TY - JOUR
T1 - BRAF mutation status is an independent prognostic factor for resected stage IIIB and IIIC melanoma
T2 - Implications for melanoma staging and adjuvant therapy
AU - Barbour, Andrew P.
AU - Tang, Yue Hang
AU - Armour, Nicola
AU - Dutton-Regester, Ken
AU - Krause, Lutz
AU - Loffler, Kelly A.
AU - Lambie, Duncan
AU - Burmeister, Bryan H
AU - Thomas, Janine
AU - Smithers, B. Mark
AU - Hayward, Nicholas K.
PY - 2014/10
Y1 - 2014/10
N2 - 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.
AB - 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.
KW - Melanoma
KW - Molecular diagnostic techniques
KW - Oncogenes
KW - Proto-oncogene proteins B-raf
KW - B-raf
KW - Proto-oncogene proteins
UR - http://www.scopus.com/inward/record.url?scp=84907260785&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2014.06.009
DO - 10.1016/j.ejca.2014.06.009
M3 - Article
SN - 0959-8049
VL - 50
SP - 2668
EP - 2676
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 15
ER -