Diagnostic Accuracy of PET Tracers for the Differentiation of Tumor Progression from Treatment-Related Changes in High-Grade Glioma: A Systematic Review and Metaanalysis

Posttreatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent Response Assessment in Neuro-Oncology recommendations, PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and metaanalysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: PubMed, Web of Science, and Embase were searched systematically. Study selection, data extraction, and quality assessment were performed independently by 2 authors. Metaanalysis was performed using a bivariate random-effects model when at least 5 studies were included. Results: The systematic review included 39 studies (11 tracers). F-18-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95% confidence interval, 72%-92%) and 84% (95% confidence interval, 69%-93%), respectively. O-(2-F-18-fluoroethyl)-L-tyrosine (F-18-FET) (7 studies, 172 lesions) demonstrated a sensitivity of 90% (95% confidence interval, 81%-95%) and specificity of 85% (95% confidence interval, 71%-93%). For S-C-11-methyl)-L-methionine (C-11-MET) (8 studies, 151 lesions), sensitivity was 93% (95% confidence interval, 80%-98%) and specificity was 82% (95% confidence interval, 68%-91%). The numbers of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93%-100% and 0%100%, respectively, for F-18-FLT; 85%-100% and 72%-100%, respectively, for 3,4-dihydroxy-6-F-18-fluoro-L-phenylalanine (F-18-FDOPA); and 100% and 70%-88%, respectively, for C-11-choline. Conclusion: F-18-FET and C-11-MET, both amino-acid tracers, showed a comparably higher sensitivity than F-18-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, F-18-FET and C-11-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas.