High BRAF variant allele frequencies are associated with distinct pathological features and responsiveness to target therapy in melanoma patients

ESMO Open

article

E. Berrino¹  A. Balsamo³  A. Pisacane¹  S. Gallo⁴  P. Becco⁴  U. Miglio¹  D. Caravelli⁴  S. Poletto⁴  L. Paruzzo⁴  C. Debernardi¹  C. Piccinelli¹  A. Zaccagna⁶  P. Rescigno⁷  M. Aglietta⁴  A. Sapino¹  F. Carnevale-Schianca⁴  T. Venesio¹ 

[1] Pathology Unit, Candiolo Cancer Institute;Department of Medical Sciences, University of Turin;Clinical Research Office, Candiolo Cancer Institute;Medical Oncology Division, Candiolo Cancer Institute;Department of Oncology, University of Turin;Dermosurgery, Candiolo Cancer Institute;Interdisciplinary Group for Research and Clinical Trials, Candiolo Cancer Institute

关键词: melanoma;    BRAF mutations;    variant allele frequency;    increased survival;   

DOI  :  10.1016/j.esmoop.2021.100133

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

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 BRAF25% 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.

【 授权许可】

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