MOLECULAR AND CLINICAL LANDSCAPE OF CNS TUMORS ARISING AMONG ADOLESCENTS AND YOUNG ADULTS (AYA) AT MEMORIAL SLOAN KETTERING CANCER CENTER (MSKCC): A SINGLE-INSTITUTIONAL EXPERIENCE

Abstract BACKGROUND: The management of CNS tumors arising among AYA represents an unmet challenge. Treatment may be split between pediatric and adult centers, often with conflicting approaches. Biology also appears to be distinct compared to younger/older age groups but has yet to be fully characterized. Such features would have important implications for prognostication and informing vulnerabilities for targeted therapies.METHODS: To establish the clinical and molecular landscape of these tumors, we analyzed all cases in patients aged 15-39 years old who were treated at MSKCC between 2018-2021. RESULTS: 302 patients with accompanying MSK-IMPACT targeted sequencing, copy number analysis, Archer fusion panel, and clinical data were found. 239/302 cases (79%) were gliomas, with the remaining consisting mainly of neuro-epithelial tumors (n=15; 5%), meningiomas (9; 3%), ependymomas (10; 3%), and embryonal tumors (7; 2%). Among gliomas, 163/239 (68%) had IDH1/2 mutations, which were significantly more enriched for TP53 (121/163; 74%) and ATRX (90/163; 55%) co-mutations compared to IDH-wild type (IDH-WT) (q<0.0001). In comparison, IDH-WT gliomas (n=76) were enriched for alterations in BRAF (16/76 with SNV, 9/76 fusion; q<0.0001), H3F3A (14/76; q<0.0001), PTEN (10/76; q=0.038), and CDKN2A (16/76; q=0.038). Among 113 patients with high-grade gliomas (WHO grade 3/4), those with IDH-WT tumors (n=34) had a poorer prognosis that those with IDH-mutant tumors (n=79) (1 and 5-year OS of 68% and 28% vs. 97% and 76%, respectively) (p<0.0001). Further, a lower frequency of alterations in TERT (26/113; 23%), EGFR (6/113; 5%), and PDGFRA (4/113; 4%) were observed compared to previous studies for adult-only cohorts (~50-70%, 40%, and 10%, respectively). CONCLUSIONS: IDH-mutant gliomas were the most common tumor type seen in this AYA cohort. However, some alterations characteristic of adult high-grade gliomas (TERT, EGFR, PDGFRA) were not as frequently observed. Additional identification of molecular features that predict response to conventional and targeted therapies is underway.