Diagnostic Accuracy of Amino Acid PET for Differentiating Tumor Recurrence or Progression from Treatment-Related Changes in Glioma Patients: A Uppstematic Review and Meta-Analysis

Background: Differentiating tumor recurrence from treatment-related changes in patients with glioma remains a major diagnostic challenge because conventional MRI has limited specificity. Amino acid positron emission tomography (PET) has emerged as a promising adjunctive imaging modality. Purpose: To evaluate the diagnostic performance of amino acid PET for distinguishing tumor recurrence from treatment-related changes in previously treated glioma patients. Methods: A systematic review and meta-analysis were conducted according to the PRISMA-DTA guidelines. PubMed, Scopus, and Web of Science were searched from inception to March 2026. Studies evaluating clinically used amino acid PET tracers (MET, FET, or FDOPA) in previously treated glioma patients and reporting sufficient data to construct 2 × 2 contingency tables were included. Pooled sensitivity and specificity were estimated using a bivariate random-effects model. The primary analysis was restricted to studies reporting patient-based data from non-overlapping cohorts. A post hoc sensitivity analysis, added in response to peer review, retained both potentially overlapping patient-based datasets. Lesion- and scan-based studies were excluded from quantitative synthesis because within-patient clustering could not be accounted for using the published aggregate data. Subgroup and meta-regression analyses explored sources of heterogeneity. Results: Sixteen studies met the inclusion criteria. The primary synthesis comprised 12 studies reporting patient-based data from non-overlapping cohorts (728 patients, one 2 × 2 table each). Amino acid PET demonstrated a pooled sensitivity of 0.87 (95% CI 0.83–0.90) and specificity of 0.78 (95% CI 0.72–0.83). The positive likelihood ratio was 3.91 (95% CI 3.04–5.02), the negative likelihood ratio was 0.17 (95% CI 0.13–0.23), and the diagnostic odds ratio was 22.8 (95% CI 14.6–35.7). At the pooled prevalence of recurrence of 68%, a positive scan corresponded to a post-test probability of 89% and a negative scan to 27%. Univariable I2 estimates were 10% for sensitivity and 0% for specificity, but these measures should not be interpreted as evidence of overall homogeneity. Estimates were essentially unchanged when both potentially overlapping datasets were retained (13 studies, 756 patients). Tracer type was nominally associated with the diagnostic odds ratio (p = 0.044), but tracer type was strongly confounded by study sample size and publication era, and the association was not robust in the sensitivity analysis. No statistically significant subgroup differences were identified; however, these analyses were limited by the small number of studies and methodological heterogeneity. Conclusions: Amino acid PET usefully but not decisively revises the probability of recurrence in patients under suspicion after treatment. At the pooled pre-test probability of 68%, a positive PET increased the post-test probability of recurrence to 89%, whereas a negative PET reduced it to 27%; therefore, a negative result does not exclude recurrence. Because positivity thresholds were largely derived post hoc and reference standards were composite, these estimates are likely to be optimistic. Apparent tracer-related differences observed in subgroup and meta-regression analyses were strongly confounded by publication era and study sample size and were not supported by head-to-head within-patient comparisons. Therefore, no superiority of MET, FET, or FDOPA can be inferred from the available evidence. The analysis was limited to MET, FET, and FDOPA, and the findings may therefore not be generalizable to other amino acid tracers.