Purpose We evaluated that early metabolic response determined by(18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiotherapy (RT), predicts outcomes in non-small cell lung cancer. Material and methods Twenty-eight patients evaluated using pretreatment(18)F-FDG-PET/CT (PETpre) and interim(18)F-FDG-PET/CT (PETinterim) after 11 fractions of RT were retrospectively reviewed. Maximum standardized uptake value (SUVmax) was calculated for primary lesion. Predictive value of gross tumor volume (Delta GTV) and SUVmax(Delta SUVmax) changes was evaluated for locoregional control (LRC), distant failure (DF), and overall survival (OS). Metabolic responders were patients with Delta SUVmax>40%. Results Metabolic responders showed better trends in 1-year LRC (90.9%) than non-responders (47.1%) (p = 0.086). Patients with large GTV(pre)(>= 120 cc) demonstrated poor LRC (hazard ratio 4.14, p = 0.022), while metabolic non-responders with small GTV(pre)(<120 cc) and metabolic responders with large GTV(pre)both had 1-year LRC rates of 75.0%. Reduction of 25% in GTV was not associated with LRC; however, metabolic responders without a GTV response showed better 1-year LRC (83.3%) than metabolic non-responders with a reduction in GTV (42.9%). Metabolic responders showed lower 1-year DF (16.7%) than non-responders (50.0%) (p = 0.025). An Delta SUV(max)threshold of 40% yielded accuracy of 64% for predicting LRC, 75% for DF, and 54% for OS. However, Delta GTV > 25% demonstrated inferior diagnostic values than metabolic response. Conclusions Changes in tumor metabolism diagnosed using PET(interim)during RT better predicted treatment responses, recurrences, and prognosis than other factors historically used.