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Genetics and Genomics

Circulating tumour cells and cell-free DNA as a prognostic factor in metastatic colorectal cancer: the OMITERC prospective study

British Journal of Cancer volume 125, pages 94–100 (2021)Cite this article

Subjects

Abstract

Background

Within the OMITERC prospective study (OMIcs application from solid to liquid biopsy for a personalised ThERapy of Cancer), we explored the prognostic role of liquid biopsy encompassing cell-free DNA (cfDNA) and circulating tumour cells (CTCs) in KRAS mutated metastatic colorectal cancer (mCRC).

Methods

We defined a workflow including pre-analytical and analytical procedures collecting blood before therapy and every 3 months until disease progression (PD). CTCs were counted by CellSearch® and isolated by DEPArray™. NGS sequencing of CTCs and cfDNA was performed using a panel of cancer/CRC related genes respectively.

Results

KRAS mutational status was mostly concordant between tumour tissues and liquid biopsy. The percentage of cfDNA samples with mutations in CRC driver genes was in line with literature. In longitudinal monitoring circulating biomarkers anticipated or overlapped conventional diagnostic tools in predicting PD. The presence of CTCs at baseline was confirmed a negative prognostic marker.

Conclusions

Cell-free DNA and CTCs are readily available candidates for clinical application in mCRC. While CTCs demonstrated a prognostic significance at baseline, cfDNA was confirmed an easily accessible material for monitoring the mutational status of the tumour over time. Moreover, in the longitudinal study, the two markers emerged as complementary in assessing disease progression.

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Fig. 1: Kaplan–Meier estimates of probabilities of progression-free survival (PFS) and overall survival (OS) of mCRC patients presenting (CTC POS) or not (CTC NEG) CTCs at baseline (time 0).
Fig. 2: Longitudinal disease monitoring in two mCRC patients by liquid biopsy evaluation.

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Acknowledgements

We wish to thank the OMITERC consortium and the Fondazione Sandro Pitigliani per la lotta contro i tumori ONLUS.

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Author notes

  1. These authors contributed equally: Pamela Pinzani, Lorenzo Antonuzzo

Authors and Affiliations

  1. Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy

    Francesca Salvianti, Stefania Gelmini, Irene Mancini, Mario Pazzagli & Pamela Pinzani

  2. Clinical Oncology Unit, Careggi University Hospital, Florence, Italy

    Serena Pillozzi, Elisa Giommoni, Marco Brugia, Francesco Di Costanzo & Lorenzo Antonuzzo

  3. Sandro Pitigliani Medical Oncology Department, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy

    Francesca Galardi & Francesca De Luca

  4. Histopathology and Molecular Diagnostics Unit, Careggi University Hospital, Florence, Italy

    Francesca Castiglione

  5. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Luca Messerini & Lorenzo Antonuzzo

Authors
  1. Francesca Salvianti
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  2. Stefania Gelmini
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Contributions

F.S.: single CTC isolation, mutational analysis of CTCs and cfDNA, data analysis and manuscript writing; S.G.: management of clinical samples, data analysis and manuscript writing; I.M.: NGS data analysis; F.G. and F.D.L.: CTC counting by CellSearch; S.P.: clinical data management and critical revision of the manuscript; E.G. and M.B.: patients’ enrolment, clinical data collection and analysis; F.C. and L.M. mutational analysis of tumour tissues; M.P. and F.D.C.: conceptualisation, funding acquisition and critical revision of manuscript; P.P.: study design, project supervision and manuscript writing; L.A.: patients’ enrolment, clinical data management and study design.

Corresponding author

Correspondence to Pamela Pinzani.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the Local Ethical Committee (Comitato Etico di Area Vasta Centro AOU Careggi, Firenze, Italy), reference number CEAVC BIO 16.028_10033_bio. Written informed consent to participate was obtained from all patients. The study was performed in accordance with the Declaration of Helsinki.

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Not applicable.

Data availability

The datasets analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare no competing interests.

Funding information

This research was funded by Regione Toscana FAS 2007-2013, call FAS salute 2014, OMITERC project, grant 4421.02102014.072000037.

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Salvianti, F., Gelmini, S., Mancini, I. et al. Circulating tumour cells and cell-free DNA as a prognostic factor in metastatic colorectal cancer: the OMITERC prospective study. Br J Cancer 125, 94–100 (2021). https://doi.org/10.1038/s41416-021-01399-6

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