Management of high-grade gliomas in the pediatric patient: Past, present, and future

Abstract

High-grade gliomas (HGGs) constitute 15% of all primary brain tumors in children and adolescents. Routine histopathological diagnosis is based on tissue obtained from biopsy or, preferably, from the resected tumor itself. The majority of pediatric HGGs are clinically and biologically distinct from histologically similar adult malignant gliomas; these differences may explain the disparate responses to therapy and clinical outcomes when comparing children and adults with HGG. The recently proposed integrated genomic classification identifies 6 distinct biological subgroups of glioblastoma (GBM) throughout the age spectrum. Driver mutations in genes affecting histone H3.3 (K27M and G34R/V) coupled with mutations involving specific proteins (TP53, ATRX, DAXX, SETD2, ACVR1, FGFR1, NTRK) induce defects in chromatin remodeling and may play a central role in the genesis of many pediatric HGGs. Current clinical practice in pediatric HGGs includes surgical resection followed by radiation therapy (in children aged . 3 years) with concurrent and adjuvant chemotherapy with temozolomide. However, these multimodality treatment strategies have had a minimal impact on improving survival. Ongoing clinical trials are investigating new molecular targets, chemoradiation sensitization strategies, and immunotherapy. Future clinical trials of pediatric HGG will incorporate the distinction between GBM molecular subgroups and stratify patients using group-specific biomarkers.

Diffusion Basis Spectrum Imaging with Deep Neural Network Differentiates Distinct Histology in Pediatric Brain Tumors

“…Pediatric brain tumors are the leading cause of cancer-related childhood death. Current curative approaches in management rely, in most cases on complete surgical resection, followed by irradiation therapy and chemotherapy (5,18). Histologic assessment of tumor cellularity, infiltration and necrosis is critical in diagnosis and grading, as well as subsequent clinical decisionmaking for patient management and follow-up (19).…”

“…Pediatric brain cancer has unfortunately surpassed leukemia to become the most common cause of death from cancer in children in the US (2). It is estimated that 2,940 new cases of childhood (0-14 age group) and adolescent (15)(16)(17)(18)(19) age group) primary malignant and non-malignant central nervous system (CNS) tumors will be diagnosed in the United States (US) in 2020 (3).…”

Diffusion Histology Imaging Differentiates Distinct Pediatric Brain Tumor Histology

“…Pediatric brain tumors are the leading cause of cancer-related death in children. Current curative approaches in management rely, in most cases, on complete surgical resection, followed by irradiation and chemotherapy [4,25]. Histologic assessment of tumor cellularity, in ltration and necrosis is critical in the diagnosis and grading, as well as subsequent clinical decision-making for patient management and follow-up [26].…”

Restriction Spectrum Imaging Improves Risk Stratification in Patients with Glioblastoma

“…Unfortunately, CE vol and FLAIR vol may have limited prognostic value in this setting once the extent of the resection is considered. Glioblastoma patients often have a more infiltrative tumor pattern and possibly a more hypoxic tumor biology (24) with some of them responding poorly to radiotherapy or conventional chemotherapy (25). The non-specificity of these conventional metrics could potentially be due to the hypoxic tumors not having contrast enhancement and the presence of infiltrative tumors not having a noticeable signal in both T1 and T2 images.…”