Early evolution of BRAFV600 status in the blood of melanoma patients correlates with clinical outcome and identifies patients refractory to therapy
Por:
Gonzalez-Cao, M, de las Casas, CM, Ariza, NJ, Manzano, JL, Molina-Vila, MA, Soriano, V, Puertolas, T, Balada, A, Soria, A, Majem, M, Montagut, C, Munoz, E, Rodriguez-Abreu, D, Perez, E, Garcia, A, Cortes, J, Drozdowskyj, A, Karachaliou, N, Rosell, R
Publicada:
1 jun 2018
Resumen:
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 (c) 2018 Wolters Kluwer Health, Inc. All rights reserved.
Filiaciones:
Gonzalez-Cao, M:
Univ Hosp Quiron Dexeus, Inst Oncol Dr Rosell IOR, Lab Oncol, Barcelona, Spain
de las Casas, CM:
Univ Hosp Quiron Dexeus, Inst Oncol Dr Rosell IOR, Lab Oncol, Barcelona, Spain
Ariza, NJ:
Univ Hosp Quiron Dexeus, Inst Oncol Dr Rosell IOR, Lab Oncol, Barcelona, Spain
Manzano, JL:
Germans Trias & Pujol Hosp, Catalan Inst Oncol, Badalona, Spain
Molina-Vila, MA:
Univ Hosp Quiron Dexeus, Inst Oncol Dr Rosell IOR, Lab Oncol, Barcelona, Spain
Soriano, V:
IVO Fundat, Valencia, Spain
Puertolas, T:
Miguel Servet Hosp, Zaragoza, Spain
Balada, A:
Univ Hosp Quiron Dexeus, Inst Oncol Dr Rosell IOR, Lab Oncol, Barcelona, Spain
Soria, A:
Ramon & Cajal Hosp, Madrid, Spain
Majem, M:
St Pau Hosp, Vancouver, BC, Canada
Montagut, C:
Del Mar Hosp IMIM, Passeig Maritim, Barcelona, Spain
Munoz, E:
VHIO, Barcelona, Spain
Rodriguez-Abreu, D:
Univ Hosp Gran Canaria, Las Palmas Gran Canaria, Spain
Perez, E:
Costa Sol Hosp, Marbella, Spain
Garcia, A:
Marques Valdecilla Hosp, Santander, Spain
Cortes, J:
VHIO, Barcelona, Spain
Ramon & Cajal Hosp, Madrid, Spain
Drozdowskyj, A:
Pivotal SL, Madrid, Spain
Karachaliou, N:
Univ Hosp Quiron Dexeus, Inst Oncol Dr Rosell IOR, Lab Oncol, Barcelona, Spain
Rosell, R:
Univ Hosp Quiron Dexeus, Inst Oncol Dr Rosell IOR, Lab Oncol, Barcelona, Spain
Germans Trias & Pujol Hosp, Catalan Inst Oncol, Badalona, Spain
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