Satoru Kameoka

Experimental verification of proton beam monitoring in a human body by use of activity image of positron-emitting nuclei generated by nuclear fragmentation reaction.

Proton therapy is a form of radiotherapy that enables concentration of dose on a tumor by use of a scanned or modulated Bragg peak. Therefore, it is very important to evaluate the proton-irradiated volume accurately. The proton-irradiated volume can be confirmed by detection of pair-annihilation gamma rays from positron-emitting nuclei generated by the nuclear fragmentation reaction of the incident protons on target nuclei using a PET apparatus. The activity of the positron-emitting nuclei generated in a patient was measured with a PET-CT apparatus after proton beam irradiation of the patient. Activity measurement was performed in patients with tumors of the brain, head and neck, liver, lungs, and sacrum. The 3-D PET image obtained on the CT image showed the visual correspondence with the irradiation area of the proton beam. Moreover, it was confirmed that there were differences in the strength of activity from the PET-CT images obtained at each irradiation site. The values of activity obtained from both measurement and calculation based on the reaction cross section were compared, and it was confirmed that the intensity and the distribution of the activity changed with the start time of the PET imaging after proton beam irradiation. The clinical use of this information about the positron-emitting nuclei will be important for promoting proton treatment with higher accuracy in the future.

GEANT4 based simulation framework for particle therapy system

The particle therapy simulation framework has been developed for radiation therapy using GEANT4 simulation toolkit. The developed simulation framework provides a common interface for composing irradiation systems of different radiation therapy facilities. A particle therapy simulator on the framework represents a treatment room with an irradiation system. Popular beam modifiers for hadron therapy are included in the framework as beam modules and are utilized for composing an irradiation system. The developed framework is designed to be able to customize beam modules as flexible as possible without modifying source codes, because end users such as medical physicists are supposed not to be familiar with developing programming code. Each three types of irradiation systems have been successfully carbon therapy.

Apparent absence of a proton beam dose rate effect and possible differences in RBE between Bragg peak and plateau

PURPOSE Respiration-gated irradiation for a moving target requires a longer time to deliver single fraction in proton radiotherapy (PRT). Ultrahigh dose rate (UDR) proton beam, which is 10-100 times higher than that is used in current clinical practice, has been investigated to deliver daily dose in single breath hold duration. The purpose of this study is to investigate the survival curve and relative biological effectiveness (RBE) of such an ultrahigh dose rate proton beam and their linear energy transfer (LET) dependence. METHODS HSG cells were irradiated by a spatially and temporally uniform proton beam at two different dose rates: 8 Gy/min (CDR, clinical dose rate) and 325 Gy/min (UDR, ultrahigh dose rate) at the Bragg peak and 1.75 (CDR) and 114 Gy/min (UDR) at the plateau. To study LET dependence, the cells were positioned at the Bragg peak, where the absorbed dose-averaged LET was 3.19 keV/microm, and at the plateau, where it was 0.56 keV/microm. After the cell exposure and colony assay, the measured data were fitted by the linear quadratic (LQ) model and the survival curves and RBE at 10% survival were compared. RESULTS No significant difference was observed in the survival curves between the two proton dose rates. The ratio of the RBE for CDR/UDR was 0.98 +/- 0.04 at the Bragg peak and 0.96 +/- 0.06 at the plateau. On the other hand, Bragg peak/plateau RBE ratio was 1.15 +/- 0.05 for UDR and 1.18 +/- 0.07 for CDR. CONCLUSIONS Present RBE can be consistently used in treatment planning of PRT using ultrahigh dose rate radiation. Because a significant increase in RBE toward the Bragg peak was observed for both UDR and CDR, further evaluation of RBE enhancement toward the Bragg peak and beyond is required.

Improved dose-calculation accuracy in proton treatment planning using a simplified Monte Carlo method verified with three-dimensional measurements in an anthropomorphic phantom

Treatment planning for proton tumor therapy requires a fast and accurate dose-calculation method. We have implemented a simplified Monte Carlo (SMC) method in the treatment planning system of the National Cancer Center Hospital East for the double-scattering beam delivery scheme. The SMC method takes into account the scattering effect in materials more accurately than the pencil beam algorithm by tracking individual proton paths. We confirmed that the SMC method reproduced measured dose distributions in a heterogeneous slab phantom better than the pencil beam method. When applied to a complex anthropomorphic phantom, the SMC method reproduced the measured dose distribution well, satisfying an accuracy tolerance of 3 mm and 3% in the gamma index analysis. The SMC method required approximately 30 min to complete the calculation over a target volume of 500 cc, much less than the time required for the full Monte Carlo calculation. The SMC method is a candidate for a practical calculation technique with sufficient accuracy for clinical application.

Validation of PTSIM for clinical usage

The Geant4 simulation toolkit has been widely accepted in particle therapy domain for more accurate treatment planning. In Japan, the PTSIM, Particle Therapy System Simulation Framework, has been developed by the fund from the Core Research for Evolutional Science and Technology of Japan Science and Technology Agency, JST/CREST. The PTSIM provides a common platform to model beam delivery systems including a DICOM data handling for hadron therapy facility. The PTSIM can simulate existing six irradiation systems in the world and try extending the scope for clinical usage. In this paper, the performance of PTSIM is described for the use of clinical applications as a dose engine. The PTSIM was examined at the National Cancer Center (NCC) and Hyogo Ion Beam Medical Center (HIBMC) in Japan. The dose calculations had been performed on CT images with the treatment parameters determined by a treatment planning system. The dose distributions were compared with pencil beam algorithm.

Experimental evaluation of a spatial resampling technique to improve the accuracy of pencil-beam dose calculation in proton therapy

PURPOSE In proton therapy, pencil-beam algorithms (PBAs) are the most widely used dose calculation methods. However, the PB calculations that employ one-dimensional density scaling neglect the effects of lateral density heterogeneity on the dose distributions, whereas some particles included in such pencil beams could overextend beyond the interface of the density heterogeneity. We have simplified a pencil-beam redefinition algorithm (PBRA), which was proposed for electron therapy, by a spatial resampling technique toward an application for proton therapy. The purpose of this study is to evaluate the calculation results of the spatial resampling technique in terms of lateral density heterogeneity by comparison with the dose distributions that were measured in heterogeneous slab phantoms. METHODS The pencil beams are characterized for multiple residual-range (i.e., proton energy) bins. To simplify the PBRA, the given pencil beams are resampled on one or two transport planes, in which smaller sub-beams that are parallel to each other are generated. We addressed the problem of lateral density heterogeneity comparing the calculation results to the dose distributions measured at different depths in heterogeneous slab phantoms using a two-dimensional detector. Two heterogeneity slab phantoms, namely, phantoms A and B, were designed for the measurements and calculations. In phantom A, the heterogeneity slab was placed close to the surface. On the other hand, in phantom B, it was placed close to the Bragg peak in the mono-energetic proton beam. RESULTS In measurements, lateral dose profiles showed a dose reduction and increment in the vicinity of x = 0 mm in both phantoms at depths z = 142 and 161 mm due to lateral particle disequilibrium. In phantom B, these dose reduction∕increment effects were higher∕lower, respectively, than those in phantom A. This is because a longer distance from the surface to the heterogeneous slab increases the strength of proton scattering. Sub-beams, which were generated from the resampling plane, formed a detouring∕overextending path that was different from that of elemental pencil beams. Therefore, when the spatial resampling was implemented at the surface and immediately upstream of the lateral heterogeneity, the calculation could predict these dose reduction∕increment effects. Without the resampling procedure, these dose reduction∕increment effects could not be predicted in both phantoms owing to the blurring of the pencil beam. We found that the PBA with the spatial resampling technique predicted the dose reduction∕increment at the dose profiles in both phantoms when the sampling plane was defined immediately upstream of the heterogeneous slab. CONCLUSIONS We have demonstrated the implementation of a spatial resampling technique for pencil-beam calculation to address the problem of lateral density heterogeneity. While further validation is required for clinical use, this study suggests that the spatial resampling technique can make a significant contribution to proton therapy.PURPOSE In proton therapy, pencil-beam algorithms (PBAs) are the most widely used dose calculation methods. However, the PB calculations that employ one-dimensional density scaling neglect the effects of lateral density heterogeneity on the dose distributions, whereas some particles included in such pencil beams could overextend beyond the interface of the density heterogeneity. We have simplified a pencil-beam redefinition algorithm (PBRA), which was proposed for electron therapy, by a spatial resampling technique toward an application for proton therapy. The purpose of this study is to evaluate the calculation results of the spatial resampling technique in terms of lateral density heterogeneity by comparison with the dose distributions that were measured in heterogeneous slab phantoms. METHODS The pencil beams are characterized for multiple residual-range (i.e., proton energy) bins. To simplify the PBRA, the given pencil beams are resampled on one or two transport planes, in which smaller sub-beams that are parallel to each other are generated. We addressed the problem of lateral density heterogeneity comparing the calculation results to the dose distributions measured at different depths in heterogeneous slab phantoms using a two-dimensional detector. Two heterogeneity slab phantoms, namely, phantoms A and B, were designed for the measurements and calculations. In phantom A, the heterogeneity slab was placed close to the surface. On the other hand, in phantom B, it was placed close to the Bragg peak in the mono-energetic proton beam. RESULTS In measurements, lateral dose profiles showed a dose reduction and increment in the vicinity ofx = 0 mm in both phantoms at depths z = 142 and 161 mm due to lateral particle disequilibrium. In phantom B, these dose reduction/increment effects were higher/lower, respectively, than those in phantom A. This is because a longer distance from the surface to the heterogeneous slab increases the strength of proton scattering. Sub-beams, which were generated from the resampling plane, formed a detouring/overextending path that was different from that of elemental pencil beams. Therefore, when the spatial resampling was implemented at the surface and immediately upstream of the lateral heterogeneity, the calculation could predict these dose reduction/increment effects. Without the resampling procedure, these dose reduction/increment effects could not be predicted in both phantoms owing to the blurring of the pencil beam. We found that the PBA with the spatial resampling technique predicted the dose reduction/increment at the dose profiles in both phantoms when the sampling plane was defined immediately upstream of the heterogeneous slab. CONCLUSIONS We have demonstrated the implementation of a spatial resampling technique for pencil-beam calculation to address the problem of lateral density heterogeneity. While further validation is required for clinical use, this study suggests that the spatial resampling technique can make a significant contribution to proton therapy.

Dosimetric verification in inhomogeneous phantom geometries for the XiO radiotherapy treatment planning system with 6-MV photon beams

We have developed a practical dose verification method for radiotherapy treatment planning systems by using only a Farmer ionization chamber in inhomogeneous phantoms. In particular, we compared experimental dose verifications of multi-layer phantom geometries and laterally inhomogeneous phantom geometries for homogeneous and inhomogenous dose calculations by using the fast-Fourier-transform convolution, fast-superposition, and superposition in the XiO radiotherapy treatment-planning system. We applied the dose verification method to three kernel-based algorithms in various phantom geometries with water-, lung- and bone-equivalent media of different field sizes. These calculations were then compared with experimental measurements by use of the Farmer ionization chamber. The fast-Fourier-transform convolution algorithm overestimated the dose by about 8% in the lung phantom geometry. The superposition algorithm and the fast-superposition algorithm were both accurate to better than 2% when compared to the measurements even for complex geometries. Our dose verification method was able to clarify the differences and equivalences of the three kernel-based algorithms and measurements with use only of commonly available apparatus. This will be generally useful in commissioning of inhomogeneity-correction algorithms in the clinical practice of treatment planning.

Locoregional control after intensity-modulated radiotherapy for nasopharyngeal carcinoma with an anatomy-based target definition.

OBJECTIVE The objective of the study was to evaluate locoregional control after intensity-modulated radiotherapy for nasopharyngeal cancer using a target definition along with anatomical boundaries. METHODS Forty patients with biopsy-proven squamous cell or non-keratinizing carcinoma of the nasopharynx who underwent intensity-modulated radiotherapy between April 2006 and November 2009 were reviewed. There were 10 females and 30 males with a median age of 48 years (range, 17-74 years). More than half of the patients had T3/4 (n = 21) and/or N2/3 (n = 24) disease. Intensity-modulated radiotherapy was administered as 70 Gy/33 fractions with or without concomitant chemotherapy. The clinical target volume was contoured along with muscular fascia or periosteum, and the prescribed radiotherapy dose was determined for each anatomical compartment and lymph node level in the head and neck. RESULTS One local recurrence was observed at Meckels cave on the periphery of the high-risk clinical target volume receiving a total dose of <63 Gy. Otherwise, six locoregional failures were observed within irradiated volume receiving 70 Gy. Local and nodal control rates at 3 years were 91 and 89%, respectively. Adverse events were acceptable, and 25 (81%) of 31 patients who were alive without recurrence at 2 years had xerostomia of ≤Grade 1. The overall survival rate at 3 years was 87%. CONCLUSIONS Target definition along with anatomically defined boundaries was feasible without compromise of the therapeutic ratio. It is worth testing this method further to minimize the unnecessary irradiated volume and to standardize the target definition in intensity-modulated radiotherapy for nasopharyngeal cancer.

SU‐E‐T‐721: Spatial Re‐Sampling of Pencil Beams to Improve the Dose‐Calculation Accuracy in Proton Therapy

Purpose: We have developed a novel dose calculation algorithm, a spatial re‐sampling pencil beam algorithm (SR‐PBA), to improve the pencil‐beam dose accuracy in heterogeneous regions of a patients body. Methods: The SR‐PBA employs more sub‐beams and splitting compared with previous methods. Sampling map analysis, which is another important concept of the SR‐PBA, is preprocessing to determine the physical parameters of re‐sampled sub‐beams at sampling plane in order to avoid a time‐consuming problem. We verified the superiority of the SR‐PBA method to the conventional PBA by comparing their calculation results with the experimentally measured dose distributions in the heterogeneous slab phantoms. In order to evaluate the depth dependence of the accuracy in the slab, we designed an L‐shaped range compensator and two phantoms (A and B) in which low‐density regions were placed. Results: In a phantom A, the density interface was located at a shallow region, which corresponds to the plateau of the depth‐dose curve. On the other hand, in a phantom B, the interface was located at a deep region, which is close to the proton range. The lateral dose distributions were measured using a two‐dimensional detector. In both phantoms, the lateral‐dose profiles showed the dose reduction in the vicinity of × = 0 mm. In the phantom A, the PBA could not reproduce this dose reduction with +10.7 % at × = 0 while the SR‐PBA could within 1.5 % when the setup error of 1 mm was taken into account. In the phantom B, only the SR‐PBA could reproduce this dose reduction with 0.4 % at × = 0. We found that the SR‐PBA reproduced the dose reduction/increment at the dose profiles of the heterogeneous slab regardless of the depth dependence. Conclusions: This study suggests that our proposed algorithm is feasible for simulating proton dose distributions in the practical proton therapy.

WE‐A‐BRA‐05: Proton Ultra High Dose‐Rate Effect on HSG Cell Survival Curve

Purpose: One of the important issues that we are facing in the current radiation process is the long treatment time for irradiating protons to the tumor moving with respiration. In order to improve this problem, we are currently developing the highly precise and very short time protonIGRT using the high intensity beam from cyclotron and the real‐time images acquired by two flat panel detectors attached to the gantry. The dose‐rate by using this method will reach 10 to 100 times of the present one. The purpose of this study is to investigate the relative biological effectiveness (RBE) of HSG cell in such an ultra high dose‐rate regime and its LET dependence by using the colony assay method. Material and method: We attached the HSG cells at the bottom of the plastic chamber, and irradiated the spatially and temporally homogeneous proton beam. We used 235MeV proton beams with the different beam current of 10nA and 300nA in order to study the dose‐rate effect. The chamber was molded in a Polyethylene block with a hole which fits tightly to the chamber. It was placed at plateau(1.75, 114Gy/min, yD=0.56keV/ m), then at Bragg‐peak(8, 325Gy/min, yD=3.19keV/ m) to see the LET dependence of RBE at high dose‐rate.Result: There were no significant splits observed in survival curves of HSG cell over the protondose‐rate. The ratio of RBE at lower dose‐rate to that at higher dose‐rate was 0.98−+0.08 at Bragg‐peak and was 0.96−+0.11 at plateau. On the other hand, the RBE ratio at Bragg‐peak to plateau was 1.13–1.20, which suggests that the position dependence of RBE cannot be neglected. Conclusion: We conclude that in the therapeutic planning of high dose‐rateradiation, the present RBE can be consistently used. Instead, the RBE enhancement toward the Bragg‐peak and beyond should be reconsidered.