Associations of Meningioma Molecular Subgroup and Tumor Recurrence.

BACKGROUND We and others have identified mutually-exclusive molecular subgroups of meningiomas, however, the implications of this classification for clinical prognostication remain unclear. Integrated genomic and epigenomic analyses implicate unique oncogenic processes associated with each subgroup, suggesting the potential for divergent clinical courses. The aim of this study was to understand the associated clinical outcomes of each subgroup, as this could optimize treatment for patients. METHODS We analyzed outcome data for 469 meningiomas of known molecular subgroup, including extent-of-resection, post-operative radiation, surveillance imaging, and time to recurrence, when applicable. Statistical relationships between outcome variables and subgroup were assessed. Features previously associated with recurrence were further investigated after stratification by subgroup. We used Kaplan-Meier analyses to compare progression free survival, and identified factors significantly associated with recurrence using Cox proportional hazards modeling. RESULTS Meningioma molecular subgroups exhibited divergent clinical courses at two years of follow-up, with several aggressive subgroups (NF2, PI3K, HH, TRAF7) recurring at an average rate of 22x higher than others (KLF4, POLR2A, SMARCB1). PI3K-activated tumors recurred earlier than other subgroups, but had intermediate long-term outcome. Among low-grade tumors, HH and TRAF7 meningiomas exhibited elevated recurrence compared to other subgroups. Recurrence of NF2 tumors was associated with male gender, high-grade, and elevated Ki-67. Multi-variate analysis identified molecular subgroup as an independent predictor of recurrence, along with grade and previous recurrence. CONCLUSION We describe distinct clinical outcomes and recurrence rates associated with meningioma molecular subgroups. Our findings emphasize the importance of genomic characterization to guide post-operative management decisions for meningiomas.