Objectives: Prediction of histopathological response with PET/CT scans after neoadjuvant chemoradiotherapy is limited by confounding factors which have been evaluated in this analysis. Methods:18F-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT findings [standard uptake value (SUV), residual tumor volume] were correlated with histopathological parameters of the resection specimens (tumor cell density, necrosis, scar, macrophage infiltration) in patients with locally advanced non-small cell lung cancer (stage IIIA/IIIB) after neoadjuvant induction chemotherapy (platinum-based doublet) and concurrent chemoradiotherapy (cisplatin/vinorelbine/45 Gy). Results: Sixty patients [40 male/20 female, median age 56 years (34–78)] completed induction therapy, 46 patients (stage IIIA/IIIB: 16/30; squamous cell carcinoma 41%, adenocarcinoma 48%, large cell carcinoma 11%) were resected. Pathologic complete response of the primary tumor was observed in 19 patients (41%) with a broad range of SUVmean (0.4–9.8, mean 3.0) after neoadjuvant therapy. A high rate of histopathological complete remissions (44%) was observed in tumors with a postinduction SUV >2.5 and volumes larger than the median (7.9 cm3) before resection. SUVmean was positively correlated with the macrophage score (r = 0.39, p = 0.007) and tumor cell density (r = 0.32, p = 0.03). Conclusions: These observations suggest that postinduction FDG uptake should be interpreted with caution in larger residual tumor volumes, since high SUV levels may be due to macrophage infiltration and not viable tumor tissue.

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