Abstract
Purpose Melanoma is the most aggressive form of skin cancer. Circulating tumor DNA (ctDNA) is a diagnostic and prognostic marker of melanoma. However, whether ctDNA mutations can independently predict survival remains controversial. This meta-analysis assessed the prognostic value of the presence or change in ctDNA mutations in melanoma patients. Methods We identified studies from the PubMed, EMBASE, Web of Science, and Cochrane databases. We estimated the combined hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) using either fixed-effect or random-effect models based on heterogeneity. Results Sixteen studies including 1,781 patients were included. Both baseline and posttreatment detectable ctDNA were associated with poor OS (baseline detectable vs. undetectable, pooled HR = 1.97, 95% CI = 1.64–2.36, P < 0.00001; baseline undetectable vs. detectable, pooled HR = 0.19, 95% CI = 0.11–0.36, P < 0.00001; posttreatment detectable vs. undetectable, pooled HR = 2.36, 95% CI = 1.30–4.28, P=0.005). For PFS, baseline detectable ctDNA may be associated with adverse PFS (baseline detectable vs. undetectable, pooled HR = 1.41, 95% CI = 0.84–2.37, P=0.19; baseline undetectable vs. detectable, pooled HR = 0.43, 95% CI = 0.19–0.95, P=0.04) and baseline high ctDNA and increased ctDNA were significantly associated with adverse PFS (baseline high vs. low/undetectable, pooled HR = 3.29, 95% CI = 1.73–6.25, P=0.0003; increase vs. decrease, pooled HR = 4.48, 95% CI = 2.45–8.17, P < 0.00001). The baseline BRAFV600 ctDNA mutation-positive group was significantly associated with adverse OS compared with the baseline ctDNA-negative group (pooled HR = 1.90, 95% CI = 1.58–2.29, P < 0.00001). There were no significant differences in PFS between the baseline BRAFV600 ctDNA mutation-detectable group and the undetectable group (pooled HR = 1.02, 95% CI = 0.72–1.44, P=0.92). Conclusion The presence or elevation of ctDNA mutation or BRAFV600 ctDNA mutation was significantly associated with worse prognosis in melanoma patients.
Highlights
Melanoma is the most aggressive form of skin cancer, originating from pigment-producing melanocytes. ough it accounts for only 10% of all skin cancers, it is responsible for more than 80% of skin cancer-related deaths. e development of targeted therapy (MAPK pathway inhibitors) [1, 2] and immunotherapy [3–5] has led to substantial improvements in overall survival (OS)
In the study [15] by Seremet et al, undetectable circulating tumor DNA (ctDNA) at baseline remained significantly correlated with progression-free survival (PFS) and OS in metastatic melanoma patients treated with anti-PD1 therapy
Studies were included in the analysis if they met the following criteria: (1) all patients enrolled in the study were diagnosed with melanoma, (2) ctDNA mutation was assessed using plasma or serum, (3) endpoints included PFS or OS, and sufficient data were presented for determining or calculating the hazard ratio (HR) and 95% confidence interval
Summary
Melanoma is the most aggressive form of skin cancer, originating from pigment-producing melanocytes. ough it accounts for only 10% of all skin cancers, it is responsible for more than 80% of skin cancer-related deaths. e development of targeted therapy (MAPK pathway inhibitors) [1, 2] and immunotherapy (checkpoint inhibitors) [3–5] has led to substantial improvements in overall survival (OS). Some studies have focused on the prognostic value of ctDNA in melanoma patients, the results are controversial. In the study [15] by Seremet et al, undetectable ctDNA at baseline remained significantly correlated with progression-free survival (PFS) and OS in metastatic melanoma patients treated with anti-PD1 therapy. Forthun et al conducted a study [16] of bevacizumab in the treatment of metastatic malignant melanoma and showed that ≤1% BRAF/NRASpositive ctDNA before and during treatment reflected a positive response to therapy, through an increase in the durations of PFS and OS. A study by Board et al [17] indicated that cfDNA BRAF detection is not associated with poorer PFS in stage III/IV advanced melanoma. Erefore, the aim of this meta-analysis was to evaluate the prognostic significance of ctDNA mutations in melanoma patients, in terms of OS and PFS Sequencing data identified melanoma as the most frequently mutated tumor type analyzed by e Cancer Genome Atlas (TCGA) [18]. erefore, the aim of this meta-analysis was to evaluate the prognostic significance of ctDNA mutations in melanoma patients, in terms of OS and PFS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
