Prognostic Factors for Pediatric, Adolescent, and Young Adult Patients with Non-DIPG Grade 4 Gliomas: A Contemporary Pooled Institutional Experience

Abstract

WHO grade 4 gliomas are rare tumors in the pediatric and AYA (adolescent and young adult) population. In this study, we evaluate prognostic factors, toxicities, and outcomes in the pediatric versus AYA population. This retrospective pooled institutional study included patients < 30 years old with grade 4 gliomas. Overall survival (OS) and progression free survival (PFS) were characterized using Kaplan-Meier and Cox regression analysis. Ninety-seven patients (n = 20 < 15y, n = 77 ≥ 15y) were identified with a median age 23.9y at diagnosis. Most had biopsy-proven glioblastoma (91%) and the remainder had diffuse midline glioma, H3K27M-altered (9%). All patients received surgery and adjuvant radiotherapy. Median PFS and OS were 20.9 months and 79.4 months, respectively. Gross total resection was associated with better PFS in multivariate analysis [HR 2.00 (1.01-3.62), p = 0.023]. Age ≥15y was also associated with improved OS [HR 0.36 (0.16-0.81), p = 0.014] while female gender [HR 2.12 (1.08-4.16), p = 0.03] and K27M altered histology [HR 2.79 (1.11-7.02), p = 0.029] were associated with worse OS. Only 7% of patients experienced grade 2 toxicity during radiation. Sixty-two percent of patients experienced tumor progression, 28% local and 34% distant. Analysis of salvage treatment found reirradiation was not associated with improved OS, but second surgery and systemic therapy significantly improved survival from the time of tumor progression. Age is a significant prognostic factor in WHO grade 4 glioma, which may reflect age-related molecular alterations in the tumor. Diffuse midline glioma was associated with worse OS compared to hemispheric glioblastoma; this may be related to lack of effective targeted therapies. Surgery and systemic therapy were effective salvage options that significantly improved outcome. Better understanding of prognostic factors may guide future treatment within this understudied patient population, and prospective studies are warranted.