HG-105: DEFORMATIONAL CHANGES IN THE HUMAN BRAIN STEM FROM CONVECTION ENHANCED DELIVERY (CED)

INTRODUCTION: Preclinical work using CED has minimized concerns regarding conformational alterations in the brain. There has been no volumetric assessments however in humans undergoing CED. As part of an ongoing Phase 1 clinical trial using CED for children with DIPG, we sought to measure any treatment-related volumetric alterations in the human brain stem. METHODS: Volumetric measurements were performed using the pre-treatment baseline and the first post-treatment MRI scans. An automated algorithm based on standard anatomical landmarks and post processing manual correction was used for 3-dimensional rendering of the brain stem. These measurements were longitudinally determined and reported as a percent change. Results were correlated with the assigned dose level and hence infusion volume. RESULTS: Brain stem volumetric assessments were performed in six patients (mean age = 9.98 years) treated on two different dose levels (mean infusate volume = 2.58 ml and 3.54 ml). At the lower dose level the mean pre-treatment brain stem volumes = 45.5 cm3, mean post-treatment volumes = 46.3 cm3, and the mean ΔV = 0.876 cm3 (SD 1.74) (2%). At the higher dose level the mean pre-treatment volumes = 35.1 cm3, mean post-treatment volumes = 39.2 cm3, and the mean ΔV = 4.017 cm3 (SD 1.6) (11.8%). CONCLUSION: CED for children with DIPG results in deformational changes of the brain stem. These volumetric alterations are dose-dependent and may have implications in assessment of disease response. Correlation of such volumetric alterations with clinical tolerance may help design future clinical trials that employ CED in the brain stem.