Introduction
The incidence of melanoma is raising, but only a small proportion of patients have advanced melanoma with poor prognosis. During last several years, the treatment of advanced melanoma has evolved. Understanding the biology of melanoma, its development and spreading are the hallmark of new treatments (target and immune therapy) of advanced melanoma. Treatment strategy is individually tailored according to the patient's and cancer's characteristics. Mutations in BRAF, NRAS and c-KIT are frequent in advanced melanoma. They influence the treatment decision, the responses to treatment and therefore the survival.
Purpose
Our aim was to determine the frequency of BRAF, NRAS and c-KIT mutations in the Slovene population of patients with advanced melanomas and to evaluate their effect on the course of the disease, treatment response and survival.
Methods
In our research, we included 230 patients with advanced melanoma who were treated at the Institute of Oncology Ljubljana between April 2013 and July 2016. We collected the data retrospectively. Information about the patients’ data, tumor characteristics and treatments were obtained from the archives of medical documentation and supplemented with data from The Cancer Registry of Republic of Slovenia. Molecular analysis was performed with a real-time PCR method. We have analysed the data with descriptive, correlation and survival analysis. As a statistical program we have used SPSS program, version 22.0.
Results
The average age of patients was 55,4 (20–83) years. 141 (61,3%) were men, 89 (38,7%) women. 167 (72,6%) had skin melanoma, 11 (4,8%) ocular melanoma, 7 (3,0%) mucous membrane melanoma, and 45 (19,6%) had melanoma of unknown primary origin. Mutation in the BRAF gene was found in 129 (56,1%), NRAS in 31 (15,1%) and c-KIT in 3 (1,5%) samples. Patients with BRAF mutation tend to be younger and with the most frequent location of melanoma on the trunk. Patients with NRAS mutation tend to be older and with the most frequent location of melanoma at the extremities. The average survival was 11, 4 months, with the lowest survival in a group of patients who didn’t receive systemic treatment 3,7 months. The longest survival of 22,0 months was observed in a group of patients who have been treated with immunotherapy. Mutation in BRAF and NRAS gene didn’t have any influence on overall survival. Among patients with BRAF mutation, the worst survival was in a group of patient with V600K mutation without treatment with BRAF inhibitors 2,7 months. Patients with V600E mutation had median survival of 4,5 months, if they received no treatment with BRAF inhibitors and 12,0 months if they did. The group with the longest survival had V600K mutation and was treated with BRAF inhibitors 15,7 months.
Conclusions
Mutation in the BRAF gene is common in the Slovene population of patients with advanced melanoma. The introductions of new systemic treatments (target and immuno therapy) have influenced on melanoma progression and survival. Mutations in the BRAF, NRAS and c-KIT genes are key elements in decision making which treatment is the most appropriate for an individual patient.
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