Basic research for clinical application of next generation multiparticle therapy

2017 Fiscal Year Annual Research Report

• Project/Area Number: 15H04901
• Research Institution: University of Tsukuba
• Principal Investigator: 櫻井 英幸 筑波大学, 医学医療系, 教授 (50235222)
• Co-Investigator(Kenkyū-buntansha): 沼尻 晴子 (橋井晴子) 筑波大学, 附属病院, 病院講師 (00712845) ; 水本 斉志 筑波大学, 医学医療系, 講師 (20512388) ; 奥村 敏之 筑波大学, 医学医療系, 准教授 (50241815) ; 大西 かよ子 筑波大学, 医学医療系, 講師 (60529832) ; 石川 仁 筑波大学, 医学医療系, 教授 (70344918) ; 松本 孔貴 筑波大学, 医学医療系, 助教 (70510395)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 粒子線治療 / 放射線治療 / 陽子線治療 / 中性子捕捉療法

Outline of Annual Research Achievements

次世代型粒子線治療のための基盤研究として，以下の４つのテーマを実行し，基礎と臨床をつなぐトランスレーショナルリサーチを行った．「粒子線による高次の抗腫瘍効果発現メカニズムの解明」では，化学療法と陽子線治療の併用について検討した．3種類のがん細胞株を用いてX線と陽子線の化学療法シスプラチン併用による効果の違いについて検討し，線質により細胞死の形態が異なることを見いだした．また，子宮頸癌の病理組織をもちいて，既知の放射線感受性因子，特に転移浸潤に関する因子をタンパクレベルで解析を行い，予後因子を見いだした．「粒子線による正常組織障害発現メカニズムの解明」においては，コントロールとなるX線でのデータ取得後に，中性子捕捉療法での正常組織への影響の検討のため，チャイニーズハムスター由来細胞（SCCVII、V79）および悪性黒色細胞に対して、フリービーム照射条件で中性子線を照射し，生存率曲線から各スペクトルを有する中性子線のRBEを算出した．今後治験のための本格的な非臨床試験に向かう基盤データとなった．「BNCTの細胞死予測とサバイバルマッピングによる治癒率予測プログラム作成」では，治療計画装置をほぼ完成し，中性子捕捉療法実施施設へ配置し，データ入力が可能となった．今後は，各施設での治療計画の比較が可能となる．「基盤研究シーズから出てくる新しい臨床試験の立案」において，陽子線治療については，脳動静脈奇形に対する臨床試験の継続に加え，新たに保険適応となった小児腫瘍に対する全国的なレジストリを実施した．肝癌，肝内胆管癌，前立腺癌に対する臨床試験を開始した．中性子捕捉療法では，皮膚悪性腫瘍を対象として，医師主導治験を行うための臨床研究計画書がほぼ完成した．

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Radiotherapy for liver cancer (2018)
  • Author(s): Fukumitsu N, Okumura T, Sakurai H
  • Journal Title: Journal of General and Family Medicine Volume: in press Pages: 126-30
  • DOI: 10.1002/jgf2.19
• [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 Pages: 677-689
  • DOI: 10.1002/cam4.1350
  • Peer Reviewed
• [Journal Article] Validation of the physical and rbe-weighted dose estimator based on phits coupled with a microdosimetric kinetic model for proton therapy (2018)
  • Author(s): Takada K, Sato T, Kumada H, Koketsu J, Takei H, Sakurai H, Sakae T
  • Journal Title: J Radiat Res Volume: 59 Pages: 91-99
  • DOI: 10.1093/jrr/rrx057
  • Peer Reviewed / Open Access
• [Journal Article] Transurethral resection for botryoid bladder rhabdomyosarcoma (2018)
  • Author(s): Nakata M, Hishiki T, Sakurai H, Saito T, Terui K, Mitsunaga T, Komatsu S, Ochiai H, Hino M, Ando K, Chikaraishi K, Aoki T, Okunushi T, Honma S, Fugo K, Yoshida H
  • Journal Title: J Ped Surg Case Reports Volume: 28 Pages: 37-40
  • DOI: 10.1016/j.epsc.2017.09.009
  • Peer Reviewed
• [Journal Article] Comparison of rigid and deformable image registration accuracy of the liver during long-term transition after proton beam therapy (2017)
  • Author(s): Fukumitsu N, Terunuma T, Okumura T, Numajiri H, Murofushi K, Ohnishi K, Mizumoto M, Aihara T, Ishikawa H, Tsuboi K, Sakurai H
  • Journal Title: Imaging Med Volume: 9 Pages: 149-154
  • Peer Reviewed
• [Journal Article] A comparative study of dose distribution of pbt, 3d-crt and imrt for pediatric brain tumors (2017)
  • Author(s): Takizawa D, Mizumoto M, Yamamoto T, Oshiro Y, Fukushima H, Fukushima T, Terunuma T, Okumura T, Tsuboi K, Sakurai H
  • Journal Title: Radiat Oncol Volume: 12 Pages: 40-1-40
  • DOI: 10.1186/s13014-017-0775-2
  • Peer Reviewed / Open Access
• [Journal Article] Long-term single-institute experience with trimodal bladder-preserving therapy with proton beam therapy for muscle-invasive bladder cancer (2017)
  • Author(s): Takaoka EI, Miyazaki J, Ishikawa H, Kawai K, Kimura T, Ishitsuka R, Kojima T, Kanuma R, Takizawa D, Okumura T, Sakurai H, Nishiyama H
  • Journal Title: Jpn J Clin Oncol Volume: 47 Pages: 67-73
  • DOI: 10.1093/jjco/hyw151
  • Peer Reviewed / Open Access
• [Journal Article] Proton beam therapy for pediatric brain tumor (2017)
  • Author(s): Mizumoto M, Oshiro Y, Yamamoto T, Kohzuki H, Sakurai H
  • Journal Title: Neurol Med Chir (Tokyo) Volume: 57 Pages: 343-355
  • DOI: 10.2176/nmc.ra.2017-0003
  • Peer Reviewed
• [Journal Article] Analysis of repeated proton beam therapy for patients with hepatocellular carcinoma (2017)
  • Author(s): Oshiro Y, Mizumoto M, Okumura T, Fukuda K, Fukumitsu N, Abei M, Ishikawa H, Takizawa D, Sakurai H
  • Journal Title: Radiother Oncol Volume: 123 Pages: 240-245
  • DOI: 10.1016/j.radonc.2017.03.004
  • Peer Reviewed
• [Journal Article] Co-morbidity and quality of life in childhood cancer survivors treated with proton beam therapy (2017)
  • Author(s): Fukushima H, Fukushima T, Suzuki R, Iwabuchi A, Hidaka K, Masumoto K, Muroi A, Yamamoto T, Mizumoto M, Sakurai H, Sumazaki R
  • Journal Title: Pediatrics international : official journal of the Japan Pediatric Society Volume: 59 Pages: 1039-1045
  • DOI: 10.1111/ped.13323
  • Peer Reviewed
• [Journal Article] A retrospective study of late adverse events in proton beam therapy for prostate cancer (2017)
  • Author(s): Makishima H, Ishikawa H, Tanaka K, Mori Y, Mizumoto M, Ohnishi K, Aihara T, Fukumitsu N, Okumura T, Sakurai H
  • Journal Title: Molecular and clinical oncology Volume: 7 Pages: 547-552
  • DOI: 10.3892/mco.2017.1372
  • Peer Reviewed
• [Journal Article] Proton beam therapy for liver metastases from gastric cancer (2017)
  • Author(s): Fukumitsu N, Okumura T, Takizawa D, Numajiri H, Ohnishi K, Mizumoto M, Aihara T, Ishikawa H, Tsuboi K, Sakurai H
  • Journal Title: Radiat Res Volume: 58 Pages: 357-362
  • DOI: 10.1093/jrr/rrw102
  • Peer Reviewed / Open Access
• [Journal Article] Registration error of the liver CT using deformable image registration of MIM Maestro and Velocity AI (2017)
  • Author(s): Fukumitsu N, Nitta K, Terunuma T, Okumura T, Numajiri H, Oshiro Y, Ohnishi K, Mizumoto M, Aihara T, Ishikawa H, Tsuboi K, Sakurai H
  • Journal Title: BMC Med Imaging Volume: 17 Pages: 30
  • DOI: 10.1186/s12880-017-0202-z
  • Peer Reviewed
• [Journal Article] Long-term outcomes of proton beam therapy in patients with previously untreated hepatocellular carcinoma (2017)
  • Author(s): Fukuda K, Okumura T, Abei M, Fukumitsu N, Ishige K, Mizumoto M, Hasegawa N, Numajiri H, Ohnishi K, Ishikawa H, Tsuboi K, Sakurai H, Hyodo I
  • Journal Title: Cancer Sci Volume: 108 Pages: 497-503
  • DOI: 10.1111/cas.13145
  • Peer Reviewed / Open Access
• [Journal Article] Proton beam therapy for bone sarcomas of the skull base and spine: A retrospective nationwide multicenter study in japan (2017)
  • Author(s): Demizu Y, Mizumoto M, Onoe T, Nakamura N, Kikuchi Y, Shibata T, Okimoto T, Sakurai H, Akimoto T, Ono K, Daimon T, Murayama S
  • Journal Title: Cancer Sci Volume: 108 Pages: 972-977
  • DOI: 10.1111/cas.13192
  • Peer Reviewed / Open Access
• [Journal Article] Phase II study of proton beam therapy as a nonsurgical approach for mucosal melanoma of the nasal cavity or para-nasal sinuses (2017)
  • Author(s): Zenda S, Akimoto T, Mizumoto M, Hayashi R, Arahira S, Okumura T, Sakurai H
  • Journal Title: Radiother Oncol Volume: 118 Pages: 267-271
  • DOI: 10.1016/j.radonc.2015.10.025
  • Peer Reviewed / Open Access
• [Journal Article] Minimally Invasive Salvage Operations for Esophageal Cancer after Definitive Chemoradiotherapy (2017)
  • Author(s): Nakajima M, Kato H, Muroi H, Kikuchi M, Takahashi M, Yamaguchi S, Sasaki K, Ishikawa H, Sakurai H, Kuwano H
  • Journal Title: Digestion Volume: 97 Pages: 64-69
  • DOI: 10.1159/000484034
  • Peer Reviewed / Open Access
• [Journal Article] Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated x-ray therapy in randomly sampled pediatric cancer patients (2017)
  • Author(s): Tamura M, Sakurai H, Mizumoto M, Kamizawa S, Murayama S, Yamashita H, Takao S, Suzuki R, Shirato H, Ito YM
  • Journal Title: J Radiat Res Volume: 58 Pages: 363-371
  • DOI: 10.1093/jrr/rrw088
  • Peer Reviewed
• [Journal Article] 前立腺癌の陽子線治療 (2017)
  • Author(s): 石川仁, 三浦航星, 関野雄太, 石田俊樹, 馬場敬一郎, 森祐太郎, 田中圭一, 大西かよ子, 奥村敏之, 櫻井英幸
  • Journal Title: 臨床放射線/金原出版 Volume: 62 Pages: 1601-1611
• [Journal Article] 膀胱癌、腎癌に対する放射線治療 (2017)
  • Author(s): 石川仁, 田中圭一, 飯泉天志, 清水翔星, 奥村敏之, 木村友和, 西山博之, 櫻井英幸
  • Journal Title: 癌の臨床 Volume: 63 Pages: 173-180
• [Journal Article] 小児がんに対する陽子線治療 (2017)
  • Author(s): 中尾朋平, 水本斉志, 沼尻晴子, 瀧澤大地, 田中圭一, 斎藤高, 穂坂翔, 鈴木涼子, 福島紘子, 福島敬, 櫻井英幸
  • Journal Title: 小児科/金原出版 Volume: 58 Pages: 485-491
• [Journal Article] 悪性黒色腫 鼻・副鼻腔悪性黒色腫に対する陽子線治療 (2017)
  • Author(s): 太西かよ子、石川仁、粟飯原輝人、斎藤高、櫻井英幸
  • Journal Title: 頭頸部癌学 －診断と治療の最新研究動- Volume: 75 Pages: 556-560
• [Journal Article] 肝細胞癌の放射線治療 (2017)
  • Author(s): 福光延吉、奥村敏之、廣嶋悠一、三浦航星、櫻井英幸
  • Journal Title: 日本臨床 Volume: 75 Pages: 1251-1255
• [Journal Article] 陽子線治療の現状と展望 (2017)
  • Author(s): 石川仁, 田中圭一, 宮内大悟, 廣嶋悠一, 飯泉天志, 中村雅俊, 奥村敏之, 櫻井英幸
  • Journal Title: 泌尿器科 Volume: 30 Pages: 395-400
• [Presentation] Biological effect of clinical proton beams (2018)
  • Author(s): Matsumoto Y, Furusawa Y, Saito T, Sekino Y, Ando K, Sakae T, Ishikawa H, Tsuboi K, Sakurai H
  • Organizer: SRN2018
  • Int'l Joint Research
• [Presentation] 進行肝癌に対する粒子線治療の役割 (2018)
  • Author(s): 櫻井英幸, 奥村敏之, 福光延吉, 石川仁, 大西かよ子, 水本斉志, 室伏景子, 沼尻晴子, 斎藤高, 田中圭一, 三浦航星, 関野雄太, 宮内大悟, 飯泉天志, 坪井康次
  • Organizer: 第31回高精度放射線外部照射部会学術大会
  • Invited
• [Presentation] 局所進行膵癌に対する化学放射線治療の治療成績及び予後因子についての検討 (2018)
  • Author(s): 廣嶋悠一, 福光延吉, 沼尻晴子, 大西かよ子, 水本斉志, 粟飯原輝人, 石川仁, 奥村敏之, 坪井康次, 櫻井英幸
  • Organizer: 日本放射線外科学会第9回学術集会
• [Presentation] 粒子線治療の現状について －体制整備と保険収載化に向けて－ (2018)
  • Author(s): 石川仁, 櫻井英幸
  • Organizer: 日本放射線外科学会第9回学術大会
  • Invited
• [Presentation] 初発孤立性肝細胞癌の陽子線治療成績 (2018)
  • Author(s): 関野雄太, 奥村敏之, 福光延吉, 沼尻晴子, 大西かよ子, 水本斉志, 粟飯原輝人, 石川仁, 坪井康次, 櫻井英幸
  • Organizer: 日本放射線外科学会第9回学術集会
• [Presentation] A comparative study of the dose distribution of pbt, 3d-crt, and imrt for pediatric brain tumors (2017)
  • Author(s): Ishida T, Takizawa D, Numajiri H, Murofushi K, Ohnishi K, Mizumoto M, Fukumitsu N, Okumura T, Sakurai H
  • Organizer: 1st NTU-UT Radiation Oncology Joint Symposium
  • Int'l Joint Research
• [Presentation] Proton beam therapy for previously untreated solitary hepatocellular carcinoma of 5cm or less (2017)
  • Author(s): Sekino Y, Okumura T, Fukumitsu N, Numajiri H, Ohnishi K, Mizumoto M, Aihara T, Ishikawa H, Tsuboi K, Sakurai H
  • Organizer: The 5th Japan-Taiwan Radiation Oncology Symposium
  • Int'l Joint Research
• [Presentation] Proton beam therapy for advanced HCC (2017)
  • Author(s): Sakurai H, Okumura T, Fukumitsu N, Ishikawa H, Ohnishi K, Mizumoto M, Murofushi K, Numajiri H, Tsuboi K, Terunuma T, Yasuoka K, Kumada H, Sakae T
  • Organizer: The 2nd Myongji International Liver Symposium
  • Int'l Joint Research
• [Presentation] Up-to-date lecture in HBP 4 proton radiotherapy for liver cancer (2017)
  • Author(s): Sakurai H
  • Organizer: 6th A-PHPBA 29th JSHBPS
  • Int'l Joint Research / Invited
• [Presentation] From pioneering to driving proton therapy -proton beam therapy for pediatric patients (2017)
  • Author(s): Sakurai H
  • Organizer: PTCOG 56
  • Int'l Joint Research
• [Presentation] Current status and perspective for radiation therapy for liver tumor (2017)
  • Author(s): Sakurai H
  • Organizer: 日本医学放射線学会
  • Invited
• [Presentation] High-dose(74GyE) proton beam therapy with concurrent chemotherapy for stage iii non-small cell (2017)
  • Author(s): Ohnishi K, Okumura T, Ishikawa H, Oshiro Y, Mizumoto M, Numajiri H, Fukumitsu N, Aihara T, Tsuboi K, Sakurai H
  • Organizer: The 5th Japan-Taiwan Radiation Oncology Symposium
  • Int'l Joint Research
• [Presentation] A retrospective multi-institutional study of proton beam therapy (PBT) for head and neck cancer with non-squamous cell histologies (2017)
  • Author(s): Nakamura N, Akimoto T, Zenda S, Demizu Y, Okimoto T, Murayama S, Sakurai H, Nakamura T, Yamamoto K, Shirato H
  • Organizer: PTCOG 56
  • Int'l Joint Research
• [Presentation] Proton beam therapy for hepatocellular carcinoma with extensive portal vein tuomor yhrombosis (2017)
  • Author(s): Miura K, Okumura T, Fukumitsu N, Mizumoto M, Ishikawa H, Ohnishi K, Aihara T, Sakae T, Tsuboi K, Sakurai H
  • Organizer: PTCOG56
  • Int'l Joint Research
• [Presentation] Edema extent of glioblastoma determined the survival and progression pattern after concurrent chemoradiotherapy with proton beam (2017)
  • Author(s): Liang HKT, Mizumoto M, Yamamoto T, Takizawa D, Tanaka K, Aihara T, Okumura T, Ishikawa H, Sakurai H
  • Organizer: PTCOG 56
  • Int'l Joint Research
• [Presentation] Proton beam therapy for bone sarcomas of the skull base and spine: A retrospective nationwide multicenter study in japan (2017)
  • Author(s): Demizu Y, Mizumoto M, Onoe T, Akimoto T, Kikuchi Y, Shibata T, Okimoto T, Sakurai H, Murayama S, Shirato H
  • Organizer: The 5th Japan-Taiwan Radiation Oncology Symposium
  • Int'l Joint Research
• [Presentation] Proton beam therapy for bone sarcomas of the skull base and spine: A retrospective nationwide multicenter study in japan (2017)
  • Author(s): Demizu Y, Mizumoto M, Onoe T, Akimoto T, Kikuchi Y, Shibata T, Okimoto T, Sakurai H, Murayama S, Shirato H
  • Organizer: PTCOG56
  • Int'l Joint Research
• [Presentation] 放射線治療歴のある婦人科再発腫瘍に対する組織内照射の成績 (2017)
  • Author(s): 加沼玲子, 沼尻晴子, 大川綾子, 室伏景子, 水本斉志, 大西かよ子, 福光延吉, 粟飯原輝人, 石川仁, 奥村敏之, 櫻井英幸
  • Organizer: 日本放射線腫瘍学会小線源治療部会第17回学術大会
• [Presentation] 日本の粒子線治療の現状-保険診療、臨床試験、統一治療方針- (2017)
  • Author(s): 櫻井英幸
  • Organizer: 日本放射線腫瘍学会第回学術大会
  • Invited
• [Presentation] 肝癌に対する放射線治療の現状・将来 (2017)
  • Author(s): 櫻井英幸
  • Organizer: 第55回日本癌治療学会学術集会
  • Invited
• [Presentation] 1-3 小児・aya世代のがんの陽子線治療 (2017)
  • Author(s): 櫻井英幸
  • Organizer: 第19回放射線腫瘍学夏季セミナー
  • Invited
• [Presentation] 肝細胞癌に対する粒子線治療 (2017)
  • Author(s): 櫻井英幸
  • Organizer: 第15回日本臨牀腫瘍学会学術集会
  • Invited
• [Presentation] 小児・AYA世代の腫瘍に対する陽子線治療の現状と問題点 (2017)
  • Author(s): 櫻井英幸
  • Organizer: 第15回日本臨牀腫瘍学会学術集会
  • Invited
• [Book] がん・放射線療法2017 改定第7版 (2017)
  • Author(s): 櫻井英幸, 石川仁,室伏景子
  • Total Pages: 1255
  • Publisher: 学研メディカル秀潤社
  • ISBN: 978-4-7809-0943-2
• [Book] スタンダード小児がん手術 臓器別アプローチと手技のポイント (2017)
  • Author(s): 櫻井英幸, 水本斉志, 中尾朋平, 福島敬, ほか
  • Total Pages: 313
  • Publisher: メディカルビュー社
  • ISBN: 978-4-7583-0465-8
• [Book] Q&Aでスッキリわかる 前立腺癌 (2017)
  • Author(s): 石川仁、櫻井英幸
  • Total Pages: 244
  • Publisher: メディカルビュー社
  • ISBN: 978-4-7583-1267-7
• [Remarks] 筑波大学附属病院 放射線腫瘍科
  • URL: http://www.pmrc.tsukuba.ac.jp/radioncology/
• [Remarks] 陽子線医学利用研究センター
  • URL: http://www.pmrc.tsukuba.ac.jp/research/
• [Remarks] 筑波大学附属病院にて 陽子線治療をお考えの方へ
  • URL: http://www.pmrc.tsukuba.ac.jp/