Total Lesion Glycolysis in Positron Emission Tomography Can Predict Gefitinib Outcomes in Non-Small-Cell Lung Cancer with Activating EGFR Mutation

Introduction:The purpose of this study was to evaluate the predictive role of quantitative metabolic parameters using total lesion glycolysis (TLG) in 18F-2-fluoro-2-deoxyglucose-positron emission tomography/computed tomography for developing gefitinib resistance in epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients treated with first-line gefitinib.Methods:A total of 75 NSCLC patients harboring activating EGFR mutation and receiving first-line gefitinib were analyzed. Whole-body 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography scans were acquired before first-line gefitinib. The maximal standardized uptake value and TLG of all lesions were calculated. Maximal standardized uptake value and TLG were categorized using the tertile cutoff. Treatment outcomes were compared between groups.Results:Overall response rate of gefitinib was 69.4%, and median progression-free survival (PFS) of gefitinib was 11.5 months. Overall response rates were similar between low, intermediate, and high TLG groups (68.0% versus 76.0% versus 68.0%, p = 0.274). However, PFS significantly differed by TLG groups, and high TLG was associated with shorter PFS (7.2 months in high TLG; 11.9 months in intermediate TLG; and 24.2 months in low, p < 0.001). Multivariate models adjusted for disease status and response to gefitinib showed that TLG was an independent predictive factor for PFS. TLG was also significantly associated with overall survival (p = 0.005).Conclusion:TLG can predict PFS and development of gefitinib resistance in EGFR-mutant NSCLC patients treated with first-line gefitinib. Baseline metabolic tumor burdens measured with TLG before first-line gefitinib will be of great help in predicting time to acquired resistance.