Clinical and Radiometabolic Correlatives of ddPCR Liquid Biopsy for BRAF V600 Mutated Melanoma

Circulating tumor DNA (ctDNA) as a liquid biopsy is an emerging tool used for diagnosis and disease monitoring, yet not all tumors shed DNA equally, thus currently limiting the clinical applicability of this tool. Our institution has developed and validated a droplet digital Polymerase Chain Reaction (ddPCR) ctDNA test for BRAF V600 mutation. We collected data on all BRAF mutated melanoma patients tested with the ddPCR BRAF assay at our institution over the years 2018-2024 and correlated the test results with clinical and radiological baseline parameters, with a focus on Positron Emission Tomography-Computed Tomography (PET-CT) data, incorporating both location of lesions and volume of disease. Linear and logistic regression modelling was used to assess possible associations between the baseline parameters and the ctDNA results. We identified 71 BRAF mutated melanoma patients, of which 65 had active disease on imaging studies and 43 had PET-CT data available for analysis. Multivariate modelling has shown that patients were more likely to have a positive ctDNA result if they had elevated serum lactate dehydrogenase (LDH) (OR = 9.9), had a higher number of lesions on imaging studies (> 10 lesions: OR = 11.3), and if they were younger than 65 (OR = 11.8), with an AUC of 0.84. The PET-CT calculated total metabolic tumor volume correlated with the quantitative ctDNA result with a Pearson r factor of 0.49. In conclusion, ctDNA ddPCR BRAF testing is easily obtained and might be especially beneficial for patients diagnosed with a clinically aggressive disease, based on elevated LDH, higher PET-CT metabolic tumor volume, and younger age.