ORIGINAL ARTICLES: Translational researchEarly evolution of BRAFV600 status in the blood of melanoma patients correlates with clinical outcome and identifies patients refractory to therapyGonzalez-Cao, Mariaa; Mayo de las Casas, Claraa; Jordana Ariza, Nuriaa; Manzano, Jose L.e; Molina-Vila, Miguel Á.a; Soriano, Virtudesf; Puertolas, Teresag; Balada, Ariadnaa; Soria, Ainarah; Majem, Margaritab; Montagut, Clarac; Muñoz, Evad; Rodriguez-Abreu, Delvysj; Perez, Elisabethk; Garcia, Almudenal; Cortes, Javierd,h; Drozdowskyj, Anai; Karachaliou, Nikia; Rosell, Rafaela,e; on behalf of the Spanish Melanoma GroupAuthor Information aLaboratory of Oncology, Institute of Oncology Dr Rosell (IOR), University Hospital Quirón Dexeus bSant Pau Hospital, Carrer de Sant Quintí cDel Mar Hospital-IMIM Passeig Marítim dVall D'Hebron Institute of Oncology (VHIO), Passeig de la Vall d'Hebron, Barcelona eCatalan Institute of Oncology, Germans Trias i Pujol Hospital, Badalona fIVO Fundation, Carrer del Professor Beltrán Báguena, Valencia gMiguel Servet Hospital, Paseo Isabel la Católica, Zaragoza hRamon y Cajal Hospital iPivotal SL, Madrid jUniversity Hospital de Gran Canaria, Las Palmas kCosta del Sol Hospital, Marbella lMarques de Valdecilla Hospital, Santander, Spain Correspondence to Maria Gonzalez-Cao, MD, Medical Oncology Service, Institute of Oncology Dr Rosell (IOR), University Hospital Quirón Dexeus, C/Sabino Arana 5-19, 08028 Barcelona, Spain Tel: +34 093 546 0135; fax: +34 935 460 196; e-mail: [email protected] Melanoma Research: June 2018 - Volume 28 - Issue 3 - p 195-203 doi: 10.1097/CMR.0000000000000432 Buy SDC Metrics Abstract 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. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.