Construction of clinical application by clarifying the biological basis of proton therapy of cutting edge scanning irradiation method

• Project/Area Number: 15H05675
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: Nagoya City University
• Principal Investigator: Iwata Hiromitsu 名古屋市立大学, 大学院医学研究科, 研究員 (40611588)
• Research Collaborator: SHIBAMOTO yuta ; NAKAJIMA koichiro ; HASHIMOTO shingo ; SUGIE chikao
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥23,660,000 (Direct Cost: ¥18,200,000、Indirect Cost: ¥5,460,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2016: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
• Keywords: 陽子線治療 / 放射線治療 / 放射線生物学 / スキャニング照射 / 陽子線 / スポットスキャニング / スポットスキャニング照射

Outline of Final Research Achievements

Proton therapy using scanning method combined with high-concentration cisplatin is considered to be very effective. It is suggested that the pattern of cell death and cell cycle may be different, which partly accounts for the difference in the combined effect. Considering the timing of the increase in G2 arrest, potent biological effects may be obtained by delivering proton irradiation during radiosensitive cell cycle phases in chemo-proton therapy. Proton beam irradiation combined with cisplatin resulted in different phenotype as compared with X rays and cisplatin.
The level of mRNA expressions after irradiation were different between proton and X-ray, especially in genes related to DNA repair. Differences of in vivo biological responses between proton and X-ray beams were found.

Academic Significance and Societal Importance of the Research Achievements

陽子線治療は、国内外でも広がり、臨床治療がさらに進む方向であるが、いまだに基礎生物学は未解明の問題が多く取り残されている。本研究で、X線と陽子線という線質の違いにより、細胞・個体に対して、様々な表現型の違いが認められ、照射単独では、細胞死という終着点である事象に違いがみられないものもあるが、併用療法によっては、差がみられるものもみられ、より至適な使用方法の開発が急務であることがわかった。このスキャニング照射法での基礎検討は世界でも類をみない検討であり、最先端のがん治療といわれる陽子線治療の礎となるものであり、今後将来の臨床応用の基礎的概念の確立に寄与する、非常に重要なものとなると考えられる。

Research Products

• [Journal Article] Patterns of proton therapy use in pediatric cancer management in 2016: An international survey (2019)
  • Author(s): Journy N, Indelicato DJ, Withrow DR, Akimoto T, Alapetite C, Araya M, Chang A, Chang JH, Chon B, Confer ME, Demizu Y, Dendale R, Doyen J, Ermoian R, Gurtner K, Hill-Kayser C, Iwata H, Kim JY, Kwok Y,... Shimizu S...
  • Journal Title: Radiotherapy and Oncology Volume: 132 Pages: 155-161
  • DOI: 10.1016/j.radonc.2018.10.022
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical outcomes of image-guided proton therapy for histologically confirmed stage I non-small cell lung cancer. (2018)
  • Author(s): Nakajima K, Iwata H, Ogino H, Hattori Y, Hashimoto S, Toshito T, Hayashi K, Akita K, Baba F, Nakamae K, Mizoe JE, Shibamoto Y.
  • Journal Title: Radiat Oncol. Volume: 13 Issue: 1 Pages: 199-199
  • DOI: 10.1186/s13014-018-1144-5
  • Peer Reviewed / Open Access
• [Journal Article] Long-term outcomes of proton therapy for prostate cancer in japan: A multi-institutional survey of the japanese radiation oncology study group (2018)
  • Author(s): Iwata H, Ishikawa H, Takagi M, Okimoto T, Murayama S, Akimoto T, Wada H, Arimura T, Sato Y, Araya M, Mizoe JE, Gosho M, Nakamura K, Shirato H, Sakurai H
  • Journal Title: Cancer Med Volume: 7 Issue: 3 Pages: 677-689
  • DOI: 10.1002/cam4.1350
  • NAID: 120007134358
  • Peer Reviewed / Open Access
• [Journal Article] Recovery from sublethal damage and potentially lethal damage. Proton beam irradiation vs. X-ray irradiation (2018)
  • Author(s): Shingo Hashimoto, Chikao Sugie, Hiromitsu Iwata, Hiroyuki Ogino, Chihiro Omachi, Keisuke Yasui, Jun-etsu Mizoe, Yuta Shibamoto
  • Journal Title: Strahlentherapie und Onkologie Volume: 194 Issue: 4 Pages: 343-351
  • DOI: 10.1007/s00066-017-1223-9
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Spot Scanning and Passive Scattering Proton Therapy: Relative Biological Effectiveness and Oxygen Enhancement Ratio in Cultured Cells (2016)
  • Author(s): Name of Authors Iwata H, Ogino H, Hashimoto S, Yamada M, Shibata H, Yasui K, Toshito T, Omachi C, Tatekawa K, Manabe Y, Mizoe JE, Shibamoto Y
  • Journal Title: International Journal of Radiation Oncology Biology Physics Volume: 95 Issue: 1 Pages: 95-102
  • DOI: 10.1016/j.ijrobp.2016.01.017
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Whole-pelvic radiotherapy with spot-scanning proton beams for uterine cervical cancer: a planning study. (2016)
  • Author(s): Hashimoto S, Shibamoto Y, Iwata H, Ogino H, Shibata H, Toshito T, Sugie C, Mizoe JE.
  • Journal Title: J Radiat Res. Volume: 57 Issue: 5 Pages: 524-532
  • DOI: 10.1093/jrr/rrw052
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] X線と陽子線の細胞・個体に対する表現型の違い (2019)
  • Author(s): 岩田 宏満、中嶌 晃一朗1,2、高 天翔、粂 和彦、平井 宗一、内藤 宗和、首藤 剛、大町 千尋、歳藤 利行、荻野 浩幸、芝本 雄
  • Organizer: 第21回菅原・大西記念癌治療増感研究シンポジウム
  • Invited
• [Presentation] 本邦における小児がんに対する陽子線治療の現状と今後 (2018)
  • Author(s): 岩田宏満 、荻野浩、伊藤康彦、村松幹司、亀井美智、橋本眞吾、中嶌晃一朗、高橋義行、前田尚子、芝本雄
  • Organizer: 第60回 日本小児血液・がん学会学術集会
  • Invited
• [Presentation] Effects of proton beams and X rays on the cell cycle of fluorescent ubiquitination-based cell cycle indicator (Fucci)-expressing cells (2018)
  • Author(s): Hiromitsu Iwata1,2*, Tsuyoshi Shuto3, Shunsuke Kamei3, Kohei Omachi3, Masataka Moriuchi3, Chihiro Omachi4, Toshiyuki Toshito4, Jumpei Nagayoshi, Koichiro Nakajima, Shingo Hashimoto, Hiroyuki Ogino, Jun-etsu Mizoe, Hirofumi Kai, Yuta Shibamoto
  • Organizer: the 60st American Society for Therapeutic Radiology and Oncology Annual Meeting
  • Int'l Joint Research
• [Presentation] Phase II study of image-guided proton therapy for solitary primary hepatocellular carcinoma with indication for standard treatment (2018)
  • Author(s): Hiromitsu Iwata1,2*, Hiroyuki Ogino1,2, Yukiko Hattori1,2, Shingo Hashimoto, Koichiro Nakajima, Kensuke Hayashi, Toshiyuki Toshito, Shigeru Sasaki, Fumiya Baba, Yoshiyuki Kuwabara, Kyoji Senoo, Jun-etsu Mizoe, Yuta Shibamoto
  • Organizer: the 60st American Society for Therapeutic Radiology and Oncology Annual Meeting
  • Int'l Joint Research
• [Presentation] Clinical and basic biological research of proton therapy at Nagoya Proton Therapy Center - 5 year’s experience and future prospects- (2018)
  • Author(s): Hiromitsu Iwata, Hiroyuki Ogino, Shingo Hashimoto, Koichiro Nakajima, Yukiko Hattori, Toshiyuki Toshito, Chihiro Omachi, Kensuke Hayashi, Jun-etsu Mizoe, Yuta Shibamoto
  • Organizer: The 2nd International Symposium for High Precision Radiotherapy
  • Int'l Joint Research / Invited
• [Presentation] Fucci発現細胞を用いた陽子線とX線の細胞周期に与える影響の検討 (2018)
  • Author(s): 岩田宏満、首藤剛、亀井竣輔、大町紘平、森内将貴、橋本眞吾、中嶌晃一朗、歳藤利行、大町千尋、永吉純平、荻野浩幸、甲斐広文、芝本雄太
  • Organizer: 日本放射線腫瘍学会第31回学術大会
• [Presentation] Fucci発現細胞を用いた陽子線治療の細胞周期に与える影響の検討：X線との比較 (2018)
  • Author(s): 岩田 宏満, 首藤剛, 亀井竣輔, 大町紘平, 森内将貴, 橋本 眞吾, 中嶌 晃一朗, 歳藤 利行, 大町 千尋, 永吉純平, 荻野 浩幸, 甲斐広文, 芝本 雄太
  • Organizer: 日本医学放射線学会第163回中部地方会
• [Presentation] Clinical and biological research at Nagoya Proton Therapy Center (2018)
  • Author(s): Hiromitsu Iwata, Shingo Hashimoto, Koichiro Nakajima, Yukiko Hattori, Toshiyuki Toshito, Chihiro Omachi, Kensuke Hayashi, Jumpei Nagayoshi,Jun-etsu Mizoe, Yuta Shibamoto, Hiroyuki Ogino
  • Organizer: the 8th Annual Meeting of ISRN
  • Int'l Joint Research / Invited
• [Presentation] 化学療法併用陽子線治療の生物学的検証 (2017)
  • Author(s): 岩田宏満、橋本眞吾、中嶌晃一朗、荻野浩幸、溝江純悦、歳藤利行、大町千尋、安井啓祐、柴田洋希、芝本雄太
  • Organizer: 日本医学放射線学会第161回中部地方会
  • Place of Presentation: プラザ洞津(三重県、津市)
  • Year and Date: 2017-02-25
• [Presentation] 陽子線治療の最前線-臨床と基礎の融合 (2017)
  • Author(s): 岩田宏満、橋本眞吾、荻野浩幸、歳藤利行、大町千尋、安井啓祐、柴田洋希、溝江純悦、芝本雄太
  • Organizer: 第19回癌増感研究シンポジウム
  • Place of Presentation: 奈良県文化会館(奈良県、奈良市)
  • Year and Date: 2017-02-03
  • Invited
• [Presentation] 名古屋陽子線治療センターにおける臨床・基礎研究 (2017)
  • Author(s): 岩田 宏満, 橋本 眞吾, 中嶌 晃一郎, 荻野 浩幸, 歳藤 利行, 大町 千尋, 林 建佑, 永吉 純平, 溝江 純悦, 芝本 雄太
  • Organizer: 第46回放射線による制癌シンホジウム
  • Invited
• [Presentation] Biological Effects of Proton and Photon Therapy in Combination with Cisplatin and Their Possible Mechanisms: an In Vitro Study (2017)
  • Author(s): Hiromitsu Iwata, Shingo Hashimoto, Koichiro Nakajima, Chihiro Omachi, Toshiyuki Toshito, Keisuke Yasui, Chikao Sugie, Hiroyuki Ogino, Jun-etsu Mizoe, Yuta Shibamoto
  • Organizer: the 59st American Society for Therapeutic Radiology and Oncology Annual Meeting
  • Int'l Joint Research
• [Presentation] Long-term Outcomes of Proton Therapy for Prostate Cancer in Japan: Retrospective Analysis of a Multi-institutional Survey (2017)
  • Author(s): Hiromitsu Iwata, Hitoshi Ishikawa, Masaru Takagi, Tomoaki Okimoto, higeyuki Murayama, Tetsuo Akimoto, Hitoshi Wada, Takeshi Arimura, Yoshitaka Sato, Masayuki Araya, Jun-etsu Mizoe, Hiroki Shirato, Hideyuki Sakurai
  • Organizer: the 59st American Society for Therapeutic Radiology and Oncology Annual Meeting
  • Int'l Joint Research
• [Presentation] 局所進行非小細胞肺癌に対するS-1とcisplatinの同時併用化学陽子線治療の第II相試験 (2017)
  • Author(s): 岩田宏満、秋田憲志、荻野浩幸、山羽悠介、國井英治、森祐太、吉原実鈴、堀内実、服部有希子、橋本眞吾、中嶌晃一朗、中前勝視、馬場二三八、芝本雄太、溝江純悦
  • Organizer: 日本放射線腫瘍学会第30回学術大会
• [Presentation] 化学療法併用陽子線治療の生物学的検証 (2017)
  • Author(s): 岩田宏満、橋本眞吾、中嶌晃一朗、歳藤利行、大町千尋、永吉純平、杉江愛生、荻野浩幸、溝江純悦、芝本雄太
  • Organizer: 日本放射線腫瘍学会第30回学術大会
• [Presentation] Phase II study of image-guided proton therapy for solitary primary hepatocellular carcinoma with indication for standard treatment (2016)
  • Author(s): Hiromitsu Iwata、Hiroyuki Ogino、Yukiko Hattori、Shingo Hashimoto、Koichiro Nakajima、Kensuke Hayashi、Toshiyuki Toshito、Shigeru Sasaki、Fumiya Baba、Yoshiyuki Kuwabara、 Kyoji Senoo、Yuta Shibamoto、Jun-etsu Mizoe
  • Organizer: 日本放射線腫瘍学会第29回学術大会
  • Place of Presentation: 国立京都国際会館(京都府、京都市)
  • Year and Date: 2016-11-25
• [Presentation] Tumor Regression Curve during and after Concurrent Chemotherapy and Proton Therapy for Unresectable Stage III Non-small Cell Lung Cancer: Comparison with Chemo-X-radiation Therapy (2016)
  • Author(s): Hiromitsu Iwata、Hiroyuki Ogino、Kenshi Akita、Natsuko Takama、Taro Murai、Kaoru Uchiyama、Katsushi Nakamae、Maho Iwana、Fumiya Baba、Yuta Shibamoto、Jun-etsu Mizoe
  • Organizer: the 58st American Society for Therapeutic Radiology and Oncology Annual Meeting
  • Place of Presentation: Boston Convention Center、Boston,、Massachusetts
  • Year and Date: 2016-09-25
  • Int'l Joint Research
• [Presentation] Proton Therapy for Non-squamous Cell Carcinomas of the Head and Neck: Planning Comparison among Spot Scanning Method with or without a Patient-specific Aperture System, Passive Scattering Method, and X-ray IMRT (2016)
  • Author(s): Hiromitsu Iwata、Toshiyuki Toshito、Kensuke Hayashi、Eiki Nikawa、Maho Yamada、Chihiro Omachi、Yukiko Hattori、Shingo Hashimoto、Hiroyuki Ogino、Yuta Shibamoto、Jun-etsu Mizoe
  • Organizer: the 58st American Society for Therapeutic Radiology and Oncology Annual Meeting
  • Place of Presentation: Boston Convention Center、Boston,、Massachusetts
  • Year and Date: 2016-09-25
  • Int'l Joint Research
• [Presentation] 陽子線Spot scanning照射の DNA損傷に対する直接効果とDistal endの生物効果の検討 (2016)
  • Author(s): 岩田宏満、橋本眞吾、荻野浩幸、歳藤利行、大町千尋、安井啓祐、柴田洋希、溝江純悦、芝本雄太
  • Organizer: 第18回癌増感研究シンポジウム
  • Place of Presentation: 奈良県文化会館(奈良県、奈良市)
  • Year and Date: 2016-02-05
• [Presentation] 陽子線Spot scanning照射の DNA損傷への直接効果とDistal endの生物効果の検討, (2016)
  • Author(s): 岩田宏満、橋本眞吾、歳藤利行、大町千尋、安井啓祐、柴田洋希、荻野浩幸、溝江純悦、芝本雄太
  • Organizer: 日本医学放射線学会第159回中部地方会
  • Place of Presentation: 名古屋市立大学(愛知県、名古屋市)
  • Year and Date: 2016-01-30
• [Presentation] 名古屋陽子線治療センターの現状 (2016)
  • Author(s): 岩田宏満、荻野浩幸、服部有希子、橋本眞吾、中嶌晃一朗 、中西未来子 、歳藤利行、林建佑、馬場二三八、山田真帆、芝本雄太、溝江純悦
  • Organizer: 日本医学放射線学会第160回中部地方会
  • Place of Presentation: 沖縄県市町村自治会館(沖縄県、那覇市)
  • Invited
• [Presentation] Tumor regression curve after concurrent chemo-proton therapy for unresectable stage III non-small cell lung cancer (2015)
  • Author(s): Hiromitsu Iwata, Hiroyuki Ogino1, Kenshi Akita, Yusuke Yamaba, Yukiko Hattori, Shingo Hashimoto, Katsushi Nakamae, Maho Yamada, Fumiya Baba, Yuta Shibamoto, Jun-etsu Mizoe
  • Organizer: 日本放射線腫瘍学会第28回学術大会
  • Place of Presentation: ベイシア文化ホール(群馬県、前橋市)
  • Year and Date: 2015-11-19
• [Presentation] 切除不能III期非小細胞肺癌に対する同時併用化学陽子線治療後の腫瘍退縮曲線 (2015)
  • Author(s): 岩田宏満、荻野浩幸、秋田憲志、山羽悠介 、服部有希子、橋本眞吾、中前勝視、馬場二三八、山田真帆、芝本雄太、溝江純悦
  • Organizer: 日本医学放射線学会第158回中部地方会
  • Place of Presentation: アクトシティ浜松(静岡県、浜松市)
  • Year and Date: 2015-07-04
• [Presentation] Oxygen enhancement ratios of proton and photon beams: comparison under identical biological conditions using clinically used machines, (2015)
  • Author(s): Hiromitsu Iwata, Hiroyuki Ogino, Shingo Hashimoto, Maho Yamada, Hiroki Shibata, Keisuke Yasui, Toshiyuki Toshito, Chihiro Omachi, Kotoha Tatekawa, Yoshihiko Manabe, Jun-etsu Mizoe, Yuta Shibamoto
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: 京都国際会議場(京都府、京都市左京区)
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Relative biological effectiveness of spot scanning proton therapy: comparison with passive scattering proton beam and X-ray irradiation (2015)
  • Author(s): Hiromitsu Iwata, Hiroyuki Ogino, Shingo Hashimoto, Maho Yamada, Keisuke Yasui, Hiroki Shibata, Toshiyuki Toshito, Chihiro Omachi, Jun-etsu Mizoe, Yuta Shibamoto
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: 京都国際会議場(京都府、京都市左京区)
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Presentation] Relative biological effectiveness of spot scanning proton therapy at the Nagoya Proton Therapy Center: comparison with passive scattering proton therapy and X-ray irradiation: in vitro study (2015)
  • Author(s): Hiromitsu Iwata, Hiroyuki Ogino, Shingo Hashimoto, Maho Yamada, Keisuke Yasui, Hiroki Shibata, Toshiyuki Toshito, Chihiro Omachi, Jun-etsu Mizoe, Yuta Shibamoto
  • Organizer: 54th Annual Conference of the Particle Therapy Co-Operative Group
  • Place of Presentation: San Diego、CA、USA、Manchester Grand Hyatt
  • Year and Date: 2015-05-18
  • Int'l Joint Research