Naruhiro Matsufuji

Biophysical characteristics of HIMAC clinical irradiation system for heavy-ion radiation therapy

PURPOSE The irradiation system and biophysical characteristics of carbon beams are examined regarding radiation therapy. METHODS AND MATERIALS An irradiation system was developed for heavy-ion radiotherapy. Wobbler magnets and a scatterer were used for flattening the radiation field. A patient-positioning system using X ray and image intensifiers was also installed in the irradiation system. The depth-dose distributions of the carbon beams were modified to make a spread-out Bragg peak, which was designed based on the biophysical characteristics of monoenergetic beams. A dosimetry system for heavy-ion radiotherapy was established to deliver heavy-ion doses safely to the patients according to the treatment planning. A carbon beam of 80 keV/microm in the spread-out Bragg peak was found to be equivalent in biological responses to the neutron beam that is produced at cyclotron facility in National Institute Radiological Sciences (NIRS) by bombarding 30-MeV deuteron beam on beryllium target. The fractionation schedule of the NIRS neutron therapy was adapted for the first clinical trials using carbon beams. RESULTS Carbon beams, 290, 350, and 400 MeV/u, were used for a clinical trial from June of 1994. Over 300 patients have already been treated by this irradiation system by the end of 1997.

Rejoining and Misrejoining of Radiation-Induced Chromatin Breaks. IV. Charged Particles

We have recently reported the kinetics of chromosome rejoining and exchange formation in human lymphocytes exposed to gamma rays using the techniques of fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC). In this paper, we have extended previous measurements to cells exposed to charged particles. Our goal was to determine differences in chromatin break rejoining and misrejoining after exposure to low- and high-linear energy transfer (LET) radiation. Cells were irradiated with hydrogen, neon, carbon or iron ions in the LET range 0.3-140 keV/microm and were incubated at 37 degrees C for various times after exposure. Little difference was observed in the yield of early prematurely condensed chromosome breaks for the different ions. The kinetics of break rejoining was exponential for all ions and had similar time constants, but the residual level of unrejoined breaks after prolonged incubation was higher for high-LET radiation. The kinetics of exchange formation was also similar for the different ions, but the yield of chromosome interchanges measured soon after exposure was higher for high-LET particles, suggesting that a higher fraction of DNA breaks are misrejoined quickly. On the other hand, the rate of formation of complete exchanges was slightly lower for densely ionizing radiation. The ratios between the yields of different types of aberrations observed at 10 h postirradiation in prematurely condensed chromosome preparations were dependent on LET. We found significant differences between the yields of aberrations measured in interphase (after repair) and metaphase for densely ionizing radiation. This difference might be caused by prolonged mitotic delay and/or interphase death. Overall, the results point out significant differences between low- and high-LET radiation for the formation of chromosome aberrations.

A CT calibration method based on the polybinary tissue model for radiotherapy treatment planning

A method to establish the relationship between CT number and effective density for therapeutic radiations is proposed. We approximated body tissues to mixtures of muscle, air, fat and bone. Consequently, the relationship can be calibrated only with a CT scan of their substitutes, for which we chose water, air, ethanol and potassium phosphate solution, respectively. With simple and specific corrections for non-equivalencies of the substitutes, a calibration accuracy of 1% will be achieved. We tested the calibration method with some biological materials to verify that the proposed method would offer the accuracy, simplicity and specificity required for a standard in radiotherapy treatment planning, in particular with heavy charged particles.

Treatment planning for a scanned carbon beam with a modified microdosimetric kinetic model

We describe a method to calculate the relative biological effectiveness in mixed radiation fields of therapeutic ion beams based on the modified microdosimetric kinetic model (modified MKM). In addition, we show the procedure for integrating the modified MKM into a treatment planning system for a scanned carbon beam. With this procedure, the model is fully integrated into our research version of the treatment planning system. To account for the change in radiosensitivity of a cell line, we measured one of the three MKM parameters from a single survival curve of the current cells and used the parameter in biological optimization. Irradiation of human salivary gland tumor cells was performed with a scanned carbon beam in the Heavy Ion Medical Accelerator in Chiba (HIMAC), and we then compared the measured depth-survival curve with the modified MKM predicted survival curve. Good agreement between the two curves proves that the proposed method is a candidate for calculating the biological effects in treatment planning for ion irradiation.

Biophysical calculation of cell survival probabilities using amorphous track structure models for heavy-ion irradiation

Both the microdosimetric kinetic model (MKM) and the local effect model (LEM) can be used to calculate the surviving fraction of cells irradiated by high-energy ion beams. In this study, amorphous track structure models instead of the stochastic energy deposition are used for the MKM calculation, and it is found that the MKM calculation is useful for predicting the survival curves of the mammalian cells in vitro for (3)He-, (12)C- and (20)Ne-ion beams. The survival curves are also calculated by two different implementations of the LEM, which inherently used an amorphous track structure model. The results calculated in this manner show good agreement with the experimental results especially for the modified LEM. These results are compared to those calculated by the MKM. Comparison of the two models reveals that both models require three basic constituents: target geometry, photon survival curve and track structure, although the implementation of each model is significantly different. In the context of the amorphous track structure model, the difference between the MKM and LEM is primarily the result of different approaches calculating the biological effects of the extremely high local dose in the center of the ion track.

Relationship between CT number and electron density, scatter angle and nuclear reaction for hadron-therapy treatment planning

The precise conversion of CT numbers to their electron densities is essential in treatment planning for hadron therapy. Although some conversion methods have already been proposed, it is hard to check the conversion accuracy during practical therapy. We have estimated the CT numbers of real tissues by a calculational method established by Mustafa and Jackson. The relationship between the CT numbers and the electron densities was investigated for various body tissues as well as some tissue-equivalent materials used for a conversion to check the accuracy of the current conversion methods. The result indicates a slight disagreement at the high-CT-number region. A precise estimation of the multiple scattering, nuclear reaction and range straggling of incident particles has been considered as being important to realize higher-level conformal therapy in the future. The relationship between these parameters and the CT numbers was also investigated for tissues and water. The result shows that it is sufficiently practical to replace these parameters for real tissues with those for water by adjusting the density.

Measurement of neutron ambient dose equivalent in passive carbon-ion and proton radiotherapies.

Secondary neutron ambient dose equivalents per the treatment absorbed dose in passive carbon-ion and proton radiotherapies were measured using a rem meter, WENDI-II at two carbon-ion radiotherapy facilities and four proton radiotherapy facilities in Japan. Our measured results showed that (1) neutron ambient dose equivalent in carbon-ion radiotherapy is lower than that in proton radiotherapy, and (2) the difference to the measured neutron ambient dose equivalents among the facilities is within a factor of 3 depending on the operational beam setting used at the facility and the arrangement of the beam line, regardless of the method for making a laterally uniform irradiation field: the double scattering method or the single-ring wobbling method. The reoptimization of the beam line in passive particle radiotherapy is an effective way to reduce the risk of secondary cancer because installing an adjustable precollimator and designing the beam line devices with consideration of their material, thickness and location, etc., can significantly reduce the neutron exposure. It was also found that the neutron ambient dose equivalent in passive particle radiotherapy is equal to or less than that in the photon radiotherapy. This result means that not only scanning particle radiotherapy but also passive particle radiotherapy can provide reduced exposure to normal tissues around the target volume without an accompanied increase in total body dose.

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy(-1) and β = 0.0615 Gy(-2) as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both physical and clinical dose distributions were compared with regard to the prescribed dose level, beam energy, and SOBP width. Both systems provided uniform clinical dose distributions within the targets consistent with the prescriptions. The mean physical doses delivered to targets by the updated system agreed with the doses by the original system within ± 1.5% for all tested conditions. The updated system reflects the physical and biological characteristics of the therapeutic C-ion beam more accurately than the original system, while at the same time allowing the continued use of the dose-fractionation protocols established with the original system at NIRS.

Biological dose calculation with Monte Carlo physics simulation for heavy-ion radiotherapy.

Treatment planning of heavy-ion radiotherapy involves predictive calculation of not only the physical dose but also the biological dose in a patient body. The biological dose is defined as the product of the physical dose and the relative biological effectiveness (RBE). In carbon-ion radiotherapy at National Institute of Radiological Sciences, the RBE value has been defined as the ratio of the 10% survival dose of 200 kVp x-rays to that of the radiation of interest for in vitro human salivary gland tumour cells. In this note, the physical and biological dose distributions of a typical therapeutic carbon-ion beam are calculated using the GEANT4 Monte Carlo simulation toolkit in comparison with those with the biological dose estimate system based on the one-dimensional beam model currently used in treatment planning. The results differed between the GEANT4 simulation and the one-dimensional beam model, indicating the physical limitations in the beam model. This study demonstrates that the Monte Carlo physics simulation technique can be applied to improve the accuracy of the biological dose distribution in treatment planning of heavy-ion radiotherapy.

Broad-beam three-dimensional irradiation system for heavy-ion radiotherapy at HIMAC

Abstract A three-dimensional irradiation system using a broad beam has been installed for heavy-ion cancer therapy at the Heavy Ion Medical Accelerator in Chiba (HIMAC) facility. Only the target region is irradiated at the 100% dose level; the dose level at other parts of irradiated tissues is less, using a range shifter, a multileaf collimator and a compensator. The devices are the same as those used in two-dimensional irradiation, except that the setting values of the devices can be dynamically changed during the treatment. The thickness of the absorber and the aperture of the multileaf collimator are dynamically controlled during irradiation, so that the Bragg peak is swept in the depth direction and the Bragg peak outside of the target volume is blocked by the multileaf collimator. The performance of this system was checked by irradiation of a phantom using a 290 MeV/nucleon carbon beam. The dose distribution realized by this three-dimensional irradiation agreed satisfactorily with the planned one.