radiochromic films showed no severe inhomogeneity with a homogeneity index greater than 0.3 caused by the mRiFis. Significance. The developed mRiFi can be used as a RiFi in charged-particle therapy. The mRiFi has three advantages: high supply stability of the material for manufacturing it, easy fabrication, and low cost.

In proton therapy, the delivered dose should be monitored to a high degree of accuracy to avoid unnecessary exposure to healthy tissues and critical organs. Although positron emission tomography (PET) is most frequently used to verify the proton range, the nuclear reactions between protons and nuclei that generate positrons do not necessarily correspond to the actual proton range. Moreover, such imaging must be conducted after the treatment irradiation, because a PET gantry cannot be used in conjunction with a proton therapy beam. In this paper, we studied one-dimensional (1D) and two-dimensional (2D) distributions of prompt gamma rays of various energies, to determine the most suitable energy window for online monitoring in proton therapy. After an initial simulation study using the particle and heavy ion transport code system (PHITS), we irradiated a poly(methyl methacrylate) (PMMA) phantom with a 70-MeV proton beam to mimic proton range verification in a clinical situation. Using a newly developed Compton camera, we have experimentally confirmed for the first time that 4.4-MeV gamma rays emitted from 12 C and 16 O match the exact position of the Bragg peak in proton range verification.

1. Introduction Ionising radiation induced DNA damage and subsequent biological responses 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. Typically, modeling of survival fraction and/or kinetics of repair proteins attracts interests of researchers in the fields of radiobiology including medical physics. 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. 2. Materials and Methods We had previously developed an application allowing simulations of radiation induced early DNA damage on a naked cell nucleus model and its sub-components model (shown in top panels of Fig.1) [1]. In the new version presented in this work [2], we have developed three additional important features: (1) modeling of a realistic cell geometry including cytoplasm and the materials surrounding irradiated cells (shown in bottom panels of Fig.1), (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 Double Strand Break (DSB) yields for human fibroblast cell as well as yield of accumulated γ-H2AX. In addition, the yields of indirect DSBs are compatible with the experimental scavengeable damage fraction. 3. Results and Discussion The simulated quantities are showing good agreements with the reference experimental quantities. For instance, as shown in Fig.2, the simulation application also demonstrates agreement with experimental data of γ-H2AX yields for gamma ray irradiation. 4. Conclusion As a new important step for radiobiological simulation using Geant4-DNA, the first fully integrated simulation chain has been developed across the physical, chemical and biological stages of cellular radiation action in a single application. The application is validated with the reference experimental results., 第121回 日本医学物理学会学術大会

The effect of a magnetic field loaded parallel to the ion-beam track on the generations of reactive oxygen species (ROS) in water was investigated. It was reported that loading magnetic field parallel to the particle beam track exaggerate the biological effects, i.e. cell lethality, of the particle beam. However, the mechanism of the enhanced cell death delivered by a logigudinal magnetic field to the beam track has not been clarified yet. Local density of •OH generation was estimated by a method based on EPR spin-trapping technique. A series of reaction mixtures containing varying concentrations (0.76‒2278 mM) of DMPO was prepared, and transferred to a polyethylene bag for irradiation. Then, the samples were irradiated 16 Gy of carbon- or iron-beam at the Heavy-Ion Medical Accelerator in Chiba (HIMAC, NIRS/QST, Chiba, Japan) with or without longitudinal magnetic field (0.0, 0.3, or 0.6 T). O2-dependent and O2-independent H2O2 yield was measured. An aliquot of ultra-pure water was irradiated by carbon-ion beam with or without longitudinal magnetic field. Irradiation experiments were performed under air or hypoxic (, 20th Biennial Meeting of SFRR International (SFRR-I 2021)

2020年度量子医科学研究所 重粒子線がん治療装置等共同利用研究報告書