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.

Figure 1

PRISMA flow chart of the study selection process. sP = pseudoprogression; TTP = true tumour progression.

Figure 2

Forest plot assessing various methods of differentiation of pseudoprogression from true progression according to measures of sensitivity and specificity. APTw-MRI = amide proton transfer-weighted MRI; ASL = arterial spin labelling; DCE-pMRI = dynamic contrast-enhanced perfusion MRI; DSC-pMRI = dynamic susceptibility contrast perfusion MRI; DWI = diffusion weighted imaging; FET PET = [18F]fluoroethyltyrosine PET.

Figure 3

Forest plot subgroup analysis assessing the diagnostic ability of DSC-MRI, DCE-MRI, and DWI. See Fig. 2 for list of abbreviations.

Figure 4

Summary receiver operating characteristics plot comparing diagnostic ability of subgrouped modalities. DSC-MRI, DCE-MRI and DWI are included in the SROC plot and compared according to the mean reported sensitivity and specificity of the studies in the subgroup.