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Background: Inadequate computed tomography (CT) number calibration curves affect dose calculation accuracy. Although CT number calibration curves registered in treatment planning systems (TPSs) should be consistent with human tissues, it is unclear whether adequate CT number calibration is performed because CT number calibration curves have not been assessed for various types of CT number calibration phantoms and TPSs., Purpose: The purpose of this study was to investigate CT number calibration curves for mass density (ρ) and relative electron density (ρ e )., Methods: A CT number calibration audit phantom was sent to 24 Japanese photon therapy institutes from the evaluating institute and scanned using their individual clinical CT scan protocols. The CT images of the audit phantom and institute-specific CT number calibration curves were submitted to the evaluating institute for analyzing the calibration curves registered in the TPSs at the participating institutes. The institute-specific CT number calibration curves were created using commercial phantom (Gammex, Gammex Inc., Middleton, WI, USA) or CIRS phantom (Computerized Imaging Reference Systems, Inc., Norfolk, VA, USA)). At the evaluating institute, theoretical CT number calibration curves were created using a stoichiometric CT number calibration method based on the CT image, and the institute-specific CT number calibration curves were compared with the theoretical calibration curve. Differences in ρ and ρ e over the multiple points on the curve (Δρ m and Δρ e,m , respectively) were calculated for each CT number, categorized for each phantom vendor and TPS, and evaluated for three tissue types: lung, soft tissues, and bones. In particular, the CT-ρ calibration curves for Tomotherapy TPSs (ACCURAY, Sunnyvale, CA, USA) were categorized separately from the Gammex CT-ρ calibration curves because the available tissue-equivalent materials (TEMs) were limited by the manufacturer recommendations. In addition, the differences in ρ and ρ e for the specific TEMs (Δρ TEM and Δρ e,TEM , respectively) were calculated by subtracting the ρ or ρ e of the TEMs from the theoretical CT-ρ or CT-ρ e calibration curve., Results: The mean ± standard deviation (SD) of Δρ m and Δρ e,m for the Gammex phantom were -1.1 ± 1.2 g/cm 3 and -0.2 ± 1.1, -0.3 ± 0.9 g/cm 3 and 0.8 ± 1.3, and -0.9 ± 1.3 g/cm 3 and 1.0 ± 1.5 for lung, soft tissues, and bones, respectively. The mean ± SD of Δρ m and Δρ e,m for the CIRS phantom were 0.3 ± 0.8 g/cm 3 and 0.9 ± 0.9, 0.6 ± 0.6 g/cm 3 and 1.4 ± 0.8, and 0.2 ± 0.5 g/cm 3 and 1.6 ± 0.5 for lung, soft tissues, and bones, respectively. The mean ± SD of Δρ m for Tomotherapy TPSs was 2.1 ± 1.4 g/cm 3 for soft tissues, which is larger than those for other TPSs. The mean ± SD of Δρ e,TEM for the Gammex brain phantom (BRN-SR2) was -1.8 ± 0.4, implying that the tissue equivalency of the BRN-SR2 plug was slightly inferior to that of other plugs., Conclusions: Latent deviations between human tissues and TEMs were found by comparing the CT number calibration curves of the various institutes., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: Boron Neutron Capture Therapy (BNCT) has recently been used in clinical oncology thanks to recent developments of accelerator-based BNCT systems. Although there are some specific processes for BNCT, they have not yet been discussed in detail., Purpose: The aim of this study is to provide comprehensive data on the risk of accelerator-based BNCT system to institutions planning to implement an accelerator-based BNCT system., Methods: In this study, failure mode and effects analysis (FMEA) was performed based on a treatment process map prepared for the accelerator-based BNCT system. A multidisciplinary team consisting of a medical doctor (MD), a registered nurse (RN), two medical physicists (MP), and three radiologic technologists (RT) identified the failure modes (FMs). Occurrence (O), severity (S), and detectability (D) were scored on a scale of 10, respectively. For each failure mode (FM), risk priority number (RPN) was calculated by multiplying the values of O, S, and D, and it was then categorized as high risk, very high risk, and other. Additionally, FMs were statistically compared in terms of countermeasures, associated occupations, and whether or not they were the patient-derived., Results: The identified FMs for BNCT were 165 in which 30 and 17 FMs were classified as high risk and very high risk, respectively. Additionally, 71 FMs were accelerator-based BNCT-specific FMs in which 18 and 5 FMs were classified as high risk and very high risk, respectively. The FMs for which countermeasures were "Education" or "Confirmation" were statistically significantly higher for S than the others (p = 0.019). As the number of BNCT facilities is expected to increase, staff education is even more important. Comparing patient-derived and other FMs, O tended to be higher in patient-derived FMs. This could be because the non-patient-derived FMs included events that could be controlled by software, whereas the patient-derived FMs were impossible to prevent and might also depend on the patient's condition. Alternatively, there were non-patient-derived FMs with higher D, which were difficult to detect mechanically and were classified as more than high risk. In O, significantly higher values (p = 0.096) were found for FMs from MD and RN associated with much patient intervention compared to FMs from MP and RT less patient intervention. Comparing conventional radiotherapy and accelerator-based BNCT, although there were events with comparable risk in same FMs, there were also events with different risk in same FMs. They could be related to differences in the physical characteristics of the two modalities., Conclusions: This study is the first report for conducting a risk analysis for BNCT using FMEA. Thus, this study provides comprehensive data needed for quality assurance/quality control (QA/QC) in the treatment process for facilities considering the implementation of accelerator-based BNCT in the future. Because many BNCT-specific risks were discussed, it is important to understand the characteristics of BNCT and to take adequate measures in advance. If the effects of all FMs and countermeasures are discussed by multidisciplinary team, it will be possible to take countermeasures against individual FMs from many perspectives and provide BNCT more safely and effectively., (© 2022 American Association of Physicists in Medicine.)

Introduction: Placenta extract is used as an ingredient in ointments for treating dermatological diseases, skin dryness, and for skin beautification. However, the clinical effects of the equine placenta on humans and the underlying mechanism of action are unclear. This randomized, controlled, double-blind study aimed to clinically evaluate the effect of oral intake of equine placental extract on human skin quality., Methods: Healthy women volunteers between the ages of 30 and 59 years (n = 29) were randomly assigned to receive 220 mg of equine placental extract-placebo orally, once daily for 4 weeks. Skin quality parameters such as skin hydration, skin barrier function (transepidermal water loss [TEWL]), and melanin index were assessed at baseline and after 4 weeks of administration., Results: The melanin index was significantly increased in the placebo group, whereas it remained unchanged in the equine placenta group. The pattern of melanin index change was significantly different due to intake or no intake of equine placenta supplements over 4 weeks. No significant difference was found in skin hydration and TEWL between the two groups at 4 weeks of postadministration. It was shown that the intake of the equine placenta was more effective in protecting the skin condition against the change of ultraviolet (UV) sensitively than the change in temperature and humidity., Conclusions: Effect of equine placental extract intake was evident on the cheek skin of the equine placenta group where participants were protected from UV-induced pigmentation. Equine placental extract is useful for decreasing melanin synthesis and melanin content in the human skin and can be used as an effective food supplement to maintain human skin quality., Competing Interests: Y.N. is the CEO of Dr. PROLABO JAPAN Co., Ltd, Inc. Except for supplement contribution; the funding sources had no role in the design, conduct, or analysis of the study or the decision to submit the manuscript for publication. All the other authors declare no competing interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Purpose: To test the measurement technique of the three-dimensional (3D) dose distribution measured image by capturing the scintillation light generated using a plastic scintillator and a scintillating screen., Methods: Our imaging system constituted a column shaped plastic scintillator covered by a Gd 2 O 2 S:Tb scintillating screen, a conical mirror and a cooled CCD camera. The scintillator was irradiated with 6 MV photon beams. Meanwhile, the irradiated plan was prepared for the static field plans, two-field plan (2F plan) and the conformal arc plan (CA plan). The 2F plan contained 16 mm 2 and 10 mm 2 fields irradiated from gantry angles of 0° and 25°, respectively. The gantry was rotated counterclockwise from 45° to 315° for the CA plan. The field size was then obtained as 10 mm 2 . A Monte Carlo simulation was performed in the experimental geometry to obtain the calculated 3D dose distribution as the reference data. Dose response was acquired by comparing between the reference and the measurement. The dose rate dependence was verified by irradiating the same MU value at different dose rates ranging from 100 to 600 MU/min. Deconvolution processing was applied to the measured images for the correction of light blurring. The measured 3D dose distribution was reconstructed from each measured image. Gamma analysis was performed to these 3D dose distributions. The gamma criteria were 3% for the dose difference, 2 mm for the distance-to-agreement and 10% for the threshold., Results: Dose response for the scintillation light was linear. The variation in the light intensity for the dose rate ranging from 100 to 600 MU/min was less than 0.5%, while our system presents dose rate independence. For the 3D dose measurement, blurring of light through deconvolution processing worked well. The 3D gamma passing rate (3D GPR) for the 10 × 10 mm 2 , 16 × 16 mm 2 , and 20 × 20 mm 2 fields were observed to be 99.3%, 98.8%, and 97.8%, respectively. Reproducibility of measurement was verified. The 3D GPR results for the 2F plan and the CA plan were 99.7% and 100%, respectively., Conclusions: We developed a plastic scintillation dosimeter and demonstrated that our system concept can act as a suitable technique for measuring the 3D dose distribution from the gamma results. In the future, we will attempt to measure the 4D dose distribution for clinical volumetric modulated arc radiation therapy (VMAT)-SBRTplans., (© 2021 American Association of Physicists in Medicine.)

Purpose: Cardiac implantable electronic devices (CIEDs) were believed to possess a tolerance dose to malfunction during radiotherapy. Although recent studies have qualitatively suggested neutrons as a cause of malfunction, numerical understanding has not been reached. The purpose of this work is to quantitatively clarify the contribution of secondary neutrons from out-of-field irradiation to the malfunction of CIEDs as well as to deduce the frequency of malfunctions until completion of prostate cancer treatment as a typical case., Materials and Methods: Measured data were gathered from the literature and were re-analyzed. Firstly, linear relationship for a number of malfunctions to the neutron dose was suggested by theoretical consideration. Secondly, the accumulated number of malfunctions of CIEDs gathered from the literature was compared with the prescribed dose, scattered photon dose, and secondary neutron dose for analysis of their correlation. Thirdly, the number of malfunctions during a course of prostate treatment with high-energy X-ray, passive proton, and passive carbon-ion beams was calculated while assuming the same response to malfunctions, where X-rays consisted of 6-MV, 10-MV, 15-MV, and 18-MV beams. Monte Carlo simulation assuming simple geometry was performed for the distribution of neutron dose from X-ray beams, where normalization factors were applied to the distribution so as to reproduce the empirical values., Results: Linearity between risk and neutron dose was clearly found from the measured data, as suggested by theoretical consideration. The predicted number of malfunctions until treatment completion was 0, 0.02 ± 0.01, 0.30 ± 0.08, 0.65 ± 0.17, 0.88 ± 0.50, and 0.14 ± 0.04 when 6-MV, 10-MV, 15-MV, 18-MV, passive proton, and passive carbon-ion beams, respectively, were employed, where the single model response to a malfunction of 8.6 ± 2.1 Sv - 1 was applied., Conclusions: Numerical understanding of the malfunction of CIEDs has been attained for the first time. It has been clarified that neutron dose is a good scale for the risk of CIEDs in radiotherapy. Prediction of the frequency of malfunction as well as discussion of the risk to CIEDs in radiotherapy among the multiple modalities have become possible. Because the present study quantitatively clarifies the neutron contribution to malfunction, revision of clinical guidelines is suggested., (© 2020 American Association of Physicists in Medicine.)

Purpose: We aim to develop a method to predict the gamma passing rate (GPR) of a three-dimensional (3D) dose distribution measured by the Delta4 detector system using the dose uncertainty potential (DUP) accumulation model., Methods: Sixty head-and-neck intensity-modulated radiation therapy (IMRT) treatment plans were created in the XiO treatment planning system. All plans were created using nine step-and-shoot beams of the ONCOR linear accelerator. Verification plans were created and measured by the Delta4 system. The planar DUP (pDUP) manifesting on a field edge was generated from the segmental aperture shape with a Gaussian folding on the beam's-eye view. The DUP at each voxel ( u ) was calculated by projecting the pDUP on the Delta4 phantom with its attenuation considered. The learning model (LM), an average GPR as a function of the DUP, was approximated by an exponential function a GPR u = e - q u to compensate for the low statistics of the learning data due to a finite number of the detectors. The coefficient q was optimized to ensure that the difference between the measured and predicted GPRs ( d GPR ) was minimized. The standard deviation (SD) of the d GPR was evaluated for the optimized LM., Results: It was confirmed that the coefficient q was larger for tighter tolerance. This result corresponds to the expectation that the attenuation of the a GPR u will be large for tighter tolerance. The p GPR and m GPR were observed to be proportional for all tolerances investigated. The SD of d GPR was 2.3, 4.1, and 6.7% for tolerances of 3%/3 mm, 3%/2 mm, 2%/2 mm, respectively., Conclusion: The DUP-based predicting method of the GPR was extended to 3D by introducing DUP attenuation and an optimized analytical LM to compensate for the low statistics of the learning data due to a finite number of detector elements. The precision of the predicted GPR is expected to be improved by improving the LM and by involving other metrics., (© 2019 American Association of Physicists in Medicine.)

Purpose: A patient's respiratory monitoring is one of the key techniques in radiotherapy for a moving target. Generally, such monitoring systems are permanently set to a fixed geometry during the installation. This study aims to enable a temporary setup of such a monitoring system by developing a fast method to automatically calibrate the geometrical position by a quick measurement of calibration markers., Methods: One calibration marker was placed on the isocenter and the other six markers were placed at positions 5-cm apart from the isocenter to the left, right, anterior, posterior, superior, and inferior directions. A near-infrared (NIR) camera (NIC) [Kinect v2 (Microsoft Corp.)] was arbitrarily set with ten different angles around the calibration phantom with a fixed tilting-down angle at approximately 45° in a linear accelerator treatment vault. The three-dimensional (3D) coordinates in the camera (Cam) coordinate system (CS; x and y are the horizontal and vertical coordinates of the image, respectively, and z is a coordinate along the NIR time-of-flight) were taken for 1 min with 30 frames per second. The data corresponding to the measurement times of 1, 3, 10, 30, and 60 s were created to mimic various measurement times. These data were used to calculate the initial matrix elements, which included six parameters of the pitching, yawing, and rolling angles; horizontal two-dimensional translation in the treatment room; and the source-to-axis distance of NIC, for a conversion from the Cam CS to the treatment room CS for which the origin was defined at the isocenter (Iso coordinate). The six parameters were then optimized to minimize the displacements of the calculated marker coordinates from the actual positions in the Iso CS. The 3D positional accuracy and angular accuracy of the conversion were evaluated. The random error of the Iso coordinates was analyzed through a relation with the angle of each measurement setup., Results: Three angles of NIC and relative translation vectors were successfully calculated from the measurement data of the calibration markers. The achieved spatial and angular accuracies were 0.02 mm and 1.6°, respectively, after the optimization. Among the mimicked measurement times investigated in this study, both spatial and angular accuracies had no dependence on the measurement time. The average random error of a static marker was 0.46 mm after the optimization., Conclusion: We developed an automatic method to calibrate the 3D patient surface monitoring system. The procedure developed in this study enabled a quick calibration of NIC, which can be easily repeated multiple times for a frequent and quick setup of the monitoring system., (© 2019 American Association of Physicists in Medicine.)

Purpose: Intensity-modulated radiation therapy (IMRT) utilizes many small fields for producing a uniform dose distribution. Therefore, there are many field junctions in the target region, and resulting dose uncertainties are accumulated. However, such accumulation of the dose uncertainty has not been implemented in the current practice of IMRT dose verification. The purpose of this study is to develop a method to predict the gamma passing rate (GPR) using a dose uncertainty accumulation model., Methods: Thirty-three intensity-modulated (IM) beams for head-and-neck cases with step-and-shoot techniques were used in this study. The treatment plan was created using the XiO treatment planning system (TPS). The IM beam was produced by the ONCOR Impression Plus linear accelerator. MapCHECK was used to measure the dose distribution. The distribution of a dose uncertainty potential (DUP) was generated by in-house software that accumulated field shapes weighted by a segmental monitor unit, followed by Gaussian folding. The width of the Gaussian was determined from the width of the lateral penumbra. The dose difference between the calculated and measured doses was compared with the estimated DUP at each point. The GPR of each beam was predicted for 2%/2-mm, 3%/2-mm, and 3%/3-mm tolerances by its own DUP histogram and a GPR-vs-DUP correlation of other beams using the leave-one-out cross-validation method. The predicted GPR was compared with the measured GPR to evaluate the performance of this prediction method. The criteria for the predicted GPR corresponding to a measured GPR ≥ 90% were estimated to examine the feasibility of estimating the measured GPR by this GPR prediction method., Results: The DUP was confirmed to have proportionality to the standard deviation (SD) of the dose difference. The SDs of the difference between the measured and predicted GPRs were 3.1, 1.7, and 1.4% for 2%/2-mm, 3%/2-mm, and 3%/3-mm tolerances, respectively. The criteria of the predicted GPR corresponding to the measured GPR ≥ 90% were 94.1 and 95.0% with confidence levels of 99 and 99.9%, respectively., Conclusion: In this study, we confirmed the good proportionality between the dose difference and the estimated DUP. The results showed a feasibility to predict the dose difference from DUP as estimated by a DUP accumulation model. The predicted GPR developed in this study showed good accuracy for planar dose distributions of head and neck IMRT. The prediction method developed in this study is considered to be feasible as a substitute for the current practice of measurement-based verification of the dose distribution with gamma analysis., (© 2018 American Association of Physicists in Medicine.)

Purpose: High accuracy of the beam-irradiated position is required for high-precision radiation therapy such as stereotactic body radiation therapy (SBRT), volumetric modulated arc therapy (VMAT), and intensity modulated radiation therapy (IMRT). Users generally perform the verification of the mechanical and radiation isocenters using the star shot test and the Winston Lutz test that allow evaluation of the displacement at the isocenter. However, these methods are unable to evaluate directly and quantitatively the sagging angle that is caused by the weight of the gantry itself along the gantry rotation axis. In addition, the verification of the central axis of the irradiated beam that is not dependent at the isocenter is needed for the mechanical quality assurance of a nonisocentric irradiation technique. In this study, we have developed a prototype system for the verification of three-dimensional (3D) beam alignment and we have verified the system concept for 3D isocentricity. Our system allows detection of the central axis in 3D coordinates and evaluation of the irradiated oblique angle to the gantry rotation axis, i.e., the sagging angle., Materials & Methods: In order to measure the central axis of the irradiated beam in 3D coordinates, we constructed the prototype verification system consisting of a column-shaped plastic scintillator (CoPS), a truncated cone-shaped mirror (TCsM), and a cooled charged-coupled device (CCD) camera. This verification system was irradiated with 6-MV photon beams and the scintillation light was measured using the CCD camera. The central axis on the axial plane (two-dimensional (2D) central axis) was acquired from the integration of the scintillation light along the major axis of the CoPS, and the central axis in 3D coordinates (3D central axis) was acquired from two curve-shaped profiles which were reflected by the TCsM. We verified the calculation accuracy of the gantry rotation axis, θ z . Additionally, we calculated the 3D central axis and the sagging angle at each gantry angle., Results: We acquired the measurement images composed of the 2D central axis and the two curve-shaped profiles. The relationship between the irradiated and measured angles with respect to the gantry rotation axis had good linearity. The mean and standard deviation of the difference between the irradiated and measured angles were 0.012 and 0.078 degrees, respectively. The size of the 2D and 3D radiation isocenters were 0.470 and 0.652 mm on the axial plane and in 3D coordinates, respectively. The sagging angles were -0.31, 0.39, and 0.38 degrees at the gantry angles of 0, 180, and 180E degrees, respectively., Conclusion: We developed a novel verification system, designated as the "kompeito shot test system," to verify the 3D beam alignment. This system concept works for both verification of the 3D isocentricity and the direct evaluation of the sagging angle. Next, we want to improve the aspects of this system, such as the shape and the type of scintillator, to increase the system accuracy and nonisocentric beam alignment performance., (© 2018 American Association of Physicists in Medicine.)

Purpose: The validation of deformable image registration (DIR)-based pulmonary ventilation mapping is time consuming and prone to inaccuracies and is also affected by deformation parameters. In this study, we developed a nonrigid phantom as a quality assurance (QA) tool that simulates ventilation to evaluate DIR-based images quantitatively., Methods: The phantom consists of an acrylic cylinder filled with polyurethane foam designed to simulate pulmonic alveoli. A polyurethane membrane is attached to the inferior end of the phantom to simulate the diaphragm. In addition, tracheobronchial-tree-shaped polyurethane tubes are inserted through the foam and converge outside the phantom to simulate the trachea. Solid polyurethane is also used to model arteries, which closely follow the model airways. Two three-dimensional (3D) CT scans were performed during exhalation and inhalation phases using xenon (Xe) gas as the inhaled contrast agent. The exhalation 3D-CT image is deformed to an inhalation 3D-CT image using our in-house program based on the NiftyReg open-source package. The target registration error (TRE) between the two images was calculated for 16 landmarks located in the simulated lung volume. The DIR-based ventilation image was generated using Jacobian determinant (JD) metrics. Subsequently, differences in the Hounsfield unit (HU) values between the two images were measured. The correlation coefficient between the JD and HU differences was calculated. In addition, three 4D-CT scans are performed to evaluate the reproducibility of the phantom motion and Xe gas distribution., Results: The phantom exhibited a variety of displacements for each landmark (range: 1-20 mm). The reproducibility analysis indicated that the location differences were <1 mm for all landmarks, and the HU variation in the Xe gas distribution was close to zero. The mean TRE in the evaluation of spatial accuracy according to the DIR software was 1.47 ± 0.71 mm (maximum: 2.6 mm). The relationship between the JD and HU differences had a large correlation (R = -0.71) for the DIR software., Conclusion: The phantom implemented new features, namely, deformation and simulated ventilation. To assess the accuracy of the DIR-based mapping of the simulated pulmonary ventilation, the phantom allows for simulation of Xe gas wash-in and wash-out. The phantom may be an effective QA tool, because the DIR algorithm can be quickly changed and its accuracy evaluated with a high degree of precision., (© 2018 American Association of Physicists in Medicine.)

Purpose: Stereotactic body radiation therapy (SBRT) combining trans-arterial chemoembolization (TACE) with Lipiodol is expected to improve local control. This study is aimed to estimate the dose enhancement in Lipiodol's proximity and to evaluate the dose calculation accuracy of the Acuros XB (AXB) algorithm and anisotropic analytical algorithm (AAA) in the Eclipse treatment planning system (TPS) (ver. 11, Varian Medical Systems, Palo Alto, USA), compared with that of the Monte Carlo (MC) calculation (using BEAMnrc/DOSXYZnrc code) for a virtual phantom and a treatment plan for liver SBRT after TACE., Methods: The MC calculation accuracy was validated by comparing its results with the percent depth dose (PDD) and the off-axis ratio (OAR) measured using a water-equivalent phantom containing Lipiodol. The dose difference in Lipiodol's proximity and the inhomogeneity correction accuracies of the AAA, AXB algorithm, and MC calculation were evaluated by calculating the PDDs and OARs for the virtual phantom with Lipiodol and the lateral profile for the clinical plan data., Results: The measured data and the MC results agreed within 3%. The average dose in the Lipiodol uptake region was higher by 8.1% for the virtual phantom and 6.0% for the clinical case compared to that in regions without Lipiodol uptake. For the virtual phantom, compared with the MC calculation, the AAA and the AXB algorithm underestimated the doses immediately upstream of the Lipiodol region by 5.0% and 4.2%, in the Lipiodol region by 7.4% and 9.8%, and downstream of the Lipiodol region by 5.5% and 3.9% respectively. These discrepancy between the AXB and MC calculations were due to the incorrect assignment of Lipiodol material properties. Namely, the bone material was assigned automatically by the AXB algorithm as the materials for the AXB algorithm do not contain iodine, which is the main constituent of Lipiodol., Conclusions: The MC calculation indicated a larger and more accurate dose increase in Lipiodol compared with the TPS algorithms. The observed dose enhancement in the tumor area could be clinically significant., (© 2016 American Association of Physicists in Medicine.)

Purpose: IAEA TRS-398 notes that cylindrical ionization chambers are preferred for reference proton dosimetry. If a cylindrical ionization chamber is used in a phantom to measure the dose as a function of depth, the effective point of measurement (EPOM) must be taken into account. IAEA TRS-398 recommends a displacement of 0.75 times the inner cavity radius (0.75R) for heavy ion beams. Theoretical models by Palmans and by Bhullar and Watchman confirmed this value. However, the experimental results vary from author to author. The purpose of this study is to accurately measure the displacement and explain the past experimental discrepancies., Methods: In this work, we measured the EPOM of cylindrical ionization chambers with high accuracy by comparing the Bragg-peak position obtained with cylindrical ionization chambers (PTW 30013, PTW 31016) to that obtained using a plane-parallel ionization chamber (PTW 34045)., Results: The EPOMs of PTW 30013 and 31016 were shifted by 0.92 ± 0.07 R with R = 3.05 mm and 0.90 ± 0.14 R with R = 1.45 mm, respectively, from the reference point toward the source., Conclusions: The EPOMs obtained were greater than the value of 0.75R proposed by the IAEA TRS-398 and the analytical results.

Purpose: Recently, much research on imaging the clinical proton-irradiated volume using positron emitter nuclei based on target nuclear fragment reaction has been carried out. The purpose of this study is to develop an activity pencil beam (APB) algorithm for a simulation system for proton-activated positron-emitting imaging in clinical proton therapy using spread-out Bragg peak (SOBP) beams., Methods: The target nuclei of activity distribution calculations are (12)C nuclei, (16)O nuclei, and (40)Ca nuclei, which are the main elements in a human body. Depth activity distributions with SOBP beam irradiations were obtained from the material information of ridge filter (RF) and depth activity distributions of compounds of the three target nuclei measured by BOLPs-RGp (beam ON-LINE PET system mounted on a rotating gantry port) with mono-energetic Bragg peak (MONO) beam irradiations. The calculated data of depth activity distributions with SOBP beam irradiations were sorted in terms of kind of nucleus, energy of proton beam, SOBP width, and thickness of fine degrader (FD), which were verified. The calculated depth activity distributions with SOBP beam irradiations were compared with the measured ones. APB kernels were made from the calculated depth activity distributions with SOBP beam irradiations to construct a simulation system using the APB algorithm for SOBP beams., Results: The depth activity distributions were prepared using the material information of RF and the measured depth activity distributions with MONO beam irradiations for clinical therapy using SOBP beams. With the SOBP width widening, the distal fall-offs of depth activity distributions and the difference from the depth dose distributions were large. The shapes of the calculated depth activity distributions nearly agreed with those of the measured ones upon comparison between the two. The APB kernels of SOBP beams were prepared by making use of the data on depth activity distributions with SOBP beam irradiations that were made from the depth activity distributions with MONO beam irradiations and sorted in terms of energy, SOBP width, and thickness of FD. The data on APB kernels of SOBP beams were determined as installment data for the simulation system using the APB algorithm for SOBP beam irradiations., Conclusions: A method of obtaining the depth activity distributions and the APB algorithm for clinical use of SOBP beams have been developed. It is suggested that the simulation system for imaging the clinical irradiated volume with the APB algorithm can be used in clinical proton therapy using SOBP beams by preparing and investigating the data on APB kernels of SOBP beams.

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: The purpose of this study is to develop a new calculation algorithm that is satisfactory in terms of the requirements for both accuracy and calculation time for a simulation of imaging of the proton-irradiated volume in a patient body in clinical proton therapy., Methods: The activity pencil beam algorithm (APB algorithm), which is a new technique to apply the pencil beam algorithm generally used for proton dose calculations in proton therapy to the calculation of activity distributions, was developed as a calculation algorithm of the activity distributions formed by positron emitter nuclei generated from target nuclear fragment reactions. In the APB algorithm, activity distributions are calculated using an activity pencil beam kernel. In addition, the activity pencil beam kernel is constructed using measured activity distributions in the depth direction and calculations in the lateral direction. (12)C, (16)O, and (40)Ca nuclei were determined as the major target nuclei that constitute a human body that are of relevance for calculation of activity distributions. In this study, "virtual positron emitter nuclei" was defined as the integral yield of various positron emitter nuclei generated from each target nucleus by target nuclear fragment reactions with irradiated proton beam. Compounds, namely, polyethylene, water (including some gelatin) and calcium oxide, which contain plenty of the target nuclei, were irradiated using a proton beam. In addition, depth activity distributions of virtual positron emitter nuclei generated in each compound from target nuclear fragment reactions were measured using a beam ON-LINE PET system mounted a rotating gantry port (BOLPs-RGp). The measured activity distributions depend on depth or, in other words, energy. The irradiated proton beam energies were 138, 179, and 223 MeV, and measurement time was about 5 h until the measured activity reached the background level. Furthermore, the activity pencil beam data were made using the activity pencil beam kernel, which was composed of the measured depth data and the lateral data including multiple Coulomb scattering approximated by the Gaussian function, and were used for calculating activity distributions., Results: The data of measured depth activity distributions for every target nucleus by proton beam energy were obtained using BOLPs-RGp. The form of the depth activity distribution was verified, and the data were made in consideration of the time-dependent change of the form. Time dependence of an activity distribution form could be represented by two half-lives. Gaussian form of the lateral distribution of the activity pencil beam kernel was decided by the effect of multiple Coulomb scattering. Thus, the data of activity pencil beam involving time dependence could be obtained in this study., Conclusions: The simulation of imaging of the proton-irradiated volume in a patient body using target nuclear fragment reactions was feasible with the developed APB algorithm taking time dependence into account. With the use of the APB algorithm, it was suggested that a system of simulation of activity distributions that has levels of both accuracy and calculation time appropriate for clinical use can be constructed.

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.

Purpose: Successful results in carbon-ion and proton radiotherapies can extend patients' lives and thus present a treatment option for younger patients; however, the undesired exposure to normal tissues outside the treatment volume is a concern. Organ-specific information on the absorbed dose and the biological effectiveness in the patient is essential for assessing the risk, but experimental dose assessment has seldom been done. In this study, absorbed doses, quality factors, and dose equivalents in water phantom outside of the irradiation field were determined based on lineal energy distributions measured with a commercial tissue equivalent proportional counter (TEPC) at passive carbon-ion and proton radiotherapy facilities., Methods: Measurements at eight positions in the water phantom were carried out at the Heavy-Ion Medical Accelerator in Chiba of the National Institute of Radiological Sciences for 400 and 290 MeV/u carbon beams and at the National Cancer Center Hospital East for a 235 MeV proton beam., Results: The dose equivalent per treatment absorbed dose at the center of the range-modulated region H/Dt, decreased as the position became farther from the beam axis and farther from the phantom surface. The values of H/Dt ranged from 6.7 to 0.16 mSv/Gy for the 400 MeV/u carbon beam, from 1.3 to 0.055 mSv/Gy for the 290 MeV/u carbon beam, and from 4.7 to 0.24 mSv/GV for the 235 MeV proton beam. The values of the dose-averaged quality factor QD ranged from 2.4 to 4.6 for the 400 MeV/u beam, from 2.8 to 5.3 for the 290 MeV/u beam, and from 5.1 to 8.2 for the proton beam. The authors also observed differences in the distributions of H/Dt and QD between the carbon and proton beams., Conclusions: The authors experimentally obtained absorbed doses, dose-averaged quality factors, and dose equivalents in water phantom outside of the irradiation field in passive carbon-ion and proton radiotherapies with TEPC. These data are very useful for estimating the risk of secondary cancer after receiving passive radiotherapies and for verifying Monte Carlo calculations.

Purpose: The purpose of this study is to verify the characteristics of the positron emitter nuclei generated at each treatment site by proton irradiation., Methods: Proton therapy using a beam on-line PET system mounted on a rotating gantry port (BOLPs-RGp), which the authors developed, is provided at the National Cancer Center Kashiwa, Japan. BOLPs-RGp is a monitoring system that can confirm the activity distribution of the proton irradiated volume by detection of a pair of annihilation gamma rays coincidentally from positron emitter nuclei generated by the target nuclear fragment reactions between irradiated proton nuclei and nuclei in the human body. Activity is measured from a start of proton irradiation to a period of 200 s after the end of the irradiation. The characteristics of the positron emitter nuclei generated in a patient's body were verified by the measurement of the activity distribution at each treatment site using BOLPs-RGp., Results: The decay curves for measured activity were able to be approximated using two or three half-life values regardless of the treatment site. The activity of half-life value of about 2 min was important for a confirmation of the proton irradiated volume., Conclusions: In each proton treatment site, verification of the characteristics of the generated positron emitter nuclei was performed by using BOLPs-RGp. For the monitoring of the proton irradiated volume, the detection of (15)O generated in a human body was important.

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.

Proton therapy is one form of radiotherapy in which the irradiation can be concentrated on a tumor using 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 emitter nuclei generated by the target nuclear fragment reaction of irradiated proton nuclei and nuclei in the irradiation target using a positron emission tomography (PET) apparatus, and dose-volume delivery guided proton therapy (DGPT) can thereby be achieved using PET images. In the proton treatment room, a beam ON-LINE PET system (BOLPs) was constructed so that a PET apparatus of the planar-type with a high spatial resolution of about 2 mm was mounted with the field of view covering the isocenter of the beam irradiation system. The position and intensity of activity were measured using the BOLPs immediately after the proton irradiation of a gelatinous water target containing 16O nuclei at different proton irradiation energy levels. The change of the activity-distribution range against the change of the physical range was observed within 2 mm. The experiments of proton irradiation to a rabbit and the imaging of the activity were performed. In addition, the proton beam energy used to irradiate the rabbit was changed. When the beam condition was changed, the difference between the two images acquired from the measurement of the BOLPs was confirmed to clearly identify the proton-irradiated volume.

In proton radiotherapy, the irradiation dose can be concentrated on a tumor. To use this radiotherapy efficiently in the clinical field, it is necessary to evaluate the proton-irradiated area and condition. The proton-irradiated area can be confirmed by coincidence detection of pair annihilation gamma rays from beta+ decayed nuclei generated by target nuclear fragment reaction of irradiated proton nuclei and nuclei in the irradiation target. In this study, we performed experiments of proton irradiation to a polyethylene (PE:CH2) target containing 12C nuclei, which is a major component of the human body, and a gelatinous water (H2O) target containing 16O nuclei at different proton irradiation energy levels under different beam conditions of mono-energetic Bragg peak and spread-out Bragg peak. The distribution of the activity in the target after proton irradiation was measured by a positron emission tomography (PET) apparatus, and compared with the calculated distribution. The temporal dependence of the activity distribution during the period between the completion of proton irradiation and the start of measurement by the PET apparatus was examined. The activity by clinical proton irradiation was 3 kB/cc in the PE target and 13 kB/cc in the water target, indicating that the intensity was sufficient for the evaluation of the distribution. The range of the activity distribution against the physical range was short (several millimeter water equivalent length), indicating the presence of target dependence. The range difference in the water target was slightly large with time dependence until the start of measurement. The difference of the lateral widths with full width half at maximum in the distributions of the measured irradiated dose and activity was within 1 mm.