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Figure S4 from Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer

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posted on 2023-03-31, 20:21 authored by Lone V. Schøler, Thomas Reinert, Mai-Britt W. Ørntoft, Christine G. Kassentoft, Sigrid S. Árnadóttir, Søren Vang, Iver Nordentoft, Michael Knudsen, Philippe Lamy, Ditte Andreasen, Frank V. Mortensen, Anders R. Knudsen, Katrine Stribolt, Kim Sivesgaard, Peter Mouritzen, Hans J. Nielsen, Søren Laurberg, Torben F. Ørntoft, Claus L. Andersen

Comparison of serial ctDNA analysis performed using SSV and SPM ddPCR assays.

Funding

Danish Council for Independent Research

Danish Council for Strategic Research

Novo Nordic Foundation

Danish Cancer Society

The Danish Cancer Research Foundation and the Faculty of Health at Aarhus University

Aase and Ejnar Danielsen

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ARTICLE ABSTRACT

Purpose: We investigated whether detection of ctDNA after resection of colorectal cancer identifies the patients with the highest risk of relapse and, furthermore, whether longitudinal ctDNA analysis allows early detection of relapse and informs about response to intervention.Experimental Design: In this longitudinal cohort study, we used massively parallel sequencing to identify somatic mutations and used these as ctDNA markers to detect minimal residual disease and to monitor changes in tumor burden during a 3-year follow-up period.Results: A total of 45 patients and 371 plasma samples were included. Longitudinal samples from 27 patients revealed ctDNA postoperatively in all relapsing patients (n = 14), but not in any of the nonrelapsing patients. ctDNA detected relapse with an average lead time of 9.4 months compared with CT imaging. Of 21 patients treated for localized disease, six had ctDNA detected within 3 months after surgery. All six later relapsed compared with four of the remaining patients [HR, 37.7; 95% confidence interval (CI), 4.2–335.5; P < 0.001]. The ability of a 3-month ctDNA analysis to predict relapse was confirmed in 23 liver metastasis patients (HR 4.9; 95% CI, 1.5–15.7; P = 0.007). Changes in ctDNA levels induced by relapse intervention (n = 19) showed good agreement with changes in tumor volume (κ = 0.41; Spearman ρ = 0.4).Conclusions: Postoperative ctDNA detection provides evidence of residual disease and identifies patients at very high risk of relapse. Longitudinal surveillance enables early detection of relapse and informs about response to intervention. These observations have implications for the postoperative management of colorectal cancer patients. Clin Cancer Res; 23(18); 5437–45. ©2017 AACR.

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