Pediatric High Grade Glioma

Pediatric high-grade gliomas (PHGGs) constitute approximately 10% of all childhood brain tumors, and more than half occur outside the pons. PHGG is a biologically heterogeneous group with several histologies and molecular subgroups. PHGG includes histologies of glial tumors that are World Health Organization (WHO) grade 3 and 4. The molecular subgroups include receptor tyrosine kinase (RTK) fusion tumors most commonly occurring in infants, H3 mutant gliomas including diffuse midline glioma (DMG) or H3 G34-mutant diffuse glioma, IDH-mutant high-grade gliomas, and several subgroups of H3 wild-type tumors. The diagnostic workup for PHGG involves conventional MRI with or without functional imaging followed by obtaining tissue from tumor resection or biopsy. The final pathologic diagnosis increasingly involves the integration of histologic and molecular features. This chapter focuses on PHGG and excludes DMG-pons (diffuse intrinsic pontine glioma (DIPG)) which is discussed in a separate chapter. Clinical symptomatology of PHGG varies greatly with age and tumor location and can be non-specific, especially in younger children. The majority of PHGGs are biologically distinct from adult malignant gliomas; these differences may underly how PHGGs respond to therapy and their varying clinical outcomes. The current standard management of PHGGs includes surgical resection followed by RT (in children >3 years old) with concurrent and adjuvant chemotherapy, often temozolomide. However, these multimodality treatment strategies have had minimal impact on improving survival, and the best chemotherapy for PHGGs remains to be determined. Ongoing clinical trials are investigating new molecular targets, chemoradiation sensitization of tumor cells, and immunotherapy. Future clinical trials should incorporate the distinction between different PHGG subgroups and stratify patients using subgroup-specific molecular markers.