Value of 18F-Fluoro-2-Deoxy-d-Glucose-Positron Emission Tomography/Computed Tomography in Non–Small-Cell Lung Cancer for Prediction of Pathologic Response and Times to Relapse after Neoadjuvant Chemoradiotherapy

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Abstract
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. 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 18F-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT scans either before treatment (t0) or after induction CTx (t1) or CTx/RTx (t2). Variables from the PET/CT studies [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. 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 = -0.54, P = 0.02). In the mediastinal lymph nodes, SUV(max,corr) values at t2 predicted an ypN0 status with a sensitivity and specificity of 73% and 89%, respectively (SUV(max,corr) threshold of 4.1, r = -0.54, P = 0.0005). Freedom from extracerebral relapse was significantly better in grade 2b/3 patients (86% at 16 months versus 20% in 2a responders; P = 0.003) and in patients with a greater percentage decrease in SUV(max,corr) in the primary tumor at t2 in relation to t0 than in patients with lesser response (83% at 16 months versus 43%; P = 0.03 for cutoff points between 0.45 and 0.55). 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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