Circulating tumour DNA (ctDNA) in metastatic melanoma, a systematic review and meta-analysis.

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dc.contributor.authorGracie, Lara
dc.contributor.authorPan, Yi
dc.contributor.authorAtenafu, Eshetu G
dc.contributor.authorWard, Douglas G
dc.contributor.authorTeng, Mabel
dc.contributor.authorPallan, Lallit
dc.contributor.authorStevens, Neil M
dc.contributor.authorKhoja, Leila
dc.contributor.departmentOncologyen_US
dc.contributor.roleMedical and Dentalen_US
dc.contributor.trustauthorTeng, Mabel
dc.date.accessioned2024-07-02T15:20:24Z
dc.date.available2024-07-02T15:20:24Z
dc.date.issued2021-10-30
dc.description.abstractIntroduction: Circulating tumour DNA (ctDNA) is an emerging biomarker in melanoma. We performed a systematic review and meta-analysis to explore its clinical utility as a prognostic, pharmacodynamic (PD) and predictive biomarker. Methods: A systematic search was conducted from Jan 2015 to April 2021, of the electronic databases PubMed, Cochrane Library and Ovid MEDLINE to identify studies. Studies were restricted to those published in English within the last 5 years, evaluating ctDNA in humans in ≥10 patients. Survival data were extracted for meta-analysis using pooled treatment effect (TE), i.e. log hazard ratios (HRs) and corresponding standard error of TE for progression-free survival or overall survival differences in patients who were ctDNA positive or negative. PRISMA statement guidelines were followed. Results: A meta-analysis of 19 studies grouped according to methodology of ctDNA detection, revealed a combined estimate for HR of progression-free survival (13 studies using droplet digital Polymerase Chain Reaction (ddPCR) methodology (N = 1002) of 2.10 (95% CI: 1.71-2.59) revealing a poorer prognosis when ctDNA was detected. This result was confirmed in the smaller analysis of (non-ddPCR, N = 347) five studies: HR = 2.45 (95% CI: 1.29-4.63). Similar findings were found in the overall survival analysis of nine studies (ddPCR methodology, N = 841) where the combined HR was 2.78 (95% CI: 2.21-3.49) and of the five studies (non-ddPCR methodology, N = 326) where the combined HR was 2.58 (95% CI: 1.74-3.84). Serial ctDNA levels on treatment showed a pharmacodynamic role reflecting response or resistance earlier than radiological assessment. Conclusions: Circulating tumour DNA is a predictive, prognostic and PD biomarker in melanoma. Technical standardisation of assays is required before clinical adoption.en_US
dc.identifier.citationGracie L, Pan Y, Atenafu EG, Ward DG, Teng M, Pallan L, Stevens NM, Khoja L. Circulating tumour DNA (ctDNA) in metastatic melanoma, a systematic review and meta-analysis. Eur J Cancer. 2021 Oct 30;158:191-207. doi: 10.1016/j.ejca.2021.09.019. Epub ahead of printen_US
dc.identifier.doi10.1016/j.ejca.2021.09.019
dc.identifier.eissn1879-0852
dc.identifier.issn0959-8049
dc.identifier.pmid34757258
dc.identifier.urihttp://hdl.handle.net/20.500.14200/5012
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.urlhttps://www.sciencedirect.com/journal/european-journal-of-canceren_US
dc.rightsCopyright © 2021 Elsevier Ltd. All rights reserved.
dc.source.beginpage191
dc.source.countryEngland
dc.source.endpage207
dc.source.journaltitleEuropean Journal of Canceren_US
dc.source.volume158
dc.subjectMicrobiology. Immunologyen_US
dc.subjectGeneticsen_US
dc.titleCirculating tumour DNA (ctDNA) in metastatic melanoma, a systematic review and meta-analysis.en_US
dc.typeArticleen_US
dc.typeOtheren_US
dspace.entity.typePublication
oa.grant.openaccessnaen_US
rioxxterms.versionNAen_US
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