Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
Circulating Tumor DNA Dynamics in Patients with Liver-Limited Metastatic Colorectal Cancer Resected after First-Line Systemic Treatment.
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Moretto Roberto, Studiale Vittorio, Hyun Seung Won, Vetere Guglielmo, Islam Farahnaz, Carullo Martina, Conca Veronica, Lo Christine, Neems Daniel, Boulos Hala, DeSantis Dana F, Germani Marco Maria, Taravella Ada, Landi Matteo, Ghelardi Filippo, De Grandis Maria Caterina, Murgioni Sabina, Abran John, Sasser Kate, Pietrantonio Filippo, Chiou Victoria L, Sangli Chithra, Nimeiri Halla, Cremolini Chiara
Аннотация
PURPOSE: Resection of liver metastases improves survival in patients with metastatic colorectal cancer (mCRC) with liver-limited disease (LLD), but relapse remains common. Postresection circulating tumor DNA (ctDNA) is a valid prognostic biomarker; however, no data are available regarding the prognostic effect of presurgery ctDNA after upfront chemotherapy.
EXPERIMENTAL DESIGN: Patients (N = 116) with initially unresectable mCRC with LLD who underwent resection after upfront chemotherapy were included. Patients were sequenced with a tumor-naïve ctDNA-based minimal residual disease (MRD) assay at baseline (before chemotherapy), before surgery, and after surgery.
RESULTS: Presurgery ctDNA status was not significantly associated with relapse-free survival (RFS). However, exploratory analyses demonstrated that a ≥50% reduction in variant allele frequency from baseline to before surgery was independently associated with improved RFS (median RFS: 21.0 vs. 9.8 months; HR: 2.19; P = 0.014), aligned with multivariate analysis (P = 0.022). Postsurgery ctDNA positivity was strongly predictive of recurrence (HR: 6.66; P < 0.001), with 100% specificity and 56.4% sensitivity. ctDNA dynamics from before to after surgery further stratified recurrence risk, regardless of adjuvant chemotherapy status. ctDNA dynamics from before to after surgery further stratified recurrence risk. Quantitative ctDNA measures (predicted tumor fragments per million) also correlated with RFS.
CONCLUSIONS: Use of a tumor-naïve MRD assay increased the accuracy of detecting ctDNA after chemotherapy treatment, when a significant drop of ctDNA amount is expected compared with tests routinely used in metastatic disease. Presurgery ctDNA dynamics were prognostic with respect to RFS and may help stratify patients' prognosis prior to resection, potentially informing personalized treatment decisions.
EXPERIMENTAL DESIGN: Patients (N = 116) with initially unresectable mCRC with LLD who underwent resection after upfront chemotherapy were included. Patients were sequenced with a tumor-naïve ctDNA-based minimal residual disease (MRD) assay at baseline (before chemotherapy), before surgery, and after surgery.
RESULTS: Presurgery ctDNA status was not significantly associated with relapse-free survival (RFS). However, exploratory analyses demonstrated that a ≥50% reduction in variant allele frequency from baseline to before surgery was independently associated with improved RFS (median RFS: 21.0 vs. 9.8 months; HR: 2.19; P = 0.014), aligned with multivariate analysis (P = 0.022). Postsurgery ctDNA positivity was strongly predictive of recurrence (HR: 6.66; P < 0.001), with 100% specificity and 56.4% sensitivity. ctDNA dynamics from before to after surgery further stratified recurrence risk, regardless of adjuvant chemotherapy status. ctDNA dynamics from before to after surgery further stratified recurrence risk. Quantitative ctDNA measures (predicted tumor fragments per million) also correlated with RFS.
CONCLUSIONS: Use of a tumor-naïve MRD assay increased the accuracy of detecting ctDNA after chemotherapy treatment, when a significant drop of ctDNA amount is expected compared with tests routinely used in metastatic disease. Presurgery ctDNA dynamics were prognostic with respect to RFS and may help stratify patients' prognosis prior to resection, potentially informing personalized treatment decisions.