Circulating Tumour DNA Is an Independent Prognostic Biomarker for Survival in Metastatic <i>BRAF</i> or <i>NRAS</i>-Mutated Melanoma Patients

• Main Authors: Guillaume Herbreteau, Audrey Vallée, Anne-Chantal Knol, Sandrine Théoleyre, Gaelle Quéreux, Cécile Frénard, Emilie Varey, Paul Hofman, Amir Khammari, Brigitte Dréno, Marc G. Denis
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Cancers
• Subjects: melanoma; circulating tumour DNA; BRAF; NRAS; mutation; prognosis
• Online Access: https://www.mdpi.com/2072-6694/12/7/1871

Circulating tumour DNA (ctDNA) can be used to identify gene alterations. The purpose of this study was to determine whether the detection of ctDNA, based on the identification of <i>BRAF</i> and <i>NRAS</i> mutations before systemic treatment initiation, was associated with the prognosis of metastatic melanoma. In total, 68 <i>BRAF</i> or <i>NRAS</i>-mutated stage IV or unresectable stage III metastatic cutaneous melanoma patients were included and tested for the presence of <i>BRAF</i> and <i>NRAS</i> mutations in circulating DNA before treatment initiation, using the Cobas BRAF/NRAS Mutation Test (Roche). The expected mutation was detected in the plasma of 34/68 patients (50% sensitivity). ctDNA detection was associated with AJCC stage, along with the number and nature of metastases. ctDNA was less frequently detected in <i>NRAS</i>-mutated than in <i>BRAF</i>-mutated melanoma (36% and 66%, respectively). At initiation of first-line treatment, ctDNA detection was associated with poor prognosis in Progression Free Survival (PFS) and Overall Survival (OS) in univariate analysis (log-rank: <i>p</i> = 0.002 and <i>p</i> < 0.0001, respectively). In multivariate analysis, ctDNA detection was an independent factor of poor prognosis in OS, after adjustment for AJCC stage, number and nature of metastases and gender (HR = 4.384; 95% CI: (1.308; 14.699); <i>p</i> = 0.017).