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

Barbour, Andrew P., Tang, Yue Hang, Armour, Nicola, Dutton-Regester, Ken, Krause, Lutz, Loffler, Kelly A., Lambie, Duncan, Burmeister, Bryan, Thomas, Janine, Smithers, B. Mark and Hayward, Nicholas K. (2014) BRAF mutation status is an independent prognostic factor for resected stage IIIB and IIIC melanoma: implications for melanoma staging and adjuvant therapy. European Journal of Cancer, 50 15: 2668-2676. doi:10.1016/j.ejca.2014.06.009


Author Barbour, Andrew P.
Tang, Yue Hang
Armour, Nicola
Dutton-Regester, Ken
Krause, Lutz
Loffler, Kelly A.
Lambie, Duncan
Burmeister, Bryan
Thomas, Janine
Smithers, B. Mark
Hayward, Nicholas K.
Title BRAF mutation status is an independent prognostic factor for resected stage IIIB and IIIC melanoma: implications for melanoma staging and adjuvant therapy
Formatted title
BRAF mutation status is an independent prognostic factor for resected stage IIIB and IIIC melanoma: implications for melanoma staging and adjuvant therapy
Journal name European Journal of Cancer   Check publisher's open access policy
ISSN 1879-0852
0959-8049
Publication date 2014-10
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.ejca.2014.06.009
Open Access Status
Volume 50
Issue 15
Start page 2668
End page 2676
Total pages 9
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon Press
Collection year 2015
Language eng
Formatted 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.
Keyword Melanoma
Molecular diagnostic techniques
Oncogenes
Proto-oncogene proteins B-raf
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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