Circulating tumor DNA for prognosis assessment and postoperative management after curative-intent resection of colorectal liver metastases.

Autor: Reinert T; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Petersen LMS; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Henriksen TV; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Larsen MØ; Department of Surgery, Aarhus University Hospital, Aarhus, Denmark., Rasmussen MH; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Johansen AFB; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Øgaard N; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Knudsen M; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Nordentoft I; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Vang S; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark., Krag SRP; Department of Pathology, Aarhus University Hospital, Aarhus, Denmark., Knudsen AR; Department of Surgery, Aarhus University Hospital, Aarhus, Denmark., Mortensen FV; Department of Surgery, Aarhus University Hospital, Aarhus, Denmark., Andersen CL; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2022 May 01; Vol. 150 (9), pp. 1537-1548. Date of Electronic Publication: 2022 Jan 19.
DOI: 10.1002/ijc.33924
Abstrakt: The recurrence rate of colorectal liver metastases (CRLM) patients treated with curative intent is above 50%. Standard of care surveillance includes intensive computed tomographic (CT) imaging as well as carcinoembryonic antigen (CEA) measurements. Nonetheless, relapse detection often happens too late to resume curative treatment. This longitudinal cohort study enrolled 115 patients with plasma samples (N = 439) prospectively collected before surgery, postoperatively at day 30 and every third month for up to 3 years. Droplet digital PCR (ddPCR) was used to monitor serial plasma samples for somatic mutations. Assessment of ctDNA status either immediately after surgery, or serially during surveillance, stratified the patients into groups of high and low recurrence risk (hazard ratio [HR], 7.6; 95% CI, 3.0-19.7; P < .0001; and HR, 4.3; 95% CI, 2.3-8.1; P < .0001, respectively). The positive predictive value (PPV) of ctDNA was 100% in all postoperative analyses. In multivariable analyses, postoperative ctDNA status was the only consistently significant risk marker associated with relapse (P < .0001). Indeterminate CT findings were observed for 30.8% (21/68) of patients. All patients (9/21) that were ctDNA positive at the time of the indeterminate CT scan later relapsed, contrasting 42.6% (5/12) of those ctDNA negative (P = .0046). Recurrence diagnoses in patients with indeterminate CT findings were delayed (median 2.8 months, P < .0001). ctDNA status is strongly associated with detection of minimal residual disease and early detection of relapse. Furthermore, ctDNA status can potentially contribute to clinical decision-making in case of indeterminate CT findings, reducing time-to-intervention.
(© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Databáze: MEDLINE
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