Identifying BRAF mutations is crucial for managing advanced melanoma in treatment-naïve patients. When tumor tissue is unavailable or inadequate, liquid biopsy represents a promising alternative. This retrospective, single-center study evaluated the effectiveness of plasma circulating tumor DNA (ctDNA) in detecting BRAF mutations and assessed patient outcomes following BRAF/MEK inhibitor therapy initiated based on ctDNA results. A total of 46 patients (21 women, 25 men) with advanced melanoma underwent ctDNA analysis. Mutations in BRAF were observed in 45.7% (21/46) of liquid biopsy samples and 44.8% (13/29) of available tissue samples. Among patients with both tissue and ctDNA data (n = 29), the two approaches agreed in 82.8% of cases. In 7 out of 17 patients assessed exclusively via ctDNA, BRAF mutations were detected. Eighteen patients received BRAF/MEK inhibitor therapy guided by liquid biopsy findings, achieving an objective response rate of 77.8% and a median progression-free survival of 6.0 months. These results demonstrate that plasma ctDNA is a reliable tool for BRAF mutation detection and that targeted therapy can be initiated based on liquid biopsy in real-world clinical practice.
