Predictive Factors of Pseudoprogression Versus True Progression In Patients Treated With Surgery And Chemoradiotherapy for Glioblastoma

Abstract

Glioblastoma (GBM) remains the most common malignant brain primary tumor in adults. The diagnosis of pseudoprogression (PsP) during follow-up is a real dilemma, and actually, no universal predictive factor of PsP has been found. The aim of this study was to determine predictive factors of PsP to help the clinician to distinguish PsP from true progression (TP) in GBM patients. Adult patients with histopathological confirmation of GBM treated with optimal surgery and standard chemoradiotherapy (CRT) according to the EORTC/NCIC protocol were included. Clinical, radiological, histopathological, and radiation data were analyzed at the time of the dosimetric magnetic resonance imaging (MRI) performed before CRT (baseline) and of the progression MRI showing a suspicion of progression. Patients were classified into the PsP group or in TP group according to the conclusion of the local multidisciplinary tumor board at the time of the MRI following the progression MRI. In parallel, patients’ data were analyzed according to the RANO criteria. An analysis of correlation was performed with the variables of P value £0.200 in univariate analysis. The multivariate model included variables such as the rcorrelation coefficient –0.5 £ r £ 0.5. A total of 57 patients were included in the study, 44 (77%) in the TP group and 13 (23%) in the PsP group. The univariate analysis identified potential predictive factors of PsP: the absence of epilepsy at the time of the dosimetric MRI (p = 0.042) and its stable evolution (p = 0.032), the MGMT promotor methylation (p = 0.044) and the ATRX mutation (p = 0.043), the decrease of the necrotic areas evaluated in two dimensions (p = 0.041) and in three dimensions (p = 0.024), the V80% and the Dmin of the volume including the contrast-enhanced lesions, the necrotic areas, and the surgical cavity in the progression MRI (p = 0.023 and p = 0.017, respectively) and the volume of the contrast-enhanced lesions alone (p = 0.039 and p = 0.029, respectively). In multivariate analysis, predictive factors of PsP were the V80% of edema areas volume (p = 0.027), the number of contrast-enhanced lesions at the time of progression MRI (p = 0.035), and the RANO response group (p = 0.019). Currently, the only method of diagnosing PsP with certainty is histopathological confirmation. But in clinical routine, the analysis of conventional MRIs during the follow-up is the most used. This study identified potential predictive factors of PsP, which remain to be confirmed with a prospective study and supplementary data on advanced MRIs and genetic analysis.