Retrospective study demonstrates that ctDNA levels correlate with tumor volume and radiologic response in advanced melanoma, highlighting its potential for longitudinal monitoring.
Key Points
To evaluate the longitudinal dynamics of circulating tumor DNA (ctDNA) relative to RECIST radiologic response and volumetric tumor burden in patients receiving immunotherapy for advanced melanoma.
Retrospectively analyzed 42 patients with unresectable stage III/IV melanoma treated with immune checkpoint inhibitors across 241 longitudinal plasma sampling time points.
Quantified ctDNA using a UMI-based amplicon next-generation sequencing assay targeting recurrent mutations in BRAF, EGFR, KRAS, NRAS, and PIK3CA.
Paired ctDNA levels with imaging to evaluate RECIST 1.1 response categories (n = 99 time points) and quantitative 3D volumetric tumor burden (n = 73 time points) using nonparametric correlation and ROC analyses.
ctDNA levels significantly increased with worsening RECIST 1.1 response categories (Spearman ρ = 0.31, 95% CI 0.20–0.52, p = 0.002) and moderately discriminated disease progression (AUC = 0.69).
ctDNA concentrations positively correlated with total tumor volume (ρ = 0.46, p < 0.0001), showing stronger association when samples were aligned within 30 days of imaging (ρ = 0.56), though dynamic changes between the two did not significantly correlate (ρ = 0.20, p = 0.25).
DNA shedding varied substantially across metastatic sites, with high detection in lymph node and peritoneal metastases but reduced detectability in lung, liver, and brain lesions, resulting in lower concordance during stable or progressive disease (72.9%) than during response (85.0%).