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

Background: 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. Methods: A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) method. The entirety of the Embase and MEDLINE databases were searched for methods differentiating PsP and TTP, and studies were selected using pre-specified eligibility criteria. The sensitivity and specificity of included studies were summarised in a forest plot. Three of the identified methods were assessed in a separate subgroup meta-analysis. Results: Twenty-six studies assessing seven distinct neuroimaging methods in 1145 patients were included in the systematic review. 18F-fluoroethyltyrosine PET (FET PET) and amide proton transfer-weighted MRI (APTw-MRI) showed high diagnostic accuracy, but results were based on single low-powered studies. The highest performing methods in the subgroup analysis were DWI (AUC = 0.95 [0.92 – 0.96]) and DSC-pMRI (AUC = 0.94 [0.91 – 0.95]), compared to DCE-pMRI (AUC = 0.90 [0.87 – 0.93]). Conclusions: Both DWI and DSC-pMRI performed with high sensitivity and specificity for differentiating PsP from TTP. Considering the technical parameters and feasibility of each identified method, DSC-pMRI was found to be the most promising technique.