2026 Proffered Presentations
S050: PROGNOSTIC UTILITY OF MOLECULAR CLASSIFICATION IN SKULL BASE MENINGIOMAS TREATED WITH STEREOTACTIC RADIOSURGERY
Motoyuki Umekawa; Satoru Miyawaki; Yuki Shinya; Yudai Hirano; Hirotaka Hasegawa; Yu Sakai; Yu Teranishi; Shotaro Ogawa; Atsuto Katano; Daisuke Komura; Hiroto Katoh; Masako Ikemura; Hideaki Ono; Tetsuo Ushiku; Shumpei Ishikawa; Nobuhito Saito; The University of Tokyo
Background: Skull base meningiomas frequently involve adjacent cranial nerves and major vessels, which often limit the extent of surgical resection. While maximal safe resection remains the standard approach, stereotactic radiosurgery (SRS) has become an effective adjuvant or salvage therapy. Outcomes of SRS for skull base meningiomas are generally considered more favorable than those of non–skull base lesions, yet heterogeneity in tumor behavior persists. Molecular classifications have recently emerged as powerful prognostic tools for meningiomas. Whole-exome sequencing offers a simplified framework, capturing both driver mutations and copy number alterations (CNAs) in a clinically applicable manner. While these molecular features have been linked to prognosis after surgery or fractionated radiotherapy, their impact on outcomes following SRS in skull base meningiomas remains poorly defined.
Methods: We retrospectively analyzed patients with surgically resected skull base meningiomas treated with SRS between 1999 and 2023. Tumors were categorized into three molecular groups using whole-exome sequencing: Group A (NF2-wildtype), Group B (NF2 mutation or 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, or CDKN2A/B homozygous deletion or TERT promoter mutation). Primary outcome was progression-free survival rates (PFS), and secondary outcome was disease-specific survival rates (DSS). Kaplan–Meier curves and log-rank tests were used for group comparisons, and associated factors were analyzed using Cox proportional hazard model.
Results: In total of 73 patients, the median age was 60 years (interquartile range [IQR] 47–70 years), 64% were female, and the median follow-up after SRS was 45 months (IQR 21–119 months). Among 75 skull base meningiomas, molecular classification assigned 34 tumors to Group A, 11 tumors to Group B, and 30 tumors to Group C. Frequent locations were petrous/clivus/foramen magnum (27 tumors, 36%) and cavernous sinus (22 tumors, 29%). Most tumors were classified as WHO grade 1 (58 tumors, 77%), while 13 tumors (17%) were grade 2 and 4 tumors (5%) were grade 3. The median prescription dose of SRS was 16 Gy (IQR 14–16 Gy).
Group C exhibited significantly inferior PFS at 3 and 5 years (56% and 50%) compared with Groups A (94% and 87%, p <0.001) and B (both 100%, p=0.008). DSS at 5 and 10 years was also significantly reduced in Group C (73% and 50%) compared to Groups A and B (both 100%, p <0.001 and p = 0.014, respectively). Within Group C, 1q gain correlated strongly with poorer outcomes, with significantly lower 5-year PFS (18% vs. 61%, p = 0.011) and DSS (51% vs. 79%, p = 0.039). In Cox proportional hazards analysis, Group C compared with Group A and B and tumor volume was significantly associated with tumor progression after SRS, while WHO grade was not.
Conclusions: Molecular profiling reveals that skull base meningiomas with high-risk CNAs, especially 1q gain, experience significantly worse outcomes after SRS. Incorporating molecular classification may refine prognostic assessment and inform surveillance strategies in this traditionally favorable subgroup.
