Development of a practical radiosensitivity prediction method for clinical applications

• Project/Area Number: 18K07684
• 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: Sapporo Medical University
• Principal Investigator: Sakata Koh-ichi 札幌医科大学, 医学部, 教授 (10235153)
• Co-Investigator(Kenkyū-buntansha): 北川 未央 札幌医科大学, 医学部, 研究員 (30608922) ; 福島 悠希 札幌医科大学, 医学部, 助教 (60749787) ; 長谷川 智一 札幌医科大学, 医学部, 助教 (80631168) ; 土屋 高旭 札幌医科大学, 医学部, 助教 (90631169)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 放射線感受性 / 予測方法 / 免疫組織染色 / 腫瘍免疫 / 乳癌 / 再発 / 非相同末端結合修復 / 放射線治療 / 子宮頸癌 / 中咽頭癌 / 予後予測 / 人工ニューラルネットワーク

Outline of Final Research Achievements

Using biopsy and surgical specimens of breast and cervical cancers, we analyzed the correlation between various protein expressions and radiotherapy outcomes. Radiotherapy of cervical cancer increased the expression of PD-L1 in tumor cells, and there was a strong correlation between the expression of PD-L1 in tumor cells after radiotherapy and overall survival. This suggests that irradiation-induced immunological changes may affect the radiotherapy effect. In patients with early-stage breast cancer treated with postoperative radiotherapy, XRCC4 expression rates in tumor cells were significantly correlated with intra-breast recurrence. By type of recurrence, there was a correlation with XRCC4 expression in True recurrence. True recurrence may be due to the low radiosensitivity of tumor cells.

Academic Significance and Societal Importance of the Research Achievements

子宮頸癌の放射線治療は、各種腫瘍免疫関連蛋白の発現に影響を与えており、それらの蛋白発現と予後に有意な相関を認めた。また、放射線治療後の腫瘍細胞に発現するPD-L1と全生存期間の強い相関関係は、放射線治療によって引き起こされる免疫学的な変化が子宮頸癌の治療効果に影響していることを示唆する。早期乳癌術後照射症例において、XRCC4が高発現の乳癌については、線量増加によって照射野内乳房内再発を低減できる可能性が示唆する結果が得られた。
これらの結果は、汎用性のある実用的な放射線感受性予測法の開発や癌細胞の生物学的特性に応じた個別化した放射線治療の実現に、貢献する結果と考えられる。

Research Products

• [Journal Article] Evaluation of the urethral α/β ratio and tissue repair half-time for iodine-125 prostate brachytherapy with or without supplemental external beam radiotherapy. (2020)
  • Author(s): Gocho T, Hori M, Fukushima Y, Someya M, Kitagawa M, Hasegawa T, Tsuchiya T, Hareyama M, Takagi M, Hashimoto K, Masumori N, Sakata KI.
  • Journal Title: Brachytherapy Volume: Epub ahead of print Issue: 3 Pages: 290-297
  • DOI: 10.1016/j.brachy.2020.02.007
  • Peer Reviewed
• [Journal Article] Association between radiotherapy-induced alteration of programmed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy. (2020)
  • Author(s): Tsuchiya T, Someya M, Takada Y, Hasegawa T, Kitagawa M, Fukushima Y, Gocho T, Hori M, Nakata K, Hirohashi Y, Torigoe T, Saito T, Sakata KI.
  • Journal Title: Strahlenther Onkol. Volume: - Issue: 8 Pages: 725-735
  • DOI: 10.1007/s00066-019-01571-1
  • Peer Reviewed
• [Journal Article] Association between cancer immunity and treatment results in uterine cervical cancer patients treated with radiotherapy (2020)
  • Author(s): Someya Masanori、Tsuchiya Takaaki、Fukushima Yuki、Hasegawa Tomokazu、Takada Yu、Hori Masakazu、Miura Katsutoshi、Kitagawa Mio、Gocho Toshio、Hirohashi Yoshihiko、Torigoe Toshihiko、Iwasaki Masahiro、Matsuura Motoki、Saito Tsuyoshi、Sakata Koh-ichi
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 50 Issue: 11 Pages: 1290-1297
  • DOI: 10.1093/jjco/hyaa149
  • Peer Reviewed / Open Access
• [Journal Article] Influence of PD-L1 expression in immune cells on the response to radiation therapy in patients with oropharyngeal squamous cell carcinoma. (2018)
  • Author(s): Fukushima Y, Someya M, Nakata K, Hori M, Kitagawa M, Hasegawa T, Tsuchiya T, Gocho T, Ikeda H, Hirohashi Y, Torigoe T, Sugita S, Hasegawa T, Himi T, Sakata K.
  • Journal Title: Radiother Oncol. Volume: 129 Pages: 409-414
  • Peer Reviewed
• [Presentation] 根治放射線治療を行った進行期子宮頸癌症例における腫瘍免疫と予後との関連 (2020)
  • Author(s): 染谷正則、長谷川智一、土屋高旭、福島悠希、北川未央、堀正和、坂田耕一
  • Organizer: 第79回日本医学放射線学会総会
• [Presentation] HPV関連癌における腫瘍免疫と放射線治療効果との関係 (2020)
  • Author(s): 染谷正則、土屋高旭、福島悠希、廣橋良彦、鳥越俊彦、坂田耕一
  • Organizer: 第33回日本放射線腫瘍学会学術大会
  • Invited
• [Presentation] HPV関連癌における腫瘍免疫と放射線治療効果との関係 (2020)
  • Author(s): 染谷正則、土屋高旭、福島悠希、廣橋良彦、鳥越俊彦、坂田耕一
  • Organizer: 第56回日本医学放射線学会秋季大会
  • Invited
• [Presentation] 子宮頸癌術前照射症例を用いた放射線治療による腫瘍免疫の変化と予後の関連の検討 (2019)
  • Author(s): 土屋高旭，染谷正則，高田優，長谷川智一，北川未央，福島悠希，後町俊夫，堀正和，中田健生，廣橋良彦，鳥越俊彦，坂田耕一
  • Organizer: 日本放射線腫瘍学会第32回学術大会
• [Presentation] Influence of PD-L1 Expression in Immene Cells on the Response to Radiation Therapy in Patients with Oropharyngeal Squamous Cell Carcinoma. (2018)
  • Author(s): Fukushima Y, Someya M, Nakata K, Hori M, Kitagawa M, Hasegawa T, Tsuchiya T, Gocho T, Ikeda H, Hirohashi Y, Torigoe T, Sugita S, Hasegawa T, Himi T, Sakata K.
  • Organizer: 2018 ASTRO(American Society for Radiation Oncology) Annual Meeting
  • Int'l Joint Research
• [Presentation] 当院で腔内照射を施行した子宮頸癌の線量解析 (2018)
  • Author(s): 染谷正則、長谷川智一、土屋高旭、北川未央、後町敏夫、福島悠希、堀正和、中田健生、坂田耕一
  • Organizer: 日本放射線腫瘍学会第31回学術大会