2025 Proffered Presentations
S197: MOLECULAR LANDSCAPE AND CLINICAL CORRELATES OF OLFACTORY GROOVE MENINGIOMAS: A MULTI-INSTITUTIONAL STUDY
M Alkhatib1; L Hua2; F Beyer1; D Podlesek1; I Prilop1; S Jeyaretna3; S Fujio4; M Teo5; A Zolal1; L Günther1; O Behl1; B Cicek1; S Herold6; J.H Juratli1; D.P Cahill7; H Wakimoto7; Y Gong2; T Pinzer1; G Schackert1; I.Y Eyüpoglu1; P.K Brastianos8; T Juratli1; 1Department of Neurosurgery, Carl Gustav Carus University Hospital, TU Dresden, Dresden, Deutschland; 2Department of Neurosurgery, Huashan University Hospital, Fudan University, Shanghai, China; 3Department of Neurosurgery, Oxford University Hospitals, Oxford, UK; 4Department of Neurosurgery, Kagoshima University Hopsital, Kagoshima, Japan; 5Department of Neurosurgery, Bristol Institute of Clinical Neuroscience, Southmead Hospital, Bristol, UK; 6Institute of Pathology, Carl Gustav Carus University Hospital, TU Dresden, Dresden, Deutschland; 7Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.; 8Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts
Objective: This study investigates the relationship between the clinical and radiological characteristics of olfactory groove meningiomas (OGMs) and their molecular profiles. It emphasizes the identification of oncogenic mutations through radiographic analysis.
Methods: We performed targeted next-generation and whole-genome sequencing on 123 OGM samples collected from four international institutions, focusing on known meningioma-driver genes. We compared the molecular data with the clinical and radiographic features of the tumors. Patient and tumor data, including age, sex, radiological features, and overall survival, were retrospectively collected and analyzed.
Results: The study cohort comprised 90 females(73%) and 33 males(27%), with median age at diagnosis of 57years (range 25-87years). The majority of tumors (88.6%, n=109) were classified as WHO grade 1 meningioma. However, only one NF2 mutation was identified across the cohort, highlighting the distinct molecular etiology of these tumors compared to convexity meningiomas. Known driver mutations were found in 86.2% of patients (n=106). The most common mutations were found in the SMOL412F/W535L /SUFU and AKT1E17K genes, each present in 36 cases (29.3%), followed by mutations in PIK3CA/PIK3R1 [(19 cases, 15.4%), (14 PIK3CA and 5 PIK3R1,)], TRAF7 alone (7 cases, 5.7%), POLR2AQ403K (4 cases, 3.3%), and TRAF7/KLF4K409Q (3 cases, 2.4%). In 17 patients (13.8%) no known meningioma driver mutations were detectable (Wild-type group). SMO and AKT1 mutations were significantly associated with the meningothelial subtype (p=0.0005). Within molecular subgroups, the youngest median age were patients with AKT1 mutations (median age 51years) and the oldest in the TRAF7 only mutant group (median 66years, range 28-76years). Median tumor volume at diagnosis was 18.04cm3. Among tumors with known driver mutations, TRAF7 only mutant OGMs presented with the largest median volume (29.5cm3), followed by SMO-mutant OGMs (19.5cm3), whereas AKT1- and TRAF7/KLF4-mutations were associated with the smallest tumor volumes (7.5cm3 and 4.9cm3, respectively). SMO-mutant tumors demonstrated significantly larger volumes compared to both AKT1-mutant (p=0.021) and TRAF7/KLF4-mutant tumors (p=0.002). Tumor-associated hyperostosis of the sphenoid planum was common (58.5%), led by PIK3CA/PIK3R1, SMO, and Wild-type groups (73.6%, 72.2%, and 70.5%, respectively), compared to a notably lower rate in AKT1-mutant tumors (25%) (p < 0.001). Tumor invasion of the ethmoid sinuses occurred in 25 cases (20.3%), most frequently in the TRAF7 only mutant OGMs (42.8%), followed by PIK3CA/PIK3R1-mutant (31.5%) and wild-type OGMs (23.5%). The mean progression-free survival was 144.4months (95% confidence interval [CI]: 123.8–165months). Within mutation-defined subgroups, patients with SMO mutations had significantly shorter progression-free survival (mean 95.7months, 95% CI: 76.4 – 115.1months), identifying a tumor type that may benefit from adjuvant treatment after subtotal resection.
Conclusions: This comprehensive study provides significant insights into the genetic underpinnings and clinical behaviors as well as radiological features of OGMs. It also highlights the prognostic implications of specific mutations: SMO mutations were linked with shorter PFS, whereas AKT1 mutations were associated with longer survival and smaller tumor volumes, suggesting a possible biomarker for prognosis and therapeutic targeting. These findings support the use of a molecularly-guided strategy in diagnosing, managing, and predicting outcomes for OGMs, highlighting the importance of genetic profiling in routine clinical practice to improve patient results.