Researcher Profile and Settings

Master

Affiliation (Master)

• Faculty of Medicine　Internal Medicine　Department of Radiology

Affiliation (Master)

• Faculty of Medicine　Internal Medicine　Department of Radiology

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Profile and Settings

Profile and Settings

• Name (Japanese)

  Uchinami

• Name (Kana)

  Yusuke

• Name

  202001014136325814

Achievement

Research Interests

• 放射線治療   

Research Areas

• Life sciences / Radiology

Research Experience

• 2020/04 - Today 北海道大学大学院医学研究院 放射線治療学教室 助教

Awards

• 第28回日本定位放射線治療学会 優秀演題賞
  

Published Papers

• Investigation of interfractional range variation owing to anatomical changes with beam directions based on water equivalent thickness in proton therapy for pancreatic cancer.

  Yuhei Kikkawa, Hideaki Ueda, Yusuke Uchinami, Norio Katoh, Hidefumi Aoyama, Yoichi M Ito, Kohei Yokokawa, Ye Chen, Taeko Matsuura, Naoki Miyamoto, Seishin Takao

  Journal of radiation research 2024/10/08 

  To assess the interfractional anatomical range variations (ARVs) with beam directions and their impact on dose distribution in intensity modulated proton therapy, we analyzed water equivalent thickness (WET) from 10 patients with pancreatic cancer. The distributions of the interfractional WET difference ($\Delta{\mathrm{WET } }^{\theta }$) across 360° were visualized using polar histograms. Interfractional ARVs were evaluated using the mean absolute error and ΔWET pass rate, indicating the percentage of $\Delta \mathrm{WE},{\mathrm{T } }^{\theta }$ < thresholds. The impact on dose distribution in proton therapy was evaluated based on two treatment plans for 40 Gy(RBE)/5 fractions: 'Plan A', using two beam angles, in which the target was closest to the body surface among four perpendicular directions; and 'Plan B', using two beam angles with small ARVs. Analysis revealed individual variations in angular trends of interfractional ARVs. Three distinct trends were identified: Group 1 exhibited small ARVs around posterior directions; Group 2 exhibited small ARVs except ~60°; Group 3 demonstrated minimal ARVs only ~90°. In dose evaluation, while 150° and 210° were selected in Plan B for 9 out of 10 patients, for the remaining patient, 60° and 90° were chosen. Comparing dose volume histogram parameters for all patients, Plan B significantly reduced target coverage loss while maintaining organ-at-risk sparing comparable to Plan A. These results demonstrated that selecting beam angles with small interfractional ARVs for each patient enhances the robustness of dose distribution, reducing target coverage loss.
• Patterns of Care for Brain Metastases in Asia: A Real-World Survey Conducted by the Federation of Asian Organizations for Radiation Oncology.

  Yusuke Uchinami, Archya Dasgupta, Kentaro Nishioka, Handoko, Jayant Sastri Goda, Jun Won Kim, Rizma Mohd Zaid, Ooi Kai Yun, Humera Mehmood, Imjai Chitapanarux, Supriya Chopra, Hidefumi Aoyama

  JCO global oncology 10 e2400222  2024/10 

  PURPOSE: To report the patterns of care for brain metastases (BMs) in the Federation of Asian Organizations for Radiation Oncology (FARO). METHODS: Overall, 37 questions were prepared. The survey was conducted online using Google Forms, and the URL was distributed to members of the FARO research committee. Radiation oncologists associated with FARO responded to the questionnaire between May 2023 and June 2023, and their answers were analyzed. RESULTS: Responses were received from 32 radiation oncologists in 13 countries participating in FARO. Twenty-six physicians (81.3%) were affiliated with academic centers, and 22 (68.8%) were able to perform stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (fSRT) for BMs at their institution. The most typically used prognostic index for BM was the recursive partitioning analysis classification (17 physicians, 53.1%). The maximum number of BMs indicated for SRT/SRS was ≤three (11 physicians, 34.4%), whereas eight (25.0%) physicians answered for 6-10 BMs. The maximum size of BMs considered for SRS/fSRT was ≤3 cm (14 physicians, 43.8%), whereas nine (28.1%) answered that SRS/fSRT was preferred if the maximum size was >4 cm. When whole-brain radiotherapy (RT) was indicated, hippocampal avoidance and memantine usage were limited to 50.0% and 25.0% of patients, respectively. The most typical RT modality after BM resection was SRS/fSRT alone, regardless of whether the margin was positive (19 physicians, 59.4%) or negative (13 physicians, 40.6%). CONCLUSION: We report the survey results of the patterns of care for BMs in the FARO. This survey was conducted only among a limited number of FARO members. Since many respondents were affiliated with relatively large-scale academic centers, large-scale surveys, including community hospitals, are warranted for future initiatives.
• Application of motion prediction based on a long short-term memory network for imaging dose reduction in real-time tumor-tracking radiation therapy.

  Kazuki Numakura, Seishin Takao, Taeko Matsuura, Kouhei Yokokawa, Ye Chen, Yusuke Uchinami, Hiroshi Taguchi, Norio Katoh, Hidefumi Aoyama, Satoshi Tomioka, Naoki Miyamoto

  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) 125 104507 - 104507 2024/09 

  PURPOSE: To demonstrate the possibility of using a lower imaging rate while maintaining acceptable accuracy by applying motion prediction to minimize the imaging dose in real-time image-guided radiation therapy. METHODS: Time-series of three-dimensional internal marker positions obtained from 98 patients in liver stereotactic body radiation therapy were used to train and test the long-short-term memory (LSTM) network. For real-time imaging, the root mean squared error (RMSE) of the prediction on three-dimensional marker position made by LSTM, the residual motion of the target under respiratory-gated irradiation, and irradiation efficiency were evaluated. In the evaluation of the residual motion, the system-specific latency was assumed to be 100 ms. RESULTS: Except for outliers in the superior-inferior (SI) direction, the median/maximum values of the RMSE for imaging rates of 7.5, 5.0, and 2.5 frames per second (fps) were 0.8/1.3, 0.9/1.6, and 1.2/2.4 mm, respectively. The median/maximum residual motion in the SI direction at an imaging rate of 15.0 fps without prediction of the marker position, which is a typical clinical setting, was 2.3/3.6 mm. For rates of 7.5, 5.0, and 2.5 fps with prediction, the corresponding values were 2.0/2.6, 2.2/3.3, and 2.4/3.9 mm, respectively. There was no significant difference between the irradiation efficiency with and that without prediction of the marker position. The geometrical accuracy at lower frame rates with prediction applied was superior or comparable to that at 15 fps without prediction. In comparison with the current clinical setting for real-time image-guided radiation therapy, which uses an imaging rate of 15.0 fps without prediction, it may be possible to reduce the imaging dose by half or more. CONCLUSIONS: Motion prediction can effectively lower the frame rate and minimize the imaging dose in real-time image-guided radiation therapy.
• Clinical application of real-time tumor-tracking for stereotactic volumetric modulated arc therapy for liver tumors.

  Naoki Miyamoto, Norio Katoh, Takahiro Kanehira, Kohei Yokokawa, Ryusuke Suzuki, Yusuke Uchinami, Hiroshi Taguchi, Daisuke Abo, Hidefumi Aoyama

  Physics and imaging in radiation oncology 31 100623 - 100623 2024/07 

  Real-time tumor-tracking volumetric modulated arc therapy (RT-VMAT) enabling beam-gating based on continuous X-ray tracking of the three-dimensional position of internal markers is relevant for moving tumors. Dose-volume characteristics and treatment time were evaluated in ten consecutive patients who underwent liver stereotactic body radiation therapy with RT-VMAT. Target dose conformity and sparing of the stomach and the intestine were improved comparing RT-VMAT with RT-3D conformal radiotherapy. The mean treatment time for each fraction was less than 10 min. RT-VMAT could be effective, especially for targets located adjacent to organs at risk.
• 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.
• 膵癌に対する動体追跡放射線治療用の経皮的あるいは経動脈的マーカー留置術の検討

  加藤 大祐, 阿保 大介, 森田 亮, 打浪 雄介, 加藤 徳雄, 山田 亮太, 木野田 直也, 藤井 宝顕, 山崎 康之, 高柳 歩, 青山 英史, 工藤 與亮

  日本インターベンショナルラジオロジー学会雑誌 (一社)日本インターベンショナルラジオロジー学会 39 (Suppl.) 191 - 191 1340-4520 2024/04
• Impact of adaptive radiotherapy on survival in locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiotherapy.

  Yusuke Uchinami, Koichi Yasuda, Hideki Minatogawa, Yasuhiro Dekura, Noboru Nishikawa, Rumiko Kinoshita, Kentaro Nishioka, Norio Katoh, Takashi Mori, Manami Otsuka, Naoki Miyamoto, Ryusuke Suzuki, Keiji Kobashi, Yasushi Shimizu, Jun Taguchi, Nayuta Tsushima, Satoshi Kano, Akihiro Homma, Hidefumi Aoyama

  Radiation oncology journal 42 (1) 74 - 82 2024/03 

  PURPOSE: To investigate the clinical significance of adaptive radiotherapy (ART) in locally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Eligible patients were treated with concurrent chemoradiotherapy using IMRT. Planning computed tomography in ART was performed during radiotherapy, and replanning was performed. Since ART was started in May 2011 (ART group), patients who were treated without ART up to April 2011 (non-ART group) were used as the historical control. The Kaplan-Meier method was used to calculate overall survival (OS), locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). LRFS for the primary tumor (LRFS_P) and regional lymph node (LRFS_LN) were also studied for more detailed analysis. Statistical significance was evaluated using the log-rank test for survival. RESULTS: The ART group tended to have higher radiation doses. The median follow-up period was 127 months (range, 10 to 211 months) in the non-ART group and 61.5 months (range, 5 to 129 months) in the ART group. Compared to the non-ART group, the ART group showed significantly higher 5-year PFS (53.8% vs. 81.3%, p = 0.015) and LRFS (61.2% vs. 85.3%, p = 0.024), but not OS (80.7% vs. 80.8%, p = 0.941) and DMFS (84.6% vs. 92.7%, p = 0.255). Five-year LRFS_P was higher in the ART group (61.3% vs. 90.6%, p = 0.005), but LRFS_LN did not show a significant difference (91.9% vs. 96.2%, p = 0.541). CONCLUSION: Although there were differences in the patient backgrounds between the two groups, this study suggests the potential effectiveness of ART in improving locoregional control, especially in the primary tumor.
• 当院における転移性脳腫瘍への術後定位照射症例の検討

  高橋 周平, 森 崇, 打浪 雄介, 西岡 健太郎, 青山 英史, 茂木 洋晃, 山口 秀

  Japanese Journal of Radiology (公社)日本医学放射線学会 42 (Suppl.) 10 - 10 1867-1071 2024/02
• Correction: Treatment outcomes of radiotherapy with concurrent weekly cisplatin in older patients with locally advanced head and neck squamous cell carcinoma.

  Yusuke Uchinami, Koichi Yasuda, Satoshi Kano, Manami Otsuka, Seijiro Hamada, Takayoshi Suzuki, Nayuta Tsushima, Shuhei Takahashi, Yoshihiro Fujita, Tomohiko Miyazaki, Hajime Higaki, Jun Taguchi, Yasushi Shimizu, Tomohiro Sakashita, Akihiro Homma, Hidefumi Aoyama

  Discover. Oncology 15 (1) 18 - 18 2024/01/25
• Radiotherapy with or without chemotherapy for locally advanced head and neck cancer in elderly patients: analysis of the Head and Neck Cancer Registry of Japan.

  Koichi Yasuda, Yusuke Uchinami, Satoshi Kano, Jun Taguchi, Daisuke Kawakita, Megumi Kitayama, Kentaro Nishioka, Takashi Mori, Fuki Koizumi, Yuri Fujii, Yasushi Shimizu, Keiji Kobashi, Seiichi Yoshimoto, Ken-Ichi Nibu, Akihiro Homma, Hidefumi Aoyama

  International journal of clinical oncology 2023/12/29 

  BACKGROUND: Whether concurrent chemotherapy with radiotherapy (CRT) is effective for elderly patients with head and neck cancer is a controversial topic. This study aimed to analyze the effectiveness of CRT vs. radiation therapy (RT) among elderly patients in Japan. METHODS: Data from the Head and Neck Cancer Registry of Japan were extracted and analyzed. Patients with locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx who received definitive CRT or RT between 2011 and 2014 were included. RESULTS: CRT was administered to 78% of the 1057 patients aged ≥ 70 years and 67% of the 555 patients aged ≥ 75 years. For the patients aged ≥ 75 years, the overall survival (OS) rate was significantly better in the CRT group than in the RT group (P < 0.05), while the progression-free survival (PFS) rate was not significantly different (P > 0.05). The add-on effect of CRT was significantly poor in elderly patients (P < 0.05), and it was not a significant factor in the multivariate analysis for patients aged ≥ 75 years. After propensity score matching, there were no significant differences in the OS and PFS rates between the patients aged ≥ 70 years and those aged ≥ 75 years (all, P > 0.05). CONCLUSION: Although aggressive CRT is administered to elderly patients in Japan, its effectiveness is uncertain. Further prospective randomized trials are needed to verify whether CRT is superior to RT alone for elderly patients.
• Treatment outcomes of radiotherapy with concurrent weekly cisplatin in older patients with locally advanced head and neck squamous cell carcinoma.

  Yusuke Uchinami, Koichi Yasuda, Satoshi Kano, Manami Otsuka, Seijiro Hamada, Takayoshi Suzuki, Nayuta Tsushima, Shuhei Takahashi, Yoshihiro Fujita, Tomohiko Miyazaki, Hajime Higaki, Jun Taguchi, Yasushi Shimizu, Tomohiro Sakashita, Akihiro Homma, Hidefumi Aoyama

  Discover. Oncology 14 (1) 226 - 226 2023/12/08 

  BACKGROUND: Tri-weekly cisplatin and radiotherapy (CDDP + RT) is a standard of care for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) but is sometimes challenging to complete in older patients. Weekly CDDP + RT has shown mild toxicity compared to tri-weekly CDDP + RT for LA-HNSCC and is a promising option for older adults. We aimed to report the treatment outcomes and prognostic factors in patients with LA-HNSCC treated with weekly CDDP + RT. METHODS: We analyzed patients aged ≥ 70 years who started weekly CDDP + RT for LA-HNSCC between July 2006 and October 2022. LA-HNSCC includes cancer in the oropharynx, hypopharynx, or larynx with a clinical stage of 3 or 4 without distant metastases based on the Union for International Cancer Control staging system 8th edition. The radiation dose of 70 Gy was delivered in 35 fractions by 3-dimensional conformal radiotherapy, intensity-modulated radiotherapy, or proton beam therapy. The primary endpoint was the 3-year overall survival (OS), and the secondary endpoints were the 3-year progression-free survival (PFS) and 3-year cause-specific survival (CSS). The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used to evaluate statistical significance. A Cox proportional hazards model was used for the multivariate analysis of prognostic factors. RESULTS: The median age of the 49 patients was 72 (range: 70-78) years. The median CDDP dose was 200 (40-280) mg/ m2, and 47 patients completed scheduled radiotherapy. Forty-eight patients (98.0%) had a performance status of ≥ 1 at the initial visit. The 3-year OS, PFS, and CSS were 80.9% (95% confidence interval [CI]: 64.8-90.7), 68.3% (95% CI 51.8-81.2), and 85.0% (95% CI 68.7-93.4), respectively. In the multivariate analysis, the cumulative CDDP dose (< 200 or ≥ 200 mg/m2) was a significant factor for OS (hazard ratio: 0.29 [95% CI 0.08-0.97], p = 0.044). There was one case of early mortality. Grade 3 or higher late adverse events were observed in four patients (8.2%). CONCLUSIONS: Weekly CDDP + RT in older patients led to good survival outcomes with an acceptable rate of adverse events. CDDP should be administered at a dose of at least 200 mg/m2 in older patients. Trial registration Retrospectively registered.
• Real-time tumor-tracking radiotherapy with SyncTraX for primary liver tumors requiring isocenter shift†.

  Yusuke Uchinami, Naoki Miyamoto, Daisuke Abo, Ryo Morita, Koji Ogawa, Tatsuhiko Kakisaka, Ryusuke Suzuki, Tomohiko Miyazaki, Hiroshi Taguchi, Norio Katoh, Hidefumi Aoyama

  Journal of radiation research 2023/11/22 

  The SyncTraX series enables real-time tumor-tracking radiotherapy through the real-time recognition of a fiducial marker using fluoroscopic images. In this system, the isocenter should be located within approximately 5-7.5 cm from the marker, depending on the version, owing to the limited field of view. If the marker is placed away from the tumor, the isocenter should be shifted toward the marker. This study aimed to investigate stereotactic body radiotherapy (SBRT) outcomes of primary liver tumors treated with SyncTraX in cases where the isocenter was shifted marginally or outside the planning target volume (PTV). Twelve patients with 13 liver tumors were included in the analysis. Their isocenter was shifted toward the marker and was placed marginally or outside the PTV. The prescribed doses were generally 40 Gy in four fractions or 48 Gy in eight fractions. The overall survival (OS) and local control (LC) rates were calculated using the Kaplan-Meier method. All patients completed the scheduled SBRT. The median distance between the fiducial marker and PTV centroid was 56.0 (interquartile range [IQR]: 52.7-66.7) mm. By shifting the isocenter toward the marker, the median distance between the marker and isocenter decreased to 34.0 (IQR: 33.4-39.7) mm. With a median follow-up period of 25.3 (range: 6.9-70.0) months, the 2-year OS and LC rates were 100.0% (95% confidence interval: 100-100). An isocenter shift makes SBRT with SyncTraX feasible in cases where the fiducial marker is distant from the tumor.
• Daily fraction dose-adjusted radiotherapy policy to avoid prolonging the overall treatment time for early glottic squamous cell carcinoma: a single-institutional retrospective study.

  Yasuhiro Dekura, Koichi Yasuda, Hideki Minatogawa, Yusuke Uchinami, Nayuta Tsushima, Takayoshi Suzuki, Satoshi Kano, Takashi Mori, Kentaro Nishioka, Keiji Kobashi, Norio Katoh, Akihiro Homma, Hidefumi Aoyama

  Journal of radiation research 2023/11/10 

  The objective of this study was to determine the outcomes of radical radiotherapy for early glottic squamous cell carcinoma (EGSCC) with the policy of increasing the fraction size during radiotherapy when the overall treatment time (OTT) was expected to be prolonged. Patients diagnosed with clinical T1-2N0M0 EGSCC, who were treated with radical radiotherapy between 2008 and 2019 at Hokkaido University Hospital, were included. Patients received 66 Gy in 33 fractions for T1 disease and 70 Gy in 35 fractions for T2 disease as our standard regimen (usual group [UG]). If the OTT was expected to extend for >1 week, the dose fraction size was increased from 2.0 to 2.5 Gy from the beginning or during radiotherapy (adjusted group [AG]). At this time, we performed a statistical analysis between UG and AG. In total, 116 patients were identified, and the treatment schedules of 29 patients were adjusted. The median follow-up was 60.9 months. In the T1 group, the cumulative 5-year local failure rate was 12.0% in the AG and 15.4% in the UG, and in the T2 group, the rate was 40.7% in the AG and 25.3% in the UG. There were no significant differences between the AG and UG. Similarly, no significant differences were observed for overall survival and progression-free survival rates. Our single-institutional retrospective analysis of EGSCC patients suggested that a method of adjusting the radiotherapy schedule to increase fraction size from the beginning or during the course may be effective in maintaining treatment outcomes.
• Proton beam therapy for hepatocellular carcinoma: Multicenter prospective registry study in Japan.

  Masashi Mizumoto, Hiroyuki Ogino, Toshiyuki Okumura, Kazuki Terashima, Masao Murakami, Takashi Ogino, Hiroyasu Tamamura, Tetsuo Akimoto, Takahiro Waki, Norio Katoh, Masayuki Araya, Tsuyoshi Onoe, Masaru Takagi, Hiromitsu Iwata, Haruko Numajiri, Tomoaki Okimoto, Yusuke Uchinami, Kazushi Maruo, Kei Shibuya, Hideyuki Sakurai

  International journal of radiation oncology, biology, physics 2023/09/29 [Refereed][Not invited]
   

  INTRODUCTION: A prospective multicenter registry study was started in May 2016 in Japan to evaluate the efficacy and safety of proton beam therapy (PBT) for hepatocellular carcinoma (HCC). METHODS: Patients who received PBT for HCC from May 2016 to June 2018 were registered in the database of the Particle Beam Therapy Committee and Subcommittee of the Japanese Society for Radiation Oncology (JASTRO). Overall survival (OS), progression-free survival (PFS) and local recurrence were evaluated. RESULTS: Of the 755 registered cases, 576 with initial PBT and no duplicate cancer were evaluated. At final follow-up, 322 patients were alive and 254 had died. The median follow-up period for survivors was 39 months (0-58 months). The median OS time of the 576 patients was 48.8 months (95% CI 42.0-55.6 months) and the 1-, 2-, 3- and 4-year OS rates were 83.8% (95% CI 80.5-86.6%), 68.5% (64.5-72.2%), 58.2% (53.9-62.2%), and 50.1% (44.9-55.0%), respectively. Recurrence was observed in 332 cases, including local recurrence in 45 cases. The median PFS time was 14.7 months (95% CI 12.4-17.0 months) and the 1-, 2-, 3- and 4-year PFS rates were 55.2% (95% CI 51.0-59.2%), 37.5% (33.5-41.5%), 30.2% (26.3-34.2%), and 22.8% (18.5-27.4%), respectively. The 1-, 2-, 3- and 4-year OS rates were significantly higher for tumor size <5 vs. 5-10 cm (p<0.001) and <5 vs. ≥10 cm (p<0.001); Child-Pugh score A/B vs. C (p<0.001); and distance of the tumor from the gastrointestinal tract <1 vs. 1-2 cm (p<0.008) and <1 vs. >2 cm (p<0.001). At final follow-up, 27 patients (4.7%) had late adverse events of grade 3 or higher, with liver failure (n=7) and dermatitis (n=7) being most common. CONCLUSION: This multicenter prospective data registry indicated that PBT for HCC gives good therapeutic effects (3-year local control rate of 90%) with a low risk of severe late adverse events.
• Predicting the daily gastrointestinal doses of stereotactic body radiation therapy for pancreatic cancer based on the shortest distance between the tumor and the gastrointestinal tract using daily computed tomography images

  Yusuke Uchinami, Takahiro Kanehira, Keiji Nakazato, Yoshihiro Fujita, Fuki Koizumi, Shuhei Takahashi, Manami Otsuka, Koichi Yasuda, Hiroshi Taguchi, Kentaro Nishioka, Naoki Miyamoto, Kohei Yokokawa, Ryusuke Suzuki, Keiji Kobashi, Keita Takahashi, Norio Katoh, Hidefumi Aoyama

  BJR|Open 5 (1) 2023/08 

  Objectives: We aimed to investigate whether daily computed tomography (CT) images could predict the daily gastroduodenal, small intestine, and large intestine doses of stereotactic body radiation therapy (SBRT) for pancreatic cancer based on the shortest distance between the gross tumor volume (GTV) and gastrointestinal (GI) tract. Methods: Twelve patients with pancreatic cancer received SBRT of 40 Gy in five fractions. We recalculated the reference clinical SBRT plan (PLAN_ref) using daily CT images and calculated the shortest distance from the GTV to each GI tract. The maximum dose delivered to 0.5 cc (D_0.5cc) was evaluated for each planning at-risk volume of the GI tract. Spearman’s correlation test was used to determine the association between the daily change in the shortest distance (Δshortest distance) and the ratio of ΔD_0.5cc dose to D_0.5cc dose in PLAN_ref (ΔD_0.5cc/PLAN_ref) for quantitative analysis. Results: The median shortest distance in PLAN_ref was 0 mm in the gastroduodenum (interquartile range, 0–2.7), 16.7 mm in the small intestine (10.0–23.7), and 16.7 mm in the large intestine (8.3–28.1 mm). The D_0.5cc of PLAN_ref in the gastroduodenum was >30 Gy in all patients, with 10 (83.3%) having the highest dose. A significant association was found between the Δshortest distance and ΔD_0.5cc/ PLAN_ref in the small or large intestine (p < 0.001) but not in the gastroduodenum (p = 0.404). Conclusions: The gastroduodenum had a higher D_0.5cc and predicting the daily dose was difficult. Daily dose calculations of the GI tract are recommended for safe SBRT. Advances in knowledge: This study aimed to predict the daily doses in SBRT for pancreatic cancer from the shortest distance between the GTV and the gastrointestinal tract. Daily changes in the shortest distance can predict the daily dose to the small or large intestines, but not to the gastroduodenum.
• Proton Beam Therapy for Intrahepatic Cholangiocarcinoma: A Multicenter Prospective Registry Study in Japan

  Masashi Mizumoto, Kazuki Terashima, Hirokazu Makishima, Motohisa Suzuki, Takashi Ogino, Takahiro Waki, Hiromitsu Iwata, Hiroyasu Tamamura, Yusuke Uchinami, Tetsuo Akimoto, Tomoaki Okimoto, Takashi Iizumi, Masao Murakami, Norio Katoh, Kazushi Maruo, Kei Shibuya, Hideyuki Sakurai

  Liver Cancer 1 - 8 2235-1795 2023/07/24 

  <b><i>Introduction:</i></b> Intrahepatic cholangiocarcinoma (ICC) can be treated with chemotherapy in unresectable cases, but outcomes are poor. Proton beam therapy (PBT) may provide an alternative treatment and has good dose concentration that may improve local control. <b><i>Methods:</i></b> Fifty-nine patients who received initial PBT for ICC from May 2016 to June 2018 at nine centers were included in the study. The treatment protocol was based on the policy of the Japanese Society for Radiation Oncology. Forty patients received 72.6–76 Gy (RBE) in 20–22 fr, 13 received 74.0–76.0 Gy (RBE) in 37–38 fr, and 6 received 60–70.2 Gy (RBE) in 20–30 fr. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. <b><i>Results:</i></b> The 59 patients (35 men, 24 women; median age: 71 years; range: 41–91 years) had PS of 0 (<i>n</i> = 47), 1 (<i>n</i> = 10), and 2 (<i>n</i> = 2). Nine patients had hepatitis and all 59 cases were considered inoperable. The Child-Pugh class was A (<i>n</i> = 46), B (<i>n</i> = 7), and unknown (<i>n</i> = 6); the median maximum tumor diameter was 5.0 cm (range 2.0–15.2 cm); and the clinical stage was I (<i>n</i> = 12), II (<i>n</i> = 19), III (<i>n</i> = 10), and IV (<i>n</i> = 18). At the last follow-up, 17 patients were alive (median follow-up: 36.7 months; range: 24.1–49.9 months) and 42 had died. The median OS was 21.7 months (95% CI: 14.8–34.4 months). At the last follow-up, 37 cases had recurrence, including 10 with local recurrence. The median PFS was 7.5 months (95% CI: 6.1–11.3 months). In multivariable analyses, Child-Pugh class was significantly associated with OS and PFS, and Child-Pugh class and hepatitis were significantly associated with local recurrence. Four patients (6.8%) had late adverse events of grade 3 or higher. <b><i>Conclusion:</i></b> PBT gives favorable treatment outcomes for unresectable ICC without distant metastasis and may be particularly effective in cases with large tumors.
• Treatment outcomes of the patient with sinonasal mucosal melanoma: the role of endoscopic resection and postoperative radiotherapy.

  Nayuta Tsushima, Satoshi Kano, Koichi Yasuda, Takayoshi Suzuki, Seijiro Hamada, Yuji Nakamaru, Masanobu Suzuki, Yusuke Uchinami, Hidefumi Aoyama, Akihiro Homma

  International journal of clinical oncology 28 (9) 1218 - 1226 2023/06/17 

  BACKGROUND: The standard of care for sinonasal mucosal melanoma is surgery and postoperative radiotherapy (PORT). Our treatment strategy comprises endoscopic resection and PORT. We performed combined endoscopic and open resection or applied an external approach alone when sufficient resection was difficult to achieve endoscopically. The objective of this study was to evaluate the validity of our treatment strategy. METHODS: We assessed 30 patients with sinonasal mucosal melanoma who underwent definitive therapy between January 2002 and April 2021, and conducted a retrospective analysis. The median follow-up period was 2.2 years. The primary endpoint was overall survival. The Kaplan-Meier method was used for the calculation of survival rates, the cumulative incidence of distant metastasis, and local recurrence. RESULTS: Twenty-eight patients underwent surgery. The other two patients were treated by definitive proton beam therapy. Twenty-one of 28 (75%) patients underwent resection by endoscopic approach alone. Postoperative radiotherapy was performed for all 28 patients who underwent surgery. Twenty-one patients (70%) experienced recurrence during the observation period. Overall, distant metastasis was observed in 19 patients. Twelve patients died during the observation period, with 10 of the 12 patients (83%) dying of distant metastasis. The overall survival rate at 2 and 5 years was 70% and 46%, respectively. The cumulative incidence rate of distant metastasis at 2 years was 63%, while the 2-year cumulative incidence rate of local recurrence was 6.7%. CONCLUSION: The local disease was controlled by our treatment strategy. To improve treatment outcomes, control of the distant metastasis is needed.
• The superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is effective for metastatic lymph nodes in head and neck squamous cell carcinoma.

  Satoshi Kano, Takayoshi Suzuki, Daisuke Yoshida, Nayuta Tsushima, Seijiro Hamada, Koichi Yasuda, Yusuke Uchinami, Hidefumi Aoyama, Akihiro Homma

  International journal of clinical oncology 28 (9) 1121 - 1128 2023/06/08 

  BACKGROUND: Superselective intra-arterial infusion of cisplatin and concomitant radiotherapy (RADPLAT) is a very promising treatment modality for locally advanced head and neck squamous cell carcinoma. However, there are some concerns regarding its potential for the control of neck lymph node metastasis. The objective of this study was to investigate whether RADPLAT provided inferior regional control compared to intravenous chemoradiotherapy (IV-CRT). METHODS: A total of 172 patients with neck lymph node metastases, 66 of whom underwent RADPLAT and 106 IV-CRT, were enrolled in this study. We retrospectively compared regional control rates between RADPLAT and IV-CRT. Furthermore, to adjust for differences in factors related to patient background between the groups, we conducted inverse probability weighting (IPW) analysis using the propensity score. RESULTS: A comparison between the two groups revealed that the regional control rates were almost equal under unadjusted conditions; however, after adjustment by IPW analysis, the RADPLAT group had a relatively better regional control rate than did the IV-CRT group (1 year regional control rate: 86.6% vs. 79.4%). In addition, the analysis of relative risk factors for regional control in the RADPLAT group showed that the absence of intra-arterial cisplatin infusion into metastatic lymph nodes was the only independent risk factor (Hazard ratio: 4.23, p = 0.04). CONCLUSION: This study showed that the regional control rate in patients treated with RADPLAT was noninferior to that for IV-CRT. Locally advanced head and neck cancers is a good indication for RADPLAT, even if the patients have neck lymph node metastases.
• PO-2122 Effect of early fractional lymphocyte loss on lymphopenia probability models for NSCLC

  T. Kanehira, H. Taguchi, N. Katoh, Y. Uchinami, T. Yoshimura, M. Tamura, R. Suzuki, T. Hashimoto, H. Aoyama

  Radiotherapy and Oncology 182 S1909 - S1911 0167-8140 2023/05
• Effectiveness of CT-image guidance in proton therapy for liver cancer and the importance of daily dose monitoring for tumors and organs at risk.

  Yoshikazu Maeda, Keiji Kobashi, Yoshitaka Sato, Hiroyasu Tamamura, Kazutaka Yamamoto, Keiichiro Matsushita, Makoto Sasaki, Hitoshi Tatebe, Tomoko Asahi, Sae Matsumoto, Shigeyuki Takamatsu, Koichi Miyazaki, Rintaro Fujimoto, Yusuke Uchinami, Norio Katoh, Hidefumi Aoyama

  Medical physics 50 (6) 3274 - 3288 2023/04/26 

  BACKGROUND: It is important to have precise image guidance throughout proton therapy in order to take advantage of the therapy's physical selectivity. PURPOSE: We evaluated the effectiveness of computed tomography (CT)-image guidance in proton therapy for patients with hepatocellular carcinoma (HCC) by assessing daily proton dose distributions. The importance of daily CT image-guided registration and daily proton dose monitoring for tumors and organs at risk (OARs) was investigated. METHODS: A retrospective analysis was conducted using 570 sets of daily CT (dCT) images throughout whole treatment fractions for 38 HCC patients who underwent passive scattering proton therapy with either a 66 cobalt gray equivalent (GyE)/10 fractions (n = 19) or 76 GyE/20 fractions (n = 19) protocol. The actual daily delivered dose distributions were estimated by forward calculation using the dCT sets, their corresponding treatment plans, and the recorded daily couch correction information. We then evaluated the daily changes of the dose indices D99% , V30GyE , and Dmax for the tumor volumes, non-tumorous liver, and other OARs, that is, stomach, esophagus, duodenum, colon, respectively. Contours were created for all dCT sets. We validated the efficacy of the dCT-based tumor registrations (hereafter, "tumor registration") by comparing them with the bone registration and diaphragm registration as a simulation of the treatment based on the positioning using the conventional kV X-ray imaging. The dose distributions and the indices of three registrations were obtained by simulation using the same dCT sets. RESULTS: In the 66 GyE/10 fractions, the daily D99% value in both the tumor and diaphragm registrations agreed with the planned value with 3%-6% (SD), and the V30GyE value for the liver agreed within ±3%; the indices in the bone registration showed greater deterioration. Nevertheless, tumor-dose deterioration occurred in all registration methods for two cases due to daily changes of body shape and respiratory condition. In the 76 GyE/20 fractions, in particular for such a treatment that the dose constraints for the OARs have to be cared in the original planning, the daily D99% in the tumor registration was superior to that in the other registration (p < 0.001), indicating the effectiveness of the tumor registration. The dose constraints, set in the plan as the maximum dose for OARs (i.e., duodenum, stomach, colon, and esophagus) were maintained for 16 patients including seven treated with re-planning. For three patients, the daily Dmax increased gradually or changed randomly, resulting in an inter-fractional averaged Dmax higher than the constraints. The dose distribution would have been improved if re-planning had been conducted. The results of these retrospective analyses indicate the importance of daily dose monitoring followed by adaptive re-planning when needed. CONCLUSIONS: The tumor registration in proton treatment for HCC was effective to maintain the daily dose to the tumor and the dose constraints of OARs, particularly in the treatment where the maintenance for the dose constraints needs to be considered throughout the treatment. Nevertheless daily proton dose monitoring with daily CT imaging is important for more reliable and safer treatment.
• The need of radiotherapy optimization for glioblastomas considering immune responses.

  Kentaro Nishioka, Shuhei Takahashi, Takashi Mori, Yusuke Uchinami, Shigeru Yamaguchi, Manabu Kinoshita, Masaaki Yamashina, Hajime Higaki, Katsuya Maebayashi, Hidefumi Aoyama

  Japanese journal of radiology 2023/04/18 

  Glioblastoma is the most common of malignant primary brain tumors and one of the tumors with the poorest prognosis for which the overall survival rate has not significantly improved despite recent advances in treatment techniques and therapeutic drugs. Since the emergence of immune checkpoint inhibitors, the immune response to tumors has attracted increasing attention. Treatments affecting the immune system have been attempted for various tumors, including glioblastomas, but little has been shown to be effective. It has been found that the reason for this is that glioblastomas have a high ability to evade attacks from the immune system, and that the lymphocyte depletion associated with treatment can reduce its immune function. Currently, research to elucidate the resistance of glioblastomas to the immune system and development of new immunotherapies are being vigorously carried out. Targeting of radiation therapy for glioblastomas varies among guidelines and clinical trials. Based on early reports, target definitions with wide margins are common, but there are also reports that narrowing the margins does not make a significant difference in treatment outcome. It has also been suggested that a large number of lymphocytes in the blood are irradiated by the irradiation treatment to a wide area in a large number of fractionations, which may reduce the immune function, and the blood is being recognized as an organ at risk. Recently, a randomized phase II trial comparing two types of target definition in radiotherapy for glioblastomas was conducted, and it was reported that the overall survival and progression-free survival were significantly better in a small irradiation field group. We review recent findings on the immune response and the immunotherapy to glioblastomas and the novel role of radiotherapy and propose the need to develop an optimal radiotherapy that takes radiation effects on the immune function into account.
• Analysis of particle therapy registries based on a unified treatment policy for esophageal cancer.

  Sunao Tokumaru, Hitoshi Ishikawa, Toshinori Soejima, Takuya Kimoto, Yosuke Takakusagi, Hiroyasu Tamamura, Hitoshi Wada, Hiroshi Taguchi, Yusuke Uchinami, Yuichi Hiroshima, Hidehiro Hojo, Takashi Kamei, Manabu Muto, Masataka Igeta

  Journal of radiation research 2023/04/07 

  This study aimed to evaluate the efficacy and safety of particle therapy (proton beam therapy and carbon-ion radiotherapy) for esophageal cancer by analyzing prospective nationwide registry data from particle therapy facilities throughout Japan. Patients diagnosed with esophageal cancer who received particle therapy between May 2016 and June 2018 were recruited from the registries of 12 particle therapy centers in Japan. Eventually, we enrolled 174 patients who met the inclusion criteria. Of the 174 patients, 137 (78.7%) were male, with a median age of 69 years (range: 41-88 years). Clinical stages included I (n = 55; 31.6%), II (n = 31; 17.8%), III (n = 82; 47.1%), IV (n = 3; 1.7%) and unknown (n = 3; 1.7%) (Union for International Cancer Control, seventh edition), and the median follow-up period was 908 days (range: 76-1669 days) for all patients. The 3-year overall survival (OS) rate, the 3-year progression-free survival (PFS) rate and the 3-year local control (LC) rates were 60.5, 53.2 and 72.7%, respectively. For each clinical stage, the 3-year OS rates were I, 84.8%; II, 60.3% and III, 42.9%; the 3-year PFS rates were I, 71.9%; II, 58.3% and III, 37.0% and the 3-year LC were I, 78.4%; II, 79.8% and III, 65.2%, respectively. Notably, four patients (2.3%) with ≥Grade 3 cardiopulmonary toxicities were observed (Common Terminology Criteria for Adverse Events, version 5.0). Our study showed that particle therapy for esophageal cancer has lower rates of adverse cardiopulmonary events than X-ray radiotherapy.
• Evaluation of short-term gastrointestinal motion and its impact on dosimetric parameters in stereotactic body radiation therapy for pancreatic cancer

  Yusuke Uchinami, Takahiro Kanehira, Yoshihiro Fujita, Naoki Miyamoto, Kohei Yokokawa, Fuki Koizumi, Motoyasu Shido, Shuhei Takahashi, Manami Otsuka, Koichi Yasuda, Hiroshi Taguchi, Keiji Nakazato, Keiji Kobashi, Norio Katoh, Hidefumi Aoyama

  Clinical and Translational Radiation Oncology 39 100576 - 100576 2405-6308 2023/03 

  BACKGROUND: The aim of this study is to quantify the short-term motion of the gastrointestinal tract (GI-tract) and its impact on dosimetric parameters in stereotactic body radiation therapy (SBRT) for pancreatic cancer. METHODS: The analyzed patients were eleven pancreatic cancer patients treated with SBRT or proton beam therapy. To ensure a fair analysis, the simulation SBRT plan was generated on the planning CT in all patients with the dose prescription of 40 Gy in 5 fractions. The GI-tract motion (stomach, duodenum, small and large intestine) was evaluated using three CT images scanned at spontaneous expiration. After fiducial-based rigid image registration, the contours in each CT image were generated and transferred to the planning CT, then the organ motion was evaluated. Planning at risk volumes (PRV) of each GI-tract were generated by adding 5 mm margins, and the volume receiving at least 33 Gy (V33) < 0.5 cm3 was evaluated as the dose constraint. RESULTS: The median interval between the first and last CT scans was 736 s (interquartile range, IQR:624-986). To compensate for the GI-tract motion based on the planning CT, the necessary median margin was 8.0 mm (IQR: 8.0-10.0) for the duodenum and 14.0 mm (12.0-16.0) for the small intestine. Compared to the planned V33 with the worst case, the median V33 in the PRV of the duodenum significantly increased from 0.20 cm3 (IQR: 0.02-0.26) to 0.33 cm3 (0.10-0.59) at Wilcoxon signed-rank test (p = 0.031). CONCLUSION: The short-term motions of the GI-tract lead to high dose differences.
• Brain metastases in Japanese NSCLC patients: prognostic assessment and the use of osimertinib and immune checkpoint inhibitors-retrospective study.

  Hajime Higaki, Kentaro Nishioka, Manami Otsuka, Noboru Nishikawa, Motoyasu Shido, Hideki Minatogawa, Yukiko Nishikawa, Rikiya Takashina, Takayuki Hashimoto, Norio Katoh, Hiroshi Taguchi, Rumiko Kinoshita, Koichi Yasuda, Takashi Mori, Yusuke Uchinami, Fuki Koizumi, Yoshihiro Fujita, Shuhei Takahashi, Takahiro Hattori, Noriaki Nishiyama, Hidefumi Aoyama

  Radiation oncology (London, England) 18 (1) 25 - 25 2023/02/07 

  BACKGROUND: The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA) has not been validated for use with Japanese non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) and the factors impacting survival need to be assessed. METHODS: We retrospectively analyzed 294 NSCLC patients who were newly diagnosed with BM between 2013 and 2020 and had received radiotherapy for BM initially at the Hokkaido Cancer Center. We evaluated the effect on the prognosis of Lung-molGPA items, the expression of PD-L1 (classified as high, low, and no expression), and the treatment history. The main outcome was the survival measured from the day of the diagnosis of BM, and log-rank tests were performed to evaluate the results. RESULTS: The median overall survival (OS) times for adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, 2.5‒3.0, and 3.5‒4.0) were 5.5, 14.8, 28.3, and 39.0 months (p < 0.0001), respectively. The median survival times for non-adenocarcinoma by groups of GPA scores (0‒1.0, 1.5‒2.0, and 2.5‒3.0) were 3.2, 11.0, and 16.0 months (p = 0.0011), respectively. In adenocarcinoma patients with gene mutations, osimertinib significantly improved the outcome (median OS: 34.2 and 17.6 months with and without osimertinib, respectively (p = 0.0164)). There was no significant difference in the OS between patients who were initially treated with tyrosine-kinase inhibitor for BM and those who initially received radiotherapy (p = 0.5337). In patients tested for PD-L1 expression, the median survival times after the diagnosis of BM were 5.6, 22.5, and 9.3 months for the high-, low- and no-expression groups (p = 0.2198), respectively. Also, in patients with high PD-L1 expressions, those with ICI had survival (median OS, 8.6 months) than those without (median OS, 3.6 months). CONCLUSIONS: We confirmed that Lung-molGPA successfully classified Japanese NSCLC patients with BM by the prognosis. Osimertinib prolonged survival of EGFR-positive NSCLC patients with BM, and ICI was effective in patients with high PD-L1 expressions.
• 肝細胞癌陽子線治療効果予測におけるADC値指標の検討

  藤田 祥博, 加藤 徳雄, 打浪 雄介, 田口 大志, 西岡 健太郎, 森 崇, 安田 耕一, 小泉 富基, 大塚 愛美, 高尾 聖心, 田村 昌也, Sutherland Kenneth, Khin Khin Tha, 伊藤 陽一, 青山 英史

  Japanese Journal of Radiology (公社)日本医学放射線学会 41 (Suppl.) 10 - 10 1867-1071 2023/02
• 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 2023/01/12 

  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 (HCC) with a maximum diameter of ≤5 cm and Child-pugh grade A (CP-A): number of tumors (one 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. CONCLUSIONS: 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.
• Distribution of human papilloma virus genotypes and treatment outcomes in definitive radiotherapy for cervical cancer.

  Rumiko Kinoshita, Takashi Mitamura, Fumi Kato, Takahiro Hattori, Hajime Higaki, Shuhei Takahashi, Yoshihiro Fujita, Manami Otsuka, Fuki Koizumi, Yusuke Uchinami, Takashi Mori, Kentaro Nishioka, Takayuki Hashimoto, Yoichi M Ito, Hidemichi Watari, Hidefumi Aoyama

  Journal of radiation research 64 (2) 463 - 470 2023/01/03 

  Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV genotyping was conducted using biopsy specimens which had been stored in these studies. We conducted the study using the HPV test performed by cytology specimens which is less invasive and more useful in clinical settings. This study enrolled 46 patients who received HPV genotyping before the definitive radiotherapy. The results of the HPV genotyping were classified into HPVα-7, HPVα-9 and negatives. Of the 46 patients, 10 were positive for HPVα-7, 21 positive for HPVα-9 and 15 were negative. The median follow-up period was 38 months (range 4-142). The HPVα-7, HPVα-9 and negative groups showed the 3-year overall survival (OS; 59.3%, 80.4% and 72.2% [P = 0.25]); local control (LC; 67.5%, 81% and 80% [P = 0.78]); pelvic control (PC) (50%, 81% and 72.7% [P = 0.032]); pelvic lymph node (PLN) control (78.7%, 95% and 92.3% [P = 0.012]); distant metastasis free (DMF) survival (50%, 75.4% and 42.8% [P = 0.098]); and progression free survival (PFS) rate of patients (30%, 66.7% and 38.9% [P = 0.085]), respectively. Patients with HPVα-7 showed statistically significant poorer PC than the HPVα-9 group, in multivariate analysis. This result is consistent with previous studies for HPV positive patients. The HPV negativity rate was higher in this study than in other studies and further work on this may be needed for clinical use.
• 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 2022/12/11 [Refereed]
   

  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. This article is protected by copyright. All rights reserved.
• Detailed analysis of failure patterns using deformable image registration in hypopharyngeal cancer patients treated with sequential boost intensity-modulated radiotherapy.

  Manami Otsuka, Koichi Yasuda, Yusuke Uchinami, Nayuta Tsushima, Takayoshi Suzuki, Satoshi Kano, Ryusuke Suzuki, Naoki Miyamoto, Hideki Minatogawa, Yasuhiro Dekura, Takashi Mori, Kentaro Nishioka, Jun Taguchi, Yasushi Shimizu, Norio Katoh, Akihiro Homma, Hidefumi Aoyama

  Journal of medical imaging and radiation oncology 67 (1) 98 - 110 2022/11/14 [Refereed]
   

  INTRODUCTION: Sequential boost intensity-modulated radiotherapy (SQB-IMRT) uses two different planning CTs (pCTs) and treatment plans. SQB-IMRT is a form of adaptive radiotherapy that allows for responses to changes in the shape of the tumour and organs at risk (OAR). On the other hand, dose accumulation with the two plans can be difficult to evaluate. The purpose of this study was to analyse patterns of loco-regional failure using deformable image registration (DIR) in hypopharyngeal cancer patients treated with SQB-IMRT. METHODS: Between 2013 and 2019, 102 patients with hypopharyngeal cancer were treated with definitive SQB-IMRT at our institution. Dose accumulation with the 1st and 2nd plans was performed, and the dose to the loco-regional recurrent tumour volume was calculated using the DIR workflow. Failure was classified as follows: (i) in-field (≥95% of the recurrent tumour volume received 95% of the prescribed dose); (ii) marginal (20-95%); or (iii) out-of-field (<20%). RESULTS: After a median follow-up period of 25 months, loco-regional failure occurred in 34 patients. Dose-volume histogram analysis showed that all loco-regional failures occurred in the field within 95% of the prescribed dose, with no marginal or out-of-field recurrences observed. CONCLUSION: The dosimetric analysis using DIR showed that all loco-regional failures were within the high-dose region. More aggressive treatment may be required for gross tumours.
• 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 2022/10/27 [Refereed]
   

  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 2405-6308 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.
• Treatment outcomes of stereotactic body radiation therapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinomas.

  Yusuke Uchinami, Norio Katoh, Daisuke Abo, Hiroshi Taguchi, Koichi Yasuda, Kentaro Nishioka, Takeshi Soyama, Ryo Morita, Naoki Miyamoto, Ryusuke Suzuki, Takuya Sho, Masato Nakai, Koji Ogawa, Tatsuhiko Kakisaka, Tatsuya Orimo, Toshiya Kamiyama, Shinichi Shimizu, Hidefumi Aoyama

  Hepatology research : the official journal of the Japan Society of Hepatology 51 (8) 870 - 879 2021/08 

  AIM: To report the outcomes of stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system for hepatocellular carcinoma patients. METHODS: From January 2005 to July 2018, 63 patients with 74 lesions with a maximum diameter ≤52 mm were treated by stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system. No patient with a Child-Pugh Score ≥9 was included, and 85.6% had a score of 5 or 6. Using the biological effective dose (BED) with an α/β ratio of 10 (BED10 ), the median dose in BED10 at the reference point was 76.8 Gy (range 60-122.5 Gy). Overall survival (OS) and local control rates were assessed using the Kaplan-Meier method. RESULTS: With a median follow-up period of 24.6 months (range 0.9-118.4 months), the 1-year and 2-year OS rates were 86.8% (95% confidence interval [95% CI] 75.8-93.3) and 71.1% (57.8-81.6), respectively. The 2-year OS was 89.6% in patients with the baseline modified albumin-bilirubin (mALBI) grade =1, and 61.7% in patients with grade ≥2a. In the multivariate analysis, the mALBI grade (=1 vs. ≥2a) was a significant factor for OS (p = 0.028, 95% CI 1.11-6.18). The 1-year and 2-year local control rates were 100% (100-100%) and 92.0% (77.5-97.5%). The local control rates were significantly higher in the BED10 ≥100 Gy group than in the BED10 <100 Gy group (2-year 100% vs. 86.5%, p = 0.049) at the reference point. CONCLUSION: This retrospective study of stereotactic body radiotherapy using real-time tumor-tracking radiotherapy for hepatocellular carcinoma showed favorable outcomes with lower incidence of toxicities, especially in patients treated with BED10 ≥100 Gy to the reference point.
• CCRTを施行した頭頸部癌患者に対する予防的胃瘻増設の有用性の検討

  加納 里志, 対馬 那由多, 鈴木 崇祥, 井戸川 寛志, 浜田 誠二郎, 横川 泰三, 安田 耕一, 湊川 英樹, 打浪 雄介, 本間 明宏

  頭頸部癌 (一社)日本頭頸部癌学会 47 (2) 211 - 211 1349-5747 2021/05
• 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 0360-3016 2020/11
• 膵癌に対するS-1併用術前化学放射線療法(S-1併用NACRT)の治療成績

  小泉 富基, 加藤 徳雄, 中村 透, 川本 泰之, 田口 大志, 打浪 雄介, 清水 伸一, 青山 英史

  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 56回 S103 - S103 0048-0428 2020/10
• Percutaneous insertion of hepatic fiducial true-spherical markers for real-time adaptive radiotherapy.

  Ryo Morita, Daisuke Abo, Yusuke Sakuhara, Takeshi Soyama, Norio Katoh, Naoki Miyamoto, Yuusuke Uchinami, Shinichi Shimizu, Hiroki Shirato, Kohsuke Kudo

  Minimally invasive therapy & allied technologies : MITAT : official journal of the Society for Minimally Invasive Therapy 29 (6) 1 - 10 2019/09/13 [Refereed][Not invited]
   

  Purpose: This study evaluated the success rate and complications of percutaneous implantation of hepatic fiducial true-spherical gold markers for real-time adaptive radiotherapy (RAR), which constitutes real-time image-guided radiotherapy with gating. Material and methods: We retrospectively evaluated 100 patients who underwent 116 percutaneous intrahepatic implantations of 2-mm-diameter, spherical, gold fiducial markers before RAR from 1999 to 2016, with Seldinger's method. We defined technical success as marker placement at the intended liver parenchyma, without mispositioning, and clinical success as successful tracking of the gold marker and completion of planned RAR. Complications related to marker placement were assessed. Results: The technical success rate for true-spherical gold marker implantation was 92.2% (107/116). Nine of 116 markers migrated (intra-procedurally in seven patients, delayed in two patients). Migration out of the liver (n = 4) or intrahepatic vessels (n = 5) occurred without complications; these markers were not retrieved. The clinical success rate was 100.0% (115/115). Abdominal pain occurred in 16 patients, fever and hemorrhage in seven patients each, and pneumothorax and nausea in one patient each. No major complications were encountered. Conclusions: Percutaneous transhepatic implantation of true-spherical gold markers for RAR is feasible and can be conducted with a high success rate and low complication rate.
• 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
• Impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with intensity-modulated radiotherapy.

  Yusuke Uchinami, Ryusuke Suzuki, Norio Katoh, Hiroshi Taguchi, Koichi Yasuda, Naoki Miyamoto, Yoichi M Ito, Shinichi Shimizu, Hiroki Shirato

  Journal of applied clinical medical physics 20 (8) 78 - 86 2019/08 [Refereed][Not invited]
   

  PURPOSE: Interplay effects may influence dose distributions to a moving target when using dynamic delivery techniques such as intensity-modulated radiotherapy (IMRT). The aim of this study was to evaluate the impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with IMRT. METHODS: Ten patients who had been treated with IMRT for stomach lymphomas were enrolled. The clinical target volume (CTV) was contoured as the whole stomach. Considering interfractional uncertainty, the internal target volume (ITV) margin was uniformly 1.5 cm to the CTV and then modified based on the 4DCT images in case of the large respiratory motion. The planning target volume (PTV) was created by adding 5 mm to the ITV. The impact of organ motion on the volumetric and dosimetric parameters was evaluated retrospectively (4D simulation). The organ motion was reproduced by shifting the isocenter on the radiation treatment planning system. Several simulation plans were created to test the influence of the beam-on timing in the respiration cycle on the dose distribution. The homogeneity index (HI), volume percentage of stomach covered by the prescribed dose (Vp ), and D99 of the CTV were evaluated. RESULTS: The organ motion was the largest in the superior-inferior direction (10.1 ± 4.5 mm [average ± SD]). Stomach volume in each respiratory phase compared to the mean volume varied approximately within a ± 5% range in most of the patients. The PTV margin was sufficiently large to cover the CTV during the IMRT. There was a significant reduction in Vp and D99 but not in HI in the 4D simulation in free-breathing and multiple fractions compared to the clinically-used plan (P < 0.05) suggesting that interplay effects deteriorate the dose distribution. The absolute difference of D99 was less than 1% of the prescribed dose. CONCLUSIONS: There were significant interplay effects affecting the dose distribution in stomach IMRT. The magnitude of the dose reduction was small when patients were treated on free-breathing and multiple fractions.
• Optimal resection area for superior mesenteric artery nerve plexuses after neoadjuvant chemoradiotherapy for locally advanced pancreatic carcinoma.

  Takahiro Einama, Hirofumi Kamachi, Yosuke Tsuruga, Toshihiro Sakata, Kazuaki Shibuya, Yuzuru Sakamoto, Shingo Shimada, Kenji Wakayama, Tatsuya Orimo, Hideki Yokoo, Toshiya Kamiyama, Norio Katoh, Yusuke Uchinami, Tomoko Mitsuhashi, Akinobu Taketomi

  Medicine 97 (31) e11309  2018/08 [Refereed][Not invited]
   

  Recently, several reports demonstrated the efficacy of neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT) for patients with borderline resectable (BRPC) and locally advanced unresectable pancreatic carcinoma (LAPC). The aim of this study was to evaluate the treatment response after NACRT, especially for nerve plexuses, and the optimal resection area for superior mesenteric artery nerve plexuses in BRPC and LAPC patients after NACRT.A total of 17 patients with BRPC and LAPC received preoperative gemcitabine-based NACRT. The numbers of BRPC and LAPC patients were 13 and 4, respectively. We evaluated nerve plexus invasion by CT before and after NACRT, decided on the resection area of plexus invasion in SMA before NACRT, and compared the preoperative evaluation and clinicopathological findings.In the plexus of the supra-mesenteric artery (pl-SMA), arterial nerve plexus invasion, in cases <90°, all patients showed the absence of residual cancer in the resected specimen after NACRT. In cases between 90° and 180°, 1 of 2 patients (50%) showed nerve plexus invasion. In cases over 180°, all patients showed nerve plexus invasion. We could perform R0 resection in all 10 cases, and pl-SMA invasion disappeared in 6 of 7 BRPC patients.We demonstrated the relationship between the angle of nerve plexus tumor invasion and treatment effect after NACRT. We could perform R0 resection in all pl-SMA invasion cases, deciding on the resection area of pl-SMA based on CT before NACRT.
• Real-Time Tumor-Tracking Radiotherapy and General Stereotactic Body Radiotherapy for Adrenal Metastasis in Patients With Oligometastasis.

  Norio Katoh, Hiroshi Onishi, Yusuke Uchinami, Tetsuya Inoue, Kengo Kuriyama, Kentaro Nishioka, Shinichi Shimizu, Takafumi Komiyama, Naoki Miyamoto, Hiroki Shirato

  Technology in cancer research & treatment 17 1533033818809983 - 1533033818809983 2018/01/01 [Refereed][Not invited]
   

  BACKGROUND: Precise local radiotherapy for adrenal metastasis can prolong the useful life of patients with oligometastasis. The aim of this retrospective, 2-center study was to establish the safety and effectiveness of real-time tumor-tracking radiotherapy and general stereotactic body radiotherapy in treating patients with adrenal metastatic tumors. MATERIALS AND METHODS: Thirteen lesions in 12 patients were treated with real-time tumor-tracking radiotherapy (48 Gy in 8 fractions over 2 weeks) and 8 lesions in 8 patients were treated with general stereotactic body radiotherapy (40-50 Gy in 5-8 fractions over 2 weeks or 60-70 Gy in 10 fractions over 2 weeks). Overall survival rates, local control rates, and adverse effects were analyzed. RESULTS: The actuarial overall survival rates for all patients at 1 and 2 years were 78.5% and 45.8%, respectively, with a median follow-up of 17.5 months, and the actuarial local control rates for all tumors at 1 and 2 years were 91.7% and 53.0%, respectively, with a median follow-up of 9 months. A complete local tumor response was obtained in 3 tumors treated by real-time tumor-tracking radiotherapy (lung adenocarcinomas with diameters of 35, 40, and 60 mm). There was a statistically significant difference in the local control between the groups treated by real-time tumor-tracking radiotherapy (100% at 1 year) and general stereotactic body radiotherapy (50% at 1 year; P < .001). No late adverse reactions at Grade 2 or higher were reported for either treatment group. CONCLUSIONS: This study showed that although both treatments are safe and effective, the real-time tumor-tracking radiotherapy is more effective than general stereotactic body radiotherapy in local control for adrenal metastasis.
• Analysis of Threshold Doses for Radiation Induced Liver Parenchymal Changes on MRI after Real Time–Image 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 0360-3016 2017/10
• An Organ Motion and Acute Toxicity Study of Image-Guided Spot-Scanning Proton Beam Therapy With An Internal Fiducial Marker for Pancreatic Cancers.

  Y. Uchinami, N. Katoh, D. Abo, K. Harada, Y. Nishikawa, T. Inoue, T. Hashimoto, R. Onimaru, N. Miyamoto, Y. Sakuhara, S. Shimizu, H. Shirato

  International Journal of Radiation Oncology*Biology*Physics 99 (2) E194 - E194 0360-3016 2017/10
• Clinical outcomes of stage I and IIA non-small cell lung cancer patients treated with stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system.

  Norio Katoh, Itaru Soda, Hiroyasu Tamamura, Shotaro Takahashi, Yusuke Uchinami, Hiromichi Ishiyama, Kiyotaka Ota, Tetsuya Inoue, Rikiya Onimaru, Keiko Shibuya, Kazushige Hayakawa, Hiroki Shirato

  Radiation oncology (London, England) 12 (1) 3 - 3 2017/01/05 [Refereed][Not invited]
   

  PURPOSE: To investigate the clinical outcomes of stage I and IIA non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT) using a real-time tumor-tracking radiotherapy (RTRT) system. MATERIALS AND METHODS: Patterns-of-care in SBRT using RTRT for histologically proven, peripherally located, stage I and IIA NSCLC was retrospectively investigated in four institutions by an identical clinical report format. Patterns-of-outcomes was also investigated in the same manner. RESULTS: From September 2000 to April 2012, 283 patients with 286 tumors were identified. The median age was 78 years (52-90) and the maximum tumor diameters were 9 to 65 mm with a median of 24 mm. The calculated biologically effective dose (10) at the isocenter using the linear-quadratic model was from 66 Gy to 126 Gy with a median of 106 Gy. With a median follow-up period of 28 months (range 0-127), the overall survival rate for the entire group, for stage IA, and for stage IB + IIA was 75%, 79%, and 65% at 2 years, and 64%, 70%, and 50% at 3 years, respectively. In the multivariate analysis, the favorable predictive factor was female for overall survival. There were no differences between the clinical outcomes at the four institutions. Grade 2, 3, 4, and 5 radiation pneumonitis was experienced by 29 (10.2%), 9 (3.2%), 0, and 0 patients. The subgroup analyses revealed that compared to margins from gross tumor volume (GTV) to planning target volume (PTV) ≥ 10 mm, margins < 10 mm did not worsen the overall survival and local control rates, while reducing the risk of radiation pneumonitis. CONCLUSIONS: This multi-institutional retrospective study showed that the results were consistent with the recent patterns-of-care and patterns-of-outcome analysis of SBRT. A prospective study will be required to evaluate SBRT using a RTRT system with margins from GTV to PTV < 10mm.
• Prognostic factors in clinical T1N0M0 thoracic esophageal squamous cell carcinoma invading the muscularis mucosa or submucosa.

  Yusuke Uchinami, Miyako Myojin, Hiroaki Takahashi, Keiichi Harada, Shinichi Shimizu, Masao Hosokawa

  Radiation oncology (London, England) 11 84 - 84 2016/06/21 [Refereed][Not invited]
   

  BACKGROUND: Multimodality treatment is widely performed for clinical T1N0M0 (UICC-TNM classification, 7th edition) thoracic esophageal squamous cell carcinoma (ESCC), but available articles regarding treatment results are limited. This study assessed the outcomes of clinical T1N0M0 thoracic ESCC invading the muscularis mucosa (MM) or submucosa (SM) treated with radiotherapy (RT) or chemoradiotherapy (CRT). METHODS: We retrospectively reviewed the medical charts of 90 patients with clinical T1N0M0 thoracic ESCC treated with RT or CRT in our hospital in 2004-2011. Of these 90 patients, we analyzed the cases of 71 patients who met our inclusion criteria. All 71 patients had MM or SM cancer. In the 47 patients treated with CRT, the chemotherapy regimen of 5-fluorouracil (5-FU) plus cisplatin (CDDP) was used for 46 patients and 5-FU and nedaplatin was used for one patient. Forty-five patients underwent endoscopic resection (ER) followed by RT or CRT as an additional treatment. Elective nodal irradiation (ENI) was used in 39 patients. For all analyses, statistical significance was defined as 0.05, and the Bonferroni correction was used for the multivariate analysis. RESULTS: The median age was 70 years (range 47-84). With a median follow-up of 43.6 months (range 1.5-124.2), the 5-year overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) rates were 64.0, 72.8 and 50.0 %, respectively. The multivariate analysis showed that performance status (PS) was an independent prognostic factors for DSS and DFS (DSS, p < 0.001; DFS, p < 0.001). Chemotherapy in addition to RT showed a trend for better DSS (p = 0.032) but was not significant following Bonferroni correction. ER and ENI were not significant predictive factors for DSS and DFS. CONCLUSIONS: PS was an independent prognostic factor for DSS and DFS. ER and ENI had no significant relationship with DSS or DFS. The present results may be helpful in treatment decisions for clinical T1N0M0 thoracic ESCC.
• 3-Methylcholanthrene-induced transforming growth factor-beta-producing carcinomas, but not sarcomas, are refractory to regulatory T cell-depletion therapy.

  Kenji Chamoto, Daiko Wakita, Takayuki Ohkuri, Yusuke Uchinami, Kouji Matsushima, Hidemitsu Kitamura, Takashi Nishimura

  Cancer science 101 (4) 855 - 61 2010/04 [Refereed][Not invited]
   

  Regulatory T cells (Tregs) are major immunosuppressors in tumor-bearing hosts. Although Treg-depletion therapy has been shown to induce a complete cure in tumor-bearing mice, this treatment is not always successful. Using 3-methylcholanthrene-induced primary mouse tumors, we examined the distinct regulation of Treg-mediated immunosuppression between carcinomas and sarcomas. We showed that the number of Tregs was greatly increased in squamous cell carcinoma (SCC)-bearing mice compared with sarcoma-bearing mice. This appeared to be because SCC produced higher levels of active transforming growth factor (TGF)-beta, which is essential for inducing Tregs, compared with sarcoma. Moreover, SCC, but not sarcomas, were refractory to Treg-depletion therapy by treatment with anti-CD25 mAb. The refractoriness of SCC against Treg-depletion therapy was due to the rapid recovery of Tregs in SCC-bearing mice compared with sarcoma-bearing mice. However, combination treatment of anti-TGF-beta mAb with anti-CD25 mAb caused a significant reduction in Treg recovery and induced a complete cure in SCC-bearing mice. Thus, we showed the refractoriness of mouse carcinoma against Treg-depletion therapy using anti-CD25 mAb treatment. We also proposed a novel Treg-blocking combination therapy using anti-CD25 mAb and anti-TGF-beta mAb to induce a complete cure of tumor-bearing hosts.

MISC

• クリニカルトピックス 膵臓がんにおける適応陽子線治療確立に向けた模索

  打浪 雄介  BIO Clinica  38-  (14)  1202  -1204  2023/12  

  2022年4月より切除不能膵臓がんに対して陽子線治療が保険適用となった。陽子線はX線に比べ腫瘍に集中して照射可能な一方で,治療期間中の体内臓器の変化が投与線量の不確実性につながりうる。このような変化に対応するため治療期間中に治療計画を修正する適応治療が提唱されており,近年X線治療で臨床応用が始まった。本研究では膵臓がんの治療成績向上に向けて,陽子線治療と適応治療を融合させた適応陽子線治療の確立を目指す。(著者抄録)
• 胸部食道がん化学放射線療法における重症放射線食道炎に関する後方視的研究

  原田 一顕, 中村 赳晶, 渡辺 亮介, 山村 貴洋, 結城 敏志, 坂本 直哉, 川本 泰之, 小松 嘉人, 打浪 雄介, 田口 大志, 加藤 徳雄, 青山 英史  北海道医学雑誌  98-  (2)  139  -140  2023/11
• 高齢者の局所進行頭頸部扁平上皮癌患者におけるweeklyシスプラチン併用放射線治療の治療成績

  打浪 雄介, 安田 耕一, 加納 里志, 対馬 那由多, 鈴木 崇祥, 浜田 誠二郎, 田口 純, 清水 康, 坂下 智博, 本間 明宏  頭頸部癌  49-  (2)  134  -134  2023/05
• 当院で治療した頭頸部原発横紋筋肉腫症例の検討

  勝俣 量平, 加納 里志, 対馬 那由多, 鈴木 崇祥, 浜田 誠二郎, 清水 康, 田口 純, 安田 耕一, 打浪 雄介, 本間 明宏  頭頸部癌  49-  (2)  161  -161  2023/05
• 高齢者の頭頸部癌に対する放射線治療と化学療法併用の実態 日本頭頸部癌学会悪性腫瘍全国登録調査の解析

  安田 耕一, 打浪 雄介, 加納 里志, 田口 純, 清水 康, 本間 明宏  頭頸部癌  49-  (2)  171  -171  2023/05
• 唾液腺癌の局所頸部制御における術後照射の有用性の検討

  加納 里志, 対馬 那由多, 鈴木 崇祥, 浜田 誠二郎, 安田 耕一, 打浪 雄介, 本間 明宏  頭頸部癌  49-  (2)  192  -192  2023/05
• 放射線治療を中心としたがん治療について-最近の変化と将来- 膠芽腫に対する免疫反応を考慮した照射野最適化の必要性

  西岡 健太郎, 高橋 周平, 森 崇, 打浪 雄介, 山口 秀, 木下 学, 山品 将祥, 前林 勝也, 青山 英史  日本医学放射線学会秋季臨床大会抄録集  58回-  S345  -S345  2022/08
• 免疫チェックポイント阻害薬と放射線治療—Clinical evidences for the combination of immune checkpoint inhibitor and radiation therapy—特集 がん免疫療法の展望 : 免疫チェックポイント阻害薬の併用療法に中心に ; 免疫チェックポイント阻害薬の併用療法のエビデンス

  安田 耕一, 志藤 元泰, 小泉 富基, 高橋 周平, 藤田 祥博, 大塚 愛美, 宮﨑 智彦, 西川 昇, 打浪 雄介, 森 崇, 西岡 健太郎, 木下 留美子, 田口 大志, 加藤 徳雄, 橋本 孝之, 青山 英史  腫瘍内科 = Clinical oncology / 腫瘍内科編集委員会 編  30-  (1)  23  -28  2022/07
• 咽喉頭癌に対するシスプラチン超選択的動注併用放射線治療(RADPLAT)による頸部制御の検討

  加納 里志, 対馬 那由多, 鈴木 崇祥, 浜田 誠二郎, 吉田 大介, 打浪 雄介, 安田 耕一, 本間 明宏  頭頸部癌  48-  (2)  151  -151  2022/05
• 高齢の頭頸部悪性腫瘍に対する放射線治療の後ろ向き検討

  安田 耕一, 打浪 雄介, 浜田 誠二郎, 鈴木 崇祥, 対馬 那由多, 田口 純, 清水 康, 加納 里志, 本間 明宏  頭頸部癌  48-  (2)  200  -200  2022/05
• 咽喉頭癌に対するシスプラチン超選択的動注併用放射線治療(RADPLAT)による頸部制御の検討

  加納 里志, 対馬 那由多, 鈴木 崇祥, 浜田 誠二郎, 吉田 大介, 打浪 雄介, 安田 耕一, 本間 明宏  頭頸部癌  48-  (2)  151  -151  2022/05
• 高齢の頭頸部悪性腫瘍に対する放射線治療の後ろ向き検討

  安田 耕一, 打浪 雄介, 浜田 誠二郎, 鈴木 崇祥, 対馬 那由多, 田口 純, 清水 康, 加納 里志, 本間 明宏  頭頸部癌  48-  (2)  200  -200  2022/05
• The survey of definitive radiotherapy for cervical cancer in affiliate facilities of department of radiation oncology Hokkaido University Hospital

  木下留美子, 打浪雄介, 高橋周平, 小泉富基, 森崇, 西岡健太郎, 田口大志, 橋本孝之, 高邑明夫, 西岡井子, 北原利博, 土屋和彦, 井上哲也, 有本卓郎, 出倉康裕, 米坂祥朗, 鈴木恵士郎, 川島和之, 小野寺俊輔, 喜多村圭, 長谷川雅一, 鬼丸力也, 富田雅義, 池田潤, 西山典明, 青山英史  北海道放射線医学雑誌  2-  13  -18  2022/03  

  子宮頸癌に対する根治的放射線治療において子宮内から照射を行う腔内照射は必要不可欠な要素である。腔内照射の設備の維持・更新および子宮頸癌根治照射人数等について北海道大学病院放射線治療科関連病院にアンケートを行った。道内の施設の子宮頸癌根治照射人数は年間10人以下の施設が大半で、腔内照射設備を保有している施設の年間の腔内照射人数は5-9人が4施設、10人以上が2施設であった。腔内照射設備を保有している6施設の内4施設で設備の維持・更新が採算面で難しいという理由で腔内照射の休止を検討している事が明らかとなった。北海道内の子宮頸癌に対する根治照射を継続して行うためには、腔内照射設備を持つ施設への適切な紹介システムの構築と腔内照射が可能な施設の地域性を考慮した適切な集約化が必要と考えられた。(著者抄録)
• 局所進行上咽頭癌におけるadaptive radiotherapyに関する検討

  打浪雄介, 安田耕一, 藤田祥博, 高橋周平, 大塚愛美, 田口純, 清水康, 加納里志, 本間明宏, 青山英史  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  35th-  2022
• 再照射 小児がんに対する陽子線再照射

  橋本 孝之, 森 崇, 西岡 健太郎, 打浪 雄介, 安田 耕一, 木下 留美子, 田口 大志, 加藤 徳雄, 清水 伸一, 青山 英史  日本小児血液・がん学会雑誌  58-  (2)  89  -93  2021/08  

  陽子線治療は通常のX線による放射線治療に比べて線量集中性に優れ,標的への線量を保ったまま周囲の正常組織線量を低減することで,小児がん患者の急性期並びに晩期有害事象の軽減が可能である.2016年4月からは20歳未満の限局性固形悪性腫瘍に対する根治的な陽子線照射が保険適応となり,各施設で小児がんの陽子線治療実施件数が増加傾向にある.局所領域再発に対する再照射は,腫瘍進行抑制・症状緩和と,時に治癒や長期の腫瘍制御による健康状態・QOLの維持をもたらす可能性がある.小児患者に対する再照射における重要臓器・器官の累積耐容線量や安全性は確立していないが,中枢神経腫瘍に対する陽子線再照射により,有害事象の発生を抑えた良好な治療成績が報告されている.今後,小児がん再発の治療選択肢における陽子線再照射の有用性については,前向き臨床試験での評価が必要と考える.(著者抄録)
• Proton beam therapy for reirradiation in pediatric cancer

  橋本孝之, 森崇, 西岡健太郎, 打浪雄介, 安田耕一, 木下留美子, 田口大志, 加藤徳雄, 清水伸一, 青山英史  日本小児血液・がん学会雑誌(Web)  58-  (2)  2021
• 肝細胞癌陽子線治療前MRIにおけるばらつきの小さいADC値指標の検討:治療効果予測に向けた前段階の研究

  藤田祥博, 加藤徳雄, 田口大志, 打浪雄介, 西岡健太郎, 森崇, 湊川英樹, 安田耕一, 清水伸一, 青山英史  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  34th-  2021
• 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
• 膵癌に対するS-1併用術前化学放射線療法(S-1併用NACRT)の治療成績

  小泉富基, 加藤徳雄, 中村透, 川本泰之, 田口大志, 打浪雄介, 清水伸一, 青山英史  日本医学放射線学会秋季臨床大会抄録集  56th-  S103  -S103  2020
• 胸部食道扁平上皮癌に対する術前補助化学療法・根治切除術および根治的化学放射線療法についての後方視的検討

  中積 宏之, 村中 徹人, 川本 泰之, 小松 嘉人, 結城 敏志, 中野 真太郎, 澤田 憲太郎, 坂本 直哉, 打浪 雄介, 田口 大志, 白土 博樹, 海老原 裕磨, 七戸 俊明, 平野 聡  北海道医学雑誌  94-  (2)  120  -121  2019/11
• 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]
  
• 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
• 聴神経鞘腫に対する定位放射線治療後に腫瘍内出血を来した2例

  打浪 雄介, 鬼丸 力也, 白土 博樹, 森 崇, 山口 秀, 寺坂 俊介, 小林 浩之, 藤原 圭志, 本間 明宏  Japanese Journal of Radiology  36-  (Suppl.)  8  -8  2018/02
• 乳癌眼窩尖部転移により視力低下をきたし、放射線治療により著明な改善を認めた1例

  湊川 英樹, 安田 耕一, 打浪 雄介, 白土 博樹, 土屋 和彦, 加藤 徳雄, 木下 留美子, 石田 直子, 山下 啓子, 石嶋 漢  Japanese Journal of Radiology  36-  (Suppl.)  11  -11  2018/02
• Stereotactic Body Radiation Therapy Using a Real-time Tumor-Tracking Radiation Therapy System for Hepatocellular Carcinomas

  Y. Uchinami, N. Katoh, D. Abo, K. Harada, T. Inoue, H. Taguchi, R. Onimaru, S. Shimizu, Y. Sakuhara, K. Ogawa, T. Kamiyama, H. Shirato  INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS  96-  (2)  E155  -E155  2016/10  [Not refereed][Not invited]
  
• Microballoon catheter併用で瘤内塞栓を施行した腎動脈瘤の2例

  吉野 裕紀, 阿保 大介, 曽山 武士, 打浪 雄介, 高橋 文也, 作原 祐介, 工藤 與亮  Japanese Journal of Radiology  34-  (Suppl.)  4  -4  2016/02
• Microballoon catheterを用いたwedge techniqueによるNBCA塞栓術の初期経験 豚動脈を用いた実行可能性の検討

  阿保 大介, 高橋 文也, 吉野 裕紀, 打浪 雄介, 曽山 武士, 作原 祐介, 工藤 與亮  Japanese Journal of Radiology  34-  (Suppl.)  4  -4  2016/02
• Histopathological analysis of uterine endometrial adenocarcinoma in Sapporo City General Hospital-Analysis of the relationship between adenomyosis and myometrial invasion in uterine endometrial adenocarcinoma

  打浪雄介, 白枝友子, 石井保志, 秋元真祐子, 秋元真祐子, 伊丹弘恵, 柳内充, 辻隆裕, 深澤雄一郎, 晴山仁志  市立札幌病院医誌  74-  (1)  49  -54  2014/10  

  当院の病理診断レポートのデータベースを用いて、2008年1月から2014年2月までに当院で子宮内膜腺癌に対して子宮全摘術を施行された147例のうち、子宮内同時多発1例を除外した146例について検討を行った。FIGO分類II期の症例では、I期と比較して有意に組織グレードが高く、1/2以上の筋層浸潤をきたす割合が高かった。次に子宮内膜腺癌のうちI期にとどまる117例についての解析では、腺筋症の有無で1/2以上の筋層浸潤をきたす割合に有意差は認められなかった。さらに組織グレードごとにG1群、G2群に分類し同様の解析を行ったが、有意差は認められなかった。当院の子宮内膜腺癌の検討では、子宮腺筋症の有無は1/2以上の筋層浸潤のリスクにはならないと考えられた。(著者抄録)
• S状結腸癌多発肝転移術後のMRSA敗血症軽快後に脾破裂を発症した1例

  打浪 有可, 常俊 雄介, 中山 雅人, 山本 浩史, 樟本 賢首, 松下 通明  北海道外科雑誌  57-  (2)  178  -179  2012/12
• 癌幹細胞は自らのTGF-βによってEMTを起こし浸潤型非癌幹細胞に分化する(The role of TGF-beta-dependent EMT for the differentiation of cancer stem cells into invasive non-cancer stem cells)

  岩澤 久美子, 茶本 健司, 打浪 雄介, 角田 健太郎, 脇田 大功, 大栗 敬幸, 北村 秀光, 西村 孝司  日本癌学会総会記事  68回-  213  -213  2009/08
• 免疫逃避機構 癌幹細胞による免疫抑制機構の解明 CD133+癌幹細胞に高発現するPAuは活性型TGF-β産生促進を介してTregを誘導する

  茶本 健司, 脇田 大功, 大栗 敬幸, 打浪 雄介, 岩澤 久美子, 角田 健太郎, 北村 秀光, 西村 孝司  日本がん免疫学会総会プログラム・抄録集  13回-  103  -103  2009/06
• Treg誘導を介した癌幹細胞の免疫抑制機構の解明(A crucial role of cancer stem cell for the regulation of immunosuppressive tumor escape via Treg induction)

  茶本 健司, 脇田 大功, 成田 義規, 大栗 敬幸, 打浪 雄介, 富樫 裕二, 北村 秀光, 西村 孝司  日本癌学会総会記事  67回-  488  -488  2008/09

Research Projects

• MR画像誘導陽子線治療システムおよび磁場下の治療計画・検証技法に関する基盤開発

  日本学術振興会：科学研究費助成事業

  Date (from‐to) : 2024/04 -2028/03 

  Author : 松浦 妙子, 宮本 直樹, 打浪 雄介, 高尾 聖心, 陳 叶, 橋本 孝之, 栗山 靖敏, 加藤 徳雄
• 膵臓がんの根治を目指した適応陽子線治療の確立

  武田科学振興財団：

  Date (from‐to) : 2023/08 -2028/03
• 膵がん・肝がんにおける治療成績向上と有害事象低減を目指した適応陽子線治療の確立

  日本学術振興会：科学研究費助成事業 若手研究

  Date (from‐to) : 2023/04 -2027/03 

  Author : 打浪 雄介
• EOB-MRIを用いた放射線治療後の肝機能予測モデルの確立

  日本医学放射線学会Bayer研究助成金：

  Date (from‐to) : 2022 -2023
• 陽子線治療における消化管の有害事象低減を目指した消化管運動の統合的解析と予測モデルの確立

  バイエル薬品アカデミックサポート：

  Date (from‐to) : 2022 -2023
• 5cm未満の原発性肝がんにおける陽子線治療の適切な症例選択に向けた研究

  公益社団法人日本放射線腫瘍学会2022・2023度研究課題：

  Date (from‐to) : 2022 -2023
• 肝胆膵領域での安全な陽子線治療を目指した胃・十二指腸の動きに関する基礎的検討

  秋山記念生命科学振興財団 2021年度研究助成（奨励）：

  Date (from‐to) : 2021 -2021