1. ctDNA-based molecular residual disease and survival in resectable colorectal cancer
- Author
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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, and Oki, Eiji
- 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.
- Published
- 2024
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