Our Science – Warren Website
Katherine E. Warren, M.D.
Pediatric brain tumors represent a heterogeneous group of diseases. A significant proportion of tumors are considered benign or low-grade. The 5-year survival for these children is currently over 70%. However, for those children with malignant tumors including diffuse intrinsic brainstem gliomas and high-grade gliomas, and those with recurrent malignant tumors, the 5-year survival is dismal. Despite neurosurgical and radiotherapeutic advances, no significant improvement in survival has been made for patients suffering from these tumors in several decades.
The armamentarium for the treatment of pediatric central nervous system (CNS) tumors includes surgery, radiation and chemotherapy. Although surgery may be curative for focal, benign tumors, adjuvant therapy is necessary for invasive, malignant lesions. Radiation therapy is toxic to the developing brain and avoided or deferred if possible, in very young children. Although chemotherapy plays an important role, improvement in the survival of pediatric patients with malignant gliomas and recurrent malignant tumors, has been modest, at best, and for some tumors, such as diffuse intrinsic pontine gliomas, no chemotherapy has ever demonstrated an ability to improve patient outcome.
Few agents are available for clinical development in children. In addition to the sometimes disparate tolerability and pharmacokinetics between adult and pediatric patients, pediatric CNS tumors differ from adult CNS tumors in histology, biology, pathophysiology and location, and therefore efficacy data available for adults may not apply to pediatric patients. Rational drug development based on relevant pharmacokinetics (PK), such as CNS penetration, is infrequently performed, and early studies instead frequently aim to identify a maximum tolerated dose rather than a targeted effective dose. The major goals of the Pediatric Neuro-Oncology Section are rational, PK-based, drug development in the pediatric population, and investigation of novel therapeutic approaches, such as convection-enhanced delivery.
Assessing tumor characteristics and treatment effects noninvasively is particularly important in pediatric neuro-oncology given the technical and ethical limitations of repeat tissue sampling in these children. Defining and incorporating innovative endpoints in clinical trials designed to determine the biologic and therapeutic activity of new agents is a major focus of our research.
This page was last updated on 10/29/2013.