ctDNA-based molecular residual disease and survival in resectable colorectal cancer
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.
Authors
- Matthew Rabinowitz (ORCID: https://orcid.org/0009-0006-3109-4232)
- Kenji Okita (ORCID: https://orcid.org/0000-0003-0254-4020)
- Yoshiaki Nakamura (ORCID: https://orcid.org/0000-0002-5241-6855)
- Masaaki Miyo (ORCID: https://orcid.org/0000-0002-8627-1308)
- Yoshinori Kagawa (ORCID: https://orcid.org/0000-0001-6876-4507)
- Adham Jurdi (ORCID: https://orcid.org/0000-0002-2985-3053)
- Atsushi Hamabe (ORCID: https://orcid.org/0000-0001-5535-3514)
- Vasily N. Aushev (ORCID: https://orcid.org/0000-0001-8003-358X)
- Koji Ando (ORCID: https://orcid.org/0000-0002-0149-1505)
- Naoya Akazawa (ORCID: https://orcid.org/0000-0002-2891-6550)
- Ichiro Takemasa (ORCID: https://orcid.org/0000-0003-1595-2453)
- Minetta C. Liu (ORCID: https://orcid.org/0000-0002-8206-5232)
- Jun Watanabe (ORCID: https://orcid.org/0000-0002-7187-3664)
- Toshihiro Misumi (ORCID: https://orcid.org/0000-0001-8339-2895)
- Satoshi Kobayashi (ORCID: https://orcid.org/0000-0001-7759-399X)
- Daisuke Kotani (ORCID: https://orcid.org/0000-0002-4196-555X)
- Kozo Kataoka (ORCID: https://orcid.org/0000-0003-2043-8184)
- Kentaro Yamazaki (ORCID: https://orcid.org/0000-0001-6269-9345)
- George Laliotis (ORCID: https://orcid.org/0000-0001-9205-8258)
- Hideaki Bando (ORCID: https://orcid.org/0000-0001-5041-2765)
- Hiroki Yukami (ORCID: https://orcid.org/0000-0001-7781-4609)
- Masahito Kotaka (ORCID: https://orcid.org/0000-0001-5976-613X)
- Saori Mishima (ORCID: https://orcid.org/0000-0002-5922-1487)
- Takayuki Yoshino (ORCID: https://orcid.org/0000-0002-0489-4756)
- Eiji Oki (ORCID: https://orcid.org/0000-0002-9763-9366)
- Alexey Aleshin (ORCID: https://orcid.org/0000-0002-0425-0301)
- Masaki Mori
- Kun‐Huei Yeh (ORCID: https://orcid.org/0000-0002-7306-174X)
- Hiroya Taniguchi (ORCID: https://orcid.org/0000-0003-1407-6682)
- Keiji Hirata (ORCID: https://orcid.org/0000-0001-6461-5109)
- Mitsuru Yokota (ORCID: https://orcid.org/0000-0002-5581-5990)
- Hiroki Sokuoka
- Hiromichi Ebi (ORCID: https://orcid.org/0000-0003-3155-7576)
- Kentaro Kato (ORCID: https://orcid.org/0000-0003-4890-567X)
- Takeshi Kato (ORCID: https://orcid.org/0000-0001-5347-550X)
- Shruti Sharma (ORCID: https://orcid.org/0000-0003-0290-1569)
Institutions
- Kansai Medical University (JP)
- Tokai University (JP)
- Kyushu University (JP)
- Sapporo Medical University (JP)
- University of Occupational and Environmental Health Japan (JP)
- Yokohama City University Medical Center (JP)
- Osaka Prefectural Medical Center (JP)
- Kobe Medical Center (JP)
- Shizuoka Cancer Center (JP)
- Kurashiki Central Hospital (JP)
- Osaka National Hospital (JP)
- Osaka City General Hospital (JP)
- Sendai Medical Center (JP)
- Natera (United States) (US)
- National Taiwan University Hospital (TW)
- Aichi Cancer Center (JP)
- Teine Keijinkai Hospital (JP)
- National Cancer Center Hospital East (JP)
- Osaka International Cancer Institute (JP)
- Kobe University (JP)
- Yokohama City University (JP)
- Osaka University of Pharmaceutical Sciences (JP)
- Kindai University (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- Nature Medicine
- Published
- 2024-09-16
- DOI
- https://doi.org/10.1038/s41591-024-03254-6
- Citations
- 148
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 42.20