Medulloblastoma.

Abstract

Medulloblastomas, primitive neuroectodermal tumors of the cerebellum, comprise 20% of all pediatric brain tumors and are the most common solid neoplasm in children. Primitive neuroectodermal tumors are believed to arise from cerebellar granule cell precursors. Occasionally, medulloblastoma occurs in children with genetically linked disorders, such as Turcot's syndrome or Gorlin's syndrome, which is also called basal cell nevus syndrome. Several genes have been implicated in the development of medulloblastoma in children, including Patched-1 and Smoothened. The protein products of these genes function within the sonic hedgehog molecular signaling pathways, which are important in neural development and disease. Through analysis of several well-designed multi-institutional trials, much has been learned about the clinical factors that influence outcome in children with medulloblastomas. Age younger than 3 years, bulky residual disease postoperatively, and metastasis constitute adverse prognostic features and indicate patients who are considered "high risk" for recurrence with standard therapy using 3600 cGy craniospinal radiation in conjunction with a posterior fossa dose of 5400 cGy. Patients lacking these features are considered "standard risk." Chemotherapeutic trials have been developed to assess the safety and efficacy of various multi-agent therapies to improve the poor results of high-risk patients and to allow reduction in the dose of radiation needed to cure standard-risk patients, which may allow a decrease in late cognitive sequelae. Currently, it is policy to evaluate all children with posterior fossa tumors characteristic of medulloblastoma with preoperative, staging neuroimaging studies of the craniospinal axis. Surgical resection is undertaken with the goal of gross total resection. Postoperative neuroimaging studies are compared with preoperative studies to determine the amount of residual disease. Cerebrospinal fluid is obtained from a lumbar puncture done at the conclusion of the surgical resection or 2 weeks after surgery in order to determine microscopic leptomeningeal spread. Children with tumor histopathology consistent with medulloblastoma are enrolled, when possible, in open clinical trials. Chemotherapy and radiation are given as per protocol. The goal of current treatment approaches is to tailor therapy based on clinical risk factors, with intensification of treatment for children with high-risk disease and reduction of radiation therapy for those with standard-risk disease. Evaluation of biologic predictors of outcome, which may further refine treatment stratification, is in progress.