Basic research of custom-made chemo heavy-ion radiotherapy based on EGFR expression difference for lung cancer

• Project/Area Number: 17K10490
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Saitama Medical University
• Principal Investigator: TAKAHASHI TAKEO 埼玉医科大学, 医学部, 教授 (70241883)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 重粒子線 / 抗癌剤 / 非小細胞肺癌 / 放射線治療 / アポトーシス / 増感効果 / セネッセンス / 化学療法 / 肺癌 / EGFR

Outline of Final Research Achievements

In addition to superb physical dose distribution, heavy-ion beam (carbon beam) has a high relative biological effectiveness against X-rays and is particularly effective for radioresistant tumors. A good local control effect has been reported for many radioresistant tumors such as head and neck non-squamous cell carcinoma and bone and soft tissue tumors, and some have been covered by insurance. In this study, we carried out a basic research of heavy-ion radiotherapy with chemotherapy for lung cancer using human lung cancer cells. It was clarified in a cultured cell experiment that the combined use of an anticancer drug used for lung cancer and heavy-ion beam irradiation enhances the cell killing effect and a synergistic effect is observed. The synergistic effect was significant with or without the EGFR mutation. The mechanism of synergistic effects involved early apoptosis after irradiation and senescence 3 days after irradiation.

Academic Significance and Societal Importance of the Research Achievements

重粒子線（炭素線）治療は難治性の放射線抵抗性腫瘍に対して有効であり、前立腺癌や骨軟部腫瘍、頭頸部癌（非扁平上皮癌）が保険適応となっている。物理学的線量分布と生物学的効果が極めて高い治療のため、局所効果が極めて良好で副作用の少ない治療が可能である。よって今後は死亡数の多く、局所制御効果が不良な局所進行肺癌に対しても、適応の拡大が期待される。標準的化学療法と重粒子線治療との併用の有効性が確立すれば、社会的な意義が高い。
本研究では培養細胞実験で重粒子線（炭素線）と殺細胞性抗癌剤の併用効果を確認し、相互作用のメカニズムを解明する意義の高い研究である。

Research Products

• [Journal Article] Evaluation of geometrical uncertainties on localized prostate radiotherapy of patients with bilateral metallic hip prostheses using 3D-CRT, IMRT and VMAT: A planning study (2020)
  • Author(s): Soda Rikana、Hatanaka Shogo、Hariu Masatsugu、Shimbo Munefumi、Yamano Takafumi、Nishimura Keiichiro、Kondo Shuichi、Utsumi Nobuko、Takahashi Takeo
  • Journal Title: Journal of X-Ray Science and Technology Volume: 28 Issue: 2 Pages: 243-254
  • DOI: 10.3233/xst-190598
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of a new commercial automated planning software for tangential breast intensity-modulated radiation therapy (2019)
  • Author(s): Mizuno Norifumi、Yamauchi Ryouhei、Kawamori Jiro、Itazawa Tomoko、Shimbo Munefumi、Nishimura Keiichiro、Yamano Takafumi、Hatanaka Shogo、Hariu Masatsugu、Takahashi Takeo
  • Journal Title: Radiological Physics and Technology Volume: 12 Issue: 3 Pages: 249-259
  • DOI: 10.1007/s12194-019-00515-9
  • Peer Reviewed / Open Access
• [Journal Article] Commissioning of the Mobius3D independent dose verification system for TomoTherapy (2019)
  • Author(s): Kodama Takumi、Saito Yoshihiro、Hatanaka Shogo、Hariu Masatsugu、Shimbo Munefumi、Takahashi Takeo
  • Journal Title: Journal of Applied Clinical Medical Physics Volume: 20 Issue: 5 Pages: 12-20
  • DOI: 10.1002/acm2.12572
  • Peer Reviewed / Open Access
• [Journal Article] Evaluation of Quality of Life and Psychological Response in Recurrent and Metastatic Tumors Treated with Palliative Radiotherapy. (2018)
  • Author(s): Yamano T, Takahashi T, Ueno S, Iigima Y, Nishimura K, Washizu K, Soda R, Utsumi N, Hondo M, Shimbo M, Hatanaka S, Haryu M
  • Journal Title: Journal of Cancer Therapy Volume: 9 Issue: 04 Pages: 351-361
  • DOI: 10.4236/jct.2018.94032
  • Peer Reviewed / Open Access
• [Journal Article] Simple index for validity of the evaluation point for dosimetric verification results of intensity-modulated radiation therapy using a Farmer-type ionization chamber. (2018)
  • Author(s): Hatanaka S, Shimbo M, Hariu M, Nakajima G, Todoroki K, Hosaka K, Watanabe T, Washizu K, Utsumi N, Yamano T, Nishimura K, Takahashi T.
  • Journal Title: Journal of X-Ray Science and Technology. Volume: 26 Issue: 3 Pages: 473-480
  • DOI: 10.3233/xst-17339
  • Peer Reviewed / Open Access
• [Journal Article] Retrospective analysis of multi-institutional, patient-specific treatment planning results of high-dose-rate intracavitary brachytherapy for gynecological cancer using V100. (2018)
  • Author(s): Watanabe T, Miyashita H, Notake R, Todoroki K, Nakajima G, Washizu K, Utsumi N, Hatanaka S, Hariu M, Yamano T, Nishimura K, Shimbo M, Takahashi T.
  • Journal Title: Australasian Physical & Engineering Sciences in Medicine. Volume: 41 Issue: 4 Pages: 1069-1074
  • DOI: 10.1007/s13246-018-0701-4
  • Peer Reviewed / Open Access
• [Journal Article] Palliative radiotherapy for breast cancer patients with skin invasion: a multi-institutional prospective observational study. (2018)
  • Author(s): Nakamura N, Kawamori J, Takahashi O, Shikama N, Sekiguchi K, Takahashi T, Kato S, Ogita M, Motegi A, Akimoto T.
  • Journal Title: Jpn J Clin Oncol Volume: 48 Issue: 6 Pages: 555-558
  • DOI: 10.1093/jjco/hyy054
  • Peer Reviewed / Open Access
• [Journal Article] Japanese expert panel meeting on the management of prostate cancer with bone metastases. (2018)
  • Author(s): Takahashi S, Kinuya S, Nonomura N, Shinohara N, Suzuki K, Suzuki H, Nakamura K, Satoh T, Tateishi U, Yoneda T, Horikoshi H, Igawa T, Kamei T, Koizumi M, Kosaka T, Matsubara N, Miyake H, Mizokami A, Mizowaki T, Nakamura N, Nozawa M, Takahashi T, Uemura H, Uemura M, Yokomizo A, Yoshimura A, Kakehi Y.
  • Journal Title: Oncol Ther. Volume: 6 Issue: 2 Pages: 157-171
  • DOI: 10.1007/s40487-018-0088-0
  • Peer Reviewed / Open Access
• [Journal Article] Prospective observational study of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck. (2017)
  • Author(s): Shirai K, Saitoh J, Musha A, Abe T, Kobayashi D, Takahashi T, Tamaki T, Kawamura H, Takayasu Y, Shino M, Toyoda M, Takahashi K, Hirato J, Yokoo S, Chikamatsu K, Ohno T, Nakano T
  • Journal Title: Cancer Science Volume: 108 Issue: 10 Pages: 2039-2044
  • DOI: 10.1111/cas.13325
  • Peer Reviewed / Open Access
• [Journal Article] 脳転移再発と放射線脳壊死の鑑別に苦慮し長期経過観察がなされた小細胞肺癌の2例 (2017)
  • Author(s): 山野貴史、鷲巣佳奈、西村敬一郎、畑中星吾、新保宗史、上野周一、清水裕次、渡部渉、長田久人、本田憲業、髙橋健夫
  • Journal Title: 断層映像研究会雑誌 Volume: 44 Pages: 1-6
  • Peer Reviewed / Open Access
• [Presentation] Hypofractionated stereotactic radiotherapy for inoperable arteriovenous malformations. (2019)
  • Author(s): Takahashi T, Yamano T, Nishimura K, Ueno S, Washizu K, Soda R, Kondo S, Utsumi N, Shimbo M, Hatanaka S, Hariu M
  • Organizer: ESTRO 38
  • Int'l Joint Research
• [Presentation] Prediction of preoperative hyperthermo-chemoradiotherapy response in locally advanced rectal cancer. (2018)
  • Author(s): 3.Takahashi T, Murata H, Shoji H, Onishi M, Takakusaki Y, Okonogi N, Okazaki A, Nishimura K, Yamano T, Ogoshi K, Nakano T.
  • Organizer: ESTRO 37
  • Int'l Joint Research
• [Presentation] Clinical outcome of hypofractionated stereotactic radiotherapy for inoperable skull base meningioma. (2018)
  • Author(s): Yamano T, Takahashi T, Nishimura K, Washizu K, Soda R, Kurosaki H, Utsumi N, Shimbo M, Hatanaka S, Hariu M.
  • Organizer: ESTRO meets Asia 2018
  • Int'l Joint Research
• [Presentation] Canges in Volume and Tumor Position during Stereotactic Body Radiotherapy of Lung. (2018)
  • Author(s): 1.Nishimura K, Shimbo M, Hatanaka S, Yamano T, Washizu K, Utsumi N, Soda R,
  • Organizer: JRS 77
• [Presentation] Therapeutic Efficacy of Hypofractionated Stereotactic Radiotherapy for Inoperable Arteriovenous Malformation. (2018)
  • Author(s): 2.Yamano T, Takahashi T, Nishimura K, Washizu K, Soda R, Utsumi N, Hatanaka S, Haryu M, Honda M, Shimbo M.
  • Organizer: JRS 77
• [Presentation] Evaluation of QOL and psychological response in patients treated with palliative radiotherapy. (2017)
  • Author(s): Takahashi T, Yamano T, Nishimura K, Utsumi N, Shimbo M, Hatanaka S, Ueno S, Iijima Y
  • Organizer: European Society for Radiotherapy & Oncology 36
  • Int'l Joint Research
• [Presentation] Palliative radiotherapy for breast cancer with skin invasion: A multi-institutional prospective observational study (2017)
  • Author(s): Nakamura N, Kawamori J, Takahashi O, Shikama N, Sekiguchi K, Takahashi T, Kato S, Ogita M, Haga C, Ito R, Nishimura K, Yamano T, Yoshida K, Motegi A, Akimoto T
  • Organizer: Annual Meeting of the American Society for Radiation Oncology
  • Int'l Joint Research
• [Presentation] Evaluation about quality of life and psychophysiological effect in patients treated with palliative radiotherapy for cancer recurrence of metastasis. (2017)
  • Author(s): Yamano T, Takahashi T, Nishimura K, Washizu K, Souda R, Ueno S, Shimbo M, Hatanaka S, Iijima Y
  • Organizer: The 76th annual meeting of the Japan radiological society
• [Presentation] Ventilation/perfusion ratio map by Dual-energy CT after Xenon inhalation and intravenous contrast media in patients with lobectomy. (2017)
  • Author(s): Honda N, Osada H, Watanabe W, Ohno H, Shimizu Y, Uehara T, Nishimura K, Yamano T, Takahashi T, Itoh T
  • Organizer: The 76th annual meeting of the Japan radiological society
• [Book] やさしくわかる放射線治療学 (2018)
  • Author(s): 1.日本放射線腫瘍学会教育委員会編集（髙橋健夫,他）
  • Total Pages: 209
  • Publisher: 秀潤社
  • ISBN: 9784780909753
• [Book] 血液内科グリーンノート (2017)
  • Author(s): 木崎昌弘、髙橋健夫
  • Total Pages: 492
  • Publisher: 中外医学社
• [Book] がん・放射線療法2017 (2017)
  • Author(s): 大西洋, 唐澤久美子, 唐澤克之, 髙橋健夫
  • Total Pages: 1255
  • Publisher: 秀潤社