This thesis describes the treatment on compassionate grounds of 15 children with diffuse intrinsic pontine glioma (DIPG), which is a lethal cancer of middle childhood. Children were treated using chemotherapy infused directly into the pons by chronic, intermittent convection enhanced delivery (CED). The use of an implantable drug delivery system connected to a transcutaneous drug administration port enabled repeated infusions without repeated surgery. Previous experience of pontine infusion in children with DIPG demonstrates that treatment is associated with neurological side-effects. As a new treatment for neurological disease, the cause of these side-effects is unknown. The possible causes can be broadly categorised into those due to the pharmacological action of the drug and the physiological impact of the infusion. This thesis describes how a novel neurological assessment scale was developed, implemented and evaluated to understand the toxicity of pontine infusion. Analysis of the results suggests that the majority of side-effects in brainstem CED are caused by the infusion. Predictive factors of neurological recovery relate to how the infusion is performed. This thesis hypothesises that side-effects are due to localised perfusion deficits arising from high local interstitial pressures within the infused brain. A method of quantitative imaging is described that could lead to a better understanding of this process. On the basis of this work recommendations are made about how a minimally symptomatic infusion could be achieved and how this could be important for the future of CED as a treatment for DIPG.
|Date of Award||1 Oct 2019|
- The University of Bristol
|Supervisor||Ali S Bienemann (Supervisor), Risto Kauppinen (Supervisor) & Steven Gill (Supervisor)|