Article
BRAF mutation status and radiotherapy are prognostic factors in brain metastasis of malignant melanoma
BRAF Mutations-Status sowie Radiotherapie bei Patienten mit Hirnmetastasen maligner Melanome sind einflussreiche prognostische Faktoren
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Published: | May 8, 2019 |
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Objective: Malignant melanoma (MM) rank among the most common cancers spreading into to central nervous system (CNS). Brain metastasis (BM) is known to essentially influence treatment options and patients’ prognosis. Beside neurosurgical resection and radiotherapy, BRAF mutations are emerging targets for systemic therapies. The aim of the present study was to elucidate the clinical course of patients with BM of MM with respect to the role of BRAF mutations.
Methods: All patients treated in our institution for CNS metastasis of MM during January 2008 and June 2018 were included. Patients’ medical records were screened with special interest to age, location of CNS metastasis, BRAF mutation status, radiotherapy and 1-year survival. Statistical analyses were conducted with SPSS (version 22.0). Data was analyzed using student’s t-test, chi-square test and Kaplan-Meier analysis.
Results: 100 patients were operated for CNS metastasis of MM and were eligible for our analyses (47 women, 53 men). 15 patients were treated for spinal metastases whereas 85 patients had BM. Of all BM, 68 metastases were singular. Time between diagnosis of MM and occurrence of BM varied greatly, ranging from 0 to 348 months (median 64 months). There was a significant association between localization of the primary tumor (body vs. extremities) and timing of BM (P=0.001). Patients, that were treated with adjuvant or neoadjuvant radiotherapy in addition to neurosurgical resection, showed a significant better 1-year survival in comparison to patients without radiotherapy (P=0.005). For 30 patients, BRAF mutation status was available. 21 patients showed a BRAF mutation (70%) and had a significant better 1-year survival (P=0.047). Patients, that developed BM during the first 36 months after diagnosis and had BRAF-wildtype tumors had a significant better 1-year survival in comparison to patients with BRAF mutated tumors. In contrast, patients with late metastasized MM (>36 months) showed a better survival with BRAF mutated tumors compared to BRAF wildtype tumors (P=0.029).
Conclusion: BM of MM is known to limit patients’ prognosis. The addition of radiotherapy in the treatment of BM improves survival. Patients with BRAF mutated tumors were showed a better 1-year survival. Furthermore, we detected an influence of BRAF mutation status on prognosis depending on the timing of BM.