The potential of (18)F-FDG PET changes was evaluated for prediction of response to concomitant chemoradiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). METHODS: For 28 patients, (18)F-FDG PET was performed before treatment, at the end of the second week of treatment, and at 2 wk and 3 mo after the completion of treatment. Standardized uptake value (SUV), maximum SUV, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained. Early metabolic changes were defined as fractional change (DeltaTLG) when (18)F-FDG PET at the end of the second week was compared with pretreatment (18)F-FDG PET. In-treatment metabolic changes, as measured by serial (18)F-FDG PET, were correlated with standard criteria of response evaluation of solid tumors by means of CT imaging (Response Evaluation Criteria In Solid Tumors 1.1). Parameters were analyzed for stratification in progression-free survival (PFS). RESULTS: When compared with early metabolic nonresponders, a DeltaTLG decrease of 38% or more was associated with a significantly longer PFS (1-y PFS 80% vs. 36%, P = 0.02). Pretreatment TLG was found to be a prognostic factor for PFS. CONCLUSION: The degree of change in TLG was predictive for response to concomitant chemoradiotherapy as early as the end of the second week into treatment for patients with locally advanced NSCLC. Pretreatment TLG was prognostic for PFS.