Impact of BRAF inhibitors on surgical outcomes in melanoma brain metastases: Evidence from a multicenter observational study

Background: Melanoma brain metastases (MBMs) pose significant clinical challenges, associated with high morbidity and mortality. Treatment with the BRAF inhibitors has demonstrated long-term clinical benefit, although data regarding their efficacy in surgical MBM patients remain limited. Methods: The study assesses the experience of 5 institutions with patients surgically treated for MBM. Clinical, treatment and performance status data were retrieved. Immunohistochemical, imaging findings, BRAF mutation status, target and systemic therapies were documented. Progression-free survival (PFS) and overall survival (OS) data were recorded. Results: 95 patients met the inclusion criteria. The population was divided into two groups: 1. patients with BRAF-mutation (n = 32, BRAF-mut); 2. patients BRAF wild-type (n = 63, BRAF-wt). BRAF-mut showed a longer time between initial diagnosis and MBMs onset (83 vs. 65.3 months, p = 0.05). Hemorrhagic presentation was more common in the BRAF-mut group (31.3% vs. 9.5%, p < 0.01). BRAF-mut group exhibited a higher extra- cranial metastases incidence (68.8% vs. 44.4%, p = 0.025) with reduced Melan-A expression (34.4% vs. 50.7%, p = 0.05). Furthermore, BRAF-mut group experienced more frequently postoperative hemorrhage (12.5% vs. 3.2%, p = 0.07) with lower performance status, a higher recurrence rates (56.3% vs. 19%, p = 0.01), but longer PFS (15.03 vs. 5 months, p = 0.04). Multivariate analysis confirmed the BRAF-mutations status as an inde- pendent factor for outcome. Conclusions: Patients with melanoma receiving BRAF inhibitors exhibit improved OS and a decreased risk of developing MBMs. When MBMs manifest in BRAF-mutated patients, they typically present a different clinical course, with a significant prevalence of bleeding lesions at onset and marked deterioration in functional status after treatments.