Prediction of radiosensitivity of head and neck cancer using comprehensive genomic analysis

• Project/Area Number: 16K10411
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: National Cancer Center Japan
• Principal Investigator: Motegi Atsushi 国立研究開発法人国立がん研究センター, 東病院, 医員 (10433997)
• Co-Investigator(Kenkyū-buntansha): 秋元 哲夫 国立研究開発法人国立がん研究センター, 先端医療開発センター, 分野長 (10261851) ; 北條 秀博 国立研究開発法人国立がん研究センター, 東病院, 医員 (60638774)
• Research Collaborator: Tsuchihara Kazuya
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 頭頸部癌 / 放射感受性予測 / HPV / 網羅的遺伝子解析 / バイオマーカー / 放射線治療感受性 / HPV関連がん / 腫瘍特異的遺伝子 / 低侵襲バイオマーカー / 頭頸部扁平上皮癌 / 中咽頭癌 / p53 / cell free DNA / 放射線感受性 / 遺伝子変異 / 放射線 / 遺伝子 / 癌 / 治療感受性予測 / 網羅的解析

Outline of Final Research Achievements

We conducted a pilot study investigating the change of the amount of cancer-specific DNA throughout radiotherapy in saliva and blood of the patients with oropharyngeal cancer. HPV-related DNA in the saliva decreased significantly during the treatment period, and part of the patients whose saliva contained large amount of HPV-related DNA experienced recurrences. Head neck cancer-specific mutation, such as TP53 and NOTCH1, were also detectable in DNA extracted from saliva. With these preliminary findings, it will be more feasible to conduct studies to predict radiosensitivity of patients with head neck cancer using their saliva which contains cancer-specific DNA.

Academic Significance and Societal Importance of the Research Achievements

頭頸部領域のがんに対する放射線治療は、粘膜炎や口腔乾燥などの副作用が問題となる。

Research Products

• [Journal Article] Effect of 5-fluorouracil on cellular response to proton beam in esophageal cancer cell lines according to the position of spread-out Bragg peak. (2019)
  • Author(s): Hojo H, Dohmae T, Hotta K, Kageyama SI, Baba H, Kohno R, Motegi A, Tsuchihara K, Akimoto T.
  • Journal Title: Acta Oncol Volume: 58(4) Issue: 4 Pages: 475-482
  • DOI: 10.1080/0284186x.2018.1555373
  • Peer Reviewed
• [Journal Article] Impact of EGFR Mutation and ALK Translocation on Recurrence Pattern After Definitive Chemoradiotherapy for Inoperable Stage III Non-squamous Non-small-cell Lung Cancer. (2019)
  • Author(s): Nakamura M, Kageyama SI, Niho S, Okumura M, Hojo H, Motegi A, Nakamura N, Zenda S, Yoh K, Goto K, Akimoto T.
  • Journal Title: Clin Lung Cancer. Volume: printing Issue: 3 Pages: e256-e264
  • DOI: 10.1016/j.cllc.2019.02.021
  • Peer Reviewed
• [Journal Article] Radiotherapy increases plasma levels of tumoral cell-free DNA in non-small cell lung cancer patients. (2018)
  • Author(s): Kageyama S, Nihei K, Karasawa K,, Sawada T, Koizumi F, Yamaguchi S, Kato S, Hojo H, Motegi A, Tsuchihara K, Akimoto T.
  • Journal Title: Oncotarget Volume: 10;9(27) Issue: 27 Pages: 19368-19378
  • DOI: 10.18632/oncotarget.25053
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The 5-year outcomes of moderately hypofractionated radiotherapy (66 Gy in 22 fractions, 3 fractions per week) for localized prostate cancer: a retrospective study. (2018)
  • Author(s): Yaichiro Hashimoto, Atsushi Motegi, Tetsuo Akimoto, Norio Mitsuhashi, Junpei Iizuka, Kazunari Tanabe, Yuka Ishii, Sawa Kono, Sachiko Izumi, and Kumiko Karasawa
  • Journal Title: Int J Clin Oncol Volume: 23(1) Issue: 1 Pages: 165-172
  • DOI: 10.1007/s10147-017-1175-1
  • Peer Reviewed / Open Access
• [Journal Article] Long-term Clinical Results of Concurrent Chemoradiotherapy for Patients with Cervical Esophageal Squamous Cell Carcinoma. (2017)
  • Author(s): Atsuhiro Kumabe, Sadatomo Zenda, Atsushi Motegi, Masakatsu Onozawa, Naoki Nakamura, Takashi Kojima, Hiroyuki Daiko, Naoyuki Shigematsu, and Tetsuo Akimoto
  • Journal Title: Anticancer Res Volume: 37(9) Issue: 9 Pages: 5039-5044
  • DOI: 10.21873/anticanres.11919
  • Peer Reviewed / Open Access
• [Journal Article] Difference in the relative biological effectiveness and DNA damage repair processes in response to proton beam therapy according to the positions of the spread out Bragg peak. (2017)
  • Author(s): Hidehiro Hojo, Takeshi Dohmae, Kenji Hotta, Ryosuke Kohno, Atsushi Motegi, Atsushi Yagishita, Hideki Makinoshima, Katsuya Tsuchihara, and Tetsuo Akimoto
  • Journal Title: 10.1186/s13014-017-0849-1 Volume: 12(1) Issue: 1 Pages: 111-111
  • DOI: 10.1186/s13014-017-0849-1
  • Peer Reviewed / Open Access
• [Journal Article] Proton beam therapy for olfactory neuroblastoma. (2017)
  • Author(s): Naoki Nakamura, Sadamoto Zenda, Makoto Tahara, Susumu Okano, Ryuichi Hayashi, Hidehiro Hojo, Kenji Hotta, Satoe Kito, Atsushi Motegi, Satoko Arahira, Hidenobu Tachibana, and Tetsuo Akimoto
  • Journal Title: Radiother Oncol Volume: 122(3) Issue: 3 Pages: 368-372
  • DOI: 10.1016/j.radonc.2016.12.020
  • Peer Reviewed / Open Access
• [Journal Article] Patterns of failure after postoperative intensity-modulated radiotherapy for locally advanced and recurrent head and neck cancer. (2016)
  • Author(s): Ooishi M, Motegi A, Kawashima M, Arahira S, Zenda S, Nakamura N, Ariji T, Tokumaru S, Sakuraba M, Tahara M, Hayashi R, Akimoto T.
  • Journal Title: Jon J Clin Oncol Volume: 46 Issue: 10 Pages: 919-927
  • DOI: 10.1093/jjco/hyw095
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced non-small cell lung cancer. (2016)
  • Author(s): Wu CT, Motegi A, Motegi K, Hotta K, Kohno R, Tachibana H, Kumagai M, Hojo H, Niho S, Goto K, Akimoto T.
  • Journal Title: Jon J Clin Oncol Volume: - Issue: 11 Pages: 1008-1014
  • DOI: 10.1093/jjco/hyw108
  • Acknowledgement Compliant
• [Journal Article] Impact of prophylactic percutaneous endoscopic gastrostomy tube placement on treatment tolerance in head and neck cancer patients treated with cetuximab plus radiation. (2016)
  • Author(s): Yamazaki T, Enokida T, Wakasugi T, Zenda S, Motegi A, Araria S, Akimoto T, Tahara M.
  • Journal Title: Jon J Clin Oncol Volume: 46 Issue: 9 Pages: 825-31
  • DOI: 10.1093/jjco/hyw079
  • Peer Reviewed
• [Presentation] 頭頸部扁平上皮癌における低侵襲バイオマーカーの開発 (2018)
  • Author(s): 茂木厚
  • Organizer: 日本放射線腫瘍学会 生物部会
• [Presentation] 新病期分類(AJCC第8版) に基づく中咽頭癌の放射線治療成績の検討 (2018)
  • Author(s): 茂木厚、全田貞幹、中村直樹、田原信、林隆一、藤井誠志、秋元哲夫
  • Organizer: 第42回頭頸部癌学会
• [Presentation] 頭頸部癌における放射線治療感受性を検討するための低侵襲バイオマーカー(遺伝子解析を含む)の開発 (2018)
  • Author(s): 茂木 厚
  • Organizer: 日本放射線腫瘍学会 生物部会 制癌シンポジウム
  • Invited
• [Presentation] 頭頸部癌に対する放射線治療計画CTにおけるMARの有用性の検討 (2017)
  • Author(s): 茂木厚、良知寿哉、関谷浩太郎、全田貞幹、荒平聡子、中村直樹、小野澤正勝、林隆一、秋元哲夫
  • Organizer: 日本頭頸部癌学会学術集会
• [Presentation] 喉頭癌の放射線治療 (2016)
  • Author(s): 茂木厚
  • Organizer: 日本医学放射線学会秋季臨床大会
  • Place of Presentation: 京王プラザホテル (東京都新宿区)
  • Year and Date: 2016-09-16
  • Invited
• [Presentation] 切除可能下咽頭癌に対する根治的放射線治療の長期成績と晩期有害事象 (2016)
  • Author(s): 茂木厚、荒平聡子、全田貞幹、中村直樹、田原信、林隆一、秋元哲夫
  • Organizer: 日本頭頸部癌学会
  • Place of Presentation: ソニックシティ (埼玉県さいたま市)
  • Year and Date: 2016-06-09
  • Invited
• [Book] 小児・AYA世代の腫瘍に対する陽子線治療診療ガイドライン 2019年版 (2019)
  • Author(s): 日本放射線腫瘍学会 ／ 日本小児血液・がん学会
  • Total Pages: 92
  • Publisher: 金原出版
  • ISBN: 9784307071116
• [Book] 頭頸部がん薬物療法ガイダンス 第2版 (2018)
  • Author(s): 公益社団法人 日本臨床腫瘍学会
  • Total Pages: 128
  • Publisher: 金原出版
  • ISBN: 4307101944