Total cell‑free DNA measurement in metastatic colorectal cancer with a fast and easy direct fluorescent assay

Callesen,Louise Bach; Sørensen,Brita Singers; Pallisgaard,Niels; Laugesen,Ina Grønkjær; Boysen,Anders Kindberg; Spindler,Karen-Lise Garm

doi:10.3892/mco.2022.2497

Total cell‑free DNA measurement in metastatic colorectal cancer with a fast and easy direct fluorescent assay

Authors:
- Louise Bach Callesen
- Brita Singers Sørensen
- Niels Pallisgaard
- Ina Grønkjær Laugesen
- Anders Kindberg Boysen
- Karen-Lise Garm Spindler
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Affiliations: Department of Experimental Clinical Oncology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark, Danish Centre for Particle Therapy, Aarhus University Hospital, DK-8200 Aarhus N, Denmark, Department of Pathology, Zealand University Hospital, DK-4700 Næstved, Denmark, Research Unit for General Practice, DK-8000 Aarhus N, Denmark, Department of Oncology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark
Published online on: January 17, 2022 https://doi.org/10.3892/mco.2022.2497
Article Number: 64

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Abstract

Treatment for metastatic colorectal cancer (mCRC) is focused on prolonging survival and maintaining quality of life. It is important to establish prognostic and predictive markers to avoid extended, ineffective treatment. The aim of the present study was, by a novel approach, to analyze the association between cell‑free (cf)DNA levels and outcome in patients receiving systemic therapy for incurable mCRC. The study was a prospective non‑interventional biomarker study for patients receiving standard of systemic treatment for mCRC. Patients with mCRC, who, according to standard guidelines, were considered for treatment with EGFR inhibitors, were included. The cfDNA levels in consecutive plasma samples were measured by a direct fluorescence assay. The study included 47 patients. Blood samples were available at baseline (n=47); prior to the third treatment cycle (n=31); the first (n=33), second (n=22) and third response evaluation during treatment (n=17); and at progression (n=22). The disease control rate was 42 and 91% in patients with high (≥75th percentile of baseline cfDNA levels) and low cfDNA levels (<75th percentile of baseline cfDNA levels), respectively (P<0.001). Median progression‑free survival (PFS) was 3.8 and 8.5 months in patients with high and low cfDNA levels, respectively (hazard ratio=3.03, 95% CI 1.46‑6.29, P<0.01). Median overall survival (OS) was 5.0 and 26.6 months in patients with high and low cfDNA levels, respectively (hazard ratio=3.48, 95% CI 1.44‑8.44, P<0.01). In the multivariate analysis, baseline cfDNA levels remained a significant predictor of PFS and OS. In conclusion, cfDNA is a promising prognostic tool in the personalized treatment of mCRC. cfDNA levels were estimated by a simple, rapid and inexpensive method (OPTIPAL II: ClinicalTrials.gov identifier no. NCT03750175; registered November 21, 2018).

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