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    Circulating tumour DNA as a biomarker in resectable and irresectable stage IV colorectal cancer; a systematic review and meta-analysis

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    Authors
    Jones, R. P.
    Pugh, S. A.
    Graham, J.
    Primrose, J. N.
    Barriuso, Jorge
    Affiliation
    School of Cancer Studies, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; Department of Hepatobiliary Surgery, Liverpool University Teaching Hospitals NHS Foundation Trust, Liverpool, UK.
    Issue Date
    2021
    
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    Abstract
    Background: For patients with metastatic colorectal cancer, stratification for treatment (surgery or chemotherapy) is often based on crude clinicopathological characteristics like tumour size and number of lesions. Circulating tumour DNA (ctDNA) acts as a potential biomarker of disease trajectory and biology, allowing better stratification. This study aims to systematically review ctDNA in stage IV colorectal cancer to assess its potential role as a prospective biomarker to guide management decisions. Methods: A literature search was performed to identify studies where the measurement of ctDNA in stage IV colorectal cancer was correlated with a clinical outcome (radiological response, secondary resection rate, PFS, DFS or OS). Results: Twenty-eight studies were included, reporting on 2823 patients. Circulating tumour DNA was detectable in between 80% and 90% of patients prior to treatment. Meta-analysis identified a strong correlation between detectable ctDNA after treatment (surgery or chemotherapy) and overall survival (HR 2.2, 95% CI 1.79-2.69, p < 0.00001), as well as progression-free survival (HR 3.15, 95% CI 2.10-4.73, p < 0.00001). ctDNA consistently offered an early marker of long-term prognosis in irresectable disease, with changes after one cycle of systemic therapy demonstrating prognostic value. In resectable disease treated with curative intent, detection of ctDNA offered a lead time over radiological recurrence of 10 months. Conclusion: Circulating tumour DNA is detectable in the majority of resectable and irresectable patients. The presence of ctDNA is clearly associated with shorter overall survival, with changes in ctDNA an early biomarker of adverse disease behaviour. Prospective trials are essential to test its clinical efficacy.
    Citation
    Jones RP, Pugh SA, Graham J, Primrose JN, Barriuso J. Circulating tumour DNA as a biomarker in resectable and irresectable stage IV colorectal cancer; a systematic review and meta-analysis. Eur J Cancer. 2021;144:368-81.
    Journal
    European Journal of Cancer
    URI
    http://hdl.handle.net/10541/623746
    DOI
    10.1016/j.ejca.2020.11.025
    PubMed ID
    33422803
    Additional Links
    https://dx.doi.org/10.1016/j.ejca.2020.11.025
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ejca.2020.11.025
    Scopus Count
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