The prognostic value of circulating tumor DNA in patients with melanoma: A systematic review and meta-analysis

Abstract

Background: Circulating tumor DNA (ctDNA) has been investigated as a potential prognostic biomarker to evaluate the therapeutic efficacy and disease progression in melanoma patients, yet results remain inconclusive. The purpose of this study was to illustrate the prognostic value of ctDNA in melanoma.

Objectives: To describe the clinical prognostic value of ctDNA for melanoma patients.

Methods: Searched for eligible articles from Pubmed, Web of Science and Embase. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the association between ctDNA at baseline or during treatment and overall survival (OS) and progression-free survival (PFS).

Results: A total of 9 articles were obtained, involving 617 melanoma patients. The pooled HRs revealed that compared with baseline undetectable ctDNA patients, detectable ctDNA was highly correlated with poor OS (HR 2.91, 95% CI: 2.22-3.82; p < 0.001) and PFS (HR 2.75, 95% CI: 1.98-3.83; p < 0.001). A meta-analysis of these adjusted HRs was performed and confirmed that ctDNA collected at baseline was associated with poorer OS/PFS (OS: HR 3.00, 95% CI 2.19-4.11, p < 0.001/PFS: HR 2.68, 95% CI 1.77-4.06, p < 0.001). During treatment, a significant association was shown between ctDNA and poorer OS/PFS (OS: HR 6.26, 95% CI 2.48-15.80, p < 0.001; PFS: HR 4.93, 95% CI 2.36-10.33, p < 0.001).

Conclusion: Investigation and application of ctDNA will improve "liquid biopsy" and play a role in early prediction, monitoring disease progression and precise adjusting treatment strategies in melanoma patients.

Keywords: Circulating tumor DNA; Melanoma; Meta-analysis; Prognostic value.

Graphical abstract

Fig. 1

PRISMA flowchart of the study. Selection process for study inclusion in the systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA).

Fig. 2

Forest plot adjusted and unadjusted hazard ratio (HR) for the correlation between ctDNA and OS in melanoma.

Fig. 3

Forest plot adjusted and unadjusted hazard ratio (HR) for the correlation between ctDNA and PFS in melanoma.

Fig. 4

Prognostic value of ctDNA in melanoma patients during treatment. (a) for OS; (b) for PFS.

Fig. 5

Cumulative meta-analysis for OS (a) and PFS (b), based on year of publication.

Fig. 6

Sensitivity analysis. (a) ctDNA for OS; (b) ctDNA for PFS.

Fig. 7

Begg's funnel plot and Egger's test to evaluate publication bias. (a) Begg's test for overall survival (OS); (b) Egger's test for OS; (c) Begg's test for progression-free survival (PFS); and (d) Egger's test for PFS.