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

Abstract

HG-105. DEFORMATIONAL CHANGES IN THE HUMAN BRAIN STEM FROM CONVECTION ENHANCED DELIVERY (CED) Karima Tizi1, Eva Wembacher3, Rowena Thomson3, Maria Donzelli2, Elizabeth Vaconcellos3, and Mark Souweidane1,2; Weill Cornell Medical College, New York, NY, USA; Memorial Sloan Kettering Cancer Center, New York, NY, USA; BrainLab, Munich, Germany 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 pretreatment baseline and the firstpost-treatment MRI scans. An automatedalgorithm 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 1⁄4 9.98 years) treated on two different dose levels (mean infusate volume 1⁄4 2.58 ml and 3.54 ml). At the lower dose level the mean pre-treatment brain stem volumes 1⁄4 45.5 cm3, mean post-treatment volumes 1⁄4 46.3 cm3, and the mean DV 1⁄4 0.876 cm3 (SD 1.74) (2%). At the higher dose level the mean pre-treatment volumes 1⁄4 35.1 cm3, mean posttreatment volumes 1⁄4 39.2 cm3, and the mean DV 1⁄4 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 dosedependent 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. Neuro-Oncology 18:iii48–iii77, 2016. doi:10.1093/neuonc/now073.101 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.