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Purpose: To determine the value of combined positron emission tomography/computed tomography (PET/CT) during induction chemotherapy (CTx) followed by chemoradiotherapy (CTx/ RTx) for non^small-cell lung cancer to predict histopathologic response in primary tumor and mediastinum and prognosis of the patient. Experimental Design: Fifty consecutive patients with locally advanced non^small-cell lung cancer received induction therapy and, if considered resectable, proceeded to surgery (37 of 50 patients). Patients had at least two repeated 18 F-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT scans either before treatment (t 0 ) or after induction CTx (t 1 ) or CTx/RTx (t 2 ).Variables from the PET/CTstudies [e.g., lesion volume and corrected maximum standardized glucose uptake values (SUV max,corr )] were correlated with histopathologic response (graded as 3, 2b, or 2a: 0%, >0-10%, or >10% residual tumor cells) and times to failure.Results: Primary tumors showed a percentage decrease in SUV max,corr during induction significantly larger in grade 2b/3 than in grade 2a responding tumors (67% versus 34% at t 1 , 73% versus 49% at t 2 ; both P < 0.005). SUV max,corr at t 2 was significantly correlated with histopathologic response in tumors smaller than the median volume (7.5 cm 3 ; r = À0.54, P = 0.02). In the mediastinal lymph nodes, SUV max,corr values at t 2 predicted an ypN 0 status with a sensitivity and specificity of 73% and 89%, respectively (SUV max,corr threshold of 4.1, r = À0.54, P = 0.0005). Freedom from extracerebral relapse was significantly better in grade 2b/3 patients (86% at16 months versus 20% in 2a responders; P = 0.003) andinpatients with a greater percentage decrease in SUV max,corr in the primary tumor at t 2 in relation to t 0 than in patients with lesser response (83% at 16 months versus 43%; P = 0.03 for cutoff points between 0.45 and 0.55). Conclusions: SUV max,corr values from two serial PET/CT scans, before and after three chemotherapy cycles or later, allow prediction of histopathologic response in the primary tumor and mediastinal lymph nodes and have prognostic value.

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