Early evolution of BRAFV600 status in the blood of melanoma patients correlates with clinical outcome and identifies patients refractory to therapy

• Published in: Melanoma research Vol. 28; no. 3; p. 195
• Main Authors: Gonzalez-Cao, Maria, Mayo de Las Casas, Clara, Jordana Ariza, Nuria, Manzano, Jose L, Molina-Vila, Miguel Á, Soriano, Virtudes, Puertolas, Teresa, Balada, Ariadna, Soria, Ainara, Majem, Margarita, Montagut, Clara, Muñoz, Eva, Rodriguez-Abreu, Delvys, Perez, Elisabeth, Garcia, Almudena, Cortes, Javier, Drozdowskyj, Ana, Karachaliou, Niki, Rosell, Rafael
• Format: Journal Article
• Language: English
• Published: England 01.06.2018
• Subjects: Adult; Aged; Aged, 80 and over; Circulating Tumor DNA - blood; Circulating Tumor DNA - genetics; DNA Mutational Analysis; Female; Humans; Male; Melanoma - enzymology; Melanoma - genetics; Melanoma - pathology; Middle Aged; Mutation; Progression-Free Survival; Prospective Studies; Proto-Oncogene Proteins B-raf - blood; Proto-Oncogene Proteins B-raf - genetics; Skin Neoplasms - enzymology; Skin Neoplasms - genetics; Skin Neoplasms - pathology
• ISSN: 1473-5636
• DOI: 10.1097/CMR.0000000000000432

Serial analysis of BRAF mutations in circulating-free DNA (cfDNA) could be of prognostic value in melanoma patients. We collected blood samples from 63 advanced BRAFV600E/K melanoma patients and determined BRAFV600E/K status in cfDNA using a quantitative 5'-nuclease PCR-based assay. Levels of BRAF mutation in pre-cfDNAs were associated significantly with tumour burden, progression-free survival and overall survival. Changes in BRAF status in cfDNA after initiation of treatment (early-cfDNA) had a significant correlation with outcome. In patients with persistent BRAF mutations (n=12), progression-free survival and overall survival were 3.5 months [95% confidence interval (CI): 1.6-4.6] and 5.3 months (95% CI: 3.4-8.1) compared with 16.6 months (95% CI: 8.2-22.3) and 21.9 months (95% CI: 10.2-NR) in patients with BRAF negativization (n=16), and 15.1 months (95% CI: 2.3-NR) and NR (95% CI: 5.1-NR) in patients who maintained their initial negative status (n=12) (P<0.0001). The median duration of response in patients with radiological response, but persistence of BRAFV600 in early-cfDNA (n=5) was 4 months. Our study indicates that serial BRAF testing in the blood of advanced melanoma identifies patients refractory to therapy.