Prognostic Impact of Brain Radiotherapy and Lactate Dehydrogenase in Melanoma with Brain Metastases: A Retrospective Cohort Study

Objective: The prognosis of patients with advanced melanoma remains poor, particularly in those with brain metastases. To date, no standardized later-line treatment regimen has been established for this patient population. This study aimed to explore prognostic factors in patients with advanced melanoma and brain metastases, with a specific focus on the prognostic significance of baseline lactate dehydrogenase (LDH) levels and cranial radiotherapy. Materials and Methods: This retrospective cohort study consecutively enrolled 145 patients diagnosed with melanoma brain metastases (MBM) between 1 December 2015 and 31 August 2024. Baseline LDH data were available for 139 patients (95.9%), while the remaining six cases were excluded from LDH-stratified analyses. Patients were divided into an elevated LDH group (>250 U/L) and a normal LDH group (≤250 U/L). Collected clinical variables included brain intensity-modulated radiotherapy (IMRT), systemic treatment strategies (immunotherapy, targeted therapy, and chemotherapy), the number of prior treatment lines, and neurological symptoms at diagnosis. The completeness of all other clinical variables reached 100%. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for overall survival (OS) and progression-free survival (PFS). All statistical analyses were conducted using SPSS 21.0. Results: The median OS of the entire cohort was 6.7 months (range: 0.4–101.0 months). Multivariate Cox regression identified three independent protective factors for superior OS and PFS: brain IMRT administration (OS: HR = 0.565, 95% CI: 0.365–0.874, p = 0.010; PFS: HR = 0.623, 95% CI: 0.420–0.924, p = 0.019), normal baseline LDH (OS: HR = 2.091, 95% CI: 1.425–3.069, p < 0.001; PFS: HR = 1.456, 95% CI: 1.023–2.071, p = 0.037), and ≤3 prior lines of systemic therapy before MBM diagnosis (OS: HR = 0.853, p = 0.004; PFS: HR = 1.679, p = 0.015). Moreover, the absence of neurological symptoms at baseline was an independent favorable prognostic factor for OS (HR = 1.919, p = 0.001) but not for PFS. Patients with normal LDH combined with brain IMRT exhibited the best OS and PFS outcomes (p < 0.001). Conclusions: Baseline LDH level and cranial radiotherapy are robust independent prognostic indicators for survival in MBM patients. More prior treatment lines and the presence of neurological symptoms correlate with inferior clinical outcomes. These findings provide evidence for clinical risk stratification and individualized treatment decision-making for this high-risk and challenging population.