BRAF mutation status is an independent prognostic factor for resected stage IIIB and IIIC melanoma: Implications for melanoma staging and adjuvant therapy

Andrew P. Barbour, Yue Hang Tang, Nicola Armour, Ken Dutton-Regester, Lutz Krause, Kelly A. Loffler, Duncan Lambie, Bryan H Burmeister, Janine Thomas, B. Mark Smithers, Nicholas K. Hayward

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

Background 5-year survival for melanoma metastasis to regional lymph nodes (American Joint Committee on Cancer stage III) is <50%. Knowledge of outcomes following therapeutic lymphadenectomy for stage III melanoma related to BRAF status may guide adjuvant use of BRAF/MEK inhibitors along with established and future therapies.

Aims To determine patterns of melanoma recurrence and survival following therapeutic lymph node dissection (TLND) associated with oncogenic mutations. Methods DNA was obtained from patients who underwent TLND and had ≥2 positive nodes, largest node >3 cm or extracapsular invasion. Mutations were detected using an extended Sequenom MelaCARTA panel.

Results Mutations were most commonly detected in BRAF (57/124 [46%] patients) and NRAS (26/124 [21%] patients). Patients with BRAF mutations had higher 3-year recurrence rate (77%) versus 54% for BRAF wild-type patients (hazard ratio (HR) 1.8, p = 0.008). The only prognostically significant mutations occurred in BRAF: median recurrence-free (RFS) and disease-specific survival (DSS) for BRAF mutation patients was 7 months and 16 months, versus 19 months and not reached for BRAF wild-type patients, respectively. Multivariate analysis identified BRAF mutant status and number of positive lymph nodes as the only independent prognostic factors for RFS and DSS.

Conclusions Patients with BRAF mutations experienced rapid progression of metastatic disease with locoregional recurrence rarely seen in isolation, supporting incorporation of BRAF status into melanoma staging and use of BRAF/MEK inhibitors post-TLND.

Original languageEnglish
Pages (from-to)2668-2676
Number of pages9
JournalEuropean Journal of Cancer
Volume50
Issue number15
Early online date25 Jul 2014
DOIs
Publication statusPublished - Oct 2014
Externally publishedYes

Keywords

  • Melanoma
  • Molecular diagnostic techniques
  • Oncogenes
  • Proto-oncogene proteins B-raf
  • B-raf
  • Proto-oncogene proteins

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