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Can OBJECTIVES: This study aimed to explore the diagnostic significance of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT for predicting the presence of epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC). DESIGN: A systematic review and meta-analysis. DATA SOURCES: The PubMed, EMBASE and Cochrane library databases were searched from the earliest available date to December 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: The review included primary studies that compared the mean maximum of standard uptake value (SUVmax) between wild-type and mutant EGFR, and evaluated the diagnostic value of 18F-FDG PET/CT using SUVmax for prediction of EGFR status in patients with NSCLC. DATA EXTRACTION AND SYNTHESIS: The main analysis was to assess the sensitivity and specificity, the positive diagnostic likelihood ratio (DLR+) and DLR-, as well as the diagnostic OR (DOR) of SUVmax in prediction of EGFR mutations. Each data point of the summary receiver operator characteristic (SROC) graph was derived from a separate study. A random effects model was used for statistical analysis of the data, and then diagnostic performance for prediction was further assessed. RESULTS: Across 15 studies (3574 patients), the pooled sensitivity for 18F-FDG PET/CT was 0.70 (95% CI 0.60 to 0.79) with a pooled specificity of 0.59 (95% CI 0.52 to 0.66). The overall DLR+ was 1.74 (95% CI 1.49 to 2.03) and DLR- was 0.50 (95% CI 0.38 to 0.65). The pooled DOR was 3.50 (95% CI 2.37 to 5.17). The area under the SROC curve was 0.68 (95% CI 0.64 to 0.72). The likelihood ratio scatter plot based on average sensitivity and specificity was in the lower right quadrant. CONCLUSION: Meta-analysis results showed 18F-FDG PET/CT had low pooled sensitivity and specificity. The low DOR and the likelihood ratio scatter plot indicated that 18F-FDG PET/CT should be used with caution when predicting EGFR mutations in patients with NSCLC.