Leptomeningeal Metastases in Glioma Revisited: Incidence and Molecular Predictors Based on Post-contrast FLAIR Imaging

Background: Leptomeningeal metastases (LM) in glioma have been underestimated due to low incidence and lack of reliable imaging. This study aimed to investigate a real-world incidence of LM using a CSF-sensitive imaging, namely post-contrast FLAIR, and analyze molecular predictors for LM in the molecular era. Patients and Methods: Total 1,405 adult glioma patients underwent post-contrast FLAIR imaging at initial diagnosis and during treatment monitoring between 2001 and 2021. Molecular data included isocitrate dehydrogenase (IDH) mutation, 1p/19q co-deletion, H3 K27M alteration, and O6-methylguanine-methyltransferase (MGMT) promoter methylation status. LM diagnosis was performed with MRI including post-contrast FLAIR. Logistic regression analysis for LM development was performed with molecular, clinical, and imaging data. Overall survival (OS) was compared between patients with and without LM. Results: LM was identified in 228 patients (16.2%), with 110 patients (7.8%) at initial diagnosis, and 118 patients (8.4%) at recurrence. Among molecular diagnostics, IDH-wildtype (odds ratio [OR] 3.14, P = .001) and MGMT promoter unmethylation (OR=1.43, P=.034) were independent predictors of LM. WHO grade 4 (OR=10.52, P <.001) and nonlobar location (OR=1.54, P=.048) were associated with LM at initial diagnosis, whereas IDH-wildtype (OR=5.04, P<.001) and H3 K27M alteration (OR=3.39, P=.003) were associated with LM at recurrence. Patients with LM had a worse median OS than those without LM (16.7 vs. 32.0 months, log-rank test; P<.001). Conclusions: CSF-sensitive imaging aid diagnosis of LM demonstrating a high incidence of LM in adult gliomas. Furthermore, molecular markers are associated with LM development in glioma, and patients with aggressive molecular markers warrant imaging surveillance of LM.