Childhood brain tumors: It is the child’s brain that really matters

Abstract

The context for research into brain tumors of childhood over the past three decades has focused upon developing an understanding of the biological mechanisms of tumor formation (1). This has been pursued in the belief that it will be the key that will unlock the tumors' vulnerability to therapeutic approaches. The "driver for change" has been improving overall survival. In childhood this has gratifyingly been associated, in high income countries (HIC), with a rise in survival rates from 40-70% (2-4). Within this statistic there are significant variations between European countries. Clinical trials have shown remarkable advances, such as intra-cranial germ cell tumors (5) and medulloblastoma (6), which have improved with combined standard approaches of well delivered chemotherapy, radiotherapy and rational approaches to surgery. Radiotherapy research and trials in the past decades have focussed upon optimising radiation doses to the tumour and surrounding brain to minimise the cognitive consequences (7).Bio-characterization of these tumors offers hope of further stratification of outcomes with biologically targeted therapies (8). There have been surprises, such as chemosensitivity of low grade glioma, offering control of this early onset, self-limiting tissue growth disorder of astrocytes ( 9). The targeted effect of mTOR inhibitors have controlled progression of sub-ependymal giant cell astrocytoma (SEGA) complicating tuberous sclerosis (10). Bio-characterization of these benign tumors has identified single pathway mutations suitable for drug targeting (11). There have been disappointments with limited or no progress in drugs contributing to cure of ependymoma (12), diffuse intrinsic pontine glioma (DIPG) (13), atypical teratoid rhabdoid tumor (ATRT) (14, 15) and high grade glioma (HGG) (16,17). Each of these tumor types have been bio-characterised with the intention of identifying targetable mutations to contribute to improved responses; a Frontiers in Oncology frontiersin.org 01

Dynamic Survival Risk Prognostic Model and Genomic Landscape for Atypical Teratoid/Rhabdoid Tumors: A Population-Based, Real-World Study

“…When it comes to childhood brain tumors, the most crucial factor to consider is the child’s brain. As highlighted by Walker’s research, conventional approaches that prioritize overall survival as the primary drive for change overlook the significant long-term significance of children’s brain health [ 32 ]. Hence, forward-focused clinical trials are essential to corroborate the efficacy and safety of this therapeutic approach.…”

Outcome after proton beam therapy versus photon-based radiation therapy in childhood-onset craniopharyngioma patients—results of KRANIOPHARYNGEOM 2007

“…However, in future studies it is important to analyze the locoregional distribution of radiation doses to normal brain tissue beyond the HPA, comparing PBT and XRT in a large cohort like that of the KRANIOPHARYNGEOM 2007 trial ( 15 ). The results need to be correlated to neurocognitive function in order to receive an idea of the brain damage caused by different irradiation techniques ( 57 ).…”

Patient‐ and parent‐reported diagnostic delay in children with central nervous system tumors in Denmark

“…A majority of long-term survivors from pediatric tumors in the central nervous system (CNS) face a significant burden of late effects, due to acquired brain injury as a result of the tumor and the treatment. 1 CNS tumors account for 20%-25% of malignancies in children. It is the most common solid malignancy in childhood and leading cause of cancer-related deaths.…”