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Prediction of response to neoadjuvant chemoradiotherapy in rectal cancer using liquid biopsy

Research Project

Project/Area Number 18K08635
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55020:Digestive surgery-related
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

UENO Masashi  公益財団法人がん研究会, 有明病院 大腸外科, 医員 (90574632)

Co-Investigator(Kenkyū-buntansha) 秋吉 高志  公益財団法人がん研究会, 有明病院 大腸外科, 副部長 (50625598)
前佛 均  公益財団法人がん研究会, がんプレシジョン医療研究センター リキッドバイオプシー診断開発プロジェクト, プロジェクトリーダー(部長クラス) (90372820)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords直腸癌 / 術前放射線化学療法 / リキッドバイオプシー / 術前化学放射線療法 / 治療効果予測
Outline of Final Research Achievements

We analyzed the clinical utility of circulating tumor DNA (ctDNA) of patients with locally advanced rectal cancer (LARC) to predict response to preoperative therapy and postoperative recurrence. A serial ctDNA analysis of 222 plasma samples from 85 patients with LARC was performed using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with over 240 hotspots. ctDNA was detected in 57.6% and 22.3% of samples at baseline and after preoperative treatment, respectively. Change in ctDNA was an independent predictor of complete response to preoperative therapy. In addition, postoperative ctDNA and carcinoembryonic antigen (CEA) were independent prognostic markers for risk of recurrence after surgery. Serial ctDNA analysis may offer clinically useful predictive and prognostic markers for response to preoperative therapy and postoperative recurrence in patients with LARC.

Academic Significance and Societal Importance of the Research Achievements

直腸癌治療におけるctDNAの臨床的有用性については、化学療法の治療効果や再発、抗がん剤抵抗性のモニタリングに関する報告がなされているが、術前治療効果予測におけるctDNAの有用性に関する報告は少ない。本研究によりctDNAが術前治療の効果予測に有用であることが示唆された。今後さらにデータを蓄積し、将来的には内視鏡やMRIなど現存する診断モダリティとctDNA解析を組み合わせることで、より正確に術前治療の効果を診断できるようになり、直腸切除を回避できる症例の増加につながることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2020 2019 2018

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (8 results)

  • [Journal Article] Serial circulating tumour DNA analysis for locally advanced rectal cancer treated with preoperative therapy: prediction of pathological response and postoperative recurrence2020

    • Author(s)
      Murahashi Satoshi、Akiyoshi Takashi、Sano Takeshi、Fukunaga Yosuke、Noda Tetsuo、Ueno Masashi、Zembutsu Hitoshi
    • Journal Title

      British Journal of Cancer

      Volume: - Issue: 5 Pages: 803-810

    • DOI

      10.1038/s41416-020-0941-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Radiomics Approach Outperforms Diameter Criteria for Predicting Pathological Lateral Lymph Node Metastasis After Neoadjuvant (Chemo)Radiotherapy in Advanced Low Rectal Cancer2020

    • Author(s)
      Nakanishi Ryota、Akiyoshi Takashi、Toda Shigeo、Murakami Yu、Taguchi Senzo、Oba Koji、Hanaoka Yutaka、Nagasaki Toshiya、Yamaguchi Tomohiro、Konishi Tsuyoshi、Matoba Shuichiro、Ueno Masashi、Fukunaga Yosuke、Kuroyanagi Hiroya
    • Journal Title

      Annals of Surgical Oncology

      Volume: 27 Issue: 11 Pages: 4273-4283

    • DOI

      10.1245/s10434-020-08974-w

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] T-cell complexity and density are associated with sensitivity to neoadjuvant chemoradiotherapy in patients with rectal cancer2020

    • Author(s)
      Akiyoshi T, Gotoh O, Tanaka N, Kiyotani K, Yamamoto N, Ueno M, Fukunaga Y, Mori S.
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: 70 Issue: 2 Pages: 509-518

    • DOI

      10.1007/s00262-020-02705-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunogenomic profiles associated with response to neoadjuvant chemoradiotherapy in patients with rectal cancer2019

    • Author(s)
      Akiyoshi T, Tanaka N, Kiyotani K, Gotoh O, Yamamoto N, Oba K, Fukunaga Y, Ueno M, Mori S
    • Journal Title

      Br J Surg

      Volume: 106 Issue: 10 Pages: 1381-1392

    • DOI

      10.1002/bjs.11179

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic value of metastatic lymph node regression grade after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer2019

    • Author(s)
      Tominaga T, Akiyoshi T, Yamamoto N, Oba K, Nagasaki T, Yamaguchi T, Konishi T, Fukunaga Y, Ueno M
    • Journal Title

      Surgery

      Volume: 166 Issue: 6 Pages: 1061-1067

    • DOI

      10.1016/j.surg.2019.06.009

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Comprehensive Comparative Analysis of Prognostic Value of Systemic Inflammatory Biomarkers for Patients with Stage II/III Colon Cancer2019

    • Author(s)
      Suzuki S, Akiyoshi T, Oba K, Otsuka F, Tominaga T, Nagasaki T, Fukunaga Y, Ueno M
    • Journal Title

      Ann Surg Oncol

      Volume: 27 Issue: 3 Pages: 844-852

    • DOI

      10.1245/s10434-019-07904-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Prognostic impact of residual lateral lymph node metastasis after neoadjuvant (chemo)radiotherapy in patients with advanced low rectal cancer2019

    • Author(s)
      Akiyoshi T, Toda S, Tominaga T, Oba K, Tomizawa K, Hanaoka Y, Nagasaki T, Konishi T, Matoba S, Fukunaga Y, Ueno M, Kuroyanagi H
    • Journal Title

      BJS Open

      Volume: 3 Issue: 6 Pages: 822-829

    • DOI

      10.1002/bjs5.50194

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 術前治療を施行した進行直腸癌症例を用いたcirculating tumor DNAと術後再発の関連解析2020

    • Author(s)
      村橋 賢, 秋吉 高志, 向井 俊貴, 山口 智弘, 長嵜 寿矢, 小西 毅, 長山 聡, 上野 雅資, 福長 洋介
    • Organizer
      第120回日本外科学会定期学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 当院における進行直腸癌に対するwatch and waitの治療成績2020

    • Author(s)
      秋吉 高志, 村橋 賢, 向井 俊貴, 長嵜 寿也, 山口 智弘, 小西 毅, 長山 聡, 上野 雅資, 福長 洋介
    • Organizer
      第75回日本消化器外科学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Immunogenomic profiles associated with response to neoadjuvant chemoradiotherapy in patients with advanced low rectal cancer2020

    • Author(s)
      秋吉 高志, 森 誠一, 清谷 一馬, 向井 俊貴, 長嵜 寿也, 山口 智弘, 小西 毅, 長山 聡, 福長 洋介, 上野 雅資
    • Organizer
      第120回日本外科学会定期学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 術前治療を施行した進行直腸癌症例を用いたctDNAの経時的変化と治療効果の関連解析2019

    • Author(s)
      村橋賢、秋吉高志、前佛均、長嵜寿矢、小西毅、長山聡、福長洋介、上野雅資
    • Organizer
      第119回日本外科学会定期学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 術前治療を施行した進行直腸癌症例を用いたcirculating tumor DNAの経時的変化と病理学的完全奏効の関連解析2019

    • Author(s)
      村橋賢、秋吉高志、前佛均、向井俊貴、山口智弘、長嵜寿矢、小西毅、長山聡、福長洋介、上野雅資
    • Organizer
      第74回日本消化器外科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 術前治療を施行した局所進行直腸癌を用いた定量的ctDNA解析と治療効果予測2019

    • Author(s)
      村橋賢、秋吉高志、前佛均、上野雅資、福長洋介、佐野武、野田哲生
    • Organizer
      第74回日本大腸肛門病学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 術前治療を施行した進行直腸癌症例を用いたcell free DNAの経時的変化と臨床病理学的因子の関連解析2018

    • Author(s)
      村橋賢、秋吉高志、前佛均、長嵜寿矢、小西毅、藤本佳也、長山聡、福長洋介、上野雅資
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 術前治療を施行した進行直腸癌症例を用いたcell free DNAの経時的変化と臨床病理学的因子の関連解析2018

    • Author(s)
      村橋賢、秋吉高志、前佛均、長嵜寿矢、小西毅、藤本佳也、長山聡、福長洋介、上野雅資
    • Organizer
      第73回日本消化器外科学会総会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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