Researcher Profile and Settings

Affiliation

• Faculty of Engineering　Applied Quantum Science and Engineering　Quantum Engineering for Life Science and Medicine

Job Title

• Associate Professor

Educational Organization

•  Bachelor's degree program　School of Engineering
•  Master's degree program　Graduate School of Biomedical Science and Engineering
•  Doctoral (PhD) degree program　Graduate School of Biomedical Science and Engineering

Research Activities

Published Papers

• A Single-Institution Prospective Study To Evaluate the Safety and Efficacy of Real- Time Image-Gated Spot-Scanning Proton Therapy (RGPT) for Prostate Cancer.

  Kentaro Nishioka, Takayuki Hashimoto, Takashi Mori, Yusuke Uchinami, Rumiko Kinoshita, Norio Katoh, Hiroshi Taguchi, Koichi Yasuda, Yoichi M Ito, Seishin Takao, Masaya Tamura, Taeko Matsuura, Shinichi Shimizu, Hiroki Shirato, Hidefumi Aoyama

  Advances in radiation oncology 9 (5) 101464 - 101464 2024/05 

  PURPOSE: In real-time image-gated spot-scanning proton therapy (RGPT), the dose distribution is distorted by gold fiducial markers placed in the prostate. Distortion can be suppressed by using small markers and more than 2 fields, but additional fields may increase the dose to organs at risk. Therefore, we conducted a prospective study to evaluate the safety and short-term clinical outcome of RGPT for prostate cancer. METHODS AND MATERIALS: Based on the previously reported frequency of early adverse events (AE) and the noninferiority margin of 10%, the required number of cases was calculated to be 43 using the one-sample binomial test by the Southwest Oncology Group statistical tools with the one-sided significance level of 2.5% and the power 80%. Patients with localized prostate cancer were enrolled and 3 to 4 pure gold fiducial markers of 1.5-mm diameter were inserted in the prostate. The prescribed dose was 70 Gy(relative biologic effectiveness) in 30 fractions, and treatment was performed with 3 fields from the left, right, and the back, or 4 fields from either side of slightly anterior and posterior oblique fields. The primary endpoint was the frequency of early AE (≥grade 2) and the secondary endpoint was the biochemical relapse-free survival rate and the frequency of late AE. RESULTS: Forty-five cases were enrolled between 2015 and 2017, and all patients completed the treatment protocol. The median follow-up period was 63.0 months. The frequency of early AE (≥grade 2) was observed in 4 cases (8.9%), therefore the noninferiority was verified. The overall 5-year biochemical relapse-free survival rate was 88.9%. As late AE, grade 2 rectal bleeding was observed in 8 cases (17.8%). CONCLUSIONS: The RGPT for prostate cancer with 1.5-mm markers and 3- or 4- fields was as safe as conventional proton therapy in early AE, and its efficacy was comparable with previous studies.
• Technical note: Application of an optical hydrophone to ionoacoustic range detection in a tissue-mimicking agar phantom.

  Shota Sueyasu, Koki Kasamatsu, Taisuke Takayanagi, Ye Chen, Yasutoshi Kuriyama, Yoshihiro Ishi, Tomonori Uesugi, Wolfgang Rohringer, Mehmet Burcin Unlu, Nobuki Kudo, Kohei Yokokawa, Seishin Takao, Naoki Miyamoto, Taeko Matsuura

  Medical physics 2023/12/21 

  BACKGROUND: Ionoacoustics is a promising approach to reduce the range uncertainty in proton therapy. A miniature-sized optical hydrophone (OH) was used as a measuring device to detect weak ionoacoustic signals with a high signal-to-noise ratio in water. However, further development is necessary to prevent wave distortion because of nearby acoustic impedance discontinuities while detection is conducted on the patient's skin. PURPOSE: A prototype of the probe head attached to an OH was fabricated and the required dimensions were experimentally investigated using a 100-MeV proton beam from a fixed-field alternating gradient accelerator and k-Wave simulations. The beam range of the proton in a tissue-mimicking phantom was estimated by measuring γ-waves and spherical ionoacoustic waves with resonant frequency (SPIRE). METHODS: Four sizes of probe heads were fabricated from agar blocks for the OH. Using the prototype, the γ-wave was detected at distal and lateral positions to the Bragg peak on the phantom surface for proton beams delivered at seven positions. For SPIRE, independent measurements were performed at distal on- and off-axis positions. The range positions were estimated by solving the linear equation using the sensitive matrix for the γ-wave and linear fitting of the correlation curve for SPIRE; they were compared with those measured using a film. RESULTS: The first peak of the γ-wave was undistorted with the 3 × 3 × 3-cm3 probe head used at the on-axis and 3-cm off-axis positions. The range positions estimated by the γ-wave agreed with the film-based range in the depth direction (the maximum deviation was 0.7 mm), although a 0.6-2.1 mm deviation was observed in the lateral direction. For SPIRE, the deviation was <1 mm for the two measurement positions. CONCLUSIONS: The attachment of a relatively small-sized probe head allowed the OH to measure the beam range on the phantom surface.
• Study of hepatic toxicity in small liver tumors after photon or proton therapy based on factors predicting the benefits of proton.

  Yusuke Uchinami, Norio Katoh, Daisuke Abo, Ryo Morita, Hiroshi Taguchi, Yoshihiro Fujita, Takahiro Kanehira, Ryusuke Suzuki, Naoki Miyamoto, Seishin Takao, Taeko Matsuura, Takuya Sho, Koji Ogawa, Tatsuya Orimo, Tatsuhiko Kakisaka, Keiji Kobashi, Hidefumi Aoyama

  The British journal of radiology 96 (1144) 20220720 - 20220720 2023/03/01 

  OBJECTIVES: In a previous study of hepatic toxicity, the following three factors were identified to predict the benefits of proton beam therapy (PBT) for hepatocellular carcinomas (HCCs) with a maximum diameter of ≤5 cm and Child-pugh grade A (CP-A): number of tumors (1 vs ≥2), the location of tumors (hepatic hilum or others), and the sum of the diameters of lesions. The aim of this study is to analyze the association between these three factors and hepatic toxicity. METHODS: We retrospectively reviewed patients of CP-A treated with PBT or photon stereotactic body radiotherapy (X-ray radiotherapy, XRT) for HCC ≤5 cm. For normal liver dose, the V5, V10, V20 (volumes receiving 5, 10, and 20 Gy at least), and the mean dose was evaluated. The albumin-bilirubin (ALBI) and CP score changes from the baseline were evaluated at 3 and 6 months after treatment. RESULTS: In 89 patients (XRT: 48, PBT: 41), those with two or three (2-3) predictive factors were higher normal liver doses than with zero or one (0-1) factor. In the PBT group, the ALBI score worsened more in patients with 2-3 factors than those with 0-1 factor, at 3 months (median: 0.26 vs 0.02, p = 0.032) and at 6 months (median: 0.35 vs 0.10, p = 0.009). The ALBI score change in the XRT group and CP score change in either modality were not significantly different in the number of predictive factors. CONCLUSION: The predictive factor numbers predicted the ALBI score change in PBT but not in XRT. ADVANCES IN KNOWLEDGE: This study suggest that the number of predictive factors previously identified (0-1 vs 2-3) were significantly associated with dosimetric parameters of the normal liver in both modalities. In the proton group, the number of predictive factors was associated with a worsening ALBI score at 3 and 6 months, but these associations were not found in the photon SBRT group.
• Technical note: Performance evaluation of volumetric imaging based on motion modeling by principal component analysis.

  Suzuka Asano, Keishi Oseki, Seishin Takao, Koichi Miyazaki, Kohei Yokokawa, Taeko Matsuura, Hiroshi Taguchi, Norio Katoh, Hidefumi Aoyama, Kikuo Umegaki, Naoki Miyamoto

  Medical physics 50 (2) 993 - 999 2023/02 

  PURPOSE: To quantitatively evaluate the achievable performance of volumetric imaging based on lung motion modeling by principal component analysis (PCA). METHODS: In volumetric imaging based on PCA, internal deformation was represented as a linear combination of the eigenvectors derived by PCA of the deformation vector fields evaluated from patient-specific four-dimensional-computed tomography (4DCT) datasets. The volumetric image was synthesized by warping the reference CT image with a deformation vector field which was evaluated using optimal principal component coefficients (PCs). Larger PCs were hypothesized to reproduce deformations larger than those included in the original 4DCT dataset. To evaluate the reproducibility of PCA-reconstructed volumetric images synthesized to be close to the ground truth as possible, mean absolute error (MAE), structure similarity index measure (SSIM) and discrepancy of diaphragm position were evaluated using 22 4DCT datasets of nine patients. RESULTS: Mean MAE and SSIM values for the PCA-reconstructed volumetric images were approximately 80 HU and 0.88, respectively, regardless of the respiratory phase. In most test cases including the data of which motion range was exceeding that of the modeling data, the positional error of diaphragm was less than 5 mm. The results suggested that large deformations not included in the modeling 4DCT dataset could be reproduced. Furthermore, since the first PC correlated with the displacement of the diaphragm position, the first eigenvector became the dominant factor representing the respiration-associated deformations. However, other PCs did not necessarily change with the same trend as the first PC, and no correlation was observed between the coefficients. Hence, randomly allocating or sampling these PCs in expanded ranges may be applicable to reasonably generate an augmented dataset with various deformations. CONCLUSIONS: Reasonable accuracy of image synthesis comparable to those in the previous research were shown by using clinical data. These results indicate the potential of PCA-based volumetric imaging for clinical applications.
• Deformed dose restoration to account for tumor deformation and position changes for adaptive proton therapy.

  Koichi Miyazaki, Yusuke Fujii, Takahiro Yamada, Takahiro Kanehira, Naoki Miyamoto, Taeko Matsuura, Koichi Yasuda, Yusuke Uchinami, Manami Otsuka, Hidefumi Aoyama, Seishin Takao

  Medical physics 50 (2) 675 - 687 2023/02 

  BACKGROUND: Online adaptation during intensity-modulated proton therapy (IMPT) can minimize the effect of inter-fractional anatomical changes, but remains challenging because of the complex workflow. One approach for fast and automated online IMPT adaptation is dose restoration, which restores the initial dose distribution on the updated anatomy. However, this method may fail in cases where tumor deformation or position changes occur. PURPOSE: To develop a fast and robust IMPT online adaptation method named "deformed dose restoration (DDR)" that can adjust for inter-fractional tumor deformation and position changes. METHODS: The DDR method comprises two steps: (1) calculation of the deformed dose distribution, and (2) restoration of the deformed dose distribution. First, the deformable image registration (DIR) between the initial clinical target volume (CTV) and the new CTV were performed to calculate the vector field. To ensure robustness for setup and range uncertainty and the ability to restore the deformed dose distribution, an expanded CTV-based registration to maintain the dose gradient outside the CTV was developed. The deformed dose distribution was obtained by applying the vector field to the initial dose distribution. Then, the voxel-by-voxel dose difference optimization was performed to calculate beam parameters that restore the deformed dose distribution on the updated anatomy. The optimization function was the sum of total dose differences and dose differences of each field to restore the initial dose overlap of each field. This method only requires target contouring, which eliminates the need for organs at risk (OARs) contouring. Six clinical cases wherein the tumor deformation and/or position changed on repeated CTs were selected. DDR feasibility was evaluated by comparing the results with those from three other strategies, namely, not adapted (continuing the initial plan), adapted by previous dose restoration, and fully optimized. RESULTS: In all cases, continuing the initial plan was largely distorted on the repeated CTs and the dose-volume histogram (DVH) metrics for the target were reduced due to the tumor deformation or position changes. On the other hand, DDR improved DVH metrics for the target to the same level as the initial dose distribution. Dose increase was seen for some OARs because tumor growth had reduced the relative distance between CTVs and OARs. Robustness evaluation for setup and range uncertainty (3 mm/3.5%) showed that deviation in DVH-bandwidth for CTV D95% from the initial plan was 0.4% ± 0.5% (Mean ± S.D.) for DDR. The calculation time was 8.1 ± 6.4 min. CONCLUSIONS: An online adaptation algorithm was developed that improved the treatment quality for inter-fractional anatomical changes and retained robustness for intra-fractional setup and range uncertainty. The main advantage of this method is that it only requires target contouring alone and saves the time for OARs contouring. The fast and robust adaptation method for tumor deformation and position changes described here can reduce the need for offline adaptation and improve treatment efficiency.
• Hyperfractionated intensity-modulated proton therapy for pharyngeal cancer with variable relative biological effectiveness: A simulation study.

  Koki Kasamatsu, Taeko Matsuura, Koichi Yasuda, Koichi Miyazaki, Seishin Takao, Masaya Tamura, Manami Otsuka, Yusuke Uchinami, Hidefumi Aoyama

  Medical physics 49 (12) 7815 - 7825 2022/12 

  BACKGROUND: The relative biological effectiveness (RBE) of proton is considered to be dependent on biological parameters and fractional dose. While hyperfractionated photon therapy was effective in the treatment of patients with head and neck cancers, its effect in intensity-modulated proton therapy (IMPT) under the variable RBE has not been investigated in detail. PURPOSE: To study the effect of variable RBE on hyperfractionated IMPT for the treatment of pharyngeal cancer. We investigated the biologically effective dose (BED) to determine the theoretical effective hyperfractionated schedule. METHODS: The treatment plans of three pharyngeal cancer patients were used to define the ΔBED for the clinical target volume (CTV) and soft tissue (acute and late reaction) as the difference between the BED for the altered schedule with variable RBE and conventional schedule with constant RBE. The ΔBED with several combinations of parameters (treatment days, number of fractions, and prescribed dose) was comprehensively calculated. Of the candidate schedules, the one that commonly gave a higher ΔBED for CTV was selected as the resultant schedule. The BED volume histogram was used to compare the influence of variable RBE and fractionation. RESULTS: In the conventional schedule, compared with the constant RBE, the variable RBE resulted in a mean 2.6 and 2.7 Gy reduction of BEDmean for the CTV and soft tissue (acute reaction) of the three plans, respectively. Moreover, the BEDmean for soft tissue (late reaction) increased by 7.4 Gy, indicating a potential risk of increased RBE. Comprehensive calculation of the ΔBED resulted in the hyperfractionated schedule of 80.52 Gy (RBE = 1.1)/66 fractions in 6.5 weeks. When variable RBE was used, compared with the conventional schedule, the hyperfractionated schedule increased the BEDmean for CTV by 7.6 Gy; however, this was associated with a 7.8 Gy increase for soft tissue (acute reaction). The BEDmean for soft tissue (late reaction) decreased by 2.4 Gy. CONCLUSION: The results indicated a potential effect of the variable RBE on IMPT for pharyngeal cancer but with the possibility that hyperfractionation could outweigh this effect. Although biological uncertainties require conservative use of the resultant schedule, hyperfractionation is expected to be an effective strategy in IMPT for pharyngeal cancer.
• A study on predicting cases that would benefit from proton beam therapy in primary liver tumors of less than or equal to 5 cm based on the estimated incidence of hepatic toxicity.

  Yusuke Uchinami, Norio Katoh, Ryusuke Suzuki, Takahiro Kanehira, Masaya Tamura, Seishin Takao, Taeko Matsuura, Naoki Miyamoto, Yoshihiro Fujita, Fuki Koizumi, Hiroshi Taguchi, Koichi Yasuda, Kentaro Nishioka, Isao Yokota, Keiji Kobashi, Hidefumi Aoyama

  Clinical and translational radiation oncology 35 70 - 75 2022/07 

  BACKGROUND: For small primary liver tumors, favorable outcomes have been reported with both of proton beam therapy (PBT) and X-ray therapy (XRT). However, no clear criteria have been proposed in the cases for which and when of PBT or XRT has to be used. The aim of this study is to investigate cases that would benefit from PBT based on the predicted rate of hepatic toxicity. MATERIALS AND METHODS: Eligible patients were those who underwent PBT for primary liver tumors with a maximum diameter of ≤ 5 cm and Child-Pugh grade A (n = 40). To compare the PBT-plan, the treatment plan using volumetric modulated arc therapy was generated as the XRT-plan. The rate of predicted hepatic toxicity was estimated using five normal tissue complication probability (NTCP) models with three different endpoints. The differences in NTCP values (ΔNTCP) were calculated to determine the relative advantage of PBT. Factors predicting benefits of PBT were analyzed by logistic regression analysis. RESULTS: From the dose-volume histogram comparisons, an advantage of PBT was found in sparing of the normal liver receiving low doses. The factors predicting the benefit of PBT differed depending on the selected NTCP model. From the five models, the total tumor diameter (sum of the target tumors), location (hepatic hilum vs other), and number of tumors (1 vs 2) were significant factors. CONCLUSIONS: From the radiation-related hepatic toxicity, factors were identified to predict benefits of PBT in primary liver tumors with Child-Pugh grade A, with the maximum tumor diameter of ≤ 5 cm.
• Impact of a spatially dependent dose delivery time structure on the biological effectiveness of scanning proton therapy.

  Koki Kasamatsu, Sodai Tanaka, Koichi Miyazaki, Seishin Takao, Naoki Miyamoto, Shusuke Hirayama, Kentaro Nishioka, Takayuki Hashimoto, Hidefumi Aoyama, Kikuo Umegaki, Taeko Matsuura

  Medical physics 49 (1) 702 - 713 2022/01 

  PURPOSE: In the scanning beam delivery of protons, different portions of the target are irradiated with different linear energy transfer protons with various time intervals and irradiation times. This research aimed to evaluate the spatially dependent biological effectiveness of protracted irradiation in scanning proton therapy. METHODS: One and two parallel opposed fields plans were created in water phantom with the prescribed dose of 2 Gy. Three scenarios (instantaneous, continuous, and layered scans) were used with the corresponding beam delivery models. The biological dose (physical dose × relative biological effectiveness) was calculated using the linear quadratic model and the theory of dual radiation action to quantitatively evaluate the dose delivery time effect. In addition, simulations using clinical plans (postoperative seminoma and prostate tumor cases) were conducted to assess the impact of the effects on the dose volume histogram parameters and homogeneity coefficient (HC) in targets. RESULTS: In a single-field plan of water phantom, when the treatment time was 19 min, the layered-scan scenario showed a decrease of <0.2% (almost 3.3%) in the biological dose from the plan on the distal (proximal) side because of the high (low) dose rate. This is in contrast to the continuous scenario, where the biological dose was almost uniformly decreased over the target by approximately 3.3%. The simulation with clinical geometry showed that the decrease rates in D99% were 0.9% and 1.5% for every 10 min of treatment time prolongation for postoperative seminoma and prostate tumor cases, respectively, whereas the increase rates in HC were 0.7% and 0.2%. CONCLUSIONS: In protracted irradiation in scanning proton therapy, the spatially dependent dose delivery time structure in scanning beam delivery can be an important factor for accurate evaluation of biological effectiveness.
• Prediction of liver Dmean for proton beam therapy using deep learning and contour-based data augmentation.

  Sira Jampa-Ngern, Keiji Kobashi, Shinichi Shimizu, Seishin Takao, Keiji Nakazato, Hiroki Shirato

  Journal of radiation research 2021/10/06 

  The prediction of liver Dmean with 3-dimensional radiation treatment planning (3DRTP) is time consuming in the selection of proton beam therapy (PBT), and deep learning prediction generally requires large and tumor-specific databases. We developed a simple dose prediction tool (SDP) using deep learning and a novel contour-based data augmentation (CDA) approach and assessed its usability. We trained the SDP to predict the liver Dmean immediately. Five and two computed tomography (CT) data sets of actual patients with liver cancer were used for the training and validation. Data augmentation was performed by artificially embedding 199 contours of virtual clinical target volume (CTV) into CT images for each patient. The data sets of the CTVs and OARs are labeled with liver Dmean for six different treatment plans using two-dimensional calculations assuming all tissue densities as 1.0. The test of the validated model was performed using 10 unlabeled CT data sets of actual patients. Contouring only of the liver and CTV was required as input. The mean relative error (MRE), the mean percentage error (MPE) and regression coefficient between the planned and predicted Dmean was 0.1637, 6.6%, and 0.9455, respectively. The mean time required for the inference of liver Dmean of the six different treatment plans for a patient was 4.47±0.13 seconds. We conclude that the SDP is cost-effective and usable for gross estimation of liver Dmean in the clinic although the accuracy should be improved further if we need the accuracy of liver Dmean to be compatible with 3DRTP.
• A treatment planning study of urethra-sparing intensity-modulated proton therapy for localized prostate cancer.

  Takaaki Yoshimura, Kentaro Nishioka, Takayuki Hashimoto, Kazuya Seki, Shouki Kogame, Sodai Tanaka, Takahiro Kanehira, Masaya Tamura, Seishin Takao, Taeko Matsuura, Keiji Kobashi, Fumi Kato, Hidefumi Aoyama, Shinichi Shimizu

  Physics and imaging in radiation oncology 20 23 - 29 2021/10 [Refereed]
   

  Background and Purpose: Urethra-sparing radiation therapy for localized prostate cancer can reduce the risk of radiation-induced genitourinary toxicity by intentionally underdosing the periurethral transitional zone. We aimed to compare the clinical impact of a urethra-sparing intensity-modulated proton therapy (US-IMPT) plan with that of conventional clinical plans without urethral dose reduction. Materials and Methods: This study included 13 patients who had undergone proton beam therapy. The prescribed dose was 63 GyE in 21 fractions for 99% of the clinical target volume. To compare the clinical impact of the US-IMPT plan with that of the conventional clinical plan, tumor control probability (TCP) and normal tissue complication probability (NTCP) were calculated with a generalized equivalent uniform dose-based Lyman-Kutcher model using dose volume histograms. The endpoints of these model parameters for the rectum, bladder, and urethra were fistula, contraction, and urethral stricture, respectively. Results: The mean NTCP value for the urethra in US-IMPT was significantly lower than that in the conventional clinical plan (0.6% vs. 1.2%, p < 0.05). There were no statistically significant differences between the conventional and US-IMPT plans regarding the mean minimum dose for the urethra with a 3-mm margin, TCP value, and NTCP value for the rectum and bladder. Additionally, the target dose coverage of all plans in the robustness analysis was within the clinically acceptable range. Conclusions: Compared with the conventional clinically applied plans, US-IMPT plans have potential clinical advantages and may reduce the risk of genitourinary toxicities, while maintaining the same TCP and NTCP in the rectum and bladder.
• Prediction of target position from multiple fiducial markers by partial least squares regression in real-time tumor-tracking radiation therapy.

  Kanako Ukon, Yohei Arai, Seishin Takao, Taeko Matsuura, Masayori Ishikawa, Hiroki Shirato, Shinichi Shimizu, Kikuo Umegaki, Naoki Miyamoto

  Journal of radiation research 62 (5) 926 - 933 2021/09/13 

  The purpose of this work is to show the usefulness of a prediction method of tumor location based on partial least squares regression (PLSR) using multiple fiducial markers. The trajectory data of respiratory motion of four internal fiducial markers inserted in lungs were used for the analysis. The position of one of the four markers was assumed to be the tumor position and was predicted by other three fiducial markers. Regression coefficients for prediction of the position of the tumor-assumed marker from the fiducial markers' positions is derived by PLSR. The tracking error and the gating error were evaluated assuming two possible variations. First, the variation of the position definition of the tumor and the markers on treatment planning computed tomograhy (CT) images. Second, the intra-fractional anatomical variation which leads the distance change between the tumor and markers during the course of treatment. For comparison, rigid predictions and ordinally multiple linear regression (MLR) predictions were also evaluated. The tracking and gating errors of PLSR prediction were smaller than those of other prediction methods. Ninety-fifth percentile of tracking/gating error in all trials were 3.7/4.1 mm, respectively in PLSR prediction for superior-inferior direction. The results suggested that PLSR prediction was robust to variations, and clinically applicable accuracy could be achievable for targeting tumors.
• First experimental results of gated proton imaging using x-ray fluoroscopy to detect a fiducial marker.

  Sodai Tanaka, Naoki Miyamoto, Yuto Matsuo, Takaaki Yoshimura, Seishin Takao, Taeko Matsuura

  Physics in medicine and biology 66 (18) 2021/09/09 

  Increasing numbers of proton imaging research studies are being conducted for accurate proton range determination in proton therapy treatment planning. However, there is no proton imaging system that deals with motion artifacts. In this study, a gated proton imaging system was developed and the first experimental results of proton radiography (pRG) were obtained for a moving object without motion artifacts. A motion management system using dual x-ray fluoroscopy for detecting a spherical gold fiducial marker was introduced and the proton beam was gated in accordance with the motion of the object. To demonstrate the performance of the gated proton imaging system, gated pRG images of a moving phantom were acquired experimentally, and the motion artifacts clearly were diminished. Also, the factors causing image deteriorations were evaluated focusing on the new gating system developed here, and the main factor was identified as the latency (with a maximum value of 93 ms) between the ideal gating signal according to the actual marker position and the actual gating signal. The possible deterioration due to the latency of the proton imaging system and proton beam irradiation was small owing to appropriate setting of the time structure.
• Real-time CT image generation based on voxel-by-voxel modeling of internal deformation by utilizing the displacement of fiducial markers.

  Risa Hayashi, Koichi Miyazaki, Seishin Takao, Kohei Yokokawa, Sodai Tanaka, Taeko Matsuura, Hiroshi Taguchi, Norio Katoh, Shinichi Shimizu, Kikuo Umegaki, Naoki Miyamoto

  Medical physics 48 (9) 5311 - 5326 2021/09 

  PURPOSE: To show the feasibility of real-time CT image generation technique utilizing internal fiducial markers that facilitate the evaluation of internal deformation. METHODS: In the proposed method, a linear regression model that can derive internal deformation from the displacement of fiducial markers is built for each voxel in the training process before the treatment session. Marker displacement and internal deformation are derived from the four-dimensional computed tomography (4DCT) dataset. In the treatment session, the three-dimensional deformation vector field is derived according to the marker displacement, which is monitored by the real-time imaging system. The whole CT image can be synthesized by deforming the reference CT image with a deformation vector field in real-time. To show the feasibility of the technique, image synthesis accuracy and tumor localization accuracy were evaluated using the dataset generated by extended NURBS-Based Cardiac-Torso (XCAT) phantom and clinical 4DCT datasets from six patients, containing 10 CT datasets each. In the validation with XCAT phantom, motion range of the tumor in training data and validation data were about 10 and 15 mm, respectively, so as to simulate motion variation between 4DCT acquisition and treatment session. In the validation with patient 4DCT dataset, eight CT datasets from the 4DCT dataset were used in the training process. Two excluded inhale CT datasets can be regarded as the datasets with large deformations more than training dataset. CT images were generated for each respiratory phase using the corresponding marker displacement. Root mean squared error (RMSE), normalized RMSE (NRMSE), and structural similarity index measure (SSIM) between the original CT images and the synthesized CT images were evaluated as the quantitative indices of the accuracy of image synthesis. The accuracy of tumor localization was also evaluated. RESULTS: In the validation with XCAT phantom, the mean NRMSE, SSIM, and three-dimensional tumor localization error were 7.5 ± 1.1%, 0.95 ± 0.02, and 0.4 ± 0.3 mm, respectively. In the validation with patient 4DCT dataset, the mean RMSE, NRMSE, SSIM, and three-dimensional tumor localization error in six patients were 73.7 ± 19.6 HU, 9.2 ± 2.6%, 0.88 ± 0.04, and 0.8 ± 0.6 mm, respectively. These results suggest that the accuracy of the proposed technique is adequate when the respiratory motion is within the range of the training dataset. In the evaluation with a marker displacement larger than that of the training dataset, the mean RMSE, NRMSE, and tumor localization error were about 100 HU, 13%, and <2.0 mm, respectively, except for one case having large motion variation. The performance of the proposed method was similar to those of previous studies. Processing time to generate the volumetric image was <100 ms. CONCLUSION: We have shown the feasibility of the real-time CT image generation technique for volumetric imaging.
• Validation of dose distribution for liver tumors treated with real-time-image gated spot-scanning proton therapy by log data based dose reconstruction.

  Takahiro Yamada, Seishin Takao, Hidenori Koyano, Hideaki Nihongi, Yusuke Fujii, Shusuke Hirayama, Naoki Miyamoto, Taeko Matsuura, Kikuo Umegaki, Norio Katoh, Isao Yokota, Hiroki Shirato, Shinichi Shimizu

  Journal of radiation research 62 (4) 626 - 633 2021/07/10 

  In spot scanning proton therapy (SSPT), the spot position relative to the target may fluctuate through tumor motion even when gating the radiation by utilizing a fiducial marker. We have established a procedure that evaluates the delivered dose distribution by utilizing log data on tumor motion and spot information. The purpose of this study is to show the reliability of the dose distributions for liver tumors treated with real-time-image gated SSPT (RGPT). In the evaluation procedure, the delivered spot information and the marker position are synchronized on the basis of log data on the timing of the spot irradiation and fluoroscopic X-ray irradiation. Then a treatment planning system reconstructs the delivered dose distribution. Dose distributions accumulated for all fractions were reconstructed for eight liver cases. The log data were acquired in all 168 fractions for all eight cases. The evaluation was performed for the values of maximum dose, minimum dose, D99, and D5-D95 for the clinical target volumes (CTVs) and mean liver dose (MLD) scaled by the prescribed dose. These dosimetric parameters were statistically compared between the planned dose distribution and the reconstructed dose distribution. The mean difference of the maximum dose was 1.3% (95% confidence interval [CI]: 0.6%-2.1%). Regarding the minimum dose, the mean difference was 0.1% (95% CI: -0.5%-0.7%). The mean differences of D99, D5-D95 and MLD were below 1%. The reliability of dose distributions for liver tumors treated with RGPT-SSPT was shown by the evaluation of the accumulated dose distributions.
• Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients.

  Koichi Yasuda, Hideki Minatogawa, Yasuhiro Dekura, Seishin Takao, Masaya Tamura, Nayuta Tsushima, Takayoshi Suzuki, Satoshi Kano, Takatsugu Mizumachi, Takashi Mori, Kentaro Nishioka, Motoyasu Shido, Norio Katoh, Hiroshi Taguchi, Noriyuki Fujima, Rikiya Onimaru, Isao Yokota, Keiji Kobashi, Shinichi Shimizu, Akihiro Homma, Hiroki Shirato, Hidefumi Aoyama

  Journal of radiation research 62 (2) 329 - 337 2021/03/10 

  Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.
• 尿量の経日変化および前立腺体積が放射線治療時の前立腺の位置に与える影響(The Impact of Daily Urinary Volume Variations and Prostate Volume on Prostate Position During Radiotherapy)

  Nishioka Kentaro, Hashimoto Takayuki, Yokota Isao, Katoh Norio, Kinoshita Rumiko, Yasuda Koichi, Takao Seishin, Yoshimura Takaaki, Aoyama Hidefumi, Shimizu Shinichi

  日本医学放射線学会学術集会抄録集 80回 S193 - S194 0048-0428 2021/03
• The Impact of Daily Urinary Volume Variations and Prostate Volume on Prostate Position During Radiotherapy(和訳中)

  Nishioka Kentaro, Hashimoto Takayuki, Yokota Isao, Katoh Norio, Kinoshita Rumiko, Yasuda Koichi, Takao Seishin, Yoshimura Takaaki, Aoyama Hidefumi, Shimizu Shinichi

  日本医学放射線学会学術集会抄録集 80回 S193 - S194 0048-0428 2021/03 [Refereed]
  
• Potential benefits of adaptive intensity-modulated proton therapy in nasopharyngeal carcinomas.

  Hideki Minatogawa, Koichi Yasuda, Yasuhiro Dekura, Seishin Takao, Taeko Matsuura, Takaaki Yoshimura, Ryusuke Suzuki, Isao Yokota, Noriyuki Fujima, Rikiya Onimaru, Shinichi Shimizu, Hidefumi Aoyama, Hiroki Shirato

  Journal of applied clinical medical physics 22 (1) 174 - 183 2021/01 

  PURPOSE: To investigate potential advantages of adaptive intensity-modulated proton beam therapy (A-IMPT) by comparing it to adaptive intensity-modulated X-ray therapy (A-IMXT) for nasopharyngeal carcinomas (NPC). METHODS: Ten patients with NPC treated with A-IMXT (step and shoot approach) and concomitant chemotherapy between 2014 and 2016 were selected. In the actual treatment, 46 Gy in 23 fractions (46Gy/23Fx.) was prescribed using the initial plan and 24Gy/12Fx was prescribed using an adapted plan thereafter. New treatment planning of A-IMPT was made for the same patients using equivalent dose fractionation schedule and dose constraints. The dose volume statistics based on deformable images and dose accumulation was used in the comparison of A-IMXT with A-IMPT. RESULTS: The means of the Dmean of the right parotid gland (P < 0.001), right TM joint (P < 0.001), left TM joint (P < 0.001), oral cavity (P < 0.001), supraglottic larynx (P = 0.001), glottic larynx (P < 0.001), , middle PCM (P = 0.0371), interior PCM (P < 0.001), cricopharyngeal muscle (P = 0.03643), and thyroid gland (P = 0.00216), in A-IMPT are lower than those of A-IMXT, with statistical significance. The means of, D0.03cc , and Dmean of each sub portion of auditory apparatus and D30% for Eustachian tube and D0.5cc for mastoid volume in A-IMPT are significantly lower than those of A-IMXT. The mean doses to the oral cavity, supraglottic larynx, and glottic larynx were all reduced by more than 20 Gy (RBE = 1.1). CONCLUSIONS: An adaptive approach is suggested to enhance the potential benefit of IMPT compared to IMXT to reduce adverse effects for patients with NPC.
• Are simple verbal instructions sufficient to ensure that bladder volume does not deteriorate prostate position reproducibility during spot scanning proton therapy?

  Kentaro Nishioka, Kento Gotoh, Takayuki Hashimoto, Takashige Abe, Takahiro Osawa, Ryuji Matsumoto, Isao Yokota, Norio Katoh, Rumiko Kinoshita, Koichi Yasuda, Toshiaki Yakabe, Takaaki Yoshimura, Seishin Takao, Nobuo Shinohara, Hidefumi Aoyama, Shinichi Shimizu, Hiroki Shirato

  BJR open 3 (1) 20210064 - 20210064 2021 

  OBJECTIVES: The purpose of this study is to investigate whether verbal instructions are sufficient for bladder volume (BV) control not to deteriorate prostate position reproducibility in image-guided spot scanning proton therapy (SSPT) for localized prostate cancer. METHODS: A total of 268 treatment sessions in 12 consecutive prostate cancer patients who were treated with image-guided SSPT with fiducial markers were retrospectively analyzed. In addition to strict rectal volume control procedures, simple verbal instructions to void urine one hour before the treatment were used here. The BV was measured by a Bladder Scan just before the treatment, and the prostate motion was measured by intraprostatic fiducial markers and two sets of X-ray fluoroscopy images. The correlation between the BV change and prostate motion was assessed by linear mixed-effects models and systematic and random errors according to the reproducibility of the BV. RESULTS: The mean absolute BV change during treatment was from -98.7 to 86.3 ml (median 7.1 ml). The mean absolute prostate motion of the patients in the left-right direction was -1.46 to 1.85 mm; in the cranial-caudal direction it was -6.10 to 3.65 mm, and in the anteroposterior direction -1.90 to 5.23 mm. There was no significant relationship between the BV change and prostate motion during SSPT. The early and late genitourinary and gastrointestinal toxicity was minimal with a minimum follow up of 4.57 years. CONCLUSIONS: Simple verbal instructions about urination was suggested to be sufficient to control the BV not to impact on the prostate motion and clinical outcomes in image-guided SSPT. Careful attention to BV change is still needed when the seminal vesicle is to be treated. ADVANCES IN KNOWLEDGE: Our data demonstrated that there was no apparent relationship between BV changes and prostate position reproducibility and simple verbal instruction about urination could be sufficient for image-guided SSPT.
• Quantitative analysis of treatments using real-time image gated spot-scanning with synchrotron-based proton beam therapy system log data.

  Takaaki Yoshimura, Shinichi Shimizu, Takayuki Hashimoto, Kentaro Nishioka, Norio Katoh, Hiroshi Taguchi, Koichi Yasuda, Taeko Matsuura, Seishin Takao, Masaya Tamura, Sodai Tanaka, Yoichi M Ito, Yuto Matsuo, Hiroshi Tamura, Kenji Horita, Kikuo Umegaki, Hiroki Shirato

  Journal of applied clinical medical physics 21 (12) 10 - 19 2020/12 

  A synchrotron-based real-time image gated spot-scanning proton beam therapy (RGPT) system with inserted fiducial markers can irradiate a moving tumor with high accuracy. As gated treatments increase the beam delivery time, this study aimed to investigate the frequency of intra-field adjustments corresponding to the baseline shift or drift and the beam delivery efficiency of a synchrotron-based RGPT system. Data from 118 patients corresponding to 127 treatment plans and 2810 sessions between October 2016 and March 2019 were collected. We quantitatively analyzed the proton beam delivery time, the difference between the ideal beam delivery time based on a simulated synchrotron magnetic excitation pattern and the actual treatment beam delivery time, frequency corresponding to the baseline shift or drift, and the gating efficiency of the synchrotron-based RGPT system according to the proton beam delivery machine log data. The mean actual beam delivery time was 7.1 min, and the simulated beam delivery time in an ideal environment with the same treatment plan was 2.9 min. The average difference between the actual and simulated beam delivery time per session was 4.3 min. The average frequency of intra-field adjustments corresponding to baseline shift or drift and beam delivery efficiency were 21.7% and 61.8%, respectively. Based on our clinical experience with a synchrotron-based RGPT system, we determined the frequency corresponding to baseline shift or drift and the beam delivery efficiency using the beam delivery machine log data. To maintain treatment accuracy within ± 2.0 mm, intra-field adjustments corresponding to baseline shift or drift were required in approximately 20% of cases. Further improvements in beam delivery efficiency may be realized by shortening the beam delivery time.
• 画像誘導治療の今後について 画像誘導陽子線治療の将来展望

  田口 大志, 橋本 孝之, 加藤 徳雄, 木下 留美子, 安田 耕一, 西岡 健太郎, 森 崇, 打浪 雄介, 宮本 直樹, 高尾 聖心, 清水 伸一, 青山 英史

  日本癌治療学会学術集会抄録集 58回 SY14 - 3 2020/10
• The impact of dose delivery time on biological effectiveness in proton irradiation with various biological parameters.

  Koki Kasamatsu, Taeko Matsuura, Sodai Tanaka, Seishin Takao, Naoki Miyamoto, Jin-Min Nam, Hiroki Shirato, Shinichi Shimizu, Kikuo Umegaki

  Medical physics 47 (9) 4644 - 4655 2020/09 

  PURPOSE: The purpose of this study is to evaluate the sublethal damage (SLD) repair effect in prolonged proton irradiation using the biophysical model with various cell-specific parameters of (α/β)x and T1/2 (repair half time). At present, most of the model-based studies on protons have focused on acute radiation, neglecting the reduction in biological effectiveness due to SLD repair during the delivery of radiation. Nevertheless, the dose-rate dependency of biological effectiveness may become more important as advanced treatment techniques, such as hypofractionation and respiratory gating, come into clinical practice, as these techniques sometimes require long treatment times. Also, while previous research using the biophysical model revealed a large repair effect with a high physical dose, the dependence of the repair effect on cell-specific parameters has not been evaluated systematically. METHODS: Biological dose [relative biological effectiveness (RBE) × physical dose] calculation with repair included was carried out using the linear energy transfer (LET)-dependent linear-quadratic (LQ) model combined with the theory of dual radiation action (TDRA). First, we extended the dose protraction factor in the LQ model for the arbitrary number of different LET proton irradiations delivered sequentially with arbitrary time lags, referring to the TDRA. Using the LQ model, the decrease in biological dose due to SLD repair was systematically evaluated for spread-out Bragg peak (SOBP) irradiation in a water phantom with the possible ranges of both (α/β)x and repair parameters ((α/β)x  = 1-15 Gy, T1/2  = 0-90 min). Then, to consider more realistic irradiation conditions, clinical cases of prostate, liver, and lung tumors were examined with the cell-specific parameters for each tumor obtained from the literature. Biological D99% and biological dose homogeneity coefficient (HC) were calculated for the clinical target volumes (CTVs), assuming dose-rate structures with a total irradiation time of 0-60 min. RESULTS: The differences in the cell-specific parameters resulted in considerable variation in the repair effect. The biological dose reduction found at the center of the SOBP with 30 min of continuous irradiation varied from 1.13% to 14.4% with a T1/2 range of 1-90 min when (α/β)x is fixed as 10 Gy. It varied from 2.3% to 6.8% with an (α/β)x range of 1-15 Gy for a fixed value of T1/2  = 30 min. The decrease in biological D99% per 10 min was 2.6, 1.2, and 3.0% for the prostate, liver, and lung tumor cases, respectively. The value of the biological D99% reduction was neither in the order of (α/β)x nor prescribed dose, but both comparably contributed to the repair effect. The variation of HC was within the range of 0.5% for all cases; therefore, the dose distribution was not distorted. CONCLUSION: The reduction in biological dose caused by the SLD repair largely depends on the cell-specific parameters in addition to the physical dose. The parameters should be considered carefully in the evaluation of the repair effect in prolonged proton irradiation.
• Difference in LET-based biological doses between IMPT optimization techniques: Robust and PTV-based optimizations.

  Shusuke Hirayama, Taeko Matsuura, Koichi Yasuda, Seishin Takao, Takaaki Fujii, Naoki Miyamoto, Kikuo Umegaki, Shinichi Shimizu

  Journal of applied clinical medical physics 21 (4) 42 - 50 2020/04 

  PURPOSE: While a large amount of experimental data suggest that the proton relative biological effectiveness (RBE) varies with both physical and biological parameters, current commercial treatment planning systems (TPS) use the constant RBE instead of variable RBE models, neglecting the dependence of RBE on the linear energy transfer (LET). To conduct as accurate a clinical evaluation as possible in this circumstance, it is desirable that the dosimetric parameters derived by TPS ( D RBE = 1.1 ) are close to the "true" values derived with the variable RBE models ( D v RBE ). As such, in this study, the closeness of D RBE = 1.1 to D v RBE was compared between planning target volume (PTV)-based and robust plans. METHODS: Intensity-modulated proton therapy (IMPT) treatment plans for two Radiation Therapy Oncology Group (RTOG) phantom cases and four nasopharyngeal cases were created using the PTV-based and robust optimizations, under the assumption of a constant RBE of 1.1. First, the physical dose and dose-averaged LET (LETd ) distributions were obtained using the analytical calculation method, based on the pencil beam algorithm. Next, D v RBE was calculated using three different RBE models. The deviation of D v RBE from D RBE = 1.1 was evaluated with D99 and Dmax , which have been used as the evaluation indices for clinical target volume (CTV) and organs at risk (OARs), respectively. The influence of the distance between the OAR and CTV on the results was also investigated. As a measure of distance, the closest distance and the overlapped volume histogram were used for the RTOG phantom and nasopharyngeal cases, respectively. RESULTS: As for the OAR, the deviations of D max v RBE from D max RBE = 1.1 were always smaller in robust plans than in PTV-based plans in all RBE models. The deviation would tend to increase as the OAR was located closer to the CTV in both optimization techniques. As for the CTV, the deviations of D 99 v RBE from D 99 RBE = 1.1 were comparable between the two optimization techniques, regardless of the distance between the CTV and the OAR. CONCLUSION: Robust optimization was found to be more favorable than PTV-based optimization in that the results presented by TPS were closer to the "true" values and that the clinical evaluation based on TPS was more reliable.
• Dynamic gating window technique for the reduction of dosimetric error in respiratory-gated spot-scanning particle therapy: An initial phantom study using patient tumor trajectory data.

  Naoki Miyamoto, Kouhei Yokokawa, Seishin Takao, Taeko Matsuura, Sodai Tanaka, Shinichi Shimizu, Hiroki Shirato, Kikuo Umegaki

  Journal of applied clinical medical physics 21 (4) 13 - 21 2020/02/18 [Refereed][Not invited]
   

  Spot-scanning particle therapy possesses advantages, such as high conformity to the target and efficient energy utilization compared with those of the passive scattering irradiation technique. However, this irradiation technique is sensitive to target motion. In the current clinical situation, some motion management techniques, such as respiratory-gated irradiation, which uses an external or internal surrogate, have been clinically applied. In surrogate-based gating, the size of the gating window is fixed during the treatment in the current treatment system. In this study, we propose a dynamic gating window technique, which optimizes the size of gating window for each spot by considering a possible dosimetric error. The effectiveness of the dynamic gating window technique was evaluated by simulating irradiation using a moving target in a water phantom. In dosimetric characteristics comparison, the dynamic gating window technique exhibited better performance in all evaluation volumes with different effective depths compared with that of the fixed gate approach. The variation of dosimetric characteristics according to the target depth was small in dynamic gate compared to fixed gate. These results suggest that the dynamic gating window technique can maintain an acceptable dose distribution regardless of the target depth. The overall gating efficiency of the dynamic gate was approximately equal or greater than that of the fixed gating window. In dynamic gate, as the target depth becomes shallower, the gating efficiency will be reduced, although dosimetric characteristics will be maintained regardless of the target depth. The results of this study suggest that the proposed gating technique may potentially improve the dose distribution. However, additional evaluations should be undertaken in the future to determine clinical applicability by assuming the specifications of the treatment system and clinical situation.
• Analysis of treatment process time for real-time-image gated-spot-scanning proton-beam therapy (RGPT) system.

  Takaaki Yoshimura, Shinichi Shimizu, Takayuki Hashimoto, Kentaro Nishioka, Norio Katoh, Tetsuya Inoue, Hiroshi Taguchi, Koichi Yasuda, Taeko Matsuura, Seishin Takao, Masaya Tamura, Yoichi M Ito, Yuto Matsuo, Hiroshi Tamura, Kenji Horita, Kikuo Umegaki, Hiroki Shirato

  Journal of applied clinical medical physics 21 (2) 38 - 49 2020/02 [Refereed][Not invited]
   

  We developed a synchrotron-based real-time-image gated-spot-scanning proton-beam therapy (RGPT) system and utilized it to clinically operate on moving tumors in the liver, pancreas, lung, and prostate. When the spot-scanning technique is linked to gating, the beam delivery time with gating can increase, compared to that without gating. We aim to clarify whether the total treatment process can be performed within approximately 30 min (the general time per session in several proton therapy facilities), even for gated-spot-scanning proton-beam delivery with implanted fiducial markers. Data from 152 patients, corresponding to 201 treatment plans and 3577 sessions executed from October 2016 to June 2018, were included in this study. To estimate the treatment process time, we utilized data from proton beam delivery logs during the treatment for each patient. We retrieved data, such as the disease site, total target volume, field size at the isocenter, and the number of layers and spots for each field, from the treatment plans. We quantitatively analyzed the treatment process, which includes the patient load (or setup), bone matching, marker matching, beam delivery, patient unload, and equipment setup, using the data obtained from the log data. Among all the cases, 90 patients used the RGPT system (liver: n = 34; pancreas: n = 5; lung: n = 4; and prostate: n = 47). The mean and standard deviation (SD) of the total treatment process time for the RGPT system was 30.3 ± 7.4 min, while it was 25.9 ± 7.5 min for those without gating treatment, excluding craniospinal irradiation (CSI; head and neck: n = 16, pediatric: n = 31, others: n = 15); for CSI (n = 11) with two or three isocenters, the process time was 59.9 ± 13.9 min. Our results demonstrate that spot-scanning proton therapy with a gating function can be achieved in approximately 30-min time slots.
• Modified fast adaptive scatter kernel superposition (mfASKS) correction and its dosimetric impact on CBCT-based proton therapy dose calculation.

  Yusuke Nomura, Qiong Xu, Hao Peng, Seishin Takao, Shinichi Shimizu, Lei Xing, Hiroki Shirato

  Medical physics 47 (1) 190 - 200 2020/01 

  PURPOSE: While cone beam computed tomography (CBCT) is able to provide patient anatomical information, its image quality is severely degraded due to scatter contamination, which degrades the accuracy of CBCT-based dose distribution estimation in proton therapy. In this work, we combined two existing scatter kernel correction methods: the point-spread function (PSF)-based scatter kernel derivation method and the fast adaptive scatter kernel superposition (fASKS) model, and evaluated the impact of the modified fASKS (mfASKS) correction on the accuracy of proton dose distribution estimation. To evaluate feasibility of the mfASKS approach using accurate scatter distributions, both Monte Carlo simulations and experiments were performed for an on-board CBCT machine integrated with a proton therapy machine. METHODS: We developed a strategy to modify central intensity, constant intensity, and amplitude of the scatter kernels derived from PSFs for the fASKS model. A parameter required for the fASKS model was derived by optimizing uniformity in the mfASKS-corrected reconstructed images. Subsequently, the mfASKS model was used to remove scatter in CBCT imaging. We quantitatively compared the Hounsfield Unit (HU) and proton stopping power ratio (SPR) images for five different phantoms. To assess improvement of dose calculation accuracy, a series of proton treatment plans were produced using the CBCT images with and without the mfASKS correction. RESULTS: The accuracies of both HU and SPR intensity quantifications are improved as a result of the mfASKS correction. Mean absolute water-equivalent path length difference to the true value decreases from 10.3 to 0.934 mm for the Gammex phantom (simulation). At the same time, mfASKS is able to offer more accurate dose distributions, especially at the distal fall-off region where noticeable dose overestimation is observed in the uncorrected scenario. Mean absolute relative error of proton range in the pelvic phantom improves from 5.03% to 2.57% (experiment). CONCLUSIONS: mfASKS enables more accurate CBCT-based proton dose calculation. This technique has significant implications in image-guided radiotherapy and dose verifications in adaptive proton therapy.
• Initial Clinical Outcomes of Real-Time-Image Gated Spot-Scanning Proton Beam Therapy for Hepatocellular Carcinomas

  N. Katoh, Y. Uchinami, D. Abo, S. Takao, T. Inoue, H. Taguchi, R. Morita, T. Soyama, T. Hashimoto, R. Onimaru, A. Prayongrat, M. Tamura, T. Matsuura, S. Shimizu, H. Shirato

  International Journal of Radiation Oncology*Biology*Physics 105 (1) E222 - E223 0360-3016 2019/09 [Refereed]
  
• 局所進行食道癌に対してspot scanning法による根治的化学陽子線療法を施行した一例

  宮崎 智彦, 打浪 雄介, 田口 大志, 加藤 徳雄, 清水 伸一, 白土 博樹, 中積 宏之, 中野 真太郎, 坂本 直哉, 高尾 聖心, 田村 昌也, 松浦 妙子

  日本医学放射線学会秋季臨床大会抄録集 (公社)日本医学放射線学会 55回 S520 - S520 0048-0428 2019/09
• The Potential Benefit of Adaptive Intensity Modulated Proton Therapy in Nasopharyngeal Carcinoma: Planning Comparison Study

  H. Minatogawa, K. Yasuda, T. Matsuura, R. Onimaru, T. Yoshimura, S. Takao, Y. Matsuo, Y. Dekura, R. Suzuki, M. Tamura, N. Miyamoto, S. Shimizu, H. Shirato

  International Journal of Radiation Oncology*Biology*Physics 105 (1) E394 - E394 0360-3016 2019/09
• Quantitative evaluation of image recognition performance of fiducial markers in real-time tumor-tracking radiation therapy.

  Naoki Miyamoto, Kenichiro Maeda, Daisuke Abo, Ryo Morita, Seishin Takao, Taeko Matsuura, Norio Katoh, Kikuo Umegaki, Shinichi Shimizu, Hiroki Shirato

  Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) 65 33 - 39 2019/09 

  PURPOSE: To quantitatively evaluate and compare the image recognition performance of multiple fiducial markers available in real-time tumor-tracking radiation therapy (RTRT). METHODS: Clinically available markers including sphere shape, coil shape, cylinder shape, line shape, and ball shape (folded line shape) were evaluated in liver and lung models of RTRT. Maximum thickness of the polymethyl metacrylate (PMMA) phantom that could automatically recognize the marker was determined by template-pattern matching. Image registration accuracy of the fiducial marker was determined using liver RTRT model. Lung RTRT was mimicked with an anthropomorphic chest phantom and a one-dimensional motion stage in order to simulate marker motion in heterogeneous fluoroscopic images. The success or failure of marker tracking and image registration accuracy for the lung model were evaluated in the same manner as that for the liver model. RESULTS: All fiducial markers except for line shape and coil shape of thinner diameter were recognized by the PMMA phantom, which is assumed to have the typical thickness of an abdomen, with two-dimensional image registration accuracy of <2 pixels. Three-dimensional calculation error with the use of real-time stereoscopic fluoroscopy in RTRT was thought to be within 1 mm. In the evaluation using the lung model, the fiducial markers were recognized stably with sufficient accuracy for clinical application. The same was true for the evaluation using the liver model. CONCLUSIONS: The image recognition performance of fiducial markers was quantified and compared. The results presented here may be useful for the selection of fiducial markers.
• Physical and biological impacts of collimator-scattered protons in spot-scanning proton therapy.

  Koki Ueno, Taeko Matsuura, Shusuke Hirayama, Seishin Takao, Hideaki Ueda, Yuto Matsuo, Takaaki Yoshimura, Kikuo Umegaki

  Journal of applied clinical medical physics 20 (7) 48 - 57 2019/07 

  To improve the penumbra of low-energy beams used in spot-scanning proton therapy, various collimation systems have been proposed and used in clinics. In this paper, focused on patient-specific brass collimators, the collimator-scattered protons' physical and biological effects were investigated. The Geant4 Monte Carlo code was used to model the collimators mounted on the scanning nozzle of the Hokkaido University Hospital. A systematic survey was performed in water phantom with various-sized rectangular targets; range (5-20 cm), spread-out Bragg peak (SOBP) (5-10 cm), and field size (2 × 2-16 × 16 cm2 ). It revealed that both the range and SOBP dependences of the physical dose increase had similar trends to passive scattering methods, that is, it increased largely with the range and slightly with the SOBP. The physical impact was maximized at the surface (3%-22% for the tested geometries) and decreased with depth. In contrast, the field size (FS) dependence differed from that observed in passive scattering: the increase was high for both small and large FSs. This may be attributed to the different phase-space shapes at the target boundary between the two dose delivery methods. Next, the biological impact was estimated based on the increase in dose-averaged linear energy transfer (LETd ) and relative biological effectiveness (RBE). The LETd of the collimator-scattered protons were several keV/μm higher than that of unscattered ones; however, since this large increase was observed only at the positions receiving a small scattered dose, the overall LETd increase was negligible. As a consequence, the RBE increase did not exceed 0.05. Finally, the effects on patient geometries were estimated by testing two patient plans, and a negligible RBE increase (0.9% at most in the critical organs at surface) was observed in both cases. Therefore, the impact of collimator-scattered protons is almost entirely attributed to the physical dose increase, while the RBE increase is negligible.
• Clinical experience of craniospinal intensity-modulated spot-scanning proton therapy using large fields for central nervous system medulloblastomas and germ cell tumors in children, adolescents, and young adults.

  Takayuki Hashimoto, Shinichi Shimizu, Seishin Takao, Shunsuke Terasaka, Akihiro Iguchi, Hiroyuki Kobayashi, Takashi Mori, Takaaki Yoshimura, Yuto Matsuo, Masaya Tamura, Taeko Matsuura, Yoichi M Ito, Rikiya Onimaru, Hiroki Shirato

  Journal of radiation research 60 (4) 527 - 537 0449-3060 2019/07/01 [Refereed][Not invited]
   

  The outcomes of intensity-modulated proton craniospinal irradiation (ipCSI) are unclear. We evaluated the clinical benefit of our newly developed ipCSI system that incorporates two gantry-mounted orthogonal online X-ray imagers with a robotic six-degrees-of-freedom patient table. Nine patients (7-19 years old) were treated with ipCSI. The prescribed dose for CSI ranged from 23.4 to 36.0 Gy (relative biological effectiveness) in 13-20 fractions. Four adolescent and young adult (AYA) patients (15 years or older) were treated with vertebral-body-sparing ipCSI (VBSipCSI). Myelosuppression following VBSipCSI was compared with that of eight AYA patients treated with photon CSI at the same institution previously. The mean homogeneity index (HI) in the nine patients was 0.056 (95% confidence interval: 0.044-0.068). The mean time from the start to the end of all beam delivery was 37 min 39 s ± 2 min 24 s (minimum to maximum: 22 min 49 s - 42 min 51 s). The nadir white blood cell, hemoglobin, and platelet levels during the 4 weeks following the end of the CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0071, 0.0453, 0.0024, respectively). The levels at 4 weeks after the end of CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0023, 0.0414, 0.0061). Image-guided ipCSI was deliverable in a reasonable time with sufficient HI. Using VBSipCSI, AYA patients experienced a lower incidence of serious acute hematological toxicity than AYA patients treated with photon CSI.
• [Department of Medical Physics, Hokkaido University Hospital].

  Ryusuke Suzuki, Naoki Miyamoto, Seishin Takao, Shinichi Shimizu

  Igaku butsuri : Nihon Igaku Butsuri Gakkai kikanshi = Japanese journal of medical physics : an official journal of Japan Society of Medical Physics 39 (2) 54 - 56 2019
• Big Data Analysis of Treatment Process Time for the Real-Time-Image Gated-Spot-Scanning Proton-Beam Therapy (RGPT) System

  T. Yoshimura, S. Shimizu, T. Hashimoto, N. Katoh, T. Inoue, K. Nishioka, T. Matsuura, S. Takao, M. Tamura, H. Tamura, K. Horita, K. Umegaki, H. Shirato

  International Journal of Radiation Oncology*Biology*Physics 102 (3) e501 - e502 0360-3016 2018/11
• An analytical dose‐averaged LET calculation algorithm considering the off‐axis LET enhancement by secondary protons for spot‐scanning proton therapy

  Shusuke Hirayama, Taeko Matsuura, Hideaki Ueda, Yusuke Fujii, Takaaki Fujii, Seishin Takao, Naoki Miyamoto, Shinichi Shimizu, Rintaro Fujimoto, Kikuo Umegaki, Hiroki Shirato

  Med. Phys. 45 (7) 3404 - 3416 2018/07 [Refereed][Not invited]
   

  PURPOSE: To evaluate the biological effects of proton beams as part of daily clinical routine, fast and accurate calculation of dose-averaged linear energy transfer (LETd ) is required. In this study, we have developed the analytical LETd calculation method based on the pencil-beam algorithm (PBA) considering the off-axis enhancement by secondary protons. This algorithm (PBA-dLET) was then validated using Monte Carlo simulation (MCS) results. METHODS: In PBA-dLET, LET values were assigned separately for each individual dose kernel based on the PBA. For the dose kernel, we employed a triple Gaussian model which consists of the primary component (protons that undergo the multiple Coulomb scattering) and the halo component (protons that undergo inelastic, nonelastic and elastic nuclear reaction); the primary and halo components were represented by a single Gaussian and the sum of two Gaussian distributions, respectively. Although the previous analytical approaches assumed a constant LETd value for the lateral distribution of a pencil beam, the actual LETd increases away from the beam axis, because there are more scattered and therefore lower energy protons with higher stopping powers. To reflect this LETd behavior, we have assumed that the LETs of primary and halo components can take different values (LETp and LEThalo ), which vary only along the depth direction. The values of dual-LET kernels were determined such that the PBA-dLET reproduced the MCS-generated LETd distribution in both small and large fields. These values were generated at intervals of 1 mm in depth for 96 energies from 70.2 to 220 MeV and collected in the look-up table. Finally, we compared the LETd distributions and mean LETd (LETd,mean ) values of targets and organs at risk between PBA-dLET and MCS. Both homogeneous phantom and patient geometries (prostate, liver, and lung cases) were used to validate the present method. RESULTS: In the homogeneous phantom, the LETd profiles obtained by the dual-LET kernels agree well with the MCS results except for the low-dose region in the lateral penumbra, where the actual dose was below 10% of the maximum dose. In the patient geometry, the LETd profiles calculated with the developed method reproduces MCS with the similar accuracy as in the homogeneous phantom. The maximum differences in LETd,mean for each structure between the PBA-dLET and the MCS were 0.06 keV/μm in homogeneous phantoms and 0.08 keV/μm in patient geometries under all tested conditions, respectively. CONCLUSIONS: We confirmed that the dual-LET-kernel model well reproduced the MCS, not only in the homogeneous phantom but also in complex patient geometries. The accuracy of the LETd was largely improved from the single-LET-kernel model, especially at the lateral penumbra. The model is expected to be useful, especially for proper recognition of the risk of side effects when the target is next to critical organs.
• Selection of external beam radiotherapy approaches for precise and accurate cancer treatment.

  Hiroki Shirato, Quynh-Thu Le, Keiji Kobashi, Anussara Prayongrat, Seishin Takao, Shinichi Shimizu, Amato Giaccia, Lei Xing, Kikuo Umegaki

  Journal of radiation research 59 (suppl_1) i2-i10  2018/03/01 

  Physically precise external-beam radiotherapy (EBRT) technologies may not translate to the best outcome in individual patients. On the other hand, clinical considerations alone are often insufficient to guide the selection of a specific EBRT approach in patients. We examine the ways in which to compare different EBRT approaches based on physical, biological and clinical considerations, and how they can be enhanced with the addition of biophysical models and machine-learning strategies. The process of selecting an EBRT modality is expected to improve in tandem with knowledge-based treatment planning.
• 同時期に異所性に発生した悪性腫瘍に対して、二部位同時にIMRTを施行した症例

  湊川 英樹, 安田 耕一, 白土 博樹, 土屋 和彦, 原田 八重, 水町 貴諭, 坂下 智博, 本間 明宏, 福田 諭, 石嶋 漢, 宮本 直樹, 高尾 聖心, 鈴木 隆介, 松浦 妙子, 牧永 綾乃, 田村 昌也

  Japanese Journal of Radiology (公社)日本医学放射線学会 36 (Suppl.) 6 - 6 1867-1071 2018/02 [Not refereed][Not invited]
  
• A simulation study on the dosimetric benefit of real-time motion compensation in spot-scanning proton therapy for prostate

  Yusuke Fujii, Taeko Matsuura, Seishin Takao, Yuka Matsuzaki, Takaaki Fujii, Naoki Miyamoto, Kikuo Umegaki, Kentaro Nishioka, Shinichi Shimizu, Hiroki Shirato

  JOURNAL OF RADIATION RESEARCH 58 (4) 591 - 597 0449-3060 2017/07 [Not refereed][Not invited]
   

  For proton spot scanning, use of a real-time-image gating technique incorporating an implanted marker and dual fluoroscopy facilitates mitigation of the dose distribution deterioration caused by interplay effects. This study explored the advantages of using a real-time-image gating technique, with a focus on prostate cancer. Two patient-positioning methods using fiducial markers were compared: (i) patient positioning only before beam delivery, and (ii) patient positioning both before and during beam delivery using a real-time-gating technique. For each scenario, dose distributions were simulated using the CT images of nine prostate cancer patients. Treatment plans were generated using a single-field proton beam with 3-mm and 6-mm lateral margins. During beam delivery, the prostate was assumed to move by 5 mm in four directions that were perpendicular to the beam direction at one of three separate timings (i.e. after the completion of the first, second and third quartiles of the total delivery of spot irradiation). Using a 3-mm margin and second quartile motion timing, the averaged values for Delta D-99, Delta D-95, Delta D-5 and D5-95 were 5.1%, 3.3%, 3.6% and 9.0%, respectively, for Scenario (i) and 2.1%, 1.5%, 0.5% and 4.1%, respectively, for Scenario (ii). The margin expansion from 3 mm to 6 mm reduced the size of Delta D-99, Delta D-95, Delta D-5 and D5-95 only with Scenario (i). These results indicate that patient positioning during beam delivery is an effective way to obtain better target coverage and uniformity while reducing the target margin when the prostate moves during irradiation.
• Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy

  N. Masuda, S. -J. Lee, S. Ohtani, Y. -H. Im, E. -S. Lee, I. Yokota, K. Kuroi, S. -A. Im, B. -W. Park, S. -B. Kim, Y. Yanagita, S. Ohno, S. Takao, K. Aogi, H. Iwata, J. Jeong, A. Kim, K. -H. Park, H. Sasano, Y. Ohashi, M. Toi

  NEW ENGLAND JOURNAL OF MEDICINE 376 (22) 2147 - 2159 0028-4793 2017/06 [Refereed][Not invited]
   

  BACKGROUND Patients who have residual invasive carcinoma after the receipt of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative breast cancer have poor prognoses. The benefit of adjuvant chemotherapy in these patients remains unclear. METHODS We randomly assigned 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy (containing anthracycline, taxane, or both) to receive standard postsurgical treatment either with capecitabine or without (control). The primary end point was disease-free survival. Secondary end points included overall survival. RESULTS The result of the prespecified interim analysis met the primary end point, so this trial was terminated early. The final analysis showed that disease-free survival was longer in the capecitabine group than in the control group (74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years; hazard ratio for recurrence, second cancer, or death, 0.70; 95% confidence interval [CI], 0.53 to 0.92; P=0.01). Overall survival was longer in the capecitabine group than in the control group (89.2% vs. 83.6% of the patients were alive at 5 years; hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P=0.01). Among patients with triple-negative disease, the rate of disease-free survival was 69.8% in the capecitabine group versus 56.1% in the control group (hazard ratio for recurrence, second cancer, or death, 0.58; 95% CI, 0.39 to 0.87), and the overall survival rate was 78.8% versus 70.3% (hazard ratio for death, 0.52; 95% CI, 0.30 to 0.90). The hand-foot syndrome, the most common adverse reaction to capecitabine, occurred in 73.4% of the patients in the capecitabine group. CONCLUSIONS After standard neoadjuvant chemotherapy containing anthracycline, taxane, or both, the addition of adjuvant capecitabine therapy was safe and effective in prolonging disease-free survival and overall survival among patients with HER2-negative breast cancer who had residual invasive disease on pathological testing. (Funded by the Advanced Clinical Research Organization and the Japan Breast Cancer Research Group; CREATE-X UMIN Clinical Trials Registry number, UMIN000000843.)
• Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients.

  Masaya Tamura, Hideyuki Sakurai, Masashi Mizumoto, Satoshi Kamizawa, Shigeyuki Murayama, Haruo Yamashita, Seishin Takao, Ryusuke Suzuki, Hiroki Shirato, Yoichi M Ito

  Journal of radiation research 58 (3) 363 - 371 2017/05/01 

  To investigate the amount that radiation-induced secondary cancer would be reduced by using proton beam therapy (PBT) in place of intensity-modulated X-ray therapy (IMXT) in pediatric patients, we analyzed lifetime attributable risk (LAR) as an in silico surrogate marker of the secondary cancer after these treatments. From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: (i) brain, head and neck, (ii) thoracic, (iii) abdominal, and (iv) whole craniospinal (WCNS) irradiation. IMXT was replanned using the same computed tomography and region of interest. Using the dose-volume histograms (DVHs) of PBT and IMXT, the LARs of Schneider et al. were calculated for the same patient. All the published dose-response models were tested for the organs at risk. Calculation of the LARs of PBT and IMXT based on the DVHs was feasible for all patients. The means ± standard deviations of the cumulative LAR difference between PBT and IMXT for the four categories were (i) 1.02 ± 0.52% (n = 7, P = 0.0021), (ii) 23.3 ± 17.2% (n = 8, P = 0.0065), (iii) 16.6 ± 19.9% (n = 8, P = 0.0497) and (iv) 50.0 ± 21.1% (n = 3, P = 0.0274), respectively (one tailed t-test). The numbers needed to treat (NNT) were (i) 98.0, (ii) 4.3, (iii) 6.0 and (iv) 2.0 for WCNS, respectively. In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. Although a validation study is required, it is suggested that the LAR would be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques.
• Impact of Real-Time Image Gating on Spot Scanning Proton Therapy for Lung Tumors: A Simulation Study

  Takahiro Kanehira, Taeko Matsuura, Seishin Takao, Yuka Matsuzaki, Yusuke Fujii, Takaaki Fujii, Yoichi M. Ito, Naoki Miyamoto, Tetsuya Inoue, Norio Katoh, Shinichi Shimizu, Kikuo Umegaki, Hiroki Shirato

  INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 97 (1) 173 - 181 0360-3016 2017/01 [Not refereed][Not invited]
   

  Purpose: To investigate the effectiveness of real-time-image gated proton beam therapy for lung tumors and to establish a suitable size for the gating window (GW). Methods and Materials: A proton beam gated by a fiducial marker entering a preassigned GW (as monitored by 2 fluoroscopy units) was used with 7 lung cancer patients. Seven treatment plans were generated: real-time-image gated proton beam therapy with GW sizes of +/- 1, 2, 3, 4, 5, and 8 mm and free-breathing proton therapy. The prescribed dose was 70 Gy (relative biological effectiveness)/10 fractions to 99% of the target. Each of the 3-dimensional marker positions in the time series was associated with the appropriate 4-dimensional computed tomography phase. The 4-dimensional dose calculations were performed. The dose distribution in each respiratory phase was deformed into the end-exhale computed tomography image. The D99 and D5 to D95 of the clinical target volume scaled by the prescribed dose with criteria of D99 > 95% and D5 to D95 < 5%, V20 for the normal lung, and treatment times were evaluated. Results: Gating windows <= +/- 2 mm fulfilled the CTV criteria for all patients (whereas the criteria were not always met for GWs >= +/- 3 mm) and gave an average reduction in V20 of more than 17.2% relative to free-breathing proton therapy (whereas GWs >= +/- 4 mm resulted in similar or increased V20). The average (maximum) irradiation times were 384 seconds (818 seconds) for the +/- 1-mm GW, but less than 226 seconds (292 seconds) for the +/- 2-mm GW. The maximum increased considerably at +/- 1-mm GW. Conclusion: Real-time-image gated proton beam therapy with a GW of +/- 2 mm was demonstrated to be suitable, providing good dose distribution without greatly extending treatment time. (C) 2016 Elsevier Inc. All rights reserved.
• 前立腺癌の放射線治療時における尿量の変動の解析

  後藤謙斗, 西岡健太郎, 松崎有華, 松浦妙子, 高尾聖心, 橋本孝之, 木下留美子, 西川由記子, 清水伸一, 白土博樹

  日本放射線腫瘍学会高精度放射線外部照射部会学術大会プログラム・抄録集 30th 55  2017 [Not refereed][Not invited]
  
• A Nucleoside Anticancer Drug, 1-(3-C-Ethynyl-beta-D-Ribo-Pentofuranosyl)Cytosine, Induces Depth-Dependent Enhancement of Tumor Cell Death in Spread-Out Bragg Peak (SOBP) of Proton Beam

  Kenichiro Maeda, Hironobu Yasui, Tohru Yamamori, Taeko Matsuura, Seishin Takao, Motofumi Suzuki, Akira Matsuda, Osamu Inanami, Hiroki Shirato

  PLOS ONE 11 (11) 1932-6203 2016/11 [Not refereed][Not invited]
   

  The effect of 1-(3-C-ethyny1-beta-D-ribo-pentofuranosyl)cytosine (ECyd) on proton-induced cell death was evaluated in human lung carcinoma cell line A549 and Chinese hamster fibroblast cell line V79 to enhance relative biological effectiveness (RBE) within the spread-out Bragg peak (SOBP) of proton beams. Treatment with ECyd significantly enhanced the proton -induced loss of clonogenicity and increased senescence at the center, but not at the distal edge of SOBP. The p53-binding protein 1 foci formation assay showed that ECyd decelerated the rate of DNA double-strand break (DSB) repair at the center, but not the distal region of SOBP, suggesting that the ECyd-induced enhancement of proton-induced cell death is partially associated with the inhibition of DSB repair. This study demonstrated that ECyd enhances proton-induced cell killing at all positions of SOBP, except for the distal region and minimizes the site-dependent differences in RBE within SOBP. Thus, ECyd is a unique radiosensitizer for proton therapy that may be useful because it levels the biological dose within SOBP, which improves tumor control and reduces the risk of adverse effects at the distal edge of SOBP.
• NTCP modeling analysis of acute hematologic toxicity in whole pelvic radiation therapy for gynecologic malignancies - A dosimetric comparison of IMRT and spot-scanning proton therapy (SSPT)

  Takaaki Yoshimura, Rumiko Kinoshita, Shunsuke Onodera, Chie Toramatsu, Ryusuke Suzuki, Yoichi M. Ito, Seishin Takao, Taeko Matsuura, Yuka Matsuzaki, Kikuo Umegaki, Hiroki Shirato, Shinichi Shimizu

  PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS 32 (9) 1095 - 1102 1120-1797 2016/09 [Not refereed][Not invited]
   

  Purpose: This treatment planning study was conducted to determine whether spot scanning proton beam therapy (SSPT) reduces the risk of grade >= 3 hematologic toxicity (HT3+) compared with intensity modulated radiation therapy (IMRT) for postoperative whole pelvic radiation therapy (WPRT). Methods and materials: The normal tissue complication probability (NTCP) of the risk of HT3+ was used as an in silico surrogate marker in this analysis. IMRT and SSPT plans were created for 13 gynecologic malignancy patients who had received hysterectomies. The IMRT plans were generated using the 7-fields step and shoot technique. The SSPT plans were generated using anterior-posterior field with single field optimization. Using the relative biological effectives (RBE) value of 1.0 for IMRT and 1.1 for SSPT, the prescribed dose was 45 Gy(RBE) in 1.8 Gy(RBE) per fractions for 95% of the planning target volume (PTV). The homogeneity index (HI) and the conformity index (CI) of the PTV were also compared. Results: The bone marrow (BM) and femoral head doses using SSPT were significantly lower than with IMRT. The NTCP modeling analysis showed that the risk of HT3+ using SSPT was significantly lower than with IMRT (NTCP = 0.04 +/- 0.01 and 0.19 +/- 0.03, p = 0.0002, respectively). There were no significant differences in the CI and HI of the PTV between IMRT and SSPT (CI = 0.97 +/- 0.01 and 0.96 +/- 0.02, p = 0.3177, and HI = 1.24 +/- 0.11 and 1.27 +/- 0.05, p = 0.8473, respectively). Conclusion: The SSPT achieves significant reductions in the dose to BM without compromising target coverage, compared with IMRT. The NTCP value for HT3+ in SSPT was significantly lower than in IMRT. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.
• Optimization and evaluation of multiple gating beam delivery in a synchrotron-based proton beam scanning system using a real-time imaging technique

  Takahiro Yamada, Naoki Miyamoto, Taeko Matsuura, Seishin Takao, Yusuke Fujii, Yuka Matsuzaki, Hidenori Koyano, Masumi Umezawa, Hideaki Nihongi, Shinichi Shimizu, Hiroki Shirato, Kikuo Umegaki

  PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS 32 (7) 932 - 937 1120-1797 2016/07 [Not refereed][Not invited]
   

  Purpose: To find the optimum parameter of a new beam control function installed in a synchrotron-based proton therapy system. Methods: A function enabling multiple gated irradiation in the flat top phase has been installed in a real-time-image gated proton beam therapy (RGPT) system. This function is realized by a waiting timer that monitors the elapsed time from the last gate-off signal in the flat top phase. The gated irradiation efficiency depends on the timer value, T-w. To find the optimum Tw value, gated irradiation efficiency was evaluated for each configurable T-w value. 271 gate signal data sets from 58 patients were used for the simulation. Results: The highest mean efficiency 0.52 was obtained in T-W = 0.2 s. The irradiation efficiency was approximately 21% higher than at T-W = 0 s, which corresponds to ordinary synchrotron operation. The irradiation efficiency was improved in 154 (57%) of the 271 cases. The irradiation efficiency was reduced in 117 cases because the T-W value was insufficient or the function introduced an unutilized wait time for the next gate-on signal in the flat top phase. In the actual treatment of a patient with a hepatic tumor at T-w = 0.2 s, 4.48 GyE irradiation was completed within 250 s. In contrast, the treatment time of ordinary synchrotron operation was estimated to be 420 s. Conclusions: The results suggest that the multiple gated-irradiation function has potential to improve the gated irradiation efficiency and to reduce the treatment time. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
• 椎体IMRTとその精度に関する研究

  安田耕一, 清水伸一, 橋本孝之, SUTHERLAND Ken, 白土博樹, 土屋和彦, 加藤徳雄, 鬼丸力也, 木下留美子, 井上哲也, 西岡健太郎, 西川由記子, 森崇, 原田慶一, 原田八重, 鈴木隆介, 寅松千枝, 松浦妙子, 高尾聖心, 宮本直樹, 伊藤陽一

  Japanese Journal of Radiology 34 (Supplement) 5  1867-1071 2016/02/25 [Not refereed][Not invited]
  
• Development and evaluation of a short-range applicator for treating superficial moving tumors with respiratory-gated spot-scanning proton therapy using real-time image guidance

  Taeko Matsuura, Yusuke Fujii, Seishin Takao, Takahiro Yamada, Yuka Matsuzaki, Naoki Miyamoto, Taisuke Takayanagi, Shinichiro Fujitaka, Shinichi Shimizu, Hiroki Shirato, Kikuo Umegaki

  PHYSICS IN MEDICINE AND BIOLOGY 61 (4) 1515 - 1531 0031-9155 2016/02 [Not refereed][Not invited]
   

  Treatment of superficial tumors that move with respiration (e.g. lung tumors) using spot-scanning proton therapy (SSPT) is a high-priority research area. The recently developed real-time image-gated proton beam therapy (RGPT) system has proven to be useful for treating moving tumors deep inside the liver. However, when treating superficial tumors, the proton's range is small and so is the sizes of range straggling, making the Bragg-peaks extremely sharp compared to those located in deep-seated tumors. The extreme sharpness of Bragg-peaks is not always beneficial because it necessitates a large number of energy layers to make a spread-out Bragg-peak, resulting in long treatment times, and is vulnerable to motion-induced dose deterioration. We have investigated a method to treat superficial moving tumors in the lung by the development of an applicator compatible with the RGPT system. A mini-ridge filter (MRF) was developed to broaden the pristine Bragg-peak and, accordingly, decrease the number of required energy layers to obtain homogeneous irradiation. The applicator position was designed so that the fiducial marker's trajectory can be monitored by fluoroscopy during proton beam-delivery. The treatment plans for three lung cancer patients were made using the applicator, and four-dimensional (4D) dose calculations for the RGPT were performed using patient respiratory motion data. The effect of the MRF on the dose distributions and treatment time was evaluated. With the MRF, the number of energy layers was decreased to less than half of that needed without it, whereas the target volume coverage values (D99%, D95%, D50%, D2%) changed by less than 1% of the prescribed dose. Almost no dose distortion was observed after the 4D dose calculation, whereas the treatment time decreased by 26%-37%. Therefore, we conclude that the developed applicator compatible with RGPT is useful to solve the issue in the treatment of superficial moving tumors with SSPT.
• 呼吸性移動の複雑さと対策:最新の動体追跡放射線治療

  宮本直樹, 高尾聖心, 原田慶一, 石川正純, 鈴木隆介, 松浦妙子, 牧永彩乃, 井上哲也, 加藤徳雄, 清水伸一, 鬼丸力也, 白土博樹

  日本放射線腫瘍学会高精度放射線外部照射部会学術大会プログラム・抄録集 29th 46  2016 [Not refereed][Not invited]
  
• Intrafractional Baseline Shift or Drift of Lung Tumor Motion During Gated Radiation Therapy With a Real-Time Tumor-Tracking System

  Seishin Takao, Naoki Miyamoto, Taeko Matsuura, Rikiya Onimaru, Norio Katoh, Tetsuya Inoue, Kenneth Lee Sutherland, Ryusuke Suzuki, Hiroki Shirato, Shinichi Shimizu

  INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 94 (1) 172 - 180 0360-3016 2016/01 [Not refereed][Not invited]
   

  Purpose: To investigate the frequency and amplitude of baseline shift or drift (shift/drift) of lung tumors in stereotactic body radiation therapy (SBRT), using a real-time tumor-tracking radiation therapy (RTRT) system. Methods and Materials: Sixty-eight patients with peripheral lung tumors were treated with SBRT using the RTRT system. One of the fiducial markers implanted near the tumor was used for the real-time monitoring of the intrafractional tumor motion every 0.033 seconds by the RTRT system. When baseline shift/drift is determined by the system, the position of the treatment couch is adjusted to compensate for the shift/drift. Therefore, the changes in the couch position correspond to the baseline shift/drift in the tumor motion. The frequency and amount of adjustment to the couch positions in the left-right (LR), cranio-caudal (CC), and antero-posterior (AP) directions have been analyzed for 335 fractions administered to 68 patients. Results: The average change in position of the treatment couch during the treatment time was 0.45 +/- 2.23 mm (mean +/- standard deviation), -1.65 +/- 5.95 mm, and 1.50 +/- 2.54 mm in the LR, CC, and AP directions, respectively. Overall the baseline shift/drift occurs toward the cranial and posterior directions. The incidence of baseline shift/drift exceeding 3 mm was 6.0%, 15.5%, 14.0%, and 42.1% for the LR, CC, AP, and for the square-root of sum of 3 directions, respectively, within 10 minutes of the start of treatment, and 23.0%, 37.6%, 32.5%, and 71.6% within 30 minutes. Conclusions: Real-time monitoring and frequent adjustments of the couch position and/or adding appropriate margins are suggested to be essential to compensate for possible underdosages due to baseline shift/drift in SBRT for lung cancers. (C) 2016 Elsevier Inc. All rights reserved.
• Optimization of the fractionated irradiation scheme considering physical doses to tumor and organ at risk based on dose-volume histograms.

  Yasutaka Sugano, Masahiro Mizuta, Seishin Takao, Hiroki Shirato, Kenneth L Sutherland, Hiroyuki Date

  Medical physics 42 (11) 6203 - 10 2015/11 

  PURPOSE: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose-volume histograms for tumor and normal tissues of organs around the tumor. METHODS: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of the tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose-volume histogram. RESULTS: It was found that the optimization of fractionation scheme incorporating the dose-volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8-32 fractions with a daily dose of 2.2-6.3 Gy. CONCLUSIONS: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose-volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.
• Proton-induced x-ray fluorescence CT imaging

  Magdalena Bazalova-Carter, Magdalena Bazalova-Carter, Moiz Ahmad, Taeko Matsuura, Taeko Matsuura, Seishin Takao, Seishin Takao, Yuto Matsuo, Rebecca Fahrig, Hiroki Shirato, Hiroki Shirato, Kikuo Umegaki, Kikuo Umegaki, Lei Xing, Lei Xing

  Medical Physics 42 900 - 907 0094-2405 2015/02/01 [Not refereed][Not invited]
   

  © 2015 American Association of Physicists in Medicine. Purpose: To demonstrate the feasibility of proton-induced x-ray fluorescence CT (pXFCT) imaging of gold in a small animal sized object by means of experiments and Monte Carlo (MC) simulations. Methods: First, proton-induced gold x-ray fluorescence (pXRF) was measured as a function of gold concentration. Vials of 2.2 cm in diameter filled with 0%5% Au solutions were irradiated with a 220 MeV proton beam and x-ray fluorescence induced by the interaction of protons, and Au was detected with a 3×3 mm 2 CdTe detector placed at 90? with respect to the incident proton beam at a distance of 45 cm from the vials. Second, a 7-cm diameter water phantom containing three 2.2-diameter vials with 3%5% Au solutions was imaged with a 7-mm FWHM 220 MeV proton beam in a first generation CT scanning geometry. X-rays scattered perpendicular to the incident proton beam were acquired with the CdTe detector placed at 45 cm from the phantom positioned on a translation/rotation stage. Twenty one translational steps spaced by 3 mm at each of 36 projection angles spaced by 10? were acquired, and pXFCT images of the phantom were reconstructed with filtered back projection. A simplified geometry of the experimental data acquisition setup was modeled with the MC TOPAS code, and simulation results were compared to the experimental data. Results: A linear relationship between gold pXRF and gold concentration was observed in both experimental and MC simulation data (R 2 > 0.99). All Au vials were apparent in the experimental and simulated pXFCT images. Specifically, the 3% Au vial was detectable in the experimental [contrast-to-noise ratio (CNR) = 5.8] and simulated (CNR = 11.5) pXFCT image. Due to fluorescence x-ray attenuation in the higher concentration vials, the 4% and 5% Au contrast were underestimated by 10% and 15%, respectively, in both the experimental and simulated pXFCT images. Conclusions: Proton-induced x-ray fluorescence CT imaging of 3%5% gold solutions in a small animal sized water phantom has been demonstrated for the first time by means of experiments and MC simulations.
• A motion-compensated image filter for low-dose fluoroscopy in a real-time tumor-tracking radiotherapy system

  Naoki Miyamoto, Masayori Ishikawa, Kenneth Sutherland, Ryusuke Suzuki, Taeko Matsuura, Chie Toramatsu, Seishin Takao, Hideaki Nihongi, Shinichi Shimizu, Kikuo Umegaki, Hiroki Shirato

  Journal of Radiation Research 56 186 - 196 0449-3060 2014/01/01 [Not refereed][Not invited]
   

  © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology. In the real-time tumor-tracking radiotherapy system, a surrogate fiducial marker inserted in or near the tumor is detected by fluoroscopy to realize respiratory-gated radiotherapy. The imaging dose caused by fluoroscopy should be minimized. In this work, an image processing technique is proposed for tracing a moving marker in low-dose imaging. The proposed tracking technique is a combination of a motion-compensated recursive filter and template pattern matching. The proposed image filter can reduce motion artifacts resulting from the recursive process based on the determination of the region of interest for the next frame according to the current marker position in the fluoroscopic images. The effectiveness of the proposed technique and the expected clinical benefit were examined by phantom experimental studies with actual tumor trajectories generated from clinical patient data. It was demonstrated that the marker motion could be traced in low-dose imaging by applying the proposed algorithm with acceptable registration error and high pattern recognition score in all trajectories, although some traj ectories were not able to be tracked with the conventional spatial filters or without image filters. The positional accuracy is expected to be kept within ±2 mm. The total computation time required to determine the marker position is a few milliseconds. The proposed image processing technique is applicable for imaging dose reduction.
• What is the appropriate size criterion for proton radiotherapy for hepatocellular carcinoma? A dosimetric comparison of spot-scanning proton therapy versus intensity-modulated radiation therapy

  Chie Toramatsu, Norio Katoh, Shinichi Shimizu, Hideaki Nihongi, Taeko Matsuura, Seishin Takao, Naoki Miyamoto, Ryusuke Suzuki, Kenneth Sutherland, Rumiko Kinoshita, Rikiya Onimaru, Masayori Ishikawa, Kikuo Umegaki, Hiroki Shirato

  Radiation Oncology 8 2013/03/05 [Not refereed][Not invited]
   

  Background: We performed a dosimetric comparison of spot-scanning proton therapy (SSPT) and intensity-modulated radiation therapy (IMRT) for hepatocellular carcinoma (HCC) to investigate the impact of tumor size on the risk of radiation induced liver disease (RILD).Methods: A number of alternative plans were generated for 10 patients with HCC. The gross tumor volumes (GTV) varied from 20.1 to 2194.5 cm 3 . Assuming all GTVs were spherical, the nominal diameter was calculated and ranged from 3.4 to 16.1 cm. The prescription dose was 60 Gy for IMRT or 60 cobalt Gy-equivalents for SSPT with 95% planning target volume (PTV) coverage. Using IMRT and SSPT techniques, extensive comparative planning was conducted. All plans were evaluated by the risk of RILD estimated using the Lyman-normal-tissue complication probability model.Results: For IMRT the risk of RILD increased drastically between 6.3-7.8 cm nominal diameter of GTV. When the nominal diameter of GTV was more than 6.3 cm, the average risk of RILD was 94.5% for IMRT and 6.2% for SSPT.Conclusions: Regarding the risk of RILD, HCC can be more safely treated with SSPT, especially if its nominal diameter is more than 6.3 cm. © 2013 Toramatsu et al.; licensee BioMed Central Ltd.
• Integration of a real-time tumor monitoring system into gated proton spot-scanning beam therapy: An initial phantom study using patient tumor trajectory data

  Taeko Matsuura, Taeko Matsuura, Taeko Matsuura, Naoki Miyamoto, Naoki Miyamoto, Naoki Miyamoto, Shinichi Shimizu, Shinichi Shimizu, Yusuke Fujii, Yusuke Fujii, Masumi Umezawa, Masumi Umezawa, Seishin Takao, Seishin Takao, Hideaki Nihongi, Hideaki Nihongi, Chie Toramatsu, Chie Toramatsu, Kenneth Sutherland, Kenneth Sutherland, Ryusuke Suzuki, Ryusuke Suzuki, Masayori Ishikawa, Masayori Ishikawa, Rumiko Kinoshita, Kenichiro Maeda, Kenichiro Maeda, Kikuo Umegaki, Hiroki Shirato

  Medical Physics 40 0094-2405 2013/01/01 [Not refereed][Not invited]
   

  Purpose: In spot-scanning proton therapy, the interplay effect between tumor motion and beam delivery leads to deterioration of the dose distribution. To mitigate the impact of tumor motion, gating in combination with repainting is one of the most promising methods that have been proposed. This study focused on a synchrotron-based spot-scanning proton therapy system integrated with real-time tumor monitoring. The authors investigated the effectiveness of gating in terms of both the delivered dose distribution and irradiation time by conducting simulations with patients' motion data. The clinically acceptable range of adjustable irradiation control parameters was explored. Also, the relation between the dose error and the characteristics of tumor motion was investigated. Methods: A simulation study was performed using a water phantom. A gated proton beam was irradiated to a clinical target volume (CTV) of 5 × 5 × 5 cm 3 , in synchronization with lung cancer patients' tumor trajectory data. With varying parameters of gate width, spot spacing, and delivered dose per spot at one time, both dose uniformity and irradiation time were calculated for 397 tumor trajectory data from 78 patients. In addition, the authors placed an energy absorber upstream of the phantom and varied the thickness to examine the effect of changing the size of the Bragg peak and the number of required energy layers. The parameters with which 95% of the tumor trajectory data fulfill our defined criteria were accepted. Next, correlation coefficients were calculated between the maximum dose error and the tumor motion characteristics that were extracted from the tumor trajectory data. Results: With the assumed CTV, the largest percentage of the data fulfilled the criteria when the gate width was ±2 mm. Larger spot spacing was preferred because it increased the number of paintings. With a prescribed dose of 2 Gy, it was difficult to fulfill the criteria for the target with a very small effective depth (the sum of an assumed energy absorber's thickness and the target depth in the phantom) because of the sharpness of the Bragg peak. However, even shallow targets could be successfully irradiated by employing an adequate number of paintings and by placing an energy absorber of sufficient thickness to make the effective target depth more than 12 cm. The authors also observed that motion in the beam direction was the main cause of dose distortion, followed by motion in the lateral plane perpendicular to the scan direction. Conclusions: The results suggested that by properly adjusting irradiation control parameters, gated proton spot-scanning beam therapy can be robust to target motion. This is an important first step toward establishing treatment plans in real patient geometry. © 2013 American Association of Physicists in Medicine.
• The Role of Spot Scanning Proton Therapy in the Treatment of Large Abdominal Tumors: A Comparative Planning Study of Hepatocellular Carcinoma

  C. Toramatsu, N. Katoh, S. Shimizu, H. Nihongi, T. Matsuura, S. Takao, N. Miyamoto, R. Kinoshita, K. Umegaki, H. Shirato

  INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 84 (3) S327 - S328 0360-3016 2012/11 [Refereed][Not invited]
  
• Graphical representation of the effects on tumor and OAR for determining the appropriate fractionation regimen in radiation therapy planning

  Masahiro Mizuta, Hiroyuki Date, Seishin Takao, Naoki Kishimoto, Kenneth L. Sutherland, Rikiya Onimaru, Hiroki Shirato

  Medical Physics 39 (11) 6791 - 6795 0094-2405 2012/11 [Refereed][Not invited]
   

  Purpose: The authors propose a graphical representation of the relation between the effect on the tumor and the damage effect on an organ at risk (OAR) against the irradiation dose, as an aid for choosing an appropriate fractionation regimen. Methods: The graphical relation is depicted by the radiation effect on the tumor E1 versus that on an OAR E0. By observing the features of the E1 vs E0 relation curve, i.e., convex or concave shape, one can judge whether multifractionation is better or not. This method is applied to the linear-quadratic model (with α and β parameters) as an example. Further, the method is extended to the general case for nonuniform dose distribution to the OAR, which is frequently seen in clinical situations. Results: The criterion for selecting multi- or hypofractionation is based on the relation between the dose for the OAR and the αβ ratio of the OAR to the tumor. It is also shown that the graphical relation enables us to estimate the final effect after multifractionated treatment by plotting a tangent line on the curve. Conclusions: The graphical representation method is of use for improving planning in radiotherapy by determining the effective fractionation scheme. © 2012 American Association of Physicists in Medicine.
• A mathematical study to select fractionation regimen based on physical dose distribution and the linear-quadratic model

  Masahiro Mizuta, Seishin Takao, Hiroyuki Date, Naoki Kishimoto, Kenneth L. Sutherland, Rikiya Onimaru, Hiroki Shirato

  International Journal of Radiation Oncology Biology Physics 84 (3) 829 - 833 0360-3016 2012/11/01 [Refereed][Not invited]
   

  Purpose: Hypofractionated irradiation is often used in precise radiotherapy instead of conventional multifractionated irradiation. We propose a novel mathematical method for selecting a hypofractionated or multifractionated irradiation regimen based on physical dose distribution adding to biologic consideration. Methods and Materials: The linear-quadratic model was used for the radiation effects on tumor and normal tissues, especially organs at risk (OARs). On the basis of the assumption that the OAR receives a fraction of the dose intended for the tumor, the minimization problem for the damage effect on the OAR was treated under the constraint that the radiation effect on the tumor is fixed. Results: For an N-time fractionated irradiation regimen, the constraint of tumor lethality was described by an N-dimensional hypersphere. The total dose of the fractionated irradiations was considered for minimizing the damage effect on the OAR under the hypersphere condition. It was found that the advantage of hypofractionated or multifractionated irradiation therapies depends on the magnitude of the ratio of α/β parameters for the OAR and tumor in the linear-quadratic model and the ratio of the dose for the OAR and tumor. Conclusions: Our mathematical method shows that multifractionated irradiation with a constant dose is better if the ratio of α/β for the OAR and tumor is less than the ratio of the dose for the OAR and tumor, whereas hypofractionated irradiation is better otherwise. © 2012 Elsevier Inc.
• 一方向X線透視による低被曝・省スペース型動体追跡装置の開発

  宮本直樹, 石川正純, SUTHERLAND Kenneth, 鈴木隆介, 松浦妙子, 高尾聖心, 寅松千枝, 二本木英明, 清水伸一, 梅垣菊男, 白土博樹

  医学物理 Supplement 32 (3) 281 - 282 1345-5362 2012/09/13 [Not refereed][Not invited]
  
• 陽子線治療における最適な治療ワークフローの検討

  高尾聖心, 松浦妙子, 寅松千枝, 二本木英明, 宮本直樹, 清水伸一, 木下留美子, 松田浩二, 木谷貴雄, 梅垣菊男, 白土博樹

  医学物理 Supplement 32 (3) 169 - 170 1345-5362 2012/09/13 [Not refereed][Not invited]
  
• 陽子線スキャニング照射における体内マーカーによる線量遮蔽のTCPを用いた評価

  前田憲一郎, 松浦妙子, 高尾聖心, SUTHERLAND Kenneth, 寅松千枝, 二本木英明, 宮本直樹, 石川正純, 清水伸一, 梅垣菊男, 白土博樹

  医学物理 Supplement 32 (3) 101 - 102 1345-5362 2012/09/13 [Not refereed][Not invited]
  
• Biological effect of dose distortion by fiducial markers in spot-scanning proton therapy with a limited number of fields: A simulation study

  Taeko Matsuura, Kenichiro Maeda, Kenneth Sutherland, Taisuke Takayanagi, Shinichi Shimizu, Seishin Takao, Naoki Miyamoto, Hideaki Nihongi, Chie Toramatsu, Yoshihiko Nagamine, Rintaro Fujimoto, Ryusuke Suzuki, Masayori Ishikawa, Kikuo Umegaki, Hiroki Shirato

  MEDICAL PHYSICS 39 (9) 5584 - 5591 0094-2405 2012/09 [Refereed][Not invited]
   

  Purpose: In accurate proton spot-scanning therapy, continuous target tracking by fluoroscopic x ray during irradiation is beneficial not only for respiratory moving tumors of lung and liver but also for relatively stationary tumors of prostate. Implanted gold markers have been used with great effect for positioning the target volume by a fluoroscopy, especially for the cases of liver and prostate with the targets surrounded by water-equivalent tissues. However, recent studies have revealed that gold markers can cause a significant underdose in proton therapy. This paper focuses on prostate cancer and explores the possibility that multiple-field irradiation improves the underdose effect by markers on tumor-control probability (TCP). Methods: A Monte Carlo simulation was performed to evaluate the dose distortion effect. A spherical gold marker was placed at several characteristic points in a water phantom. The markers were with two different diameters of 2 and 1.5 mm, both visible on fluoroscopy. Three beam arrangements of single-field uniform dose (SFUD) were examined: one lateral field, two opposite lateral fields, and three fields (two opposite lateral fields + anterior field). The relative biological effectiveness (RBE) was set to 1.1 and a dose of 74 Gy (RBE) was delivered to the target of a typical prostate size in 37 fractions. The ratios of TCP to that without the marker (TCPr) were compared with the parameters of the marker sizes, number of fields, and marker positions. To take into account the dependence of biological parameters in TCP model, alpha/beta values of 1.5, 3, and 10 Gy (RBE) were considered. Results: It was found that the marker of 1.5 mm diameter does not affect the TCPs with all alpha/beta values when two or more fields are used. On the other hand, if the marker diameter is 2 mm, more than two irradiation fields are required to suppress the decrease in TCP from TCPr by less than 3%. This is especially true when multiple (two or three) markers are used for alignment of a patient. Conclusions: It is recommended that 1.5-mm markers be used to avoid the reduction of TCP as well as to spare the surrounding critical organs, as long as the markers are visible on x-ray fluoroscopy. When 2-mm markers are implanted, more than two fields should be used and the markers should not be placed close to the distal edge of any of the beams. (c) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4745558]
• Dosimetric Study for Shallow-Seated Tumor Using Passive/active Scanning Proton Beam

  C. Toramatsu, T. Matsuura, H. Nihongi, S. Takao, N. Miyamoto, S. Shimizu, R. Kinoshita, K. Umegaki, H. Shirato

  MEDICAL PHYSICS 39 (6) 3821 - 3822 0094-2405 2012/06 [Refereed][Not invited]
  
• 治療計画シミュレーションによる陽子線スキャニング専用機の線量分布の検証

  二本木英明, 寅松千枝, 松浦妙子, 高尾聖心, 宮本直樹, 梅垣菊男, 清水伸一, 木下留美子, 白土博樹

  医学物理 Supplement 32 (1) 190  1345-5362 2012/04/01 [Not refereed][Not invited]
  
• Excitation System for Magnetic Resonance Elastography Using Micro MRI

  TADANO Shigeru, FUJISAKI Kazuhiro, SUZUKI Hayato, TAKAO Seishin, SUGA Mikio, KAJIWARA Itsuro, YAMAMOTO Toru, JIANG Yu, NAKAMURA Gen

  Journal of Biomechanical Science and Engineering 一般社団法人 日本機械学会 7 (4) 463 - 474 1880-9863 2012 [Refereed][Not invited]
   

  Magnetic resonance elastography (MRE) is a nondestructive method for measuring the hardness and softness of living tissue by means of magnetic resonance imaging (MRI) coupled with mechanical excitation of the subject. The shear modulus of a tissue is related to the velocity of transverse waves propagating through it, and local movements are obtained from MRI phase images. Micro MRI systems are available for high-resolution MRE measurements of soft materials. Longitudinal waves are effective for long-distance wave propagation from small excitation areas in micro MRI systems, and the transverse waves produced by the longitudinal waves can be used for elastography. This study proposes an excitation system comprising a high-power vibration generator and bar-shaped vibration transmitter made from an elastic material. The transmission characteristics of the glass-fiber-reinforced plastic bar-shaped transducer were evaluated by measuring the accelerations at its base and tip. The performance of the excitation system, which focused on the effects of frequency and amplitude, was investigated for measuring storage and loss modulus distributions in agarose gel. This system could transfer longitudinal waves with an amplitude of 0.5 mm and frequency between 50 and 250 Hz, without significant damping. Moreover, the excitation capabilities for gel phantoms were evaluated by MRE using 0.3T micro MRI equipment. A large amplitude of 0.5 mm and high frequency of 250 Hz produced less data scatter than smaller amplitudes and lower frequencies. MRE performance improved upon using strong excitations.
• Improvement of tracking accuracy and stability by recursive image processing in real-time tumor-tracking radiotherapy system

  Miyamoto Naoki, Sutherland Kenneth, Suzuki Ryusuke, Matsuura Taeko, Toramatsu Chie, Takao Seishin, Nihongi Hideaki, Kinoshita Rumiko, Shimizu Shinichi, Onimaru Rikiya, Umegaki Kikuo, Shirato Hiroki, Ishikawa Masayori

  MEDICAL IMAGING 2012: IMAGE-GUIDED PROCEDURES, ROBOTIC INTERVENTIONS, AND MODELING 8316 0277-786X 2012 [Refereed][Not invited]
  
• Computational Model for Radiotherapeutic Response of Metastatic Cervical Lymph Nodes

  S. Takao, S. Tadano, H. Taguchi, H. Shirato

  6TH WORLD CONGRESS OF BIOMECHANICS (WCB 2010), PTS 1-3 31 1483 - + 1680-0737 2010 [Refereed][Not invited]
   

  This study proposes a computational simulation method to calculate therapeutic outcomes in radiotherapy for head and neck carcinoma. As a tumor shrinks due to radiation exposure, it was possible to express the radiotherapeutic effects in terms of tumor volume changes and geometric distortion. The shrinking was assumed to conform to the deformation of solid body. The relationships between radiation energy and tumor deformation were estimated from solid mechanics equations. The simulation model was applied to six clinical cases of lymph node metastasis in patients with head and neck carcinoma. Three-dimensional solid models of tumors were constructed based on computed tomography (CT) images taken before the start of treatment. Follow up CT images were also taken weekly during the treatment period, to evaluate the changes in tumor volumes. The values of parameters prescribing tumor radiosensitivity or growth rates of tumor cells were identified so that the calculated results fit the clinical results. The simulated results represented the tumor decreases well in all cases. Average differences between measured and calculated tumor volume for all the cases were less than 10%. In conclusions, simulation results show that the simulation model can be applied to a variety of clinical cases by determining the tumor parameters appropriately.

MISC

• Automatic Bladder Delineation on MR Images Using a Convolution Neural Network for Online Image-Guided Radiotherapy

  K. Nishioka, Y. Nomura, T. Hashimoto, R. Kinoshita, N. Katoh, H. Taguchi, K. Yasuda, T. Mori, Y. Uchinami, M. Otsuka, T. Matsuura, S. Takao, R. Suzuki, S. Tanaka, T. Yoshimura, H. Aoyama, S. Shimizu  International Journal of Radiation Oncology*Biology*Physics  108-  (3)  e288  -e289  2020/11  [Refereed]
  
• Normal Tissue Complication Probability for Hematologic and Gastrointestinal Toxicity in Postoperative Whole Pelvic Radiotherapy for Gynecologic Malignancies using Intensity Modulated Proton Therapy with Robust Optimization

  T. Yoshimura, R. Yamada, R. Kinoshita, H. Tamura, T. Matsuura, S. Takao, M. Tamura, S. Tanaka, N. Nagae, K. Kobashi, H. Aoyama, S. Shimizu  International Journal of Radiation Oncology*Biology*Physics  108-  (3)  e494  -e494  2020/11  [Refereed]
  
• 画像誘導陽子線治療の将来展望

  田口大志, 橋本孝之, 橋本孝之, 加藤徳雄, 木下留美子, 安田耕一, 西岡健太郎, 西岡健太郎, 森崇, 打浪雄介, 宮本直樹, 高尾聖心, 清水伸一, 清水伸一, 青山英史  日本癌治療学会学術集会(Web)  58th-  2020
• OC-078: Development of Gated Proton Imaging System for Moving Target

  S. Tanaka, N. Miyamoto, T. Nishio, T. Yoshimura, S. Takao, Y. Matsuo, S. Shimizu, H. Shirato, T. Matsuura  Radiotherapy and Oncology  141-  S32  -S33  2019/12  [Refereed]
  
• 局所進行食道癌に対してspot scanning法による根治的化学陽子線療法を施行した一例

  宮崎 智彦, 打浪 雄介, 田口 大志, 加藤 徳雄, 清水 伸一, 白土 博樹, 中積 宏之, 中野 真太郎, 坂本 直哉, 高尾 聖心, 田村 昌也, 松浦 妙子  日本医学放射線学会秋季臨床大会抄録集  55回-  S520  -S520  2019/09  [Not refereed][Not invited]
  
• Analysis of Beam Delivery Times and Dose Rates for the Treatment of Mobile Tumors Using Real Time Image Gated Spot-Scanning Proton Beam Therapy

  S. Shimizu, T. Yoshimura, N. Katoh, T. Inoue, T. Hashimoto, K. Nishioka, S. Takao, T. Matsuura, N. Miyamoto, Y.M. Ito, K. Umegaki, H. Shirato  International Journal of Radiation Oncology*Biology*Physics  102-  (3)  S182  -S183  2018/11  [Refereed]
  
• Intensity-Modulated Proton Therapy with Dose Painting based on Hypoxia Imaging for Nasopharyngeal Cancer

  K. Yasuda, S. Takao, Y. Matsuo, T. Yoshimura, M. Tamura, H. Minatogawa, Y. Dekura, T. Matsuura, R. Onimaru, T. Shiga, S. Shimizu, K. Umegaki, H. Shirato  International Journal of Radiation Oncology*Biology*Physics  102-  (3)  e378  -e378  2018/11  [Refereed]
  
• 前立腺癌治療の新たな展開:ハイリスク前立腺癌に対する拡大手術、粒子線治療、ネオアジュバント治療 ハイリスク前立腺がんに対する強度変調放射線治療・陽子線治療 現状と可能性

  清水 伸一, 橋本 孝之, 西岡 健太郎, 安部 崇重, 大澤 崇宏, 松本 隆児, 松浦 妙子, 宮本 直樹, 高尾 聖心, 鈴木 隆介, 梅垣 菊男, 篠原 信雄, 白土 博樹  日本癌治療学会学術集会抄録集  56回-  SY5  -2  2018/10  [Not refereed][Not invited]
  
• 全脳全脊髄強度変調陽子線照射(IMPT)が骨髄抑制軽減に有用であったAYA世代胚細胞腫瘍の2例

  橋本 孝之, 寺坂 俊介, 井口 晶裕, 山口 秀, 小林 浩之, 杉山 未奈子, 長 祐子, 森 崇, 高尾 聖心, 松浦 妙子, 鬼丸 力也, 清水 伸一, 白土 博樹  日本小児血液・がん学会雑誌  55-  (1)  76  -76  2018/06  [Not refereed][Not invited]
  
• An investigation of biological impact caused by using a collimator in pencil beam scanning proton therapy.

  UENO Koki, MATSUURA Taeko, MATSUURA Taeko, TAKAO Seishin, HIRAYAMA Shusuke, HIRAYAMA Shusuke, UEDA Hideaki, YOSHIMURA Takaaki, MATSUO Yuto, UMEGAKI Kikuo, UMEGAKI Kikuo  医学物理 Supplement  38-  (1)  71  2018/04/01  [Not refereed][Not invited]
  
• ヘリウム・陽子線ハイブリッド治療に関する考察(コンセプト)

  白土博樹, 清水伸一, 鬼丸力也, 高尾聖心, 松浦妙子, 梅垣菊雄  Japanese Journal of Radiology  36-  (Supplement)  7  -7  2018/02/25  [Not refereed][Not invited]
  
• Benefits of Craniospinal Intensity-modulated Proton Beam Therapy in Reducing the Myelosuppression for Adolescent Germ Cell Tumors: Two Case Reports

  Takayuki Hashimoto, Syunsuke Terasaka, Akihiro Iguchi, Shigeru Yamaguchi, Hiroyuki Kobayashi, Minako Sugiyama, Yuko Cho, Takashi Mori, Seishin Takao, Taeko Matsuura, Rikiya Onimaru, Shinichi Shimizu, Hiroki Shirato  PEDIATRIC BLOOD & CANCER  64-  S87  -S88  2017/11  [Not refereed][Not invited]
  
• Analysis of Threshold Doses for Radiation Induced Liver Parenchymal Changes on MRI after Real TimeeImage Gated Spot-Scanning Proton Beam Therapy of Hepatocellular Carcinomas

  N. Katoh, Y. Uchinami, S. Takao, K. Yasuda, K. Harada, T. Inoue, T. Matsuura, T. Hashimoto, S. Shimizu, H. Shirato  INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS  99-  (2)  E159  -E160  2017/10  [Not refereed][Not invited]
  
• Kasabach-Merritt症候群を合併した血管腫に対する陽子線治療の有用性について

  渡邊 敏史, 井口 晶裕, 長 祐子, 杉山 未奈子, 廣瀬 文, 森 崇, 高尾 聖心, 橋本 孝之, 鬼丸 力也, 清水 伸一, 白土 博樹  日本小児血液・がん学会雑誌  54-  (4)  347  -347  2017/10  [Not refereed][Not invited]
  
• Commissioning of Eclipse Treatment Planning System for Spot-scanning Nozzle in Hokkaido University Proton Therapy Center

  YOSHIMURA Takaaki, YOSHIMURA Takaaki, MATSUO Yuto, MATSUURA Taeko, MATSUURA Taeko, TAKAO Seishin, FUJII Takaaki, HIRAYAMA Shusuke, UMEGAKI Kikuo, SHIMIZU Shinichi, SHIRATO Hiroki  医学物理 Supplement  37-  (1)  176  2017/04/01  [Not refereed][Not invited]
  
• Feasibility Study of Using Dual-Energy Cone Beam Computed Tomography (DE-CBCT) in Proton Therapy Treatment Planning

  H. Peng, T. Kanehira, S. Takao, T. Matsuura, K. Umegaki, H. Shirato, L. Xing  INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS  96-  (2)  E697  -E697  2016/10  [Not refereed][Not invited]
  
• Enabling Conventional Cone Beam Computed Tomography With the Capability of Dual Energy Imaging Using a Simple Add-on Beam Modifier

  R. Vinke, S. Takao, K. Umegaki, H. Shirato, H. Peng, L. Xing  INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS  96-  (2)  E636  -E636  2016/10  [Not refereed][Not invited]
  
• Analysis of Durations and Dose Rates for Treatment of Moving Liver Tumors Using Real-Time Image Gated Spot Scanning Proton Beam Therapy

  S. Shimizu, N. Katoh, T. Hashimoto, K. Nishioka, T. Yoshimura, S. Takao, T. Matsuura, N. Miyamoto, K. Umegaki, H. Shirato  International Journal of Radiation Oncology*Biology*Physics  96-  (2)  S211  -S212  2016/10  [Refereed]
  
• Enabling Conventional Cone Beam CT with the Capability of Dual Energy Imaging Using a Simple Add-On Beam Modifier

  R. Vinke, S. Takao, K. Umegaki, H. Shirato, H. Peng, L. Xing  MEDICAL PHYSICS  43-  (6)  3457  -3457  2016/06  [Not refereed][Not invited]
  
• An Evaluation Method of Lifetime Attributable Risk for Comparing Between Proton Beam Therapy and Intensity Modulated X-Ray Therapy for Pediatric Cancer Patients by Averaging Four Dose-Response Models for Carcinoma Induction

  M. Tamura, Y. Ito, H. Sakurai, M. Mizumoto, S. Kamizawa, S. Murayama, H. Yamashita, S. Takao, R. Suzuki, H. Shirato  MEDICAL PHYSICS  43-  (6)  3508  -3508  2016/06  [Not refereed][Not invited]
  
• Feasibility Study of Using a Dual-Energy Cone Beam CT (DECBCT) in Proton Therapy Treatment Planning

  H. Peng, T. Kanehira, S. Takao, T. Matsuura, K. Umegaki, H. Shirato, L. Xing  MEDICAL PHYSICS  43-  (6)  3457  -3458  2016/06  [Not refereed][Not invited]
  
• Simulation Study of Real-Time-Image Gating On Spot Scanning Proton Therapy for Lung Tumors

  T. Kanehira, T. Matsuura, S. Takao, Y. Matsuzaki, Y. Fujii, T. Fujii, N. Miyamoto, T. Inoue, N. Katoh, S. Shimizu, K. Umegaki, H. Shirato  MEDICAL PHYSICS  43-  (6)  2016/06  [Not refereed][Not invited]
  
• Dosimetric Comparison of Spot-Scanning Proton Therapy Techniques for Liver Tumors Close to the Skin Surface

  S. Takao, T. Matsuura, Y. Matsuzaki, Y. Fujii, T. Fujii, N. Katoh, S. Shimizu, K. Umegaki, H. Shirato  MEDICAL PHYSICS  43-  (6)  3505  -3505  2016/06  [Not refereed][Not invited]
  
• Software Development for 4D-CBCT Research of Real-Time-Image Gated Spot Scanning Proton Therapy

  T. Fujii, T. Matsuura, S. Takao, N. Miyamoto, Y. Matsuzaki, Y. Fujii, K. Umegaki, S. Shimizu, H. Shirato  MEDICAL PHYSICS  43-  (6)  3389  -3389  2016/06  [Not refereed][Not invited]
  
• No Increase in Biological Effectiveness Through Collimator Scattered Low Energy Protons

  T. Matsuura, S. Takao, Y. Matsuzaki, Y. Fujii, T. Fujii, K. Maeda, H. Ueda, H. Koyano, K. Umegaki, H. Shirato  MEDICAL PHYSICS  43-  (6)  3492  -3492  2016/06  [Not refereed][Not invited]
  
• Treatment Time and Dose Rate Analysis for Respiratory Moving Liver Tumor Using Real-time-image Gated Spot Scanning Proton Beam Therapy System

  SHIMIZU Shinichi, KATOH Norio, TAKAO Seishin, MATSUURA Taeko, MIYAMOTO Naoki, HASHIMOTO Takayuki, NISHIOKA Kentaro, YOSHIMURA Takaaki, UMEGAKI Kikuo, SHIRATO Hiroki  日本医学放射線学会総会抄録集  75th-  S225  2016/02/29  [Not refereed][Not invited]
  
• A phase Ill trial of adjuvant capecitabine in breast cancer patients with HER2-negative pathologic residual invasive disease after neoadjuvant chemotherapy (CREATE-X, JBCRG-04)

  M. Toi, S-J Lee, E. S. Lee, S. Ohtani, Y-H Im, S-A Im, B-W Park, S-B Kim, Y. Yanagita, S. Takao, S. Ohno, K. Aogi, H. Iwata, A. Kim, H. Sasano, I. Yokota, Y. Ohashi, N. Masuda  CANCER RESEARCH  76-  2016/02  [Not refereed][Not invited]
  
• Target Residual Motion During Beam Delivery in Gated Irradiation Using Real Time Tumor Tracking Radiation Therapy System: Analysis of Simultaneous Motion of Multiple Internal Fiducial Markers

  N. Miyamoto, M. Ishikawa, R. Suzuki, A. Makinaga, T. Matsuura, S. Takao, Y. Matsuzaki, T. Inoue, N. Katoh, S. Shimizu, R. Onimaru, H. Shirato  INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS  93-  (3)  E554  -E554  2015/11  [Not refereed][Not invited]
  
• NTCP Modeling Analysis of Acute Hematologic Toxicity in Whole-Pelvic Radiation Therapy for Gynecologic Malignancies: A Dosimetric Comparison of IMRT and Spot-Scanning Proton Therapy

  T. Yoshimura, R. Kinoshita, S. Onodera, C. Toramatsu, R. Suzuki, Y.M. Ito, S. Takao, T. Matsuura, Y. Matsuzaki, S. Shimizu, K. Umegaki, H. Shirato  International Journal of Radiation Oncology*Biology*Physics  93-  (3)  E254  -E254  2015/11  [Refereed]
  
• Development of a Real-Time Image Gated Proton Beam Therapy (RGPT) System and Its Initial Clinical Application to Respiratory Moving Liver Tumors

  S. Shimizu, N. Katoh, S. Takao, T. Matsuura, N. Miyamoto, T. Hashimoto, K. Nishioka, T. Yoshimura, Y. Matsuzaki, R. Kinoshita, Y. Nishikawa, R. Onimaru, K. Umegaki, H. Shirato  International Journal of Radiation Oncology*Biology*Physics  93-  (3)  S42  -S42  2015/11
• 1‐(3‐C‐ethynyl‐β‐D‐ribo‐pentofuranosyl)cytosine(ECyd)併用による陽子線増感治療の実現に向けた基礎研究

  前田憲一郎, 安井博宣, 山盛徹, 松浦妙子, 高尾聖心, 鈴木基史, 松田彰, 稲波修, 白土博樹  放射線ワークショップ講演論文集  1st-  70‐71  2015/10/16  [Not refereed][Not invited]
  
• Development of Evaluation System of Optimal Synchrotron Controlling Parameter for Spot Scanning Proton Therapy with Multiple Gate Irradiations in One Operation Cycle

  T. Yamada, N. Miyamoto, T. Matsuura, S. Takao, Y. Matsuzaki, Y. Fujii, H. Koyano, H. Nihongi, M. Umezawa, K. Matsuda, K. Umegaki, H. Shirato  MEDICAL PHYSICS  42-  (6)  3394  -3394  2015/06  [Not refereed][Not invited]
  
• X-Ray Fluorescence CT Induced by Proton Beam: Experiments and Simulations

  M. Bazalova-Carter, M. Ahmad, T. Matsuura, S. Takao, Y. Matsuo, R. Fahrig, H. Shirato, K. Umegaki, L. Xing  MEDICAL PHYSICS  42-  (6)  3716  -3716  2015/06  [Not refereed][Not invited]
  
• Development and Commissioning of Real-Time Imaging Function for Respiratory-Gated Spot-Scanning Proton Beam Therapy

  N. Miyamoto, S. Takao, T. Matsuura, Y. Matsuzaki, T. Yamada, Y. Fujii, Y. Matsuo, T. Kidani, Y. Egashira, T. Umekawa, S. Shimizu, H. Shirato, K. Umegaki  MEDICAL PHYSICS  42-  (6)  3678  -3678  2015/06  [Not refereed][Not invited]
  
• Startup Experience of the New Proton Beam Therapy System with Gated Spot Scanning and Real-Time Tumor-Tracking

  K. Umegaki, T. Matsuuta, S. Takao, Y. Matsuzaki, T. Yamada, Y. Fujii, N. Miyamoto, S. Shimizu, H. Shirato  MEDICAL PHYSICS  42-  (6)  3728  -3728  2015/06  [Not refereed][Not invited]
  
• Development of An Applicator for Treating Shallow and Moving Tumors with Respiratory-Gated Spot-Scanning Proton Therapy Using Real-Time Image Guidance

  T. Matsuura, Y. Fujii, S. Takao, T. Yamada, Y. Matsuzaki, N. Miyamoto, T. Takayanagi, S. Fujitaka, S. Shimizu, H. Shirato, K. Umegaki  MEDICAL PHYSICS  42-  (6)  3207  -3208  2015/06  [Not refereed][Not invited]
  
• Influence of the Intrafraction Patient Repositioning On Spot Scanning Proton Therapy for Prostate Cancer

  Y. Fujii, T. Matsuura, S. Takao, Y. Matsuzaki, T. Yamada, N. Miyamoto, S. Shimizu, K. Umegaki, H. Shirato  MEDICAL PHYSICS  42-  (6)  3449  -3449  2015/06  [Not refereed][Not invited]
  
• 分割照射放射線治療における一回線量および分割数最適化の検討

  菅野康貴, 水田正弘, 高尾聖心, 白土博樹, SUTHERLAND Kenneth L, 伊達広行  日本放射線技術学会雑誌  70-  (9)  1022  -1022  2014/09/20  [Not refereed][Not invited]
  
• Realization of the Cone Beam CT by FPDs That Mounted on the Spot-Scanning Dedicated Proton Beam Gantry

  S. Shimizu, S. Takao, T. Matsuura, N. Miyamoto, R. Baba, T. Umekawa, K. Matsuda, T. Sasaki, Y. Nagamine, K. Umegaki, H. Shirato  INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS  90-  S920  -S920  2014/09  [Not refereed][Not invited]
  
• 頸部転移性骨腫瘍におけるスポットスキャニング照射法を用いた陽子線治療の線量分布評価

  吉村 高明, 安田 耕一, 寅松 千枝, 高尾 聖心, 松浦 妙子, 二本木 英明, 木下 留美子, 鬼丸 力也, 白土 博樹, 石川 正純  Japanese Journal of Radiology  32-  (Suppl.)  7  -7  2014/02  [Not refereed][Not invited]
  
• [Advanced radiation therapy project for cancer treatment--from Hokkaido to the world, the world access to Hokkaido].

  Shinichi Shimizu, Kazuhiko Tsuchiya, Seishin Takao, Hiroki Shirato  [Hokkaido igaku zasshi] The Hokkaido journal of medical science  89-  25  -28  2014/01/01  [Not refereed][Not invited]
   

  Cancer is the most major cause of death in Japan recently. In this symposium, we explained advanced treatment technology for cancer treatment, now used and that will be used in near future at the Hokkaido University Hospital. Intensity Moderated Radiation Therapy (IMRT) and Proton Beam Therapy (PBT) are considered to be the most promising and advanced technologies for cancer treatment. Various kinds of radiation treatment equipment and methods have been developed and constructed at the Hokkaido University. One of the most worlds wide famous one is the real time tumor tracking radiotherapy system. The FIRST (Funding for World-Leading Innovative R & D on Science and Technology) Program has been supporting us to produce cutting-edge technology. We hope that this symposium would help the audience to understand the latest technology for cancer treatment especially in the field of radiation therapy and also we wish the audience would recognize the importance of the research aspect that have been performed at Hokkaido University and its Hospital.
• UNIVERSAL SURVIVAL CURVEを用いた分割照射放射線治療法の最適化

  菅野康貴, 水田正弘, 小宮由里子, 高尾聖心, 白土博樹, 伊達広行  北海道放射線技術雑誌  75-  (75)  138  -138  2013/10/25  [Not refereed][Not invited]
  
• SU‐E‐T‐448: Effectiveness of An In‐Gate Beam Tracking Method in Spot‐Scanning Proton Therapy

  T. Matsuura, Y. Fujii, R. Fujimoto, M. Umezawa, N. Miyamoto, K. Sutherland, S. Takao, H. Nihongi, C. Toramatsu, S. Shimizu, K. U. Megaki, H. Shirato  Medical Physics  40-  308  2013/01/01  [Not refereed][Not invited]
   

  Purpose: To mitigate the impact of tumor motion in spot‐scanning proton beam therapy, the gating technique has been considered as a powerful tool. Although residual tumor motion of a few millimeters of gate volume can still cause a dose error, the error can be minimized by repainting. However, a larger number of paintings also results in the prolongation of treatment time. We propose a method which improves the dose uniformity while minimally increasing the number of paintings. Methods: Lateral beam tracking was applied in conjunction with gating. A simulation study was performed using the VQA treatment planning system (Hitachi Ltd., Japan) to assess the effectiveness of this method. A gated proton beam provided by a synchrotron was irradiated to spherical clinical target volumes (CTVs) with a diameter of 5 cm located at 10 cm and 15 cm depth in a heterogeneous phantom. The system delay time was 66 ms. Gate width was set to 2 mm. Rigid motion was assumed for CTVs which were shifted in synchronization with 20 patients' tumor trajectory data. A dose of 2 Gy was prescribed with the minimum repainting scheme. The cases that fulfilled the ICRU 50 criteria (CTVmax < 107% and CTVmin > 95%) were accepted. Results: When only gating was used, 12 and 16 out of 20 cases were accepted for targets at 10 cm and 15 cm depth, respectively. On the other hand, when beam tracking was also applied, all cases were accepted for both target depths. Conclusion: The results suggest that the application of lateral beam tracking in gate volume can improve the dose uniformity without (or minimally) increasing the number of paintings. A simulation including non‐rigid patient motion will be considered in the future. © 2013, American Association of Physicists in Medicine. All rights reserved.
• 腫瘍の放射線治療における数理モデルについて

  水田正弘, 高尾聖心, 伊達広行, 白土博樹  統計関連学会連合大会講演報告集  2012-  45  2012/09  [Not refereed][Not invited]
  
• SU‐E‐J‐42: Motion Adaptive Image Filter for Low Dose X‐Ray Fluoroscopy in the Real‐Time Tumor‐Tracking Radiotherapy System

  N. Miyamoto, M. Ishikawa, K. Sutherland, R. Suzuki, T. Matsuura, S. Takao, C. Toramatsu, H. Nihongi, S. Shimizu, R. Onimaru, K. Umegaki, H. Shirato  Medical Physics  39-  (6)  3661  -3662  2012/06  [Not refereed][Not invited]
   

  Purpose: In the real‐time tumor‐tracking radiotherapy system, fiducial markers are detected by X‐ray fluoroscopy. The fluoroscopic parameters should be optimized as low as possible in order to reduce unnecessary imaging dose. However, the fiducial markers could not be recognized due to effect of statistical noise in low dose imaging. Image processing is envisioned to be a solution to improve image quality and to maintain tracking accuracy. In this study, a recursive image filter adapted to target motion is proposed. Methods: A fluoroscopy system was used for the experiment. A spherical gold marker was used as a fiducial marker. About 450 fluoroscopic images of the marker were recorded. In order to mimic respiratory motion of the marker, the images were shifted sequentially. The tube voltage, current and exposure duration were fixed at 65 kV, 50 mA and 2.5 msec as low dose imaging condition, respectively. The tube current was 100 mA as high dose imaging. A pattern recognition score (PRS) ranging from 0 to 100 and image registration error were investigated by performing template pattern matching to each sequential image. The results with and without image processing were compared. Results: In low dose imaging, theimage registration error and the PRS without the image processing were 2.15±1.21 pixel and 46.67±6.40, respectively. Those with the image processing were 1.48±0.82 pixel and 67.80±4.51, respectively. There was nosignificant difference in the image registration error and the PRS between the results of low dose imaging with the image processing and that of high dose imaging without the image processing. Conclusions: The results showed that the recursive filter was effective in order to maintain marker tracking stability and accuracy in low dose fluoroscopy. © 2012, American Association of Physicists in Medicine. All rights reserved.
• Improvement of tracking accuracy and stability by recursive image processing in real-time tumor-tracking radiotherapy system

  Naoki Miyamoto, Kenneth Sutherland, Ryusuke Suzuki, Taeko Matsuura, Chie Toramatsu, Seishin Takao, Hideaki Nihongi, Rumiko Kinoshita, Shinichi Shimizu, Rikiya Onimaru, Kikuo Umegaki, Hiroki Shirato, Masayori Ishikawa  Progress in Biomedical Optics and Imaging - Proceedings of SPIE  8316-  2012/05/01  [Not refereed][Not invited]
   

  In the real-time tumor-tracking radiotherapy (RTRT) system, the fiducial markers are inserted in or near the target tumor in order monitor the respiratory-induced motion of tumors. During radiation treatment, the markers are detected by continuous fluoroscopy operated at 30 frames/sec. The marker position is determined by means of a template pattern matching technique which is based on the normalized cross correlation. With high tube voltage, large current and long exposure, the fiducial marker will be recognized accurately, however, the radiation dose due to X-ray fluoroscopy increases. On the other hand, by decreasing the fluoroscopy parameter settings, the fiducial marker could be lost because the effect of statistical noise is increased. In the respiratory-gated radiotherapy, the error of the image guidance will induce the reduction of the irradiation efficiency and accuracy. In order to track the marker stably and accurately in low dose fluoroscopy, we propose the application of a recursive filter. The effectiveness of the image processing is investigated by tracking the static marker and the dynamic marker. The results suggest that the stability and the accuracy of the marker tracking can be improved by applying the recursive image filter in low dose imaging. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).
• MO‐F‐213AB‐04: Biological Effect of Dose Shadowing by Fiducial Markers in Spot Scanning Proton Therapy with a Limited Number of Fields

  T. Matsuura, K. Maeda, K. Sutherland, T. Takayanagi, S. Shimizu, S. Takao, H. Nihongi, C. Toramatsu, N. Miyamoto, Y. Nagamine, R. Fujimoto, K. Umegaki, H. Shirato  Medical Physics  39-  3872  2012/01/01  [Not refereed][Not invited]
   

  Purpose: In spot scanning proton therapy, accurate patient positioning before and during treatment is essential. A small gold ball marker is suitable as a fiducial for prostate treatment. However, it has been pointed out that the marker causes dose shadowing because the protons are scattered with their energy quickly diminished. In this research we explore the possibility that the biological effect of dose shadowing can be mitigated with a limited number of fields. Methods: The proton dose distribution in prostate was simulated using Geant4. The simulations include the Hokkaido University spot scanning nozzle and a water phantom positioned isocentrically. The PTV was delineated at the center of the phantom and a gold ball of 2 mm in diameter was placed at the middle of the PTV. The plan was created by single‐field optimization and each of the following beam arrangements was investigated; (1) single lateral field (2) two lateral fields (3) two lateral + one anterior fields (4) four‐field box. The dose prescription was D95 = 74 GyE (37 fr). The minimum dose and tumor control probability (TCP) were compared for the four beam arrangements. Results: For (1)–(4), the minimum dose values were 55%, 77%, 78%, and 84% of the prescribed dose, respectively. The reduction of the TCP values from those in the absence of the gold marker were 50%, 2%, 1.1%, and 0.7%, using the TCP model by Wang et al. (Int.J.Radiat.Oncol.Biol.Phys. 55, 2003) and 2%, 0.7%, 0.5%, and 0.4%, using the biological parameters in Levegrün et al. (Int.J.RadiatOncol.Biol.Phys. 51, 2001), respectively. Conclusions: Although dose shadowing by the gold marker is locally non‐negligible, the size of the affected domain is tiny. It was found that with a minimum number of fields, the TCP nearly recovers to the value without the gold marker. © 2012, American Association of Physicists in Medicine. All rights reserved.
• 腫瘍の体内変動を考慮した放射線治療における照射法の検討

  高尾聖心, 但野茂, BENGUA Gerard, 石川正純, 白土博樹  バイオエンジニアリング講演会講演論文集  23rd-  443-444  2011/01/07  [Not refereed][Not invited]
  
• Theoretical Comparison between Availabilities of Single- and Fractionated- Irradiation Therapies

  M. Mizuta, S. Takao, H. Date, N. Kishimoto, H. Shirato  INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS  81-  (2)  S728  -S728  2011  [Not refereed][Not invited]
  
• システムバイオロジーに基づく癌放射線治療における細胞周期シミュレーション

  鈴木逸人, 高尾聖心, 但野茂, 白土博樹  バイオエンジニアリング講演会講演論文集  281  -282  2011/01  [Not refereed][Not invited]
  
• 頭頸部リンパ節腫瘍における放射線治療効果予測

  高尾聖心, 但野茂, 田口大志, 安田耕一, 鬼丸力也, 石川正純, 鈴木隆介, GERARD Bengua, 白土博樹  日本生体医工学会大会プログラム・論文集(CD-ROM)  50th-  ROMBUNNO.O1-9-5  2011  [Not refereed][Not invited]
  
• Accurate analysis of the change in volume, location, and shape of metastatic cervical lymph nodes during radiotherapy.

  TAKAO Seishin, TADANO Shigeru, TAGUCHI Hiroshi, YASUDA Koichi, ONIMARU Rikiya, SHIRATO Hiroki, ISHIKAWA Masayori, BENGUA Gerard, SUZUKI Ryusuke  Int J Radiat Oncol Biol Phys  81-  (3)  871  -879  2011  [Not refereed][Not invited]
  
• システムバイオロジーによる癌放射線治療モデル

  高尾聖心, 但野茂, 鈴木逸人, 白土博樹  日本機械学会年次大会講演論文集  2010-  (Vol.6)  83  -84  2010/09  [Not refereed][Not invited]
  
• Computational Simulation of Three-dimensional Tumor Geometry during Radiotherapy

  Seishin Takao, S. Tadano, H. Taguchi, H. Shirato  IFMBE Proceedings  23-  2083  -2087  2009/12/01  [Not refereed][Not invited]
   

  In Radiotherapy, shapes of tumors are important information to determine irradiation area and energy. In this study a simulation method is proposed to calculate changes of tumor geometry during radiotherapy. Relationships between tumor geometry and the amount of radiation energy were estimated from fundamental equations in solid mechanics as a mechanical analogy. Parameters between the radiotherapeutic effect and the geometric factor were defined as reduction resistance and reduction ratio. The values of these parameters were initially determined based on a widely-used radiobiological model (Linear-Quadratic model) and then revised by comparing with the change of actual tumor shape. To simulate uneven tumor shrinkage, the values of reduction resistance were varied depending on the tumor heterogeneity. Finite element models of tumors were constructed from CT images taken before the start of radiotherapy. For precise assessment of therapeutic effect, it would be useful to examine tumor morphological features. Three-dimensional (3D) tumor shape was represented in twodimensional (2D) map like a global map. Distances from origin (center of gravity of the tumor) to surface were visually indicated by colors in this map. Tumor volumes were indicated by sizes of the maps. Tumors in head and neck were analyzed in this study. Simulation results of tumor geometries were compared with actual tumor geometries and found to have similar tendencies. The 2D color maps enabled to evaluate the 3D morphological features of the tumors. Therefore this study provides the methodology to evaluate changes of 3D tumor geometry during radiotherapy. © 2009 International Federation of Medical and Biological Engineering.
• Computer simulation of radiotherapy for malignant tumor - A mechanical analogy method

  Seishin Takao, Shigeru Tadano, Hiroshi Taguchi, Hiroki Shirato  Journal of Biomechanical Science and Engineering  4-  576  -588  2009/12/01  [Not refereed][Not invited]
   

  A new simulation method was developed that considered a tumor as a solid body and therapeutic response as deformation of the tumor using mechanical analogy. As radiation exposure to the tumor was related to the external force to the solid body, the geometrical change of the tumor could be estimated from fundamental equations in solid mechanics. A change in tumor volume was calculated using finite element (FE) method. The FE models were constructed from CT images of patients before the radiotherapy. The initial radiotherapeutic parameters of tumor radioresistance and repopulation rate were determined based on a linear-quadratic model and then revised by the comparison with actual tumor volume change. Three patients with uterine cervix carcinoma were applied in this method. Simulation results well showed tendencies of tumor volume changes with radiotherapy. In addition, this method could provide the appropriate value of radiotherapeutic parameters for individual case. In conclusion, our approach could calculate three-dimensional tumor deformation during the course of radiotherapy and will provide useful information for more effective treatment.
• Analysis of three-dimensional characteristics in tumor morphology

  Seishin Takao, Shigeru Tadano, Hiroshi Taguchi, Hiroki Shirato  Journal of Biomechanical Science and Engineering  4-  221  -229  2009/09/07  [Not refereed][Not invited]
   

  Precise assessment of therapeutic response in radiotherapy has been an important issue in the field of radiation oncology. This study proposed a methodology to evaluate therapeutic response based on tumor geometries. Three-dimensional (3D) tumor shapes were obtained from follow-up CT scans taken once a week throughout the treatment period. Tumor geometries were represented in two-dimensional (2D) surface geometry maps. These maps indicated the distances from the tumor center to surface at each azimuthal and horizontal angle by colors, in order to represent the characteristics of tumor morphologies. This method was applied to three clinical cases of head and neck cancer. The changes of tumor geometries could be represented visually and quantitatively using surface geometry maps. These maps provided valuable information about tumors for accurate diagnosis of tumor response to radiotherapy. Copyright © 2009 by The Japan Society of Mechanical Engineers.
• 力学アナロジーに基づく放射線治療中の腫瘍形状変化シミュレーション

  高尾 聖心, 但野 茂, 田口 大志, 白土 博樹  生体医工学  47-  (3)  323  -323  2009/06  [Not refereed][Not invited]
  
• A206 Computer Simulation of Reduction Process of Malignant Tumor in Radiation Therapy

  TAKAO Seishin, TADANO Shigeru, TODOH Masahiro, SHIRATO Hiroki  Proceedings of the ... JSME Conference on Frontiers in Bioengineering  2006-  (17)  89  -90  2006/11/10  [Not refereed][Not invited]
  
• Prediction of four-dimensional (4D) tumor response using finite element method (FEM) and radiobiological model for adaptive radiotherapy

  H. Taguchi, S. Takao, Y. Kogure, H. Shirato, S. Tadano, K. Suzuki, R. Onimaru, N. Katoh, R. Kinoshita  INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS  66-  (3)  S596  -S596  2006  [Not refereed][Not invited]
  

Industrial Property Rights

• 特開2023-008382:動体追跡装置、放射線照射システム及び動体追跡方法  2023/01/19

  山田 貴啓, 藤井 祐介, 宮本 直樹, 清水 伸一, ▲高▼尾 聖心, 宮崎 康一  株式会社日立製作所, 国立大学法人北海道大学  202303006796752290
• 特開2022-154269:治療計画装置、治療計画生成方法及びコンピュータプログラム  2022/10/13

  高柳 泰介, 山田 貴啓, 藤井 祐介, 梅川 徹, 白土 博樹, 清水 伸一, 松浦 妙子, 宮本 直樹, 高尾 聖心, 平田 雄一, 田中 創大  株式会社日立製作所, 国立大学法人北海道大学  202203003533802874
• 特許第7122003号:放射線治療装置  

  藤井 孝明, ▲高▼尾 聖心, 宮本 直樹, 松浦 妙子, 梅垣 菊男  国立大学法人北海道大学  202203013414957822
• 特開2021-083481:患者体内構造変化検出方法、患者体内構造変化検出装置およびコンピュータプログラム  2021/06/03

  藤井 孝明, 藤井 祐介, 山田 貴啓, 平山 嵩祐, ▲高▼尾 聖心, 梅垣 菊男  株式会社日立製作所, 国立大学法人北海道大学  202103010612372230
• 特許第6823299号:放射線治療計画装置および放射線治療システム  

  高柳 泰介, 梅川 徹, 藤高 伸一郎, ▲高▼尾 聖心  株式会社日立製作所, 国立大学法人北海道大学  202103018485562114
• 特開2020-156562:動体追跡装置とそれを備えた放射線治療システム、プログラム、および動体の追跡方法  2020/10/01

  梅川 徹, 宮崎 康一, 藤井 孝, 清水 伸一, ▲高▼尾 聖心, 梅垣 菊男, 宮本 直樹, 加藤 徳雄  株式会社日立製作所, 国立大学法人北海道大学  202003018251233772
• WO2020-012785:放射線治療装置および放射線治療方法  2020/01/16

  宮本 直樹, 梅垣 菊男, 清水 伸一, 富岡 智, ▲高▼尾 聖心  国立大学法人北海道大学  202103013693852825
• 特開2019-170612:治療計画装置、放射線治療システム、治療計画方法、及びプログラム  2019/10/10

  平山 嵩祐, 梅川 徹, ▲高▼尾 聖心, 檜山 悠宇, 松浦 妙子  株式会社日立製作所, 国立大学法人北海道大学  201903013280855631
• WO2018-168766:放射線治療装置  2018/09/20

  藤井 孝明, ▲高▼尾 聖心, 宮本 直樹, 松浦 妙子, 梅垣 菊男  国立大学法人北海道大学  202003014835370660
• 特開2018-075150:放射線治療計画装置および放射線治療システム  2018/05/17

  高柳 泰介, 梅川 徹, 藤高 伸一郎, ▲高▼尾 聖心  株式会社日立製作所, 国立大学法人北海道大学  201803016767326334
• 特許第6181459号:放射線治療システム  

  梅川 徹, 平本 和夫, 馬場 理香, 佐々木 淑江, 長峯 嘉彦, 清水 伸一, 高尾 聖心, 宮本 直樹, 松浦 妙子, 梅垣 菊男  株式会社日立製作所  201703011249649538
• 特許第6004464号:放射線治療制御装置および放射線治療制御プログラム  

  宮本 直樹, 清水 伸一, 松浦 妙子, 寅松 千枝, ▲高▼尾 聖心, 二本木 英明, 平田 雄一, 梅垣 菊男  国立大学法人北海道大学  201603019624240786
• 特開2016-144573:画像処理装置および粒子線治療装置  2016/08/12

  藤井 孝明, 梅川 徹, 梅垣 菊男, 高尾 聖心, 宮本 直樹, 藤井 祐介, 山田 貴啓, 平田 雄一  株式会社日立製作所, 国立大学法人北海道大学  201603007823714870
• 特許第5976474号:粒子線照射システムおよび治療計画装置  

  藤井 祐介, 藤本 林太郎, 梅澤 真澄, 松浦 妙子, 宮本 直樹, 清水 伸一, 寅松 千枝, 高尾 聖心, 二本木 英明, 平田 雄一, 梅垣 菊男  株式会社日立製作所  201603018990101580
• 特許第5976353号:荷電粒子照射システムおよび照射計画装置  

  藤井 祐介, 藤本 林太郎, 梅澤 真澄, 松浦 妙子, 宮本 直樹, 清水 伸一, 寅松 千枝, ▲高▼尾 聖心, 二本木 英明, 平田 雄一, 梅垣 菊男  株式会社日立製作所  201603003850165645
• 特開2016-131737:放射線治療システムおよび放射線治療プログラム  2016/07/25

  宮本 直樹, 清水 伸一, 松浦 妙子, ▲高▼尾 聖心, 平田 雄一, 梅垣 菊男, 加藤 徳雄  国立大学法人北海道大学  201603011303099827
• 特許第5773171号:MRE用の加振装置、加振システム、および加振方法  

  但野 茂, 梶原 逸朗, 藤崎 和弘, 高尾 聖心, 中村 玄, 江 渝, 菅 幹生  国立大学法人北海道大学, 国立大学法人 千葉大学  201503008653869830
• 特開2015-029793:放射線治療システム  2015/02/16

  梅川 徹, 平本 和夫, 馬場 理香, 佐々木 淑江, 長峯 嘉彦, 清水 伸一, 高尾 聖心, 宮本 直樹, 松浦 妙子, 梅垣 菊男  株式会社日立製作所, 国立大学法人北海道大学  201503030136731229
• 特開2014-057738:粒子線照射システムおよび治療計画装置  2014/04/03

  藤井 祐介, 藤本 林太郎, 梅澤 真澄, 松浦 妙子, 宮本 直樹, 清水 伸一, 寅松 千枝, 高尾 聖心, 二本木 英明, 平田 雄一, 梅垣 菊男  株式会社日立製作所, 国立大学法人北海道大学  201403053688422495
• 特開2013-198579:荷電粒子照射システムおよび照射計画装置  2013/10/03

  藤井 祐介, 藤本 林太郎, 梅澤 真澄, 松浦 妙子, 宮本 直樹, 清水 伸一, 寅松 千枝, ▲高▼尾 聖心, 二本木 英明, 平田 雄一, 梅垣 菊男  株式会社日立製作所, 国立大学法人北海道大学  201303076421392280
• 特開2013-192702:放射線治療制御装置および放射線治療制御プログラム  2013/09/30

  宮本 直樹, 清水 伸一, 松浦 妙子, 寅松 千枝, ▲高▼尾 聖心, 二本木 英明, 平田 雄一, 梅垣 菊男  国立大学法人北海道大学  201303037143290467
• WO2012-026543:MRE用の加振装置、加振システム、および加振方法  2012/03/01

  但野 茂, 梶原 逸朗, 藤崎 和弘, 高尾 聖心, 中村 玄, 江 渝, 菅 幹生  国立大学法人北海道大学, 国立大学法人 千葉大学  201303012684223948
• 特許第4474548号:放射線治療効果予測方法およびプログラム  

  白土 博樹, 但野 茂, 高尾 聖心  国立大学法人北海道大学  201103084545245488
• 特開2006-223425:放射線治療効果予測方法およびプログラム  2006/08/31

  白土 博樹, 但野 茂, 高尾 聖心  国立大学法人 北海道大学  200903051003060399

Research Grants & Projects

• 肺癌に対する陽子線治療の選択基準確立に向けた心肺相互作用勘案NTCPモデル構築

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2022/04 -2025/03 

  Author : 青山 英史, 鈴木 隆介, 宮本 直樹, 高尾 聖心, 金平 孝博, 橋本 孝之, 小橋 啓司, 西岡 健太郎, 田口 大志
• AIを活用した小児がん陽子線照射のトリプルハイブリッド遠隔治療計画システムの開発

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2022/04 -2025/03 

  Author : 橋本 孝之, 高尾 聖心, 小橋 啓司, 吉村 高明, 西岡 健太郎
• MR画像誘導と併用可能なリアルタイム陽子線飛程検出法の開発

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2021/04 -2025/03 

  Author : 松浦 妙子, 宮本 直樹, 高尾 聖心, 栗山 靖敏
• Research and development about helium and proton hybrid system with proton CT and Immuno-radiotherapy

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2019/04 -2024/03 

  Author : 白土 博樹, 宮本 直樹, 高尾 聖心, 茶本 健司, 橋本 孝之, Nam JinMin, 西岡 健太郎, 久我 悠馬, 小野寺 康仁, 松浦 妙子, 梅垣 菊男, 平田 雄一, 田中 創大, 清水 伸一

   

  ① 2019年度に決定した、短時間（0.1秒以下）でエネルギー変更可能な小型加速器の基本設計に基づき、小型加速器の要素技術の設計を行い、短時間（0.1秒以下）でエネルギー変更を可能とする回転ガントリーを含む照射・輸送系の磁場制御設計を行った。 ② 陽子からヘリウムに短時間で加速粒子を変更できる混合加速方式を検討、2023年度に制作開始するべく、陽子線CTの機器としての仕様を検討した。 ③ 陽子線CT値-ヘリウムSPR変換プロセスと、X線CT値利用時の精度を比較し、高エネルギー陽子線CTに必要な要素機器と制御方式の仕様を明確化した。 ④ 高エネルギー陽子線ビームを照射する場合に、ビームの人体への入射方向を意図的に偏心させ、ノズルの外側から照射野中心に向かったビームアングルとするための加速器・照射系の検討を行った。 ⑤ PD-1阻害剤およびPD-L1阻害剤を用いて、がん細胞の制御に最適なLET、ROSとミトコンドリアの分布を計測し、放射線と阻害剤の組み合わせによる相関を検討した。T細胞のPD-1阻害に関する条件検討を行っていたところ、当初の想定に反し、がん細胞での観察と類似の条件ではT細胞の観察が困難であることが判明した。T細胞を観察した上で条件決定することが不可欠であるため、T細胞のPD-1阻害に関する条件決定のための追加検討事項として、培養条件や使用する蛍光色素の種類を複数追加し、T細胞を観察するための至適条件の検討を行った。
• Marker-less volume imaging technique for real-time tumor tracking radiation therapy

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2020/04 -2023/03 

  Author : 宮本 直樹, 田中 創大, 高尾 聖心, 富岡 智, 松浦 妙子, 清水 伸一

   

  本研究では、放射線治療中に得られる2方向X線透視画像を利用し、体内マーカを利用することなく（マーカーレス）、リアルタイムに体内の3次元構造を取得するボリュームイメージング技術を開発することを目的とする。この提案技術の実現により、体内にマーカーを留置するという侵襲性のあるプロセスを無くすことができ、加えて、ボリュームイメージを得ることによる高精度な呼吸性移動対策をFLASH などの超高線量率照射を含むあらゆる照射において実施可能となる。本研究では、研究期間内に各要素技術の開発を進め、十分な質と量のデータにより精度検証を実施し、ボリュームイメージングを利用した治療ビーム照射制御の臨床的有用性を明らかにする。 2021年度は、昨年度のデジタルファントムによる画像合成精度評価に続き、実際の患者の4DCTデータによる評価を進めた。同一患者で異なる日に撮影された4DCTデータを利用し、1つの4DCTデータを変形モデリング用、残りの4DCTデータを検証に用い、モデリングの課程で得られた固有体内変形ベクトルの線形結合にもとづくボリュームイメージングにより、検証データをどこまで再現できるか評価した。合成画像の画素値と構造の再現性を評価した結果、先行研究（主にデジタルファントムでの評価）と同等の性能が得られた。したがって、放射線治療中に正確な固有値を評価することにより、標的の位置や体内構造の評価に応用できるボリュームイメージをリアルタイムで合成できると考えられ、提案手法の臨床的な実行可能性を示すことができた。
• Development of less toxic radiotherapy using IMPT for head and neck cancer

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2019/04 -2023/03 

  Author : 安田 耕一, 加納 里志, 水町 貴諭, 高尾 聖心, 田村 昌也

   

  前年度の皮膚炎と皮膚線量に関する解析において、皮膚表面から3mmの深さのROI（region of interest）を使用することが最も適切と判断されNTCPモデルも作成されたが、これを実臨床で使用しやすいものとするため、このROIに関するDVH（dose volume histogram）解析を行い、具体的な指標を複数設定した。この指標を使った陽子線治療を実臨床で開始した。variable marginについて、実際の放射線治療を行った患者が毎回位置照合のために撮像されるCBCT（cone-beam CT）のデータを用いて、各臓器の位置ずれに関する解析を行った。基本的に骨をベースに毎回照合されるが、様々な頭頸部癌において、どの骨を中心に日々照合するかを整理し、その照合位置における各臓器の位置ずれの範囲を計測した。最終的には脊髄に対するvariable PRV marginの設定が、臨床において恩恵が大きいと判断した。脊髄に対するvariable PRV marginを設定し、実臨床での使用を開始した。放射線治療計画において、NTCP（Normal Tissue Complication Probability）モデルを算出し、将来的な副作用を予測しながらプランの質を評価する試みを実臨床で開始した。頭頸部の放射線治療において、長期間にわたる一連の治療の最中に、体重減少などで体の構造が変化し、線量分布が変化する事象が確認された。事前の計画がどの程度変化するか、そしてそれがどのような患者で起こりやすいかに関して、線量分布変化に関する解析を行った。患者が感じる「辛さ」を客観的に把握するためのQOL調査を引き続き行っている。その患者の放射線治療計画において設定すべき臓器を、文献レビューのもとに決定した。QOL調査とその臓器線量の関係性に関する検討を開始した。
• 陽子線治療におけるパラメトリックDVH予測モデルの構築と治療高度化の試み

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2019/04 -2023/03 

  Author : 高尾 聖心, 田村 昌也, 松浦 妙子, 清水 伸一

   

  前年度に実施した、臨床パラメータを指標とした類似症例選択に基づく新たなDose Volume Histogram（DVH）予測モデル構築をさらに発展させるため、臨床パラメータとDVH予測精度の詳細な評価を行った。 臨床パラメータとして、前年度に導入した、標的と周辺正常組織（OAR）の近接の状態を表すOverlap Volume Histogram(OVH)を引き続き用いた。前立腺がん陽子線治療症例においてOVHとDVHの関係を調査したところ、OVHにおいて標的から遠位の割合が大きい症例ほどDVHが低線量側で急峻となり、OVHがなだらかな増加傾向を示す症例ではDVHも同様の傾向を示すことが明らかとなった。この知見に基づき、DVH予測精度とOVHの関係をより詳細に評価するため、DVH予測モデルにおける歪正規分布を記述する各パラメータのばらつきとOVHの相関の評価を行った。全体的には明確な相関関係は認められなかったものの、標的近位から2～5番目のsub volumeにおいて、歪正規分布の平均を表すパラメータであるμおよび歪度を表すλについて、OVHに対するばらつきが顕著に大きいことが明らかとなった。これにより、OVHを指標とした類似症例選択に基づくDVH予測の精度向上において、2～5番目のsub volumeのOVHに注目し類似症例を選択することが重要であることが示され、前年度のモデル構築が妥当であることが確認された。 今後は本知見に基づく予測モデルの更なる精度向上の検討および臨床データに基づく検証を実施する予定である。
• Development of a therapeutic effect evaluation system that simultaneously considers the dose rate of proton beam irradiation and LET fluctuations

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2018/04 -2022/03 

  Author : Matsuura Taeko

   

  In the scanning beam delivery of protons, different portions of the target are irradiated with different linear energy transfer protons with various time intervals and irradiation times. To evaluate the sublethal damage (SLD) repair effect in prolonged scanning proton irradiation using the biophysical model, we extended the dose protraction factor in the LQ model for the arbitrary number of different LET proton irradiations delivered sequentially with arbitrary time lags, referring to the theory of dual radiation action (TDRA). The model enables us to evaluate the biological effectiveness in clinical settings within a reasonable calculation time. In addition, we have performed the cell experiment using proton beam to investigate the LET dependence of the SLD repair time.
• Real-time volumetric image generation based on CT deformation driven by simultaneous monitoring of internal landmarks and object surface

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2018/06 -2021/03 

  Author : Miyamoto Naoki

   

  We developed a method to reconstruct 3D in vivo information in real time by using the positional information of biological surfaces and in vivo markers through modeling of in vivo deformations using pre-learning data. Using a patient's 4DCT acquired for radiotherapy, we evaluated the image synthesis accuracy of the in vivo reconstruction method developed in this project as the normalized root mean square error (NRMSE) between the ground truth image and the synthesized image. The image synthesis accuracies for the training data and the validation with motion beyond the training data were about 7% and 11%, respectively. In addition, the accuracy of tumor location evaluation was less than 1 mm. These results suggest that the accuracy is sufficient for application in radiotherapy.
• Development of minimum invasive real-time markerless image guided radiotherapy technique using minimum space information.

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2018/04 -2021/03 

  Author : Shimizu Shinichi

   

  In the real-time tumor tracking radiotherapy, feature point information, that is used for gating, is obtained by fluoroscopic X-ray images. There still problems exist:1.X-ray exposure from diagnostic X ray that used for gating 2.insertion of a gold marker etc. as a feature pointReduce or eliminate X-ray exposure by making the observing area through diagnostic X-rays as small as possible to acquire target movement information or establishing the method of processing gating information obtained using MRI technology without using fluoroscopy were considered to be the goal of this study. X-rays are still optimal for acquiring organ motion information within human body necessary for gating treatment in real time, but a method for limiting the range was achieved in this study. In addition, we succeeded in trying to visualize the position of organs with MRI image data without using X-rays when preparing for treatment, and there were expectations for the promotion of future research.
• Development of robust proton beam scanning treatment technology considering target heterogeneity and movement

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2016/04 -2020/03 

  Author : Umegaki Kikuo

   

  We have proposed a new approach of treatment plan optimization method considering the probability distribution of dose error caused by the various uncertainties in proton beam therapy. The three-dimensional dose distribution is optimized to irradiate the target tumor while sparing the normal tissue by controlling the dose for each spot with intensity modulation. We have evaluated probabilistic dose errors caused by variation of individual device performance, patient positioning error, target tumor movement under respiration, etc.. The dose error considering the anisotropy unique to the proton beam is also clarified. Beyond the conventional treatment plan concept of contouring the tumor shape and providing a uniform margin, we have constructed a robust optimization method considering the probability distribution of dose error. The method was evaluated and demonstrated using the actual proton beam therapy system.
• Development of therapeutic response-guided radiotherapy based on dose evaluation using CBCT images

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2016/04 -2020/03 

  Author : Takao Seishin

   

  In this study, we have developed the therapeutic response-guided radiotherapy technique based on the quantitative estimation of changes of therapeutic response using cone-beam CT (CBCT) images. We improved the image quality of CBCT images, calculated the water equivalent thickness in spot scanning proton beam thereapy, and established a method to estimate the treatment response from changes in the water equivalent thickness.
• Research and Development of Helium and Proton Hybrid Beam Therapy

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2015/04 -2019/03 

  Author : Shirato Hiroki

   

  The carbon beam therapy requires huge accelerator and very expensive. Proton beam therapy system has gantry, image-guidance, and const-effective but less sharpness of the beam at the shallow area. We built a concept and requirement to build a new generation particle beam therapy system which has rotating gantry, real-time tumour-tracking image guidance in the deep part of the body, and sharp beam-edge at the shallow part of the body. Hybrid Helium and proton beams can be used for the same patient by our development with the size of synchrotron similar to the proton beam therapy system. We also developed a new in-silico biomarker to select the optimal particle beam therapy for each patient using normal tissue complication probability (NTCP) model with the confidence interval. We will be able to predict which particle beam therapy is the best choice for the patient using the difference of NTCP, ΔNTCP, between two options of radiotherapy with a statistical significance level.
• Attempt of 4D-IGRT by Volume Matching Method of 4D-CBCT and Therapy Planning CT

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2015/04 -2018/03 

  Author : Shimizu Shinichi

   

  We conduct research using 2 axis of diagnostic X-ray fluoroscope that consist real-time tumour-tracking (RTRT) system installed in a proton beam treatment gantry. With the use of the system, we conduct a research aimed constructing a 4D-IGRT radiotherapy system that can treat cancer in consideration of spatial and temporal fluctuations and also respiratory movement of tumors. Four-dimensional cone beam CT (4D-CBCT) image is obtained from the fluoroscopic image of the RTRT system. From the 4D-CBCT image group composed of a plurality of respiratory phases, a CT image that represent the same respiratory phase as the CT image used for the treatment plan is selected. We develop an advanced real time image guidance system aiming marker-less 4D-RT using selected CBCT image and its source image.
• Development of respiratory phase segmentation algorithm based on the analysis of internal target motion for high accurate respiratory-gated radiation therapy

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2014/04 -2017/03 

  Author : Miyamoto Naoki

   

  Respiratory-gated irradiation is realized by monitoring three-dimensional location of internal fiducial marker in real-time tumor-tracking radiation therapy. Irradiation accuracy could be improved by monitoring respiratory phase in addition to the marker location. In this research, the novel algorithm of respiratory phase segmentation based on the analysis of three-dimensional trajectory data of the fiducial marker. Irradiation efficiency was evaluated from the log data retrospectively assuming that patient setup was conducted by proposed method. About 20 % of irradiation efficiency was obtained by proposed method even in the small gating windows size, +/- 1 mm. The evaluated efficiency was less than 10 % in conventional setup procedure. Hence, it is expected that the irradiation accuracy can be improved while keeping the acceptable irradiation efficiency.
• Development of dose-guided radiotherapy technique using cone-beam CT

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2014/04 -2016/03 

  Author : Takao Seishin

   

  Proton beam therapy requires highly-precise image guidance in patient setup to ensure accurate dose delivery. Cone-beam CT (CBCT) is expected to play an important role to reduce uncertainties in patient setup. Particularly in particle therapy, the methodology to evaluate setup error considering dose distribution is to be established. This study aimed to develop the intelligent patient setup technique considering not only geometrical position of the patients but also dose distribution. Quantitative performance evaluation of CBCT image quality and mechanical accuracy of the system was performed. Accuracy of three-dimensional images registration between CBCT and reference CT images was evaluated. Moreover, the method to evaluate dose distribution under possible setup error was developed. Through these techniques feasibility of dose-guided radiotherapy has been established.
• Approaches to the 4D-CBCT using 2 axis fluoroscopic X-ray

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2012/04 -2015/03 

  Author : SHIMIZU Shinichi, MIYAMOTO Naoki, TAKAO Seishin

   

  Construction of a radiation therapy system which can consider respiratory movement of tumor and organs. Location variation and irradiation time are also considered using the 2 axis of X-ray fluoroscopic motion tracking device that are installed at the proton therapy within the gantry. To enable image of the cone-beam CT to get the original source image of 4-dimensional CBCT (4D-CBCT) with the use of the motion tracking device and try to develop the principle and performs imaging test by phantom. Morphological changes of the patients on the treatment couch by imaging moving tumors and organs by 4D-CBCT, the appropriateness of the treatment planning time and compare present status of tumor irradiated and the condition of the normal tissues are to be verified.
• Development of the real-time four-dimensional cone beam CT reconstruction technique for interactive radiotherapy

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2012/04 -2014/03 

  Author : TAKAO Seishin

   

  We have proposed a novel method for four-dimensional (4D) cone-beam computed tomography (CBCT) reconstruction with real-time tumor tracking technique. In the real-time tumor tracking, a fiducial marker inserted near the tumor is detected in the orthogonal fluoroscopic images. The three-dimensional position of the marker is calculated every 33 msec with an accuracy of 1 mm. According to the position of the marker, projection images can be classified into some phases. Four dimensional CBCT reconstruction is therefore available in each phase. Feasibility of the 4D CBCT reconstruction was evaluated through the experience using the testing machine, which has the same imaging devices in the proton therapy system in Hokkaido University Hospital. Additionally, characteristics of intrafractional baseline shift of tumor motion were analyzed to investigate efficacy of the 4D CBCT reconstruction method. Through the study, the feasibility and efficacy of the 4D CBCT reconstruction was confirmed.
• Research for Real-time Tracking Medical Science

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research

  Date (from‐to) : 2009 -2012 

  Author : SHIRATO Hiroki, HONMA Sato, TAMAKI Nagara, KUGE Yuji, MIZUTA Masahiro, DATE Hiroyuki, TANAKA Masaki, HAGA Hisashi, NISHIOKA Takeshi, KATO Motothugu, CHAMOTO Kenji, OIZUMI Satoshi, MATSUNAGA Naofumi, OKIMOTO Tomoaki, HAYAKAWA Kazushige, NISHIO Teiji, TADANO Shigeru, ISHIKAWA Masayori, ONODERA Yasuhito, SHIBUYA Keiko, HAMADA Toshiyuki, ONIMARU Rikiya, SHIMIZU Shinichi, TSUCHIYA Kazuhiko, KATOH Norio, KINOSHITA Rumiko, INOUE Tetsuya, ONODERA Syunsuke, TAKAO Seishin, KAGA Kichizo, TERAE Satoshi, ONODERA Yuya, SAKUHARA Yusuke, MANABE Noriko, ABO Daisuke, KATO Fumi, KHIN KHIN Tha, NAM Jin-min, SABE Hisataka, INUBUSHI Masayuki, SHINAGAWA Naofumi, KENNETH Sutherland

   

  Up to now, in the field of basic medicine from micro-level to animal level, to track and quantify the three-dimensional spatial information along the time axis in real-time has not caught up with the accuracy in the field of clinical medicine. By handing big data of “motion in life, a new idea of real-time radiotherapy and a new precise four-dimensional computed tomography has been developed based on the data of actual tumor motion in the human body.
• 腫瘍の放射線治療効果予測システムに関する研究

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2009 -2010 

  Author : 高尾 聖心

   

  前年度に確立した放射線治療における腫瘍縮小シミュレーション手法に基づく腫瘍縮小の予測手法を提案し,その精度を検証した.治療効果の予測においては放射線感受性(あるいは抵抗性)を表すパラメータを症例毎に適切に決定することが重要となる.本研究では本シミュレーション手法において腫瘍の放射線抵抗性を表すパラメータである放射線抵抗係数νを治療期間初期における腫瘍体積の変化を基に最小二乗法によって決定し,治療終了時の腫瘍体積を予測した.また,パラメータ決定に要する経過観察期間と予測精度の関係について調査した.対象は頭頸部リンパ節腫瘍6例とした.結果,治療開始後からの二～三週間の経過観察に基づくパラメータ推定によって,治療終了時の腫瘍体積を誤差10%以内で予測可能であることが示された.また,四週間以上の経過観察期間を設けた場合でも予測誤差はほとんど変わらず,二～三週間の経過観察は治療効果の予測に必要十分であることが明らかとなった.本結果は現実的な手法と精度での放射線治療効果予測が可能であることを示しており,治療期間中の腫瘍の縮小に応じて照射法を最適化する適応放射線治療への応用など,その臨床的意義は大きい. また,シミュレーションの更なる発展を目的とし,システムバイオロジーの概念に基づく放射線治療のモデル化を行った.細胞の分裂・増殖の過程である細胞周期の進行を促進あるいは阻害する因子のはたらきをシステムバイオロジーの観点からモデル化し,細胞の分裂,癌化および放射線治療効果のシミュレーションを行った.シミュレーション結果は細胞周期の各制御因子が相互作用によって適切に発現・不活性化することで細胞周期が進行する様子を示し,癌細胞の分裂・増殖や治療の機序の理解に不可欠な細胞周期シミュレーションモデルが構築された.

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