Discriminators of pseudoprogression and true progression in high-grade gliomas: A systematic review and meta-analysis

Abstract

High-grade gliomas remain the most common primary brain tumour with limited treatments options and early recurrence rates following adjuvant treatments. However, differentiating true tumour progression (TTP) from treatment-related effects or pseudoprogression (PsP), may critically influence subsequent management options. Structural MRI is routinely employed to evaluate treatment responses, but misdiagnosis of TTP or PsP may lead to continuation of ineffective or premature cessation of effective treatments, respectively. A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses method. Embase, MEDLINE, Web of Science and Google Scholar were searched for methods applied to differentiate PsP and TTP, and studies were selected using pre-specified eligibility criteria. The sensitivity and specificity of included studies were summarised. Three of the identified methods were compared in a separate subgroup meta-analysis. Thirty studies assessing seven distinct neuroimaging methods in 1372 patients were included in the systematic review. The highest performing methods in the subgroup analysis were DWI (AUC = 0.93 [0.91–0.95]) and DSC-MRI (AUC = 0.93 [0.90–0.95]), compared to DCE-MRI (AUC = 0.90 [0.87–0.93]). 18F-fluoroethyltyrosine PET (18F-FET PET) and amide proton transfer-weighted MRI (APTw-MRI) also showed high diagnostic accuracy, but results were based on few low-powered studies. Both DWI and DSC-MRI performed with high sensitivity and specificity for differentiating PsP from TTP. Considering the technical parameters and feasibility of each identified method, the authors suggested that, at present, DSC-MRI technique holds the most clinical potential.

Hybrid18F-Fluoroethyltyrosine PET and MRI with Perfusion to Distinguish Disease Progression from Treatment-Related Change in Malignant Brain Tumors: The Quest to Beat the Toughest Cases

“…For ATDG patients, our rCBV (DSC MRI) sensitivity of 84%, specificity of 80%, and AUC of 0.88 were within the confidence bounds of a recent metaanalysis released by Fu et al (33). Additionally, the K trans (dynamic contrast-enhanced MRI) specificity of 80% and AUC of 0.88 for ATDG patients were within the confidence bounds of a metaanalysis released by Taylor et al, whereas our reported sensitivity was slightly higher, at 94% (34). Evidence for PWI is limited in BM patients, but Cicone et al reported an rCBV accuracy of 76% and AUC within 0.65-0.96, which complement our 76% accuracy and AUC of 0.74 (35).…”

Diagnostic accuracy of glioma pseudoprogression identification with positron emission tomography imaging: a systematic review and meta-analysis

“…In addition, compared with the studies which only included patients with high-grade gliomas (HGGs; WHO III–IV), the summary specificity of those studies which enrolled patients with LGGs (WHO I–II) and HGGs was lower (0.87 vs. 0.83; P<0.05). We believe this may be attributable to an increase in radiotracer uptake with increasing glioma grade ( 45 - 49 ). Usually, HGGs have a greater tumor cell density, microvascular density, and more efficient amino acid transport system, which can more quickly absorb amino acid radioactive tracers from blood pools ( 50 , 51 ).…”

Dynamic Susceptibility Contrast-Enhanced Perfusion-Weighted Imaging in Differentiation Between Recurrence and Pseudoprogression in High-Grade Glioma: A Meta-analysis

“…World Health Organization grade 3 or higher glioma cases were designated as cases of HGG for this study 34 . Pseudoprogression and RT were respectively defined by negative and positive results.…”

“…World Health Organization grade 3 or higher glioma cases were designated as cases of HGG for this study. 34 Pseudoprogression and RT were respectively defined by negative and positive results. Specifically, RT diagnoses were made based on histopathological results or the observation of lesion growth corresponding to the deterioration of the overall condition of the patient during follow-up, 2 whereas PsP diagnoses were made based on histopathological results or the observation that the identified lesion shrunk with improvements in the overall condition of the patient during follow-up.…”