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Genetics and Genomics

CEA, CA19-9, circulating DNA and circulating tumour cell kinetics in patients treated for metastatic colorectal cancer (mCRC)



We previously reported that CEA kinetics are a marker of progressive disease (PD) in metastatic colorectal cancer (mCRC). This study was specifically designed to confirm CEA kinetics for predicting PD and to evaluate CA19-9, cell-free DNA (cfDNA), circulating tumour DNA (ctDNA) and circulating tumour cell (CTC) kinetics.


Patients starting a chemotherapy (CT) with pre-treatment CEA > 5 ng/mL and/or CA19.9 > 30 UI/mL were prospectively included. Samples were collected from baseline to cycle 4 for CEA and CA19-9 and at baseline and the sixth week for other markers. CEA kinetics were calculated from the first to the third or fourth CT cycle.


A total of 192 mCRC patients were included. CEA kinetics based on the previously identified >0.05 threshold was significantly associated with PD (p < 0.0001). By dichotomising by the median value, cfDNA, ctDNA and CA19-9 were associated with PD, PFS and OS in multivariate analysis. A circulating scoring system (CSS) combining CEA kinetics and baseline CA19-9 and cfDNA values classified patients based on high (n = 58) and low risk (n = 113) of PD and was independently associated with PD (ORa = 4.6, p < 0.0001), PFS (HRa = 2.07, p < 0.0001) and OS (HRa = 2.55, p < 0.0001).


CEA kinetics alone or combined with baseline CA19-9 and cfDNA are clinically relevant for predicting outcomes in mCRC.

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Fig. 1: Flow diagram illustrating all the biomarkers of the Coca Colon cohort study.
Fig. 2: Result of biomarkers for prediction of progression at 12-weeks evaluation.
Fig. 3: Survival according to the circulating markers.
Fig. 4: Forest plot of hazard ratios for patient’s survival.


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The authors thank the patients and their families, investigators and staff from all the participating sites. The authors also thank American Journal Expert ( for English language editing.

Author information




Conception and design: P.M. and F.D.F. Administrative support: P.M. and F.D.F. Provision of study materials or patients: D.S., A.G., M.H., C.E., A.-L.B., A.P., P.G., K.B.-L., M.-P.G., P.M., and F.D.F. Collection and assembly of data: D.S., L.B., A.G., E.T., C.B., A.P., F.Z., F.B., C.T., F.C., J.-C.S., T.F., J.B., N.S.-V., P.M., and F.D.F. Data analysis and interpretation: D.S., L.B., A.G., E.T., C.B., A.P., F.Z., F.B., C.T., J.B., N.S.-V., P.M., and F.D.F. Manuscript writing, final approval of manuscript and accountable for all aspects of the work: all authors.

Corresponding author

Correspondence to David Sefrioui.

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Ethics approval and consent to participate

The study was approved by the institutional review board (Northwest I), and all patients provided written informed consent (NCT01212510). The study was performed in accordance with the Declaration of Helsinki.

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Data availability

Raw data are available from the corresponding author upon request.

Competing interests

The authors declare no competing interests.


This study was supported in part by the Grant “Pierre DURAND & Marie-Thérèse CHEVALIER (2013)” and the pharmaceutical industrial partners Roche, Merck and Amgen France. A grant was also provided by the Charles Nicolle Foundation and the association “des tulipes contre le cancer-Lions Club de France” for financing and acquisition of the digital PCR system used for the detection of circulating tumour DNA. The Northwest Data Center (CTD-CNO) that managed the data was supported by grants from the French National League Against Cancer (LNC) and the French National Cancer Institute (INCa).

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Sefrioui, D., Beaussire, L., Gillibert, A. et al. CEA, CA19-9, circulating DNA and circulating tumour cell kinetics in patients treated for metastatic colorectal cancer (mCRC). Br J Cancer (2021).

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