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ctDNA-based molecular residual disease and survival in resectable colorectal cancer.
Nakamura, Yoshiaki; Watanabe, Jun; Akazawa, Naoya; Hirata, Keiji; Kataoka, Kozo; Yokota, Mitsuru; Kato, Kentaro; Kotaka, Masahito; Kagawa, Yoshinori; Yeh, Kun-Huei; Mishima, Saori; Yukami, Hiroki; Ando, Koji; Miyo, Masaaki; Misumi, Toshihiro; Yamazaki, Kentaro; Ebi, Hiromichi; Okita, Kenji; Hamabe, Atsushi; Sokuoka, Hiroki; Kobayashi, Satoshi; Laliotis, George; Aushev, Vasily N; Sharma, Shruti; Jurdi, Adham; Liu, Minetta C; Aleshin, Alexey; Rabinowitz, Matthew; Bando, Hideaki; Taniguchi, Hiroya; Takemasa, Ichiro; Kato, Takeshi; Kotani, Daisuke; Mori, Masaki; Yoshino, Takayuki; Oki, Eiji.
Affiliation
  • Nakamura Y; Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
  • Watanabe J; Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.
  • Akazawa N; International Research Promotion Office, National Cancer Center Hospital East, Kashiwa, Japan.
  • Hirata K; Department of Colorectal Surgery, Kansai Medical University, Hirakata, Japan.
  • Kataoka K; Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan.
  • Yokota M; Department of Gastroenterological Surgery, Sendai City Medical Center Sendai Open Hospital, Sendai, Japan.
  • Kato K; Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
  • Kotaka M; Division of Lower GI, Department of Gastroenterological Surgery, Hyogo Medical University, Kobe, Japan.
  • Kagawa Y; Department of General Surgery, Kurashiki Central Hospital, Kurashiki, Japan.
  • Yeh KH; Department of Surgery, Teine-Keijinkai Hospital, Sapporo, Japan.
  • Mishima S; Gastrointestinal Cancer Center, Sano Hospital, Kobe, Japan.
  • Yukami H; Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan.
  • Ando K; Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka, Japan.
  • Miyo M; Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
  • Misumi T; Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
  • Yamazaki K; Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
  • Ebi H; Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Okita K; Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan.
  • Hamabe A; Department of Data Science, National Cancer Center Hospital East, Kashiwa, Japan.
  • Sokuoka H; Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Sunto-gun, Japan.
  • Kobayashi S; Division of Molecular Therapeutics, Aichi Cancer Center Research Institute, Nagoya, Japan.
  • Laliotis G; Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan.
  • Aushev VN; Department of Gastroenterological Surgery, Osaka University, Osaka, Japan.
  • Sharma S; Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.
  • Jurdi A; EPS Corporation, Tokyo, Japan.
  • Liu MC; Natera, Inc., Austin, TX, USA.
  • Aleshin A; Natera, Inc., Austin, TX, USA.
  • Rabinowitz M; Natera, Inc., Austin, TX, USA.
  • Bando H; Natera, Inc., Austin, TX, USA.
  • Taniguchi H; Natera, Inc., Austin, TX, USA.
  • Takemasa I; Natera, Inc., Austin, TX, USA.
  • Kato T; Natera, Inc., Austin, TX, USA.
  • Kotani D; Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
  • Mori M; Translational Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan.
  • Yoshino T; Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.
  • Oki E; Department of Surgery, Surgical Oncology and Science, Sapporo Medical University, Sapporo, Japan.
Nat Med ; 2024 Sep 16.
Article in En | MEDLINE | ID: mdl-39284954
ABSTRACT
The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II-III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR) 11.99, P < 0.0001) and overall survival (OS; HR 9.68, P < 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR 2.71, P < 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS 89.0% versus 3.3%; 24-month OS 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Nat Med Journal subject: BIOLOGIA MOLECULAR / MEDICINA Year: 2024 Document type: Article Affiliation country: Japan Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Nat Med Journal subject: BIOLOGIA MOLECULAR / MEDICINA Year: 2024 Document type: Article Affiliation country: Japan Country of publication: United States