P20.15.B MOLECULAR CHARACTERIZATION OF ADULT NON-GLIOBLASTOMA CENTRAL NERVOUS SYSTEM (CNS) TUMORS TO IDENTIFY POTENTIAL TARGETTABLE ALTERATIONS

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Abstract BACKGROUND NGS panels in oncology offer personalized therapies based on genomic alterations, but data on their clinical use and efficacy for non-glioblastoma CNS tumors is limited. MATERIAL AND METHODS This study aimed to explore the molecular landscape of non-glioblastoma CNS tumors in patients (pts) who underwent FoundationOne®CDx testing between 11/2019 and 04/2023 at Veneto Institute of Oncology, Padua (Italy), while also assessing access to TT. Analysis was conducted on formalin-fixed paraffin-embedded tumor samples, comprising a cohort of 176 adult CNS tumor pts. Brain tumors were classified per WHO 2021. RESULTS Our cohort was constituted by: 19 Grade 2 IDH mut astrocytomas (A); 35 G3 IDH mut A; 34 G4 A; 29 oligodendrogliomas; 4 diffuse midline gliomas; 3 gangliogliomas; 3 pleomorphic xanthoA; 30 meningiomas; 4 medulloblastomas; 5 ependymomas; 2 neuroblastomas; 3 schwannomas; 4 pituitary adenomas; 1 hemangiopericytoma.The most frequent targettable molecular alterations (ESCAT ESMO Scale for Clinical Actionability of molecular Targets IIB-IIIB) were: PIK3CA/B mutations (14.2%), NF1 and NF2 mutations (10.2 and 13%, respectively), BRCA 1-2 mutations (8%), POLE mutation (7.4%), high tumor mutational burden (TMB) (>10 mut/megabase) (6.8%), PDGFRA alterations (6.2%), BRAF non-V600E alterations (5.1%), RET and ROS1 mutations (3.4% and 2.8% respectively), MDM2 amplification (2.3%), FGFR1-2-3 alterations and H3K28M (1.7%), MET amplification (1.7%), ALK rearrangements (1%). NTRK fusions and BRAF V600E mutations have not been detected. 3 of 4 medulloblastomas pts exhibited a PTCH1 mutation.4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. Immune checkpoint inhibitors have shown remarkable activity in a meningioma patient, who is undergoing treatment for 12 months and has achieved a complete response according to RANO criteria, while another has had stable disease with alectinib for 7 months. In other cases TT did not demonstrate activity in controlling disease. CONCLUSION The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

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