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Lookup NU author(s): Dr Pasquale RescignoORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2021 The Authors. Background: BRAF mutant melanoma patients are commonly treated with anti-BRAF therapeutic strategies. However, many factors, including the percentage of BRAF-mutated cells, may contribute to the great variability in patient outcomes. Patients and methods: The BRAF variant allele frequency (VAF; defined as the percentage of mutated alleles) of primary and secondary melanoma lesions, obtained from 327 patients with different disease stages, was assessed by pyrosequencing. The BRAF mutation rate and VAF were then correlated with melanoma pathological features and patients’ clinical characteristics. Kaplan–Meier curves were used to study the correlations between BRAF VAF, overall survival (OS), and progression-free survival (PFS) in a subset of 62 patients treated by anti-BRAF/anti-MEK therapy after metastatic progression. Results: A highly heterogeneous BRAF VAF was identified (3%-90%). Besides being correlated with age, a higher BRAF VAF level was related to moderate lymphocytic infiltration (P = 0.017), to melanoma thickness according to Clark levels, (level V versus III, P = 0.004; level V versus IV, P = 0.04), to lymph node metastases rather than cutaneous (P = 0.04) or visceral (P = 0.03) secondary lesions. In particular, a BRAF VAF >25% was significantly associated with a favorable outcome in patients treated with the combination of anti-BRAF/anti-MEK drug (OS P = 0.04; PFS P = 0.019), retaining a significant value as an independent factor for the OS and the PFS in the multivariate analysis (P = 0.014 and P = 0.003, respectively). Conclusion: These results definitively support the role of the BRAF VAF as a potential prognostic and predictive biomarker in melanoma patients in the context of BRAF inhibition.
Author(s): Berrino E, Balsamo A, Pisacane A, Gallo S, Becco P, Miglio U, Caravelli D, Poletto S, Paruzzo L, Debernardi C, Piccinelli C, Zaccagna A, Rescigno P, Aglietta M, Sapino A, Carnevale-Schianca F, Venesio T
Publication type: Article
Publication status: Published
Journal: ESMO Open
Year: 2021
Volume: 6
Issue: 3
Print publication date: 01/06/2021
Online publication date: 10/05/2021
Acceptance date: 02/04/2018
Date deposited: 06/11/2024
ISSN (electronic): 2059-7029
Publisher: Elsevier BV
URL: https://doi.org/10.1016/j.esmoop.2021.100133
DOI: 10.1016/j.esmoop.2021.100133
PubMed id: 33984673
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