Development of a therapeutic effect evaluation system that simultaneously considers the dose rate of proton beam irradiation and LET fluctuations

• Project/Area Number: 18K07621
• 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: Matsuura Taeko 北海道大学, 工学研究院, 准教授 (90590266)
• Co-Investigator(Kenkyū-buntansha): 平山 嵩祐 北海道大学, 医学研究院, 特任助教 (00769177) ; 安井 博宣 北海道大学, 獣医学研究院, 准教授 (10570228) ; 高尾 聖心 北海道大学, 大学病院, 助教 (10614216)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 陽子線生物効果 / 陽子線生物モデル / 亜致死損傷回復 / 陽子線生物 / LET

Outline of Final Research Achievements

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

Academic Significance and Societal Importance of the Research Achievements

近年の陽子線治療の進展として，物理的な照射精度の高度化に加え，生物線量分布の高精度化が重要視されている．これは，陽子線のLETの違いが治療効果に与える生物学的影響を考慮した治療を目指すものである．実際，治療成績に関する報告でも，LETと治療効果の相関が見られている．一方で，陽子線治療の高度化とともに，スキャニング法を用いた動きのある部位への照射の割合が増えており，また，寡分割治療への試みも始まっている．このような治療では，照射時間の延長によって治療効果が低下する可能性がある．本研究はこれらの効果を同時に考慮できるモデルを構築し，症例に対する効果予測を可能にした．

Research Products

• [Journal Article] Impact of a spatially dependent dose delivery time structure on the biological effectiveness of scanning proton therapy (2021)
  • Author(s): Kasamatsu Koki、Tanaka Sodai、Miyazaki Koichi、Takao Seishin、Miyamoto Naoki、Hirayama Shusuke、Nishioka Kentaro、Hashimoto Takayuki、Aoyama Hidefumi、Umegaki Kikuo、Matsuura Taeko
  • Journal Title: Medical Physics Volume: 49 Issue: 1 Pages: 702-713
  • DOI: 10.1002/mp.15367
  • Peer Reviewed / Open Access
• [Journal Article] The impact of dose delivery time on biological effectiveness in proton irradiation with various biological parameters (2020)
  • Author(s): Kasamatsu Koki、Matsuura Taeko、Tanaka Sodai、Takao Seishin、Miyamoto Naoki、Nam Jin‐Min、Shirato Hiroki、Shimizu Shinichi、Umegaki Kikuo
  • Journal Title: Medical Physics Volume: 47 Issue: 9 Pages: 4644-4655
  • DOI: 10.1002/mp.14381
  • Peer Reviewed / Open Access
• [Journal Article] Difference in LET‐based biological doses between IMPT optimization techniques: Robust and PTV‐based optimizations (2020)
  • Author(s): Hirayama Shusuke、Matsuura Taeko、Yasuda Koichi、Takao Seishin、Fujii Takaaki、Miyamoto Naoki、Umegaki Kikuo、Shimizu Shinichi
  • Journal Title: Journal of Applied Clinical Medical Physics Volume: - Issue: 4 Pages: 1-9
  • DOI: 10.1002/acm2.12844
  • Peer Reviewed / Open Access
• [Journal Article] Physical and biological impacts of collimator-scattered protons in spot-scanning proton therapy (2019)
  • Author(s): Ueno Koki、Matsuura Taeko、Hirayama Shusuke、Takao Seishin、Ueda Hideaki、Matsuo Yuto、Yoshimura Takaaki、Umegaki Kikuo
  • Journal Title: Journal of Applied Clinical Medical Physics Volume: 20 Issue: 7 Pages: 48-57
  • DOI: 10.1002/acm2.12653
  • Peer Reviewed / Open Access
• [Journal Article] A novel range-verification method using ionoacoustic wave generated from spherical gold markers for particle-beam therapy: a simulation study (2019)
  • Author(s): T. Takayanagi, T. Uesaka, M. Kitaoka, MB.Unlu, K.Umegaki, H. Shirato, L. Xing, T. Matsuura
  • Journal Title: Sci. Rep. Volume: 9 Issue: 1 Pages: 4011-4011
  • DOI: 10.1038/s41598-019-38889-w
  • NAID: 120006626576
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 北海道大学における陽子線医学物理研究の現状とこれから (2022)
  • Author(s): 松浦妙子
  • Organizer: 第123回 日本医学物理学会
  • Invited
• [Presentation] Influence of Sub-Lethal Damage Repair On Biological Effectiveness of Proton with the Consideration of Dose Delivery Time Structure in Scanning Proton Therapy (2021)
  • Author(s): K Kasamatsu, H Hosoi, S Tanaka, K Miyazaki, S Takao, N Miyamoto, K Umegaki, T Hashimoto, K Nishioka, S Shimizu, T Matsuura
  • Organizer: AAPM 63rd Annual Meeting & Exhibition
  • Int'l Joint Research
• [Presentation] Inclusion of Energy Layer Structure into an Evaluation of Dose Delivery Time Effect in Scanning Proton Therapy (2021)
  • Author(s): Koki Kasamatsu
  • Organizer: 日本医学物理学会
• [Presentation] SLD Repair Impact On Treatment Effectiveness of Proton Therapy with Various Cell Specific Parameters (2020)
  • Author(s): K Kasamatsu, T Matsuura, S Tanaka, K Umegaki
  • Organizer: Joint AAPM/COMP meeting
  • Int'l Joint Research
• [Presentation] Dependence of the Sub-Lethal Damage Repair Rate on LET in Proton Irradiation: An Initial Study (2019)
  • Author(s): Koki Kasamatsu, Memu Hosoda, Jin-Min Nam, Hironobu Yasui, Sodai Tanaka, Shusuke Hirayama, Naoki Miyamoto, Kikuo Umegaki, Hiroki Shirato, Taeko Matsuura
  • Organizer: 第118回日本医学物理学会学術大会
• [Presentation] An Investigation of Biological Impact Caused by Edge-Scattered Protons in Pencil Beam Scanning Proton Therapy (2018)
  • Author(s): K.Ueno, T. Matsuura, S. Takao, S. Hirayama, H. Ueda, Y. Matsuo, T. Yoshimura, S. Shimizu, K. Umegaki, H. Shirato
  • Organizer: AAPM 60th Annual Meeting
  • Int'l Joint Research
• [Presentation] A Study On the Influence of Changing the Motion Recognition Rate On the Dose Accuracy of (2018)
  • Author(s): T. Sodeta, T. Matsuura, S. Takao, S. Hirayama, T. Kanehira, N. Miyamoto, K. Nishioka, N. Kato, S. Shimizu, K. Umegaki, H. Shirato
  • Organizer: AAPM 60th Annual Meeting
  • Int'l Joint Research