Establishment of new selection system for adjuvant chemotherapy of colorectal cancer

• Project/Area Number: 20K09011
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kyushu University
• Principal Investigator: OKI Eiji 九州大学, 大学院医学研究院, 准教授 (70380392)
• Co-Investigator(Kenkyū-buntansha): 北尾 洋之 九州大学, 薬学研究院, 教授 (30368617)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: ゲノム検査 / 遺伝子検査 / 遺伝子サブタイプ / ctDNA / 大腸癌 / 術後補助療法 / cDNAマクロアレイ / 補助化学療法 / LGR5 / NGS解析 / 遺伝子変異 / 周術期治療 / 術後化学療法

Outline of Research at the Start

がんの治療手段には、外科治療、薬物療法、放射線治療、それに免疫療法を加えた４つの治療法があり、それらを効果的に組み合わせてきた。消化器癌の周術期治療の場合、大量の癌細胞を対象とする通常のがん薬物療法と全く異なる考え方で治療ストラテジーを構築する必要がある。本研究では癌が周術期に発現する遺伝子とそのゲノム異常、癌の微小環境を検討した上で、独自開発のゲノム診断法で画期的な術後化学療法プログラムを開発する。

Outline of Final Research Achievements

Collaborated with other universities and companies to develop a genetic diagnosis system for the purpose of determining postoperative treatment strategy through genome testing. In collaboration with Sysmex, we developed a new postoperative prognostic system using budding signature, and confirmed in clinical cases that budding signature can be used to predict the prognosis of cancer. In collaboration with Natera, we conducted a prospective observational study of postoperative colorectal cancer cases using ctDNA. In this ctDNA assay, whole exome sequencing (WES) is performed on surgical specimens, and a custom panel of 16 gene sets is selected for each case, taking tumor-specific single nucleotide substitution variants (SNVs) into account. We found thata positive circulating tumor DNA in the blood at 4 weeks postoperatively was associated with a significantly higher risk of recurrence compared with negative results.

Academic Significance and Societal Importance of the Research Achievements

大腸癌は切除可能であっても、3割程度の患者が術後に再発する。本検討により、これら遺伝子検査が、腫瘍マーカーや画像検査と比較して鋭敏、迅速に術後の再発予測ができることが明らかとなった。これら方法を使い、再発しにくい患者、再発しやすい患者を層別化し、術後の治療を省略する、もしくは強力な術後治療を行うことができる。結果的に大腸癌の予後が飛躍的に改善することが期待される。

Research Products

• [Journal Article] Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer. (2023)
  • Author(s): Kotani D, Oki E, Takemasa I. et al.
  • Journal Title: Nat Med Volume: 29(1) Issue: 1 Pages: 127-134
  • DOI: 10.1038/s41591-022-02115-4
  • Peer Reviewed / Open Access
• [Journal Article] Molecular Residual Disease-guided Adjuvant Treatment in Resected Colorectal Cancer: Focus on CIRCULATE-Japan (2023)
  • Author(s): Sato Seiya、Nakamura Yoshiaki、Oki Eiji、Yoshino Takayuki
  • Journal Title: Clinical Colorectal Cancer Volume: 22 Issue: 1 Pages: 53-58
  • DOI: 10.1016/j.clcc.2022.12.001
  • Peer Reviewed
• [Journal Article] Final Analysis of 3 Versus 6 Months of Adjuvant Oxaliplatin and Fluoropyrimidine-Based Therapy in Patients With Stage III Colon Cancer: The Randomized Phase III ACHIEVE Trial (2022)
  • Author(s): Yoshino Takayuki、Oki Eiji、Misumi Toshihiro、Mori Masaki et al.
  • Journal Title: Journal of Clinical Oncology Volume: 40 Issue: 29 Pages: 3419-3429
  • DOI: 10.1200/jco.21.02628
  • Peer Reviewed
• [Journal Article] Patient-specific meta-analysis of 12-gene colon cancer recurrence score validation studies for recurrence risk assessment after surgery with or without 5FU and oxaliplatin (2022)
  • Author(s): Yothers G, Venook AP, Oki E, Niedzwiecki D, Lin Y, Crager MR, Chao C, Baehner FL, Wolmark N, Yoshino T
  • Journal Title: J Gastrointest Oncol . Volume: 13 Issue: 1 Pages: 0000-0000
  • DOI: 10.21037/jgo-21-620
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage III colon cancer patients (2021)
  • Author(s): Oki Eiji、Shinto Eiji、Shimokawa Mototsugu、Yamaguchi Shigeki、Ishiguro Megumi、Hasegawa Seiji、Takii Yasumasa、Ishida Hideyuki、Kusumoto Tetsuya、Morita Masaru、Tomita Naohiro、Shiozawa Manabu、Tanaka Masafumi、Ozawa Heita、Hashiguchi Yojiro、Ohnuma Shinobu、Tada Sachiyo、Matsushima Tomoko、Hase Kazuo
  • Journal Title: BMC Cancer Volume: 21 Issue: 1 Pages: 1332-1332
  • DOI: 10.1186/s12885-021-09088-6
  • Peer Reviewed / Open Access
• [Journal Article] Sustainable Clinical Development of Adjuvant Chemotherapy for Colon Cancer (2021)
  • Author(s): Oki E, Ando K, Taniguchi H, Yoshino T, Mori M.
  • Journal Title: Ann Gastroenterol Surg Volume: 9 Issue: 1 Pages: 37-45
  • DOI: 10.1002/ags3.12503
  • Peer Reviewed / Open Access
• [Journal Article] Early-Onset Colorectal Adenocarcinoma in the IDEA Database: Treatment Adherence, Toxicities, and Outcomes With 3 and 6 Months of Adjuvant Fluoropyrimidine and Oxaliplatin (2021)
  • Author(s): Fontana E, Meyers J, Sobrero A, Iveson T, Shields AF, Taieb J, Yoshino T, Souglakos I, Smyth EC, Lordick F, Moehler M, Giraut A, Harkin A, Labianca R, Meyerhardt J, Andrre; T, Boukovinas I, Lonardi S, Saunders M, Vernerey D, Oki E, Georgoulias V, Ben-Aharon I, Shi Q.
  • Journal Title: J Clin Oncol Volume: 39 Issue: 36 Pages: 4009-4019
  • DOI: 10.1200/jco.21.02008
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer (2021)
  • Author(s): Yoshino T, Argils G, Oki E, Martinelli E, Taniguchi H, Arnold D, Mishima S, Li Y, Smruti BK, Ahn JB, Faud I, Chee CE, Yeh KH, Lin PC, Chua C, Hasbullah HH, Lee MA, Sharma A, Sun Y, Curigliano G, Bando H, Lordick F, Yamanaka T, Tabernero J, Baba E, Cervantes A, Ohtsu A, Peters S, Ishioka C, Pentheroudakis G.
  • Journal Title: Ann Oncol Volume: 32 Issue: 12 Pages: 1496-1510
  • DOI: 10.1016/j.annonc.2021.08.1752
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of the 12-gene recurrence score assay on deciding adjuvant chemotherapy for stage II and IIIA/B colon cancer: the SUNRISE-DI study (2021)
  • Author(s): Oki E, Watanabe J, Sato T, Kagawa Y, Kuboki Y, Ikeda M, Ueno H, Kato T, Kusumoto T, Masuishi T, Yamaguchi K, Kanazawa A, Nishina T, Uetake H, Yamanaka T, Yoshino T.
  • Journal Title: ESMO Open . Volume: 6 Issue: 3 Pages: 0000-0000
  • DOI: 10.1016/j.esmoop.2021.100146
  • Peer Reviewed / Open Access
• [Journal Article] Real‐world data on microsatellite instability status in various unresectable or metastatic solid tumors (2021)
  • Author(s): Akagi Kiwamu、Oki Eiji、Taniguchi Hiroya、Nakatani Kaname、Aoki Daisuke、Kuwata Takeshi、Yoshino Takayuki
  • Journal Title: Cancer Science Volume: 112 Issue: 3 Pages: 1105-1113
  • DOI: 10.1111/cas.14798
  • Peer Reviewed / Open Access
• [Journal Article] A Validation Study for Recurrence Risk Stratification of Stage II Colon Cancer Using the 55-Gene Classifier (2020)
  • Author(s): Shinto Eiji、Oki Eiji、Shimokawa Mototsugu、Yamaguchi Shigeki、Ishiguro Megumi、Morita Masaru、Kusumoto Tetsuya、Tomita Naohiro、Hashiguchi Yojiro、Tanaka Masafumi、Ohnuma Shinobu、Tada Sachiyo、Matsushima Tomoko、Hase Kazuo
  • Journal Title: Oncology Volume: 98 Issue: 8 Pages: 534-541
  • DOI: 10.1159/000506369
  • Peer Reviewed
• [Presentation] CIRCULATE-JAPAN：Nationwide large-scale clinical trial for circulating tumor DNA-guided management for colorectal cancer (2023)
  • Author(s): 沖 英次
  • Organizer: 日本消化器病学会総会
  • Invited
• [Presentation] Current status and future perspectives of clinical research in colorectal surgery: Establishment of evidence by integration of art and science (2020)
  • Author(s): 沖 英次、竹政伊知朗、加藤健志、吉野孝之、谷口浩也、中村能章、小谷大輔、衣斐寛倫, 山中竹春、安藤幸滋、森 正樹
  • Organizer: 第75回 日本消化器外科学会
• [Presentation] Genome医療は外科医の臨床を変えるか (2020)
  • Author(s): 沖 英次
  • Organizer: 第58回日本癌治療学会総会
  • Invited