Molecular insights into prognostic model for meningiomas treated with stereotactic radiosurgery: negative impacts of 1q gain on tumor control and survival

Molecular classifications enhance prognostic accuracy in meningiomas; however, their predictive significance following stereotactic radiosurgery (SRS) remains unclear. This study aimed to assess whether molecular characteristics identified by whole-exome sequencing (WES), specifically driver mutations and copy number alterations (CNAs), are prognostic indicators of outcomes after SRS. This retrospective cohort study included 95 patients (median age 61; 66% female) with 97 surgically resected meningiomas treated with SRS between 1999 and 2023. Primary outcomes were progression-free survival (PFS) and disease-specific survival (DSS). Tumors were molecularly classified using WES into Group A (NF2-wildtype), Group B (NF2 mutation/22q loss without high-risk CNAs), and Group C (high-risk CNAs including 1p loss, 1q gain, 6p/6q loss, 10p/10q loss, 14q loss, 18p/18q loss, and CDKN2A/B homozygous deletion). Group C exhibited significantly inferior PFS at 5 years (49.7%) compared with Groups A (88.5%, p < 0.001) and B (100%, p = 0.002). DSS at 10 years was also significantly reduced in Group C (60.4%) relative to Groups A and B (100%, p < 0.001 and p = 0.016, respectively). Within Group C, 1q gain correlated strongly with poorer outcomes, with significantly lower 5-year PFS (15.9% vs. 64.3%, p < 0.001) and DSS (51.3% vs. 90.4%, p < 0.001). Furthermore, even WHO grade 1 tumors with 1q gain demonstrated significantly worse outcomes (5-year PFS: 33.3% vs. 76.5%, p = 0.023; DSS: 44.4% vs. 89.3%, p = 0.011). Molecular classification utilizing WES-derived CNAs substantially improves prognostic prediction after SRS for meningiomas. Chromosome 1q gain was a critical biomarker indicating elevated risk for tumor progression and mortality, even among WHO grade 1 tumors.