Clinical factors associated with leptomeningeal disease in patients with melanoma brain metastasis

Abstract Background Leptomeningeal disease (LMD) is a severe manifestation of metastatic cancer with limited treatment options and a poor prognosis. Melanoma has one of the highest rates of leptomeningeal spread among solid tumors. Given the associated morbidity and mortality, identifying clinical factors linked to LMD in patients with melanoma brain metastases (MBM) is crucial. Methods We conducted a retrospective study of 829 MBM patients diagnosed at MD Anderson Cancer Center (2009-2018). The primary outcome measure was time from MBM-to-LMD. Cumulative incidence of LMD was determined using the competing risks method, where death was the competing risk. Differences in cumulative incidences were assessed using Gray’s test, and associations between measures of interest and cumulative incidence were determined using proportional sub-distribution hazards models. Results Among 829 patients, 129 (16%) developed LMD (median follow-up: 12.1 months, range: 0.03-156 months). Median time from MBM diagnosis to LMD was 5.5 months. Of those with known mutation status (n = 713), BRAF V600 mutation was present in 74% of patients who developed LMD versus 50% in those who did not (p < 0.001). Multivariable analysis (MVA) showed BRAF V600 mutation (p = 0.009) and craniotomy (p = 0.035) were associated with the development of LMD. In a sub-analysis of BRAF V600 mutant patients (n = 380), MVA revealed that primary melanoma site (upper extremity vs. head/neck) and number of MBMs at diagnosis were associated with LMD development. Conclusion LMD is a dire consequence of advanced melanoma, yet the clinical features associated with its development are not fully characterized. Identifying clinical predictors may guide management of high-risk populations.