Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer.

Autor:	Schøler LV; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Reinert T; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Ørntoft MW; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Kassentoft CG; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Árnadóttir SS; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Vang S; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Nordentoft I; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Knudsen M; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Lamy P; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Andreasen D; Exiqon A/S, Vedbaek, Denmark., Mortensen FV; Department of Surgical Gastroenterology, Aarhus University Hospital, Aarhus, Denmark., Knudsen AR; Department of Surgical Gastroenterology, Aarhus University Hospital, Aarhus, Denmark., Stribolt K; Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark., Sivesgaard K; Department of Radiology, Aarhus University Hospital, Aarhus, Denmark., Mouritzen P; Exiqon A/S, Vedbaek, Denmark., Nielsen HJ; Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark., Laurberg S; Department of Surgery, Aarhus University Hospital, Aarhus, Denmark., Ørntoft TF; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Andersen CL; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark. cla@clin.au.dk.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2017 Sep 15; Vol. 23 (18), pp. 5437-5445. Date of Electronic Publication: 2017 Jun 09.
DOI:	10.1158/1078-0432.CCR-17-0510
Abstrakt:	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 . (©2017 American Association for Cancer Research.)
Databáze:	MEDLINE
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