Meningiomas classified as grade 2 due to brain invasion alone have better progression-free survival than other atypical meningiomas.

Abstract

Background: Brain invasion (BI) was incorporated as a major criterion for grade 2 meningiomas in the 2016 WHO guidelines. However, its prognostic value remains controversial due to variability in surgical sampling and histopathologic interpretation, as well as BI may be the consequence of mechanical forces related more with the size of the tumor than the biologic presence of an innately more aggressive biologic lesion. Despite advances in molecular characterization of meningiomas, the relevance of BI as an independent prognostic indicator remains unresolved. We sought to determine whether BI alone, taken out of context of other parameters, particularly tumor size, truly represents a more aggressive standalone feature, by comparing time-to-progression (TTP) in atypical meningiomas classified as such due to BI alone versus other atypical meningiomas.

Methods: A single-institutional retrospective cohort study of patients with resected meningiomas from 2003 to 2023 was performed. Pathology reports were reviewed and tumors were re-graded using current WHO criteria. Only WHO Grade 2 patients were included in the study. Patients were then divided into two cohorts: The BIOB (Brain Invasion Otherwise Benign) group and "other criteria" (OC) group. Primary outcome was TTR and association of factors with TTR were assessed using Cox regression.

Results: 131 patients with a mean age of 59.2 ± 15.9 years were included. Median (IQR) preoperative tumor volume was 34.3 cm³ (16-57.9). Gross total resection was achieved in 69 (53%) tumors. 18 patients (14%) had adjuvant radiation. BI was noted in 78 (60%) patients, 45 (34%) of which were classified as BIOB. Mean radiographic follow-up was 74 ± 56 months. Progression was noted in 40 (31%) patients at a mean of 40 ± 39 months post-resection. Progression occurred in 17.8% of BIOB patients (8/45) and 37.2% of OC patients (32/86). Baseline demographic, radiologic, and treatment characteristics did not differ significantly between BIOB and OC groups (all P > 0.3). On univariate Cox regression, TTR was associated with the BIOB group (Hazard Ratio [HR] = 0.44, P = 0.036), GTR (HR = 0.29, P < 0.001), and residual volume (HR = 1.04, P = 0.002). On multivariable Cox regression, BIOB was associated with longer TTR (HR = 0.44, P = 0.041), when controlling for GTR and posterior fossa location.

Conclusions: Atypical meningiomas secondary to brain invasion alone were associated with significantly longer TTR than tumors with other Grade 2 criteria. This was especially robust for larger BI-only tumors. Further research is needed to delineate if brain invasion should truly be a standalone criterion for Grade 2 classification.