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Introduction: Recurrence risk after curative surgery for colorectal liver metastases (CRLM) remains high, underlining the need for novel prognostic markers. Liquid biopsies provide promising biomarkers to detect minimal residual disease (MRD) after local treatment. The aim of this study was to determine and compare the characteristics of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) in liquid biopsies taken before and after surgical treatment of CRLM. Materials & Methods: Patients with isolated CRLM were recruited before undergoing potentially curative hepatic resection. Only patients who did not receive per-operative chemotherapy were selected. Peripheral blood samples were collected in CellSave preservative tubes at four different time points and processed into plasma within 96 hours after withdrawal. Subsequently, cfDNA was isolated from 4mL plasma, in which the total cfDNA concentration was measured. Mutations characterizing ctDNA were determined before surgery by next generation sequencing (NGS) using a colon-specific targeted panel (Oncomine Colon cfDNA assay, 14 genes). Samples were sequenced at >20.000 average reads depth and variants were called mutations when the variant allele frequency was above their predefined limit of detection. Longitudinal blood samples of ctDNA-positive patients were evaluated by digital PCR (dPCR) using mutation-specific assays, in which samples were considered ctDNA positive when >5 mutant copies were detected. Results: Blood samples of 231 patients were collected one day before surgery (T0), and were repeated one day (T1), one week (T2), and three weeks (T3) after surgery. The cfDNA yields per mL plasma were higher at T1 and T2 (median 93 ng and 64 ng, respectively) compared to T0 (6 ng, p Discussion/Conclusion: ctDNA is a potential biomarker to detect MRD after curative treatment for CRLM. Our results demonstrate that out of all patients with detectable ctDNA at baseline (before surgery), ctDNA is still present in 36% of patients three weeks after resection. Citation Format: Lissa Wullaert, Maurice P. Jansen, Jaco Kraan, Jan M. van Rees, Corine M. Beaufort, Yannick M. Meyer, Boris Galjart, Pieter M. Nierop, Florian E. Buisman, Diederik J. Höppener, Erik P. van der Stok, Gianmarco Motta, Dirk J. Grünhagen, Henk M. Verheul, Stefan Sleijfer, Saskia M. Wilting, Cornelis Verhoef, John W. Martens. Circulating tumor DNA in colorectal cancer patients with resectable liver metastases: Preliminary results of the MIRACLE study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5715.