Abstract

BackgroundPatients (pts) with melanoma brain metastases (BM) have a historically poor prognosis, with a reported median overall survival (mOS) of 4-6 months. Aim of this study is to evaluate predictive factors of survival in pts with melanoma BM. Secondly, a multivariate model was used to define groups with distinct prognosis. MethodsConsecutive pts with melanoma BM treated in two Italian cancer centers were included in this 10-year retrospective cohort study (2008-2018). Baseline clinicopathological factors, systemic and loco-regional treatments were registered. The Kaplan-Meier method and the Cox model were used to analyze the association of prognostic factors and OS. Results150 pts with melanoma BM were enrolled in this study: 42% with a single BM, 51.3% with ≥ 3 extracranial metastatic sites and 38% with an ECOG performance status (PS) of 0. About 50.7% of pts had a BRAF mutation. Notably, 56% of pts were asymptomatic at BM diagnosis, and 40% presented high LDH levels at baseline. Overall, mOS after BM diagnosis was 5.78 months (95% CI 4.80-6.67), and median intracranial progression-free survival was 4.63 months (95% CI 3.81-5.12). According to treatment modality, stereotactic radiosurgery/neurosurgery plus systemic therapy showed the best outcome (mOS 12.32 months, 95% CI 7.92-25.30). A multivariate model was used to identify baseline prognostic factors independently associated with OS (Table). Conversely, sex and symptomatic BM did not significantly impact on OS. Predicted survival functions defined 3 distinct prognostic groups (P<0.0001): favorable (≤ 2 points: mOS 8.47 months, 95% CI 7.52-12.71), intermediate (3 points: mOS 4.93 months, 95% CI 3.84-6.01), poor (≥ 4points: mOS 2.66 months, 95% CI 2.23-3.61).Table1363PTableCovariatesHR95% CIPPointsBRAF wild type1.951.22-3.12< 0.011BM>12.201.35-3.59< 0.011LDH ≥ 2 x upper normal limit1.831.07-3.110.0261ECOG PS>02.681.62-4.430.00011Extracranial metastatic sites ≥ 31.911.17-3.1< 0.011Age ≥ 651.861.15-3.020.0121 ConclusionsThis score can be useful for stratifying prognosis in pts with melanoma BM. Prospective studies are needed to validate this score and to explore how it may guide treatment strategy. Legal entity responsible for the studyDipartimento di Oncologia, Azienda Sanitaria Universitaria Integrata di Udine. FundingHas not received any funding. DisclosureF. Puglisi: Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: Celgene; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Research grant / Funding (self): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self): Pierre Fabre; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Takeda; Research grant / Funding (self): Astrazeneca. All other authors have declared no conflicts of interest.

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