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Previously reported studies have revealed that the application of a magnetic field longitudinal to a carbon-ion beam enhances its biological effectiveness. Here we 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 immediately 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 LETs.

Purpose: Our previous study revealed that the application of a magnetic field longitudinal to a carbon-ion beam of 0.1 ≤  B // Most experimental conditions other than the magnetic field direction were the same as those used in the previous study to allow comparison of their results. Human cancer and normal cells were exposed to low (12 keV/μm) and high (50 keV/μm) linear energy transfer (LET) carbon-ion beams under the perpendicular magnetic fields of B ⊥ = 0, 0.15, 0.3, or 0.6 T generated by a dipole magnet. The effects of the magnetic fields on the biological effectiveness were evaluated by clonogenic cell survival. Doses that would result in the survival of 10%, Methods and materials: Most experimental conditions other than the magnetic field direction were the same as those used in the previous study to allow comparison of their results. Human cancer and normal cells were exposed to low (12 keV/μm) and high (50 keV/μm) linear energy transfer (LET) carbon-ion beams under the perpendicular magnetic fields of B ⊥ = 0, 0.15, 0.3, or 0.6 T generated by a dipole magnet. The effects of the magnetic fields on the biological effectiveness were evaluated by clonogenic cell survival. Doses that would result in the survival of 10%, D 10 For both cancer and normal cells treated by low- and high-LET carbon-ion beams, the t -tests. Results: For both cancer and normal cells treated by low- and high-LET carbon-ion beams, the D 10 Exposure of human cancer and normal cells to the perpendicular magnetic fields of B ⊥ ≤ 0.6 T did not alter significantly the biological effectiveness of the carbon-ion beams, unlike the exposure to longitudinal magnetic fields of the same strength. Although the mechanisms underlying the observed results still require further exploration, these findings indicate that the influence of the magnetic field on biological effectiveness of the carbon-ion beam depends on the applied field direction with respect to the beam.p  ≫ .05) from the D 10 s measured in the absence of the magnetic fields, B ⊥ = 0 T. Conclusions: Exposure of human cancer and normal cells to the perpendicular magnetic fields of B ⊥ ≤ 0.6 T did not alter significantly the biological effectiveness of the carbon-ion beams, unlike the exposure to longitudinal magnetic fields of the same strength. Although the mechanisms underlying the observed results still require further exploration, these findings indicate that the influence of the magnetic field on biological effectiveness of the carbon-ion beam depends on the applied field direction with respect to the beam.

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 of such effects. Methods and materials: Human cancer and normal cell lines were exposed to low (12 keV/ μ m) and high (50 keV/ μ m) linear energy transfer (LET) carbon-ion beams under the longitudinal magnetic fields of B // = 0, 0.1, 0.2, 0.3, or 0.6 T generated by a solenoid magnet. The effects of the magnetic fields on the biological effectiveness were evaluated by clonogenic cell survival. Doses that would result in a survival fraction of 10% ( D 10 s) were determined for each cell line and magnetic field. Results: For cancer cells exposed to the low (high)-LET beams, D 10 decreased from 5.2 (3.1) Gy at 0 T to 4.3 (2.4) Gy at 0.1 T, while no further decrease in D 10 was observed for higher magnetic fields. For normal cells, decreases in D 10 of comparable magnitudes were observed by applying the magnetic fields. Conclusions: Significant decreases in D 10 , i.e. significant enhancements of the biological effectiveness, were observed in both cancer and normal cells by applying longitudinal magnetic fields of B //  ≥ 0.1 T. These effects were enhanced with LET. Further studies are required to figure out the mechanism underlying the observed results.

Background: To moving lung tumors, we applied a respiratory-gated strategy to carbon-ion pencil beam scanning with multiple phase-controlled rescanning (PCR). In this simulation study, we quantitatively evaluated dose distributions based on 4-dimensional CT (4DCT) treatment planning., Methods: Volumetric 4DCTs were acquired for 14 patients with lung tumors. Gross tumor volume, clinical target volume (CTV) and organs at risk (OARs) were delineated. Field-specific target volumes (FTVs) were calculated, and 48Gy(RBE) in a single fraction was prescribed to the FTVs delivered from four beam angles. The dose assessment metrics were quantified by changing the number of PCR and the results for the ungated and gated scenarios were then compared., Results: For the ungated strategy, the mean dose delivered to 95% of the volume of the CTV (CTV-D95) was in average 45.3 ± 0.9 Gy(RBE) even with a single rescanning (1 × PCR). Using 4 × PCR or more achieved adequate target coverage (CTV-D95 = 46.6 ± 0.3 Gy(RBE) for ungated 4 × PCR) and excellent dose homogeneity (homogeneity index =1.0 ± 0.2% for ungated 4 × PCR). Applying respiratory gating, percentage of lung receiving at least 20 Gy(RBE) (lung-V20) and heart maximal dose, averaged over all patients, significantly decreased by 12% (p < 0.05) and 13% (p < 0.05), respectively., Conclusions: Four or more PCR during PBS-CIRT improved dose conformation to moving lung tumors without gating. The use of a respiratory-gated strategy in combination with PCR reduced excessive doses to OARs.

Our institution established a new treatment facility for carbon ion beam scanning therapy in 2010. The major advantages of scanning beam treatment compared to the passive beam treatment are the following: high dose conformation with less excessive dose to the normal tissues, no bolus compensator and patient collimator/multi-leaf collimator, better dose efficiency by reducing the number of scatters. The new facility was designed to solve several problems encountered in the existing facility, at which several thousand patients were treated over more than 15 years. Here, we introduce the patient handling system in the new treatment facility. The new facility incorporates three main systems, a scanning irradiation system (S-IR), treatment planning system (TPS), and patient handling system (PTH). The PTH covers a wide range of functions including imaging, geometrical/position accuracy including motion management (immobilization, robotic arm treatment bed), layout of the treatment room, treatment workflow, software, and others. The first clinical trials without respiratory gating have been successfully started. The PTH allows a reduction in patient stay in the treatment room to as few as 7 min. The PTH plays an important role in carbon ion beam scanning therapy at the new institution, particularly in the management of patient handling, application of image-guided therapy, and improvement of treatment workflow, and thereby allows substantially better treatment at minimum cost.

Purpose: In radiotherapy with a scanned carbon-ion beam, its Bragg peak is shifted along the depth direction either by inserting the range shifter plates or by changing the beam-extraction energy of a synchrotron. In the former technique (range shifter scanning: RS), the range shifter plates broaden the beam size and produce secondary fragments through nuclear reactions. In the latter technique (active-energy scanning: ES), it may take several seconds to change the beam energy depending on the synchrotron operation cycle, leading to a long treatment time. The authors propose a hybrid depth scan technique (hybrid scanning: HS), where several beam energies are used in conjunction with the range shifter plates for finer range shift. In this study, HS is evaluated from the viewpoints of dose distribution and treatment time., Methods: Assuming realistic accelerator and beam-delivery systems, the authors performed computer simulations using GEANT4 Monte Carlo code for beam modeling and a treatment planning system to evaluate HS. Three target volumes with the same dimensions of 60 × 60 × 60 mm(3) were generated at depths of 45, 85, and 125 mm in water phantom, and uniform clinical dose was planned for these targets. The sizes of lateral dose falloff and the peak to plateau ratio defined as the ratio of the clinical dose averaged over the target to the clinical dose at the entrance as well as the treatment time were compared among the three depth scan techniques., Results: The sizes of lateral dose falloffs at the center of SOBP are 11.4, 8.5, and 5.9 mm for the three targets in RS, while they are 5.7, 4.8, and 4.6 mm in ES and 6.6, 5.7, and 5.0 mm in HS, respectively. The peak to plateau ratios are 1.39, 1.96, and 2.15 in RS, while they are 1.48, 2.04, and 2.19 in ES and 1.47, 2.03, and 2.18 in HS, respectively. The treatment times are 128.7, 128.6, and 128.6 s in ES, while they are 61.2, 54.6, and 47.8 s in RS and 43.2, 44.1, and 44.7 s in HS, respectively. The multiple scattering and the nuclear reaction by range shifter degraded the beam qualities such as lateral dose falloff and peak to plateau ratio, which was especially pronounced for the shallow target in RS. The depth scan timing was limited by accelerator cycle in ES. That increased the treatment time by a few times., Conclusions: This study revealed that HS can provide dose distributions with steeper lateral dose falloffs and higher peak to plateau ratio comparing to RS and comparable to ES. In addition, the treatment time can be considerably reduced in HS compared to ES.

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.

In the last few years, hospital-based facilities for carbon-ion radiotherapy are being constructed and proposed in Europe and Asia. During the next few years, several new facilities will be opened for carbon-ion radiotherapy in the world. These facilities in operation or under construction are categorized in two types by the beam shaping method used. One is the passive beam shaping method that is mainly improved and systematized for routine clinical use at HIMAC, Japan. The other method is active beam shaping which is also known as beam scanning adopted at GSI/HIT, Germany. In this paper an overview of some technical aspects for beam shaping is reported. The technique of passive beam shaping is established for stable clinical application and has clinical result of over 4000 patients in HIMAC. In contrast, clinical experience of active beam shaping is about 400 patients, and there is no clinical experience to respiratory moving target. A great advantage of the active beam shaping method is patient-specific collimator-less and compensator-less treatment. This may be an interesting potential for adaptive radiotherapy.

A field-size effect of physical doses was studied in scanning irradiation with carbon ions. For the target volumes of 60 x 60 x 80, 40 x 40 x 80, and 20 x 20 x 80 mm3, the doses along the beam axis within the spread-out Bragg peaks reduced to 99.4%, 98.2%, and 96.0% of the dose for the target of 80 x 80 x 80 mm3, respectively. The present study revealed that the observed reductions can be compensated for by adopting the three-Gaussian form of lateral dose distributions for the pencil beam model used in the treatment planning system. The parameters describing the form were determined through the irradiation experiments making flat concentric squared frames with a scanned carbon beam. Since utilizing the three-Gaussian model in the dose optimization loop is at present time consuming, the correction for the field-size effect should be implemented as a "predicted-dose scaling factor." The validity of this correction method was confirmed through the irradiation of a target of 20 x 20 x 80 mm3.

The authors have developed a method to reconstruct the 3D dose distribution in a particle beam scanning irradiation system. In this scheme, 3D dose distribution is reconstructed by using the measured images of fluence distribution, which are taken for each iso-energy slice (i.e., the unit of the depth scanning). A fluorescent screen with a CCD camera is used to measure the fluence distribution. This system was installed at the HIMAC experimental port and tested by using carbon ion beams. Since a maximum difference between the reconstructed dose and the ionization chamber measurement was around 5% in the target volume, this system can be useful for quick verification of 3D dose distribution.

Clinical trials of carbon radiotherapy started at HIMAC in 1994 using three treatment rooms and four beam ports, two horizontal and two vertical. The broad beam method was adopted to make a three-dimensionally uniform field at an isocenter. A spot beam extracted from an accelerator was laterally spread out by using a pair of wobbler magnets and a scatterer. A bar ridge filter modulated the beam energy to obtain the spread out Bragg peak (SOBP). The SOBP was designed to be flat in terms of the biological dose based on the consideration that the field consisted of various beams with different LET. Finally, the field of 20 cm in diameter with +/- 2.5% uniformity was formed at the isocenter. The width of the maximum SOBP was 15 cm. When treating the lung or liver, organs that move due to breathing, the beam was irradiated only during the expiration period in a respiration-gated irradiation method. This reduced the treatment margin of the moving target. In order to prevent normal tissues adjacent to the target volume from irradiation by an unwanted dose, a layer-stacking method was developed. In this method, thin SOBP layers which have different ranges were piled up step by step from the distal end to the entrance of the target volume. At the same time, a multi-leaf collimator was used to change the aperture shape to match the shape of each layer to the cross-sectional shape of the target. This method has been applied to rather large volume cancers including bone and soft-tissue cancers. Only a few serious problems in the irradiation systems have been encountered since the beginning of the clinical trials. Overall the systems have been working stably and reliably.

For widespread use of rotating gantries for carbon radiotherapy, we designed a new compact gantry. This new gantry consists of three combined-function superconducting magnets having a bending angle of 90°. The dipole field of the superconducting magnets is set to be B\max=5.02 T, corresponding to a bending radius of 1.32 m for transporting carbon ions having kinetic energy of 430 MeV/u. The superconducting magnet also has three independent superconducting quadrupole coils, which are to be wound inside the dipole coil for beam focusing. The dipole and quadrupole coils are electrically isolated in the magnet and connected to independent power supplies so that each field component can be independently excited. Having used the combined-function superconducting magnets, the size of the rotating gantry would become very compact; the length and radius are 5.1 and 4.0 m, respectively. The magnetic field distributions of the superconducting magnets were calculated with a 3-D electromagnetic field solver, Opera-3d code. With calculated fields, the superconducting coils were designed to obtain uniform field distributions. In this paper, the design of this compact rotating gantry and the superconducting magnets is presented. [ABSTRACT FROM PUBLISHER]

Purpose: Three-dimensional irradiation with a scanned carbon-ion beam has been performed from 2011 at the authors' facility. The authors have developed the rotating-gantry equipped with the scanning irradiation system. The number of combinations of beam properties to measure for the commissioning is more than 7200, i.e., 201 energy steps, 3 intensities, and 12 gantry angles. To compress the commissioning time, quick and simple range verification system is required. In this work, the authors develop a quick range verification system using scintillator and charge-coupled device(CCD)camera and estimate the accuracy of the range verification. Methods: A cylindrical plastic scintillator block and a CCDcamera were installed on the black box. The optical spatial resolution of the system is 0.2 mm/pixel. The camera control system was connected and communicates with the measurement system that is part of the scanning system. The range was determined by image processing. Reference range for each energy beam was determined by a difference of Gaussian (DOG) method and the 80% of distal dose of the depth-dose distribution that were measured by a large parallel-plate ionization chamber. The authors compared a threshold method and a DOG method. Results: The authors found that the edge detection method (i.e., the DOG method) is best for the range detection. The accuracy of range detection using this system is within 0.2 mm, and the reproducibility of the same energy measurement is within 0.1 mm without setup error. Conclusions: The results of this study demonstrate that the authors' range check system is capable of quick and easy range verification with sufficient accuracy. [ABSTRACT FROM AUTHOR]

Purpose: Accurate dose measurement in radiotherapy is critically dependent on correction for gain drop, which is the difference of the measured current from the ideal saturation current due to general ion recombination. Although a correction method based on the Boag theory has been employed, the theory assumes that ionized charge density in an ionization chamber (IC) is spatially uniform throughout the irradiation volume. For particle pencil beam scanning, however, the charge density is not uniform, because the fluence distribution of a pencil beam is not uniform. The aim of this study was to verify the effect of the nonuniformity of ionized charge density on the gain drop due to general ion recombination. Methods: The authors measured the saturation curve, namely, the applied voltage versus measured current, using a large plane-parallel IC and 24-channel parallel-plate IC with concentric electrodes. To verify the effect of the nonuniform ionized charge density on the measured saturation curve, the authors calculated the saturation curve using a method which takes into account the nonuniform ionized charge density and compared it with the measured saturation curves. Results: Measurement values of the different saturation curves in the different channels of the concentric electrodes differed and were consistent with the calculated values. The saturation curves measured by the large plane-parallel IC were also consistent with the calculation results, including the estimation error of beam size and of setup misalignment. Although the impact of the nonuniform ionized charge density on the gain drop was clinically negligible with the conventional beam intensity, it was expected that the impact would increase with higher ionized charge density. Conclusions: For pencil beam scanning, the assumption of the conventional Boag theory is not valid. Furthermore, the nonuniform ionized charge density affects the prediction accuracy of gain drop when the ionized charge density is increased by a higher dose rate and/or lower beam size. [ABSTRACT FROM AUTHOR]

Abstract: Based on 10 years experience of carbon therapy at HIMAC, new facility project is in progress at NIRS. In this paper, the design of the synchrotron and its transport system dedicated for carbon therapy based on the machine study at HIMAC and the results of the studies are presented. © 2001 Elsevier Science. All rights reserved [Copyright &y& Elsevier]

Purpose: Having implemented amplitude-based respiratory gating for scanned carbon-ion beam therapy, we sought to evaluate its effect on positional accuracy and throughput.Methods and Materials: A total of 10 patients with tumors of the lung and liver participated in the first clinical trials at our center. Treatment planning was conducted with 4-dimensional computed tomography (4DCT) under free-breathing conditions. The planning target volume (PTV) was calculated by adding a 2- to 3-mm setup margin outside the clinical target volume (CTV) within the gating window. The treatment beam was on when the CTV was within the PTV. Tumor position was detected in real time with a markerless tumor tracking system using paired x-ray fluoroscopic imaging units.Results: The patient setup error (mean ± SD) was 1.1 ± 1.2 mm/0.6 ± 0.4°. The mean internal gating accuracy (95% confidence interval [CI]) was 0.5 mm. If external gating had been applied to this treatment, the mean gating accuracy (95% CI) would have been 4.1 mm. The fluoroscopic radiation doses (mean ± SD) were 23.7 ± 21.8 mGy per beam and less than 487.5 mGy total throughout the treatment course. The setup, preparation, and irradiation times (mean ± SD) were 8.9 ± 8.2 min, 9.5 ± 4.6 min, and 4.0 ± 2.4 min, respectively. The treatment room occupation time was 36.7 ± 67.5 min.Conclusions: Internal gating had a much higher accuracy than external gating. By the addition of a setup margin of 2 to 3 mm, internal gating positional error was less than 2.2 mm at 95% CI. [ABSTRACT FROM AUTHOR]