Prognostic Utility of Molecular Classification in Skull Base Meningiomas Treated with Stereotactic Radiosurgery

Abstract Molecular analysis has emerged as a prognostic tool for meningiomas; however, its impact on outcomes following stereotactic radiosurgery (SRS) in skull base meningiomas remains unclear. This is a retrospective study of patients with surgically resected skull base meningiomas followed by SRS between 1999 and 2023. Tumors were categorized into three molecular groups using whole-exome sequencing (WES): Group A (NF2-wildtype), Group B (NF2-mutant/22q loss), and Group C (TERT promoter mutation or high-risk copy number alterations [CNAs]). The primary outcome was progression-free survival (PFS) rates, and the secondary outcome was disease-specific survival (DSS) rates. A total of 75 skull base meningiomas in 73 patients were included in this study (median age, 60 years; follow-up after SRS, 45 months; prescription dose, 16 Gy; 64% female), with predominant diagnosis of World Health Organization (WHO) grade 1 (58 tumors). After WES, 34 tumors were molecularly classified for Group A, 11 for Group B, and 30 for Group C. Group C exhibited significantly poorer PFS at 5 years (50%; vs. A 87%, p < 0.001; and B 100%, p = 0.008: log-rank test), and poorer DSS at 10 years (50%; vs. A 100%, p < 0.001; and B 100%, p = 0.014). In Cox proportional hazards analysis, Group C (vs. A/B) and tumor volume were significantly associated with tumor progression after SRS, while WHO grade and tumor location were not. Molecular profiling revealed that skull base meningiomas with high-risk CNAs experience significantly worse outcomes after SRS, implying potentially individualized strategies in this traditionally favorable subgroup.