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Purpose To estimate relative biological effectiveness (RBE) ascribed to secondary fragments in a lateral distribution of carbon ion irradiation. The RBE was estimated with the microdosimetric kinetic (MK) model and measured linear energy transfer (LET) obtained with CR‐39 plastic detectors. Methods A water phantom was irradiated by a 12C pencil beam with energy of 380 MeV/u at the Gunma University Heavy Ion Medical Center (GHMC), and CR‐39 detectors were exposed to secondary fragments. Because CR‐39 was insensitive to low LET, we conducted Monte Carlo simulations with Geant4 to calculate low LET particles. The spectra of low LET particles were combined with experimental spectra to calculate RBE. To estimate accuracy of RBE, we calculated RBE by changing yield of low LET particles by ±10% and ±40%. Results At a small angle, maximum RBE by secondary fragments was 1.3 for 10% survival fractions. RBE values of fragments gradually decreased as the angle became larger. The shape of the LET spectra in the simulation reproduced the experimental spectra, but there was a discrepancy between the simulation and experiment for the relative yield of fragments. When the yield of low LET particles was changed by ±40%, the change of RBE was smaller than 10%. Conclusions RBE of 1.3 was expected for secondary fragments emitted at a small angle. Though, we observed a discrepancy in the relative yield of secondary fragments between simulation and experiment, precision of RBE was not so sensitive to the yield of low LET particles.

We report our experience with extended usage of range compensators in heavy-ion radiotherapy with broad beams to lighten the management task of the beam data library, which is a collection of the standard beams to be referenced in treatment planning. Partly due to interference between lateral spreading and range shifting, as many as hundreds of beam entries may be necessary to cover all the possible clinical situations. We have introduced downstream secondary range shifting with a range compensator to reduce the interference and consequently to simplify the library. In our case, 30?% reduction in beam entries is achieved without significantly degrading the beam quality nor increasing the material consumption by more than 3%, which is experimentally verified with carbon-ion beams or statistically estimated from the clinical records.

Gunma University Heavy Ion Medical Center (GHMC) is a compact heavy ion treatment facility* and have experienced 5 years of successful treatment operation. GHMC has 3 treatment room using broad beam (wobbling) irradiation system and 1 experimental irradiation room for the research and development of a spot-scanning irradiation. During the study toward the treatment, several improvements were done in both accelerator and irradiation system. For accelerators, slow extraction from a synchrotron using a transverse rf field is tested**. Compared with conventional extraction system of rf acceleration, ripples of the beam spill (peak to bottom ratio) is reduced from almost 100% to 60%; the deviation of the beam center position and the deviation of the beam size (1σ) are reduced to the order of 0.1 mm. For irradiation system, regularly operation for biological experiments has started form June 2014. In order to shorten the experiment time, 2-dimensional optimization of the irradiation planning was carried out. After the optimization, the irradiation time was reduced by 30% with keeping the dose uniformity within ±2.5%., Proceedings of the 7th Int. Particle Accelerator Conf., IPAC2016, Busan, Korea

Facilities for heavy ion therapies are steadily increasing in number worldwide. One of the advantages of heavy ions is their high relative biological effect (RBE). In a model used at NIRS (National Institute of Radiological Sciences), linear energy transfer (LET) spectra are required to estimate biological dose (physical dose × RBE). The CR-39 plastic charged-particle detector (CR-39) is suitable for measurement of LET. For the present study, done at the Gunma University Heavy Ion Medical Center (GHMC), we measured LET spectra at 11 depths in spread-out Bragg peak (SOBP) irradiation by a 12C beam of 380 MeV/u. The lower threshold of the CR-39 to measure LET was about 5 keV μm−1 due to poor sensitivity for low LET. Then we calculated biological dose and survival fraction distributions and compared them with treatment planning results at GHMC. We used Monte Carlo simulation (Geant4) to calculate LET spectra. The simulation results were in good agreement with the experimental spectra. Moreover, the biological dose and survival fraction distributions estimated from the CR-39 reproduced the treatment planning. The CR-39 is suitable for estimating biological dose in carbon ion therapy.

Information on electron density is important for radiotherapy treatment planning in order to optimize the dose distribution in the target volume of a patient. At present, the electron density is derived from a computed tomography (CT) number measured in x-ray CT scanning; however, there are uncertainties due to the beam hardening effect and the method by which the electron density is converted from the CT number. In order to measure the electron density with an accuracy of +-1%, the authors have developed dual-energy x ray CT using monochromatic x rays. They experimentally proved that the measured linear attenuation coefficients were only a few percent lower than the theoretical ones, which led to an accuracy within 2% for the electron density. There were three factors causing inaccuracy in the linear attenuation coefficient and the electron density: the influence of scattered radiation, the nonlinearity in the detector response function, and a theoretical process to derive the electron density from the linear attenuation coefficients. The linear attenuation coefficients of water were experimentally proved to differ by 1 - 2 % from the theoretical one even when the scattering effect was negligible. The nonlinearity of the response function played an important role in correcting the difference in the linear attenuation coefficient. Furthermore, the theoretical process used for deriving the electron density from the linear attenuation coefficients introduces about 0.6% deviation from the theoretical value into the resultant electron density. This deviation occurs systematically so that it can be corrected. The authors measured the electron densities for seven samples equivalent to soft tissue in dual-energy x-ray CT, and finally obtained them with an accuracy of around +-1%.

A multi-slit collimator was designed and fabricated for basic studies on microbeam radiation therapy (MRT) with an X-ray energy of about 100 keV. It consists of 30 slits that are 25 um high, 30 mm wide, and 5 mm thick in the beam direction. The slits were made of 25um-thick polyimide sheets that were separated by 175um-thick tungsten sheets. We measured the dose distribution of a single microbeam with a mean energy of 125 keV by a scanning slit method using a phosphor coupled to a CCD camera and found that the ratios of the dose at the center of a microbeam to that at mid-positions to adjacent slits were 1050 and 760 for each side of the microbeam. This dose distribution was well reproduced by the Monte Carlo simulation code Phits.

The first clinical trial with carbon beams generated from the HIMAC was conducted in June 1994. The total number of patients treated as of December 2006 was in excess of 3,000. In view of the significant growth in the number of protocols, the Japanese government gave its approval for carbon-ion therapy at NIRS as an advanced medical technology in 2003. The impressive advances of carbon-ion therapy using HIMAC have been supported by high-reliability operation and by advanced developments of beam-delivery and accelerator technologies. Based on our ten years of experience with HIMAC, we recently proposed a new accelerator facility for cancer therapy with carbon ions for widespread use in Japan. The key technologies of the accelerator and beam-delivery systems for this proposed facility have been under development since April 2004, with the main thrust being focused on downsizing the facility for cost reduction. Based on the design and R&D studies for the proposed facility, its construction was begun at Gunma University in April 2006. In addition, our future plans for HIMAC also include the design of a new treatment facility. The design work has already been initiated, and will lead to the further development of therapy using HIMAC. The following descriptions give a summary account of the new accelerator facility for cancer therapy with carbon ions and of the new treatment facility at HIMAC.

The commissioning of conformal radiotherapy system using heavy-ion beams at the Heavy Ion Medical Accelerator in Chiba (HIMAC) is described in detail. The system at HIMAC was upgraded for a clinical trial using a new technique: large spot uniform scanning with conformal layer stacking. The system was developed to localize the irradiation dose to the target volume more effectively than with the old system. With the present passive irradiation method using a ridge filter, a scatterer, a pair of wobbler magnets, and a multileaf collimator, the width of the spread-out Bragg peak (SOBP) in the radiation field could not be changed. With dynamic control of the beam-modifying devices during irradiation, a more conformal radiotherapy could be achieved. In order to safely perform treatments with this conformal therapy, the moving devices should be watched during irradiation and the synchronousness among the devices should be verified. This system, which has to be safe for patient irradiations, was constructed and tested for safety and for the quality of the dose localization realized. Through these commissioning tests, we were successfully able to prepare the conformal technique using layer stacking for patients. Subsequent to commissioning the technique has been applied to patients in clinical trials.

The RF-knockout (RF-KO) slow-extraction method with frequency modulation (FM) and amplitude modulation (AM) has brought high-accuracy irradiation to the treatment ofa cancer tumor moving with respiration, because of a quick response to beam start/stop. However, a beam spill extracted from a synchrotron ring through RF-KO slowextraction has a huge ripple with a frequency of around 1 kHz related to the FM. The spill ripple will disturb the lateral dose distribution in the beam scanning methods. Thus, the source ofthe spill ripple has been investigated through experiments and simulations. There are two tune regions for the extraction process through the RF-KO method: the extraction region and the diffusion region. The particles in the extraction region can be extracted due to amplitude growth through the transverse RF field, only when its frequency matches with the tune in the extraction region. For a large chromaticity, however, the particles in the extraction region can be extracted through the synchrotron oscillation, even when the frequency does not match with the tune in the extraction region. Thus, the spill structure during one period ofthe FM strongly depends on the horizontal chromaticity. They are repeated with the repetition frequency of the FM, which is the very source ofthe spill ripple in the RF-KO method.

Based on more than ten years of experience with HIMAC, we have proposed a new treatment facility for the further development of therapy with HIMAC. The new facility, as an extension of the existing one, has been designed, and the related R&D work has been carried out. The new treatment-facility project was approved at December 2007.

In ion beam cancer therapy, it is generally essential for a scanning-irradiation method and a rotating gantry system to deliver a circular beam profile with a Gaussian distribution. A slow beam extraction method utilized in a synchrotron ring, however, can not deliver a beam with a Gaussian distribution in the horizontal phase space, because of its extraction mechanism. Thus, we have proposed a thin scatterer method in order to compensate for the phase-space distribution of a slowly extracted beam, although the emittance is slightly enlarged by scattering. As a result of particle tracking, we verified that the proposed method could change an asymmetric distribution to a Gaussian one in the horizontal phase space and realize a symmetric beam condition for the rotating gantry.

The new carbon-therapy facility has been constructed at Gunma University since April 2006, based on the design study and R&D works at HIMAC. As a future plan for the HIMAC, further, a new treatment facility was initiated at NIRS from April 2006.

Purpose: This work is aimed to improve the computational model of the beam-customization devices for treatment planning of radiotherapy with heavy charged particles, where only a single collimator and a compensator have been commonly handled with inaccuracy of unphysical collimator dependence in the middle of large fields. Method and Materials: The phase-space theory is applied to the beam transport through the beam-customization devices to enable handling of multiple collimators and a compensator in any order. The theoretical model was experimentally tested with a carbon-ion beam, where two jaw and a multileaf collimators, a 3-cm PMMA half plate for a range compensator, and an 8-cm square aperture for a patient collimator were concurrently used. In the model, a matrix of pencil beams was transported through the devices and a two-dimensional in-air dose distribution on the isocenter plane was computed within ten seconds. For comparison, the penumbra sizes at the field edges formed by the effective collimators were analytically estimated and the dose profiles along four axes on the isocenter plane were experimentally measured. Results: The model computation agreed with the measurement and analytic estimation at a submillimeter level in penumbra size and reproduced the measured dose fluctuation in the middle of the field due to the range-compensator scatter. Conclusions: The model computation is fast, accurate, and readily applicable to pencil-beam algorithms in treatment planning to enable combinational collimation for the best use of beam-customization devices., AAPM Annual Meeting 2008

Medical Application of Synchrotron Radiation 2007

13th International Congress of Radiation Research

The electron density is indispensable to the treatment planning for heavy-ion radiotherapy, so that the precise measurement of that is important for advancing radiotherapy. Usually the electron density for the radiotherapy is derived from an image based on CT number by conventional CT. CT number include ambiguilty due to the beam hardening. In a method of dual-energy x-ray CT, the information on an electron density can be obtained directly using monochromatic x-rays. The precision of the electron density was experimentally proved to be about 1%., The 8th Conference on Biology and Synchrotron Radiation

The 8th International Conference on Biology and Synchrotron Radiation

The electron density is one of the most important element for the treatment planning in the radiotherapy, because this information is used for the range estimation of the heavy-ion beam. Although the electron density has been converted from CT number obtained by conventional x-ray computed tomography(CT) at present, it is not enough for the more detailed planning due to uncertainties that arise from the beam hardening effect and the conversion process. In order to take more accurate electron density, we have developed the dual-energy x-ray CT system using the synchrotron radiation. The dual-energy x-ray CT has no influence of the beam hardening because of scanning using monochromatic x-rays. The experiments were carried out using two monochromatic x-rays at the monochromatic beam-lines in KEK-AR and SPring-8. As the result, it was succeeded that the electron densities by the dual-energy x-ray CT were agreement with the theoretical values with the accuracy less than 1% for some materials. In addition, as the application for more practical use in diagnostics, the CT using the mixture of main and harmonics x-rays produced by the monochromator has been investigated. From the preliminary experiments, it was found that the accuracy was as same as that by dual-energy x-ray CT. We will describe the dual-energy x-ray CT system and discuss the quantitativity and the image characteristic for this system., Eighth International Conference on Synchrotron Radiation Instrumentation

Nuclear Science Symposium and Medical Imaging Conference

EPAC 2002