Inter-observer variability in the measurement of diffuse intrinsic pontine gliomas

Abstract

Diffuse intrinsic pontine glioma (DIPG) is an invasive pediatric brainstem tumor with a poor prognosis. Patients commonly enter investigational trials, many of which use radiographic response as an endpoint for assessing drug efficacy. However, DIPGs are difficult to measure on magnetic resonance imaging (MRI). In this study, we characterized the reproducibility of these commonly performed measurements. Each of four readers measured 50 MRI scans from DIPG patients and inter-observer variability was estimated with descriptive statistics. Results confirmed that there is wide variability in DIPG tumor measurements between readers for all image types. Measurements on FLAIR imaging were most consistent. For patients on clinical trials, measurement of DIPG should be performed by a single reader while comparing prior images side-by-side. Endpoints for clinical trials determining efficacy in this population should also include more objective measures, such as survival, and additional endpoints need to be investigated.

Proton magnetic resonance spectroscopy predicts survival in children with diffuse intrinsic pontine glioma

“…Criteria for tumor progression are generally defined by both clinical symptoms and imaging characteristics. Radiographic tumor measurements are highly variable [41], and treatment-related changes such as radiation necrosis and progressive disease are not easily distinguished using standard MRI [7, 8, 42–44]. To avoid the subjectivity associated with identifying tumor progression by tumor measurement, we used overall survival rather than time to progression for our analysis.…”

Single- and Multivoxel Proton Spectroscopy in Pediatric Patients With Diffuse Intrinsic Pontine Glioma

“…Treatment-related changes such as enhancement, mass effect and edema can mimic changes observed with tumor progression (5). Moderate tumor growth is difficult to detect and verify using current measurement standards (6). Advanced imaging techniques, including proton magnetic resonance spectroscopy (MRS), are under investigation to identify potential prognostic and surrogate markers of outcome in order to improve patient management and evaluate the underlying biology of these devastating tumors.…”

New approaches to pharmacotherapy of tumors of the nervous system during childhood and adolescence

“…Initial results showed a 71% survival at 24 months and a mean tumor volume that went from 20 to 9 cc. However, the small size of this series, the varied tumor types included (Lopez-Aguilar et al, 2008), and the difficulty in reproducibly assessing tumor size from MRI images (Hayward et al, 2008) make these results difficult to evaluate.…”