Development of less toxic radiotherapy using IMPT for head and neck cancer

• Project/Area Number: 19K08088
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Hokkaido University
• Principal Investigator: Yasuda Koichi 北海道大学, 大学病院, 助教 (00431362)
• Co-Investigator(Kenkyū-buntansha): 加納 里志 北海道大学, 大学病院, 講師 (00374421) ; 水町 貴諭 北海道大学, 医学研究院, 客員研究員 (00507577) ; 高尾 聖心 北海道大学, 大学病院, 助教 (10614216) ; 田村 昌也 北海道大学, 大学病院, 助教 (40504775)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: IMPT / 陽子線治療 / 頭頸部癌 / 強度変調陽子線治療

Outline of Research at the Start

頭頸部癌の放射線治療は、副作用のために患者に我慢を強いる「辛い」治療となっている。近年発展したスポットスキャニングIMPT（強度変調陽子線治療、intensity-modulated proton therapy）を用いて線量を細かく制御することにより、腫瘍の線量を下げることなく、副作用の原因となる皮膚、唾液腺、舌、粘膜の正常臓器線量を全て大幅に低減させ、患者にとって「辛くない」頭頸部癌放射線治療法を確立することを目的とする。
頭頸部領域の様々な癌で、皮膚炎、口渇、味覚障害、粘膜炎を低減させたスポットスキャニングIMPTが実施可能であることをシミュレーションにて示し、汎用性のある技術を開発する。

Outline of Final Research Achievements

DVH analysis, development of the NTCP model and establishment of indicators for radiation therapy planning to reduce adverse effects such as dermatitis, dry mouth, dysgeusia, mucositis and dysphagia were performed. A methodology was established to objectively demonstrate a lower probability of adverse effects. Comparisons using the NTCP models and attempts to assess the quality of the radiation therapy plan while predicting the probability of adverse effects were initiated in clinical practice. A quality-of-life survey was conducted to objectively identify the 'pain' felt by patients. A comparison of actual adverse effects between IMPT and IMRT showed that dysgeusia was lower with IMPT, but did not show a statistically significant difference. Dysphagia due to mucositis was significantly lower with IMPT. At 6 months after radiation therapy, dysgeusia, dysphagia and dry mouth were significantly lower with IMPT. These results suggest the potential benefits of spot-scanning IMPT.

Academic Significance and Societal Importance of the Research Achievements

頭頸部癌に対する放射線治療は、近年IMRTなどの技術開発があるものの、未だに辛い副作用を患者さんに強いている。本研究は最先端放射線治療の一つであるスポットスキャニングIMPTの技術を用いてその副作用を低減させる試みである。いくつかの副作用やその回復においてスポットスキャニングIMPTの利点が示され、その有用性が示唆される結果である。最先端放射線治療の技術開発という点で学術的な価値を持つとともに、患者のQOLをできるだけ維持した癌治療法開発という点で、社会に広く利益をもたらしうる研究と考えられる。

Research Products

• [Journal Article] Detailed analysis of failure patterns using deformable image registration in hypopharyngeal cancer patients treated with sequential boost intensity-modulated radiotherapy. (2023)
  • Author(s): Otsuka M, Yasuda K, Uchinami Y, Tsushima N, Suzuki T, Kano S, Suzuki R, Miyamoto N, Minatogawa H, Dekura Y, Mori T, Nishioka K, Taguchi J, Shimizu Y, Katoh N, Homma A, Aoyama H.
  • Journal Title: J Med Imaging Radiat Oncol. Volume: 67 Issue: 1 Pages: 98-110
  • DOI: 10.1111/1754-9485.13491
  • Peer Reviewed
• [Journal Article] Hyperfractionated intensity-modulated proton therapy for pharyngeal cancer with variable relative biological effectiveness: A simulation study. (2022)
  • Author(s): Kasamatsu K, Matsuura T, Yasuda K, Miyazaki K, Takao S, Tamura M, Otsuka M, Uchinami Y, Aoyama H.
  • Journal Title: Med Phys. Volume: 49 Issue: 12 Pages: 7815-7825
  • DOI: 10.1002/mp.16064
  • Peer Reviewed
• [Journal Article] Salvage surgery improves the treatment outcome of patients with residual/recurrent maxillary sinus cancer after superselective intra-arterial cisplatin infusion with concomitant radiation therapy (2021)
  • Author(s): Tsushima Nayuta、kano Satoshi、Suzuki Takayoshi、Idogawa Hiroshi、Yoshida Daisuke、Yasuda Koichi、Otsuka Manami、Aoyama Hidefumi、Homma Akihiro
  • Journal Title: European Archives of Oto-Rhino-Laryngology Volume: 279 Issue: 2 Pages: 899-905
  • DOI: 10.1007/s00405-021-06822-5
  • Peer Reviewed
• [Journal Article] Multiparametric Analysis of Tumor Morphological and Functional MR Parameters Potentially Predicts Local Failure in Pharynx Squamous Cell Carcinoma Patients (2021)
  • Author(s): Fujima Noriyuki、Shimizu Yukie、Yoshida Daisuke、Kano Satoshi、Mizumachi Takatsugu、Homma Akihiro、Yasuda Koichi、Onimaru Rikiya、Sakai Osamu、Kudo Kohsuke、Shirato Hiroki
  • Journal Title: The Journal of Medical Investigation Volume: 68 Issue: 3.4 Pages: 354-361
  • DOI: 10.2152/jmi.68.354
  • NAID: 130008115660
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prediction of the local treatment outcome in patients with oropharyngeal squamous cell carcinoma using deep learning analysis of pretreatment FDG-PET images (2021)
  • Author(s): Fujima Noriyuki、Andreu-Arasa V. Carlota、Meibom Sara K.、Mercier Gustavo A.、Truong Minh Tam、Hirata Kenji、Yasuda Koichi、Kano Satoshi、Homma Akihiro、Kudo Kohsuke、Sakai Osamu
  • Journal Title: BMC Cancer Volume: 21 Issue: 1 Pages: 900-900
  • DOI: 10.1186/s12885-021-08599-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Predictors of the need for prophylactic percutaneous endoscopic gastrostomy in head and neck cancer patients treated with concurrent chemoradiotherapy (2021)
  • Author(s): Kano Satoshi、Tsushima Nayuta、Suzuki Takayoshi、Hamada Seijiro、Yokokawa Taizo、Idogawa Hiroshi、Yasuda Koichi、Minatogawa Hideki、Dekura Yasuhiro、Aoyama Hidefumi、Homma Akihiro
  • Journal Title: International Journal of Clinical Oncology Volume: 26 Issue: 7 Pages: 1179-1187
  • DOI: 10.1007/s10147-021-01889-w
• [Journal Article] Potential benefits of adaptive intensity-modulated proton therapy in nasopharyngeal carcinomas. (2021)
  • Author(s): Minatogawa H, Yasuda K, Dekura Y, Takao S, Matsuura T, Yoshimura T, Suzuki R, Yokota I, Fujima N, Onimaru R, Shimizu S, Aoyama H, Shirato H.
  • Journal Title: Journal of Applied Clinical Medical Physics Volume: 22 Issue: 1 Pages: 174-183
  • DOI: 10.1002/acm2.13128
  • Peer Reviewed / Open Access
• [Journal Article] SMARCB1欠損篩骨洞癌に対する強度変調陽子線治療：症例報告と文献レビュー (2021)
  • Author(s): 宮﨑智彦、安田耕一、志藤元泰、小泉富基、藤田祥博、高橋周平、湊川英樹、大塚愛美、加藤徳雄、清水伸一、青山英史.
  • Journal Title: 北海道放射線医学雑誌 Volume: 1 Pages: 1-6
  • Peer Reviewed
• [Journal Article] Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients (2020)
  • Author(s): Yasuda K, Minatogawa H, Dekura Y, Takao S, Tamura M, Tsushima N, Suzuki T, Kano S, Mizumachi T, Mori T, Nishioka K, Shido M, Katoh N, Taguchi H, Fujima N, Onimaru R, Yokota I, Kobashi K, Shimizu S, Homma A, Shirato H, Aoyama H.
  • Journal Title: Journal of Radiation Research Volume: 62 Issue: 2 Pages: 329-337
  • DOI: 10.1093/jrr/rraa130
  • Peer Reviewed / Open Access
• [Journal Article] Machine-Learning-Based Prediction of Treatment Outcomes Using MR Imaging-Derived Quantitative Tumor Information in Patients with Sinonasal Squamous Cell Carcinomas: A Preliminary Study. (2019)
  • Author(s): Fujima N, Shimizu Y, Yoshida D, Kano S, Mizumachi T, Homma A, Yasuda K, Onimaru R, Sakai O, Kudo K, Shirato H
  • Journal Title: Cancers Volume: 11 Issue: 6 Pages: 800-800
  • DOI: 10.3390/cancers11060800
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with intensity‐modulated radiotherapy (2019)
  • Author(s): Uchinami Yusuke、Suzuki Ryusuke、Katoh Norio、Taguchi Hiroshi、Yasuda Koichi、Miyamoto Naoki、Ito Yoichi M.、Shimizu Shinichi、Shirato Hiroki
  • Journal Title: Journal of Applied Clinical Medical Physics Volume: 20 Issue: 8 Pages: 78-86
  • DOI: 10.1002/acm2.12681
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of treatment process time for real‐time‐image gated‐spot‐scanning proton‐beam therapy (RGPT) system (2019)
  • Author(s): Yoshimura Takaaki、Shimizu Shinichi、Hashimoto Takayuki、Nishioka Kentaro、Katoh Norio、Inoue Tetsuya、Taguchi Hiroshi、Yasuda Koichi、Matsuura Taeko、Takao Seishin、Tamura Masaya、Ito Yoichi M.、Matsuo Yuto、Tamura Hiroshi、Horita Kenji、Umegaki Kikuo、Shirato Hiroki
  • Journal Title: Journal of Applied Clinical Medical Physics Volume: 21 Issue: 2 Pages: 38-49
  • DOI: 10.1002/acm2.12804
  • Peer Reviewed / Open Access
• [Presentation] 上咽頭癌に対する強度変調陽子線治療の初期経験 (2022)
  • Author(s): 依田恵, 安田耕一, 打浪雄介, 西川昇, 志藤元泰, 宮﨑智彦, 高橋周平, 藤田祥博, 高尾聖心, 田村昌也, 田口純, 清水康, 加納里志, 本間明宏, 青山英史.
  • Organizer: 日本放射線腫瘍学会第35回学術大会
• [Presentation] 北海道大学病院における上咽頭癌治療 - 10年間（2011-2020年）のまとめ - (2022)
  • Author(s): 安田耕一, 打浪雄介, 宮﨑智彦, 藤田祥博, 西川昇, 志藤元泰, 高橋周平, 田口純, 鈴木崇祥, 対馬那由多, 加納里志, 出倉康裕, 大塚愛美, 湊川英樹, 長谷川雅一, 土屋和彦, 鬼丸力也, 清水康, 本間明宏, 青山英史.
  • Organizer: 第26回北日本頭頸部癌治療研究会
• [Presentation] Radiotherapy Strategy for H＆N cancer in Japan (2022)
  • Author(s): Yasuda K
  • Organizer: The 9th GCB Biomedical Science and Engineering Symposium
  • Int'l Joint Research
• [Presentation] 高齢者頭頸部癌の放射線治療 (2022)
  • Author(s): 安田耕一
  • Organizer: 第46回日本頭頸部癌学会
  • Invited
• [Presentation] 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 (2022)
  • Author(s): 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.
  • Organizer: 第46回日本頭頸部癌学会
• [Presentation] 上咽頭癌の放射線治療 (2022)
  • Author(s): 安田耕一
  • Organizer: 第81回日本医学放射線学会総会
  • Invited
• [Presentation] Preliminary Results of Proton Beam Therapy (PBT) for Rare Head and Neck Tumors. (2021)
  • Author(s): Koichi Yasuda, Hideki Minatogawa, Yasuhiro Dekura, Seishin Takao, Masaya Tamura, Nayuta Tsushima, Satoshi Kano, Shinichi Shimizu, Akihiro Homma, Hidefumi Aoyama.
  • Organizer: The 80th Annual Meeting of the Japan Radiological Society.
• [Presentation] 咽喉頭扁平上皮癌IMRTの照射中における線量分布変化に関する解析. (2021)
  • Author(s): 安田耕一、打浪雄介、湊川英樹、小泉富基、大塚愛美、藤田祥博、井戸川寛志、鈴木崇祥、対馬那由多、加納里志、本間明宏.
  • Organizer: 第45回日本頭頸部癌学会.
• [Presentation] 頭頸部がんへの陽子線治療の立場から (2020)
  • Author(s): 安田耕一
  • Organizer: 日本放射線腫瘍学会第33回学術大会
  • Invited
• [Presentation] 上・中・下咽頭癌に対する陽子線治療の初期経験 (2020)
  • Author(s): 安田耕一, 湊川英樹, 出倉康裕, 対馬那由多, 鈴木崇祥, 加納里志, 鬼丸力也, 清水伸一, 本間明宏, 青山英史.
  • Organizer: 第44回日本頭頸部癌学会
• [Presentation] 咽頭癌への陽子線治療 (Proton Beam Therapy for Pharyngeal Cancer) (2019)
  • Author(s): 安田耕一、湊川英樹、出倉康裕、高尾聖心、田村昌也、鬼丸力也、清水伸一、本間明宏、梅垣菊男、白土博樹.
  • Organizer: The 78th Annual Meeting of the Japan Radiological Society
• [Presentation] 強度変調X線治療および強度変調陽子線治療における皮膚炎と皮膚線量に関する検討. (2019)
  • Author(s): 安田耕一、湊川英樹、出倉康裕、対馬那由多、鈴木崇祥、加納里志、水町貴諭、鬼丸力也、清水伸一、本間明宏、白土博樹.
  • Organizer: 第43回日本頭頸部癌学会
• [Presentation] Clinical Usefulness of model-based approach (MBA) in Head and Neck Cancer. (2019)
  • Author(s): Koichi Yasuda
  • Organizer: The 7th GI-CoRE Medical Science and Engineering Symposium.
  • Int'l Joint Research / Invited
• [Presentation] 咽頭癌に対する強度変調陽子線治療の初期経験. (2019)
  • Author(s): 安田耕一, 湊川英樹, 出倉康裕, 高尾聖心, 田村昌也, 対馬那由多, 鈴木崇祥, 加納里志, 水町貴諭, 松尾勇斗, 鈴鹿正顕, 山野茂, 鬼丸力也, 清水伸一, 本間明宏, 白土博樹.
  • Organizer: 日本放射線腫瘍学会第32回学術大会