HGG-03. HIGH-GRADE GLIOMA IN YOUNG CHILDREN IS HISTOLOGICALLY, MOLECULARLY, AND CLINICALLY DIVERSE—RESULTS FROM THE SJYC07 TRIAL AND INSTITUTIONAL EXPERIENCE

Abstract BACKGROUND High-grade gliomas (HGG) in young children pose a challenge due to favorable but unpredictable outcomes. While retrospective studies have broadened our understanding of tumor biology, prospective data regarding outcomes and molecular predictors is lacking. METHODS Young (0-5 years) histologically diagnosed with HGG enrolled on the SJYC07 trial or treated at St Jude Children’s Research Hospital from November 2007 December 2020 were included. DNA methylation, whole genome (WGS), exome (WES), RNA (RNA-seq) sequencing performed available samples these integrated standard histopathological tests yield diagnosis. Clinical characteristics pre-operative imaging analyzed. RESULTS Fifty-six (0.0-4.4 identified. Integrated analysis split tumors into four categories: infant-type hemispheric glioma (IHG), HGG, low-grade (LGG), other-central nervous system (CNS) (i.e., CNS embryonal tumors, sarcomas, neuroepithelial tumors). IHG was most prevalent (N=22), occurred youngest patients (median age 0.4 years; 0-4.4 years), commonly harbored receptor tyrosine kinase gene fusions (7 ALK, 2 ROS1, 3 NTRK1/2/3, 4 MET). The 5-year event-free (EFS) overall survival (OS) for 53.13% (95% CI: 35.52 -79.47) 90.91% (95%CI: 79.66-100.00) vs. 0.0% 16.67% 2.78-99.74%) (p= 0.0043, 0.00013). EFS OS not different between LGG (p=0.95, 0.43). Imaging review , Other showed that IHGs are associated circumscribed margins (p=0.0047), location (p=0.0010), hemorrhage (p=0.0149). CONCLUSIONS single-entity best defined by an display good survival, as compared other pediatric HGGs, they still suffer severe treatment-related morbidities. Therefore, prompt consideration reduced adjuvant molecularly targeted therapies warranted.