New Developments in the Pathogenesis, Therapeutic Targeting, and Treatment of Pediatric Medulloblastoma

Abstract

Pediatric medulloblastoma (MB) is the most common pediatric brain tumor with varying prognoses depending on the distinct molecular subtype. The four consensus subgroups are WNT, Sonic hedgehog (SHH), Group 3, and Group 4, which underpin the current 2021 WHO classification of MB. While the field of knowledge for treating this disease has significantly advanced over the past decade, a deeper understanding is still required to improve the clinical outcomes for pediatric patients, who are often vulnerable in ways that adult patients are not. Here, we discuss how recent insights into the pathogenesis of pediatric medulloblastoma have directed current and future research. This review highlights new developments in understanding the four molecular subtypes' pathophysiology, epigenetics, and therapeutic targeting. In addition, we provide a focused discussion of recent developments in imaging, and in the surgery, chemotherapy, and radiotherapy of pediatric medulloblastoma. The article includes a brief explanation of healthcare costs associated with medulloblastoma treatment.

Keywords: chemotherapy; cost of treatment; imaging; medulloblastoma; molecular subtype; pediatric brain tumors; radiotherapy; surgery.

Figure 1

5 year old boy with non-SHH/WNT medulloblastoma. Axial (a) and sagittal (b) T1-weighted MRI scans after intravenous contrast demonstrate a mass with cystic and solid components that enhances and extends into the fourth ventricle. The axial diffusion-weighted image (DWI) (c) shows restricted diffusion (higher signal intensity) within the tumor. The temporal horns of the lateral ventricles are distended, signifying obstructive hydrocephalus.

Figure 2

Molecular features (somatic mutations and amplifications), prognosis, and location of the medulloblastoma subtypes (axial images adapted from Juraschka, et al., 2019 [14]).