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

Abstract

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). 18 F-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-(2-18 F-fluoroethyl)-L-tyrosine (18 F-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-11 C-methyl)-L-methionine (11 C-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 18 F-FLT; 85%-100% and 72%-100%, respectively, for 3,4-dihydroxy-6-18 F-fluoro-L-phenylalanine (18 F-FDOPA); and 100% and 70%-88%, respectively, for 11 C-choline. Conclusion: 18 F-FET and 11 C-MET, both amino-acid tracers, showed a comparably higher sensitivity than 18 F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, 18 F-FET and 11 C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas.

Diagnostic and Prognostic Potential of 18F-FET PET in the Differential Diagnosis of Glioma Recurrence and Treatment-Induced Changes After Chemoradiation Therapy

“…A meta-analysis from Kim et al. considering six studies on 18 F-FET PET (212 scans overall) in this clinical scenario found a pooled sensitivity and specificity of 89% (95% CI, 82–94%) and 88% (95% CI, 76–94%) ( 26 , 27 ).…”

MRI and 18FET-PET Predict Survival Benefit from Bevacizumab Plus Radiotherapy in Patients with Isocitrate Dehydrogenase Wild-type Glioblastoma: Results from the Randomized ARTE Trial

“…Positron emission tomography (PET) utilizing the amino acid tracers O-(2-18 Ffluoroethyl)-L-tyrosine ( 18 FET) or (S-11 C-methyl)-L-methionine ( 11 C-MET) can be utilized to differentiate viable glioma tissue from treatment-induced changes with high sensitivity and specificity (21). Uncontrolled studies suggest that 18 FET-PET may detect tumor progression during anti-angiogenic treatment earlier than MRI (20,22,23).…”

Enzymatic synthesis of fluorinated compounds

“…Nevertheless, 18 F-FDG-PET is far from meeting the requirements of modern disease detection technology. 18 F-FDG is based on glucose, but most disease tissues contain a lot of glucose which interfere with accuracy (de Zwart et al 2020 ; Langen et al 2017 ; Lohmann et al 2019 ). Therefore, more and more fluorinated PET tracers are being developed.…”