Gliomas in Children

Jane E. Minturn, Michael J. Fisher

Gliomas are the most common brain tumor in children and represent nearly 50 % of all pediatric central nervous system (CNS) tumors. They are a heterogeneous group of diseases, ranging from highly malignant and frequently fatal to histologically benign and curable by surgery alone. A uniform treatment approach to these tumors is not practical, due to their histological and biological heterogeneity. Low-grade gliomas (LGGs) are best treated with maximally safe surgical resection, generally achievable for hemispheric or cerebellar locations. Patients with deep midline, optic pathway/hypothalamic, and brain stem locations should undergo subtotal resection or biopsy only. If a complete resection is not feasible, subtotal resection followed by adjuvant chemotherapy or radiotherapy is the standard approach; however, observation alone with serial neuroimaging is used in some asymptomatic, surgically inaccessible lesions. Chemotherapy is used first-line in cases of residual or progressive disease, to avoid or delay radiation therapy and its associated side effects. Regimens demonstrating objective responses and increased progression free survival (PFS) include carboplatin and vincristine (CV), thioguanine/procarbazine/CCNU/vincristine (TPCV), or weekly vinblastine. High-grade gliomas (HGGs) are less common in children than in adults, though are similar in their aggressive clinical behavior, resistance to therapy, and dismal outcomes. There is not a single "standard of care" therapy for non-metastatic HGGs, but generally accepted is an aggressive attempt at a complete surgical resection, followed by multimodality therapy with focal radiation and chemotherapy. The use of temozolomide (TMZ) during and following radiotherapy is common, though it appeared not to improve the outcome in a cooperative group clinical trial when compared to an historical control cohort. The angiogenesis inhibitor bevacizumab, used alone or in combination with irinotecan, is also commonly used as maintenance therapy after radiation. Current trials are prospectively comparing TMZ to newer agents (vorinostat, bevacizumab) in a randomized phase II trial. Brainstem gliomas are a unique category of childhood gliomas. Approximately 80 % of childhood brainstem gliomas arise within the pons as diffuse intrinsic pontine gliomas (DIPG). When biopsied, these are usually HGGs and carry a dismal prognosis. Standard therapy is focal radiation (54-58 Gy), preferably on a clinical trial testing concurrent chemotherapy or biologic agent. No standard chemotherapy agent has impacted survival. The remaining 20 % of brainstem gliomas are low-grade, arise in the midbrain, dorsal medulla, or cervicomedullary junction, and are indolent in nature with a much better prognosis. Improvement in the outcome of all childhood gliomas will require increased knowledge of the underlying biology of these tumors, in order to treat with more biologically based and precise therapies.