Interstitial Infusion for Pediatric Brain Tumors
A major limitation in treating pediatric brain tumors has been the ability to achieve adequate levels of a therapeutic agent within the tumor. This limitation stems principally from the presence of the blood brain barrier (BBB), a cellular characteristic that effectively isolates the brain tissue from the blood. A major advance in the field of neurooncology has been the introduction of local delivery schemes. Local delivery, the administration of therapeutic molecules directly into the tumor, has significant advantages over conventional systemic administration. First, the ability to achieve high concentrations of an agent by bypassing the BBB is far superior. Second, by avoiding systemic administration, the majority of dose limiting toxicities seen with conventional chemotherapeutic approaches, are avoided. These features have been integrated into one particular form of local delivery called interstitial infusion or convection-enhanced delivery.Interstitial infusion has been investigated in Dr. Mark Souweidane#146;s laboratory as a potential form of therapy for children with unresectable brain tumors. Specifically, this route of delivery is being studied in the hopes of applying such a therapeutic route for children with brain stem gliomas, a form of brain stem tumor in children that currently has no effective therapy and universally is fatal. The laboratory has gained national recognition in establishing the feasibility of using interstitial infusion for treating children with brain stem gliomas. The laboratory focuses upon the safety, the distributive properties, and the radiographic correlates of interstitial delivery in the brain stem.In addition to the mechanical considerations, the laboratory is also investigating the use of a number of different therapeutic compounds. By using a variety of therapeutic compounds, the toxicity of direct interstitial infusion is being studied as part of a preclinical initiative leading toward Phase I studies in children. Conventional chemotherapeutic compounds, conjugated immunotoxins, and radiolabelled monoclonal antibodies are all in different phases of preclinical investigation. Medical students, neurosurgery residents, and postdoctoral fellows have all enthusiastically been employed in the laboratory. Their efforts have been critical to the function of the laboratory.It is the ultimate goal of this research to obtain information that will lead toward the design of clinical studies for children with diffuse pontine gliomas, a goal that would offer a novel form of treatment for children who currently have no proven alternative form of therapy.