Abstract
INTRODUCTION: In diffuse intrinsic pontine glioma (DIPG) drug resistance is in part due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered drugs. Convection enhanced drug delivery (CED) techniques have been established to bypass the BBB. Trial design to measure efficacy requires evidence to justify a power calculation. AIMS: To apply the SIOPe DIPG registry survival prediction tool (1) to a pilot cohort of children with DIPG treated with CED of carboplatin and sodium valproate. METHODS: Case note and imaging review of 9 children with typical DIPG on imaging, treated on a compassionate basis with CED intra-tumoural infusions of carboplatin (0.12 mg/ml) and sodium valproate (14.4 mg/ml), given after radiotherapy (n=9) and chemotherapy (n=4). Each had a skull-based Renishaw device placed with 4 micro-catheters located within the tumour mass. Up to 8 treatment cycles of CED infusions delivered through 2 pairs of catheters on 2 days to encompass the pontine tumour volume. Survival prediction was performed using clinical criteria: age, sex, duration of symptoms, prior chemotherapy; radiological criteria: absence of distant metastases; disease involving more than 50% of, and confined to, the pons, ring enhancement at diagnosis. RESULTS: Cases were categorized as intermediate or high-risk using SIOPe risk scoring with predicted median overall survival (OS) of 9.7, and 7.0 months, respectively. Four cases, who were categorized as high-risk, had median OS of 14.2 months. Five children, categorized as standard-risk, had median OS of 16.0 months. CONCLUSIONS: OS of CED treated cases compared favourably with the SIOPe DIPG registry survival prediction tool. This supports the justification of phase 2 trial of CED carboplatin and sodium valproate powered to detect at least a 4 month prolongation of survival.