Brain tumors are the most common category of childhood solid tumors. In the 1970s and 1980s, treatment protocols for benign tumors focused almost exclusively on surgery, with radiation treatment as a salvage modality, whereas the management of malignant tumors employed a combination of surgery, radiation therapy, and chemotherapy, with therapeutic approaches such as “8-in-1” chemotherapy often applied across histological tumor subsets that are now recognized to be prognostically distinct. During the ensuing years, treatment has become increasingly refined, based on clinical and, more recently, molecular factors, which have supported risk-adapted treatment stratification. The goal of this report is to provide an overview of recent progress in the field.
A review of the literature was undertaken to examine recent advances in the management of the most common childhood brain tumor subsets, and in particular to identify instances in which molecular categorization and treatment stratification offer evidence or promise for improving outcome.
For both medulloblastomas and infant tumors, refinements in clinical and molecular stratification have already facilitated efforts to achieve risk-adapted treatment planning. Current treatment strategies for children with these tumors focus on improving outcome for tumor subsets that have historically been relatively resistant to therapy and reducing treatment-related sequelae for children with therapy-responsive tumors. Recent advances in molecular categorization offer the promise of further refinements in future studies. For children with ependymomas and low-grade gliomas, clinical risk stratification has facilitated tailored approaches to therapy, with improvement of disease control and concomitant reduction in treatment sequelae, and recent discoveries have identified promising therapeutic targets for molecularly based therapy. In contrast, the prognosis remains poor for children with diffuse intrinsic pontine gliomas and other high-grade gliomas, despite recent identification of biological correlates of tumor prognosis and elucidation of molecular substrates of tumor development.
Advances in the clinical and molecular stratification for many types of childhood brain tumors have provided a foundation for risk-adapted treatment planning and improvements in outcome. In some instances, molecular characterization approaches have also yielded insights into new therapeutic targets. For other tumor types, outcome remains discouraging, although new information regarding the biological features critical to tumorigenesis are being translated into novel therapeutic approaches that hold promise for future improvements.