Melanoma Brain Metastases: A Retrospective Analysis of Prognostic Factors and Efficacy of Multimodal Therapies

SIMPLE SUMMARY: The treatment strategies of patients with melanoma brain metastases are continually evolving, although this remains a poor prognostic subset. We report a real-life retrospective analysis of 105 patients with melanoma brain metastases aiming to analyze the impact of clinical–pathological features and multimodal therapies, such as neurological symptom occurrence, on overall survival in the pre-combined immunotherapy era. We observed a significant improvement in the survival of patients treated with encephalic radiotherapy (eRT) despite the type of systemic treatment performed. The only subset of patients that did not experience survival improvement from eRT was identified by LDH levels higher than two times the upper limit normal. In our opinion, our results, if confirmed by prospective analysis, may help to identify the correct therapeutic strategy for the worst prognostic subgroup of patients with melanoma brain metastases. ABSTRACT: Brain metastasis in cutaneous melanoma (CM) has historically been considered to be a dismal prognostic feature, although recent evidence has highlighted the intracranial activity of combined immunotherapy (IT). Herein, we completed a retrospective study to investigate the impact of clinical–pathological features and multimodal therapies on the overall survival (OS) of CM patients with brain metastases. A total of 105 patients were evaluated. Nearly half of the patients developed neurological symptoms leading to a negative prognosis (p = 0.0374). Both symptomatic and asymptomatic patients benefited from encephalic radiotherapy (eRT) (p = 0.0234 and p = 0.011). Lactate dehydrogenase (LDH) levels two times higher than the upper limit normal (ULN) at the time of brain metastasis onset was associated with poor prognosis (p = 0.0452) and identified those patients who did not benefit from eRT. Additionally, the poor prognostic role of LDH levels was confirmed in patients treated with targeted therapy (TT) (p = 0.0015) concerning those who received immunotherapy (IT) (p = 0.16). Based on these results, LDH levels higher than two times the ULN at the time of the encephalic progression identify those patients with a poor prognosis who did not benefit from eRT. The negative prognostic role of LDH levels on eRT observed in our study will require prospective evaluations.