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

Authors

Merve Hasanov, Christina A Faraj, Denai R Milton, Subhiksha Srinivasan, Eric A Goethe, Ian E McCutcheon, Jeffrey S Weinberg, Isabella C Glitza Oliva, Sherise D Ferguson

Published in

Neuro-oncology advances. Volume 8. Issue 1. Pages vdag232. Epub Sep 15, 2026.

Abstract

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.
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.
Among 829 patients, 129 (16%) developed LMD (median follow-up: 12.1 months, range: 0.0-156.2 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 < .001). Multivariable analysis (MVA) showed BRAF V600 mutation (P = .009) and craniotomy (P = .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.
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.

PMID:
42841061
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.

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