IM-03 * SERIAL METABOLISM OF DIFFUSE INTRINSIC PONTINE GLIOMA TREATED WITH PEPTIDE BASED VACCINE THERAPY

Abstract

PURPOSE: Diffuse intrinsic pontine glioma (DIPG) carries the worst prognosis in pediatric neurooncology, with no improvement in outcomes for decades. The goal of this study was to examine myo-inositol (mI)/choline and other metabolites (measured by serial MRS) as predictors of overall survival in (1) a DIPG cohort treated with standard radiochemotherapy and (2) a DIPG cohort treated with radio-therapy followed by peptide-based vaccine therapy. METHODS: 50 MRS studies were performed in 11 patients with DIPG enrolled in a phase 1 clinical trial of peptide based vaccine therapy. 56 MRS studies were performed in 14 patients receiving only radio-chemotherapy. Metabolic profiles were binned into comparable time points after radiation therapy. All spectra were acquired using a single-voxel PRESS sequence (TE = 35ms, TR = 1.5s, 128 averages). Spectra were processed with fully automated LCModel (version 6.3-1c) software. Concentrations of the main metabolites (NAA, Cr, Cho, mI) and metabolite ratios relative to Cho were evaluated. Generalized estimating equations were used to evaluate longitudinal associations between metabolites and/or therapy group and overall survival. RESULTS: The 25 patients survived 6-25 months after diagnosis. Study baseline (post radiotherapy/pre-vaccine, 78-116 days post-diagnosis) mI/choline measures did not predict overall survival, but at subsequent time points higher mI/choline was associated with longer overall survival (p <0.05). A statistical interaction in the model with scans 159-250 days post-diagnosis (p < 0.001) suggested that the association with survival was much greater in the vaccine group (47 days' greater expected survival for each unit higher mI/choline ratio, after ∼2 vaccine doses) than for the non-vaccine group (13 days). DISCUSSION: mI/choline ratio may be a predictive marker for early response to peptide-based vaccine therapy of pediatric DIPG. A larger sample study is needed to further validate that MRS could be used to optimize/adjust peptide based vaccine therapy of DIPG patients.