Comparison of Volumetric and 2D-based Response Methods in the PNOC-001 Pediatric Low-Grade Glioma Clinical Trial

Abstract

Although response in pediatric low-grade glioma (pLGG) includes volumetric assessment, more simplified 2D-based methods are often used in clinical trials. The study purpose was to compare volumetric to 2D methods. An expert neuroradiologist performed solid and whole tumor (including cyst and edema) volumetric measurements on MR images using a PACS-based manual segmentation tool in 43 pLGG participants (213 total follow-up images) from the PNOC-001 trial. Classification based on changes in volumetric and 2D measurements of solid tumor were compared to neuroradiologist visual response assessment using the Brain Tumor Reporting and Data System (BT-RADS) criteria for a subset of 65 images using receiver operating characteristic (ROC) analysis. Longitudinal modeling of solid tumor volume was used to predict BT-RADS classification in 54 of the 65 images. There was a significant difference in ROC area under the curve (AUC) between 3D solid tumor volume and 2D area (0.96 vs. 0.78, p = 0.005) and between 3D solid and 3D whole volume (0.96 vs. 0.84, p = 0.006) when classifying BT-RADS progressive disease (PD). Thresholds of 15-25% increase in 3D solid tumor volume had an 80% sensitivity in classifying BT-RADS PD included in their 95% confidence intervals. The longitudinal model of solid volume response had a sensitivity of 82% and positive predictive value of 67% for detecting BT-RADS PD. Volumetric analysis of solid tumor was significantly better than 2D measurements in classifying tumor progression as determined by BT-RADS criteria and will enable more comprehensive clinical management.