Biological Correlates of the Maximum 18-Fluoro-2-Deoxy-Glucose Uptake on Positron Emission Tomography in Non-small Cell Lung Carcinoma after Induction Chemotherapy

Introduction:The magnitude of change in quantitative 18-fluoro-2-deoxy-glucose (FDG) uptake in the primary tumor after induction chemotherapy (IC) strongly correlates with the histologic response. We aimed to investigate the mechanisms that drive persistent FDG uptake in non-small cell lung carcinoma treated with IC.Patients and Methods:Baseline and repeat positron emission tomography using 18-fluoro-2-deoxy-glucose after IC and completely resected primary tumor after IC was available in 30 patients. The surgical specimens were quantitatively analyzed for tumor architecture on hematoxylin and eosin staining. Immunohistochemical staining was assessed for microvessel density, markers of cell proliferation (Ki-67), hypoxia (HIF-1α), extracellular acidification (CAIX), and p-Akt.Results:The percentage viable tumor cells and Ki-67 length density after IC were significantly lower in metabolic responders compared with nonresponders. Hypoxia-related and acidity-related markers did not show a significant difference between metabolic responders and nonresponders.Conclusions:Tumor response after IC is related to both a decline in the number of viable tumor cells and FDG consumption. Although surrogate markers for tumor hypoxia and acidity showed a trend for correlation with increased glycolysis in pretreated stage IIIA-N2 non-small cell lung carcinoma, these markers did not contribute to the recognition of metabolic responders versus nonresponders. We observed that only surrogate markers of cell proliferation correlate with a metabolic response after IC.