DDDR-04. A retrospective study: can next-generation sequencing predict resistance or sensitivity mechanisms to somatostatin analogues in meningioma?

Abstract Meningiomas are the most common benign primary adult brain tumor. While surgery and radiation remain standard treatments, therapeutic options for recurrent or progressive disease are limited. Somatostatin analogues (SSAs), such as octreotide, have demonstrated modest efficacy, particularly in SSTR2-expressing tumors. Progression-free survival (PFS) at 6 months is a commonly used clinical trial endpoint, with PFS at 12 and 24 months also relevant given the typically indolent course of these tumors. This single-center, retrospective study evaluated whether next-generation sequencing (NGS) can identify molecular predictors of SSA response or resistance in meningioma. We reviewed records of patients with WHO grade I–III meningiomas treated with ≥3 doses of octreotide between 2012 and 2024 at the University of California, Irvine. Nineteen patients (9 male, 10 female; median age 65) were included. Data collected included demographics, histomolecular pathology, WHO grade, prior treatments, SSA treatment duration, and SSTR2 expression. NGS analysis included somatic/germline variants as well as genetic mutations and variable RNA expression in TERT, CDKN2A/B, PIK3CA, AKT1, NF2, SMO, EGFR, NFKB1/2, PTEN, CREBBP, BRAF, and other variants of unknown significance (VUS). We applied a Cox proportional hazard model to analyze the impact of all NGS variants on PFS6, adjusting for age and sex. We created an expression score that summarizes the total expressed variants and found a significant association with 6-month PFS (HR 0.496, P=0.028), suggesting the potential benefits of incorporating the NGS to improve PFS6. Individual variants did not show any significant association after multiple testing corrections when analyzed separately. No significant associations for PFS12 and PFS24 were found. SSTR2 analysis is ongoing. NGS profiling may aid in identifying molecular predictors of SSA response in meningioma. Further studies with larger cohorts are needed to validate these findings and to continue to explore mechanisms of resistance.