HG-91: TOPOGRAPHIC HISTOLOGICAL AND MOLECULAR STUDIES OF DIFFUSE INTRINSIC PONTINE GLIOMA TREATED WITH CONVECTION ENHANCED DELIVERY

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a pediatric brain tumor with grim prognosis. Treatment is hindered by the impermeable blood brain barrier (BBB). To combat this, convection-enhanced delivery (CED) has been employed to deliver drugs directly into the tumor. CED's ability to bypass the BBB, has made it a promising delivery method for treatment of primary brain tumors including DIPG. OBJECTIVE: To perform analyses of sections across a CED received DIPG brain obtained at autopsy to determine cellular and molecular effect of CED. DESIGN/METHODS: Whole brain was obtained postmortem from a DIPG patient who received CED treatment (124I-8H9) six months before death. Sagittal sections representing cortex, brainstem and cerebellum were generated. Sub-blocks were produced and used for histological staining including hematoxylin and eosin (H&E), and cellular proliferation marker Ki67. Procedural MR scans were used to discriminate CED treated area versus non-CED regions. RESULTS/DISCUSSION: CED treated tumor regions were compared to untreated tumor regions. Non-CED treated tumor regions show an increased hypercellularity compared to CED-treated regions. To assess CED-induced DNA damage, histological assays were done using phopho-Histone H2A.X (phospho-H2A.X), which indicate double stranded DNA break. Our study indicated that the 124I-8H9 CED treated brain regions exhibited localized necrosis, decreased cellularity, and enhanced DNA damage. Our preliminary data is the first study to show the effect of CED in DIPG using rapid autopsy tissue. Further studies are required to investigate the molecular effects of CED treatment on tumor cell DNA.