P11.53.B MOLECULAR PROFILING AND ACTIONABLE MUTATIONS IN ADULT PATIENTS WITH IDH WILD TYPE GLIOMAS AND GLIONEURONAL AND NEURONAL TUMORS

Abstract

Abstract BACKGROUND Next generation sequencing (NGS) assays enable the identification of genetic alterations that may guide a personalized treatment in glioma patients. MATERIAL AND METHODS From July 2021 to March 2023 a NGS analysis (Myriapod® NGS Cancer DNA and RNA panels) was performed in a large prospective cohort of adults with an histological diagnosis of IDH wild type glioma or circumscribed astrocytoma or glioneuronal and neuronal tumor at the Division of Neuro-Oncology, University and City of Health and Science Hospital, Turin, Italy. The aim was to identify potential actionable molecular alterations and provide targeted therapy at recurrence accordingly. RESULTS We collected tumor samples from 221 patients. NGS analysis was available in 211 patients (95.5%), while NGS was not feasible in 10 patients (4.5%). 188 patients out of 211 (89.1%) had an IDH wild type glioblastoma (GBM) (median age 61 years, range 24-84; F/M: 97/91), 6 patients (2.8%) had IDH wild type lower grade gliomas (LGG) (median age 63 years, range 43-78; F/M: 3/3), and 17 patients (8.1%) had circumscribed astrocytoma or glioneuronal and neuronal tumor (median age 37 years, range 18-67; F/M: 13/4). Overall, actionable molecular alterations were found in 13/211 patients (6.2%). In this regard, 7/211 patients (3.3%) had BRAF V600E mutation (3 IDH wild type GBM, 1 IDH wild type LGG, and 3 circumscribed/glioneuronal and neuronal tumor), 4/211 patients (1.9%) had FGFR3-TACC3 fusion (all GBM), 1/211 patients (0.5%) had PIK3CA mutation (GBM), and 1/211 patients (0.5%) had NTRK1 fusion (glioneuronal tumor). Other molecular mutations, including ALK, ERBB2, MET, KIT, KRAS, PDGFRA, and RET have not been detected in our cohort. Three patients with druggable mutations recurred after first-line therapy: 1 patient with BRAF mutated GBM, 1 patient with GBM harboring FGFR3-TACC3 fusion, and 1 patient with NTRK1 fusion positive glioneuronal tumor received specific BRAF/MEK inhibitor (dabrafenib/trametinib), FGFR inhibitor (pemigatinib), and NTRK inhibitor (larotrectinib), respectively. A remarkable activity of BRAF/MEK and NTRK inhibitors was observed (8 months and 5 months, respectively *), while FGFR inhibitor did not display a significant activity to control disease (9 weeks). * ongoing CONCLUSION The incidence of actionable molecular alterations in IDH wild type gliomas and glioneuronal and neuronal tumors was low. However, the possibility of using targeted therapies may lead to an important impact on the outcome.