OTHR-29. A SINGLE INSTITUTION REVIEW REGARDING TRENDS IN THE MOLECULAR ANALYSIS OF PEDIATRIC CENTRAL NERVOUS SYSTEM (CNS) TUMORS AND GERMLINE ANALYSIS BETWEEN 2019 – 2023, EMPHASIZING THE IMPORTANCE OF EASY ACCESS TO COMPREHENSIVE TESTING

Abstract

Abstract BACKGROUND Molecular characterization of pediatric CNS tumors improves diagnostic accuracy and guides treatment. Germline analysis is also important to uncover cancer predisposition syndromes, which influence the approach to treatment and tumor surveillance. The options for molecular assessment are influenced by availability, including access through a trial or insurance approval. METHODS A retrospective review of the molecular workup performed on all CNS tumors biopsied/resected at Children’s Minnesota from 2019 – 2023 was undertaken to look at trends in the specific tests performed over time and how the molecular results guided treatment. RESULTS Between 2019 – 2023, 220 patients at Children’s Minnesota were diagnosed with a CNS tumor. A total of 191 underwent surgery and 162 (85%) had sufficient tissue for molecular analysis. There was no apparent difference in the percentage of patients who underwent IHC/FISH/NGS between 2019 - 2023, but methylation profiling frequency increased over time (2019 2%, 2020 and 2021 10%, 2022 58% and 2023 71%). Frequency of germline analysis also increased (2019-2021 29%, 2022-52% and 2023-63%). Easy availability of comprehensive molecular and germline analysis for patients enrolled on COG-APEC14B1 is credited for these improving trends. Molecular analysis confirmed (59%) or supported (36%) the diagnosis, and guided treatment in 30% of cases (stratification of treatment in 89% of medulloblastoma and targeted treatment in 63% of high-grade glioma, 9% of medulloblastoma and 6% of low-grade glioma). Methylation profiling alone accurately diagnosed 79% of cases, including subtyping tumors. Germline analysis detected a pathogenic germline alteration in 14% of CNS tumor patients (NF1 5%; TP53 and BRIP1 1%; PALB1, NF2, TS2, SMARCB1, biallelic PMS2, CHEK2, FANCA, ORICH1 and SDHA 0.5%). CONCLUSION These findings demonstrate the importance of easy access to comprehensive molecular and germline analysis with quick turnaround time to provide the best diagnosis, prognosis and treatment options for pediatric CNS tumor patients.