Impact of aggressive treatment on outcomes in IDH-wildtype glioblastoma patients with leptomeningeal dissemination.

PURPOSE: Prognosis of leptomeningeal dissemination (LMD) in IDH-wildtype glioblastoma (GBM) patients is dismal, but prognostic factors and optimal treatment strategy for LMD are still not clearly defined. This multi-institutional study aims to analyze clinical factors that affect the outcomes of GBM patients with LMD. METHODS: A total of 221 IDH-wildtype GBM patients with LMD diagnosed between March 2009 and March 2024 in five institutions were analyzed, including 66 primary LMD and 155 recurrent LMD. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were identified using Cox regression model. RESULTS: LMD was confined to the intracranial compartment in most patients (primary LMD, 86.4%; recurrent LMD, 78.7%) based on available imaging. Patients with recurrent LMD had significantly worse OS (median 4.4 vs. 12.1 months; P < 0.001) and PFS (median 2.9 vs. 6.7 months; P < 0.001) compared with those with primary dissemination. Among patients with primary LMD, longer OS was associated with better performance status and younger age, while gross total resection was also associated with improved PFS. In the recurrent setting, male sex, MGMT promoter methylation, comprehensive radiotherapy field coverage, and administration of systemic therapy were associated with both OS and PFS, with bevacizumab and non-bevacizumab regimens showed similar survival benefit. CONCLUSION: Our findings suggest that the prognostic impact of clinical and treatment-related factors on outcomes may be different between primary and recurrent LMD. In particular, aggressive intervention, including comprehensive radiotherapy field coverage and systemic therapy, may improve outcomes in selected patients with IDH-wildtype GBM who develop LMD at recurrence.