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.

The simulation and experimental results demonstrated that the phase controlled rescanning method makes it possible to deliver the dose distribution close to the expected one. As an experimental result for 3D irradiation, it was estimated that blurring by the probability density function was not only for a lateral distribution, but also for a distal distribution, even in the lateral rescanning.

As a result of this study, the authors verified that the new scanning delivery system can produce an accurate 3D dose distribution for the target volume in combination with the planning software.

A project to construct a new treatment facility as an extension of the existing heavy-ion medical accelerator in chiba (HIMAC) facility has been initiated for further development of carbon-ion therapy. The greatest challenge of this project is to realize treatment of a moving target by scanning irradiation. For this purpose, we decided to combine the rescanning technique and the gated irradiation method. To determine how to avoid hot and/or cold spots by the relatively large number of rescannings within an acceptable irradiation time, we have studied the scanning strategy, scanning magnets and their control, and beam intensity dynamic control. We have designed a raster scanning system and carried out a simulation of irradiating moving targets. The result shows the possibility of practical realization of moving target irradiation with pencil beam scanning. We describe the present status of our design study of the raster scanning system for the HIMAC new treatment facility.

Treatment plans of carbon-ion radiotherapy have been made on the assumption that the beams are delivered instantaneously irrespective to the dose delivery time as well as the interruption time. The advanced therapeutic techniques such as a hypofractionation and a respiratory gating usually require more time to deliver a fractioned dose than conventional techniques. The purpose of this study was to investigate the effects of dose-delivery time structure on biological effectiveness in carbon-ion radiotherapy. The rate equations defined in the microdosimetric kinetic model (MKM) for primary lesions caused in the DNA were reanalyzed and applied to continuous or interrupted irradiation with therapeutic carbon-ion beams. The rate constants characterizing the time of the primary nonlethal lesions to repair or to convert to lethal lesion were experimentally determined for human salivary gland (HSG) tumor cells. Treatment plans were made for a patient case on the assumption that the beam is delivered instantaneously. The RBE weighted absorbed doses of 2.65, 3.45 and 6.86 Gy (RBE) was prescribed to the target. These plans were recalculated by varying the dose delivery time and the interruption time ranging from 1-60 min based on the MKM with the determined parameters. The sum of rate constants for nonlethal lesion to repair a and to convert to lethal lesion c, (a + c), is 2.19 ± 0.40 h⁻¹. The biological effectiveness in the target decreases with the dose delivery time T in continuous irradiation compared to the planned one due to the repair of nonlethal lesions during the irradiation. The biological effectiveness in terms of equivalent acute dose decreases to 99.7% and 96.4% for T = 3 and 60 min in 2.65 Gy (RBE), 99.5% and 94.3% in 4.35 Gy (RBE), and 99.4% and 91.7% in 6.86 Gy (RBE), respectively. For all the cases, the decrease of biological effectiveness is larger at the proximal side with low-LET than the distal side with high-LET. Similar reductions of biological effectiveness with comparable amounts are observed in the interrupted irradiations with prolonged interruption time τ. For the fraction time, i.e., T and/or τ, shorter than 3 min, the decrease of the biological effectiveness with respect to the planned one is less than 1.0%. However, if the fraction time prolongs to 30 min or longer, the biological effectiveness is significantly influenced in carbon-ion radiotherapy, especially with high-prescribed doses. These effects, if confirmed by clinical studies, should be considered in designing the carbon-ion treatment planning.

Challenging issues in treatment planning for scanned carbon-ion (C-ion) therapy are (i) accurate calculation of dose distribution, including the contribution of large angle-scattered fragments, (ii) reduction in the memory space required to store the dose kernel of individual pencil beams and (iii) shortening of computation time for dose optimization and calculation. To calculate the dose contribution from fragments, we modeled the transverse dose profile of the scanned C-ion beam with the superposition of three Gaussian distributions. The development of pencil beams belonging to the first Gaussian component was calculated analytically based on the Fermi-Eyges theory, while those belonging to the second and third components were transported empirically using the measured beam widths in a water phantom. To reduce the memory space for the kernels, we stored doses only in the regions of interest considered in the dose optimization. For the final dose calculation within the patient's whole body, we applied a pencil beam redefinition algorithm. With these techniques, the triple Gaussian beam model can be applied not only to final dose calculation but also to dose optimization in treatment planning for scanned C-ion therapy. To verify the model, we made treatment plans for a homogeneous water phantom and a heterogeneous head phantom. The planned doses agreed with the measurements within ±2% of the target dose in both phantoms, except for the doses at the periphery of the target with a high dose gradient. To estimate the memory space and computation time reduction with these techniques, we made a treatment plan for a bone sarcoma case with a target volume of 1.94 l. The memory space for the kernel and the computation time for final dose calculation were reduced to 1/22 and 1/100 of those without the techniques, respectively. Computation with the triple Gaussian beam model using the proposed techniques is rapid, accurate and applicable to dose optimization and calculation in treatment planning for scanned C-ion therapy.

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.

A superconducting rotating gantry for heavy-ion therapy is being designed. This isocentric rotating gantry can transport heavy ions with the maximum energy of 430 MeV=u to an isocenter with irradiation angles of over 0-360 degrees, and is further capable of performing three-dimensional raster-scanning irradiation. The combined-function superconducting magnets will be employed for the rotating gantry. The superconducting magnets with optimized beam optics allow a compact gantry design with a large scan size at the isocenter; the length and the radius of the gantry will be approximately 13 and 5.5 m, respectively, which are comparable to those for the existing proton gantries. Furthermore, the maximum scan size at the isocenter is calculated to be as large as approximately 200 mm square for heavy-ion beams at the maximum energy of 430 MeV=u. Based on the design of the beam optics, specifications of the superconducting magnets were determined. The superconducting magnets and magnetic-field distributions are designed using a three-dimensional field solver. With the calculated magnetic fields, beam-tracking simulations were performed to verify the design of the superconducting magnets, and concurrently to evaluate the field quality. With calculated beam profiles at the isocenter, we found that the positions of beam spots as well as their size and shape could be well reproduced as designed, proving validity of our design.