TY - JOUR
T1 - Total cell-free DNA measurement in metastatic colorectal cancer with a fast and easy direct fluorescent assay
AU - Callesen, Louise Bach
AU - Sørensen, Brita Singers
AU - Pallisgaard, Niels
AU - Laugesen, Ina Grønkjær
AU - Boysen, Anders Kindberg
AU - Spindler, Karen Lise Garm
N1 - Funding Information:
This project was funded by grants from The Danish Cancer Society (Kræftens Bekæmpelse; grant nos. R99‑A6323‑14 ‑S25 and R269‑A15652), Novo Nordisk Foundation (grant no. 9297), Health Research Foundation of Central Denmark Region (grant no. A1602) and Aase and Ejner Danielsen Foundation (grant no. 10‑002001). The funding sources had no influence on the study design, data collection, analysis and interpretation of data and neither took part in the writing of the report nor in the decision to submit the article for publication.
Publisher Copyright:
© 2022, Spandidos Publications. All rights reserved.
PY - 2022/3
Y1 - 2022/3
N2 - 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).
AB - 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).
KW - Biomarker
KW - Cell-free DNA
KW - Colorectal adenocarcinomametastatic colorectal cancer
KW - Systemic therapy
UR - http://www.scopus.com/inward/record.url?scp=85124161051&partnerID=8YFLogxK
U2 - 10.3892/mco.2022.2497
DO - 10.3892/mco.2022.2497
M3 - Journal article
C2 - 35154704
AN - SCOPUS:85124161051
SN - 2049-9450
VL - 16
JO - Molecular and Clinical Oncology
JF - Molecular and Clinical Oncology
IS - 3
M1 - 64
ER -