Association Between 18F-Fluoro-2-Deoxy-d-Glucose Uptake Values and Tumor Vitality: Prognostic Value of Positron Emission Tomography in Early-Stage Non-small Cell Lung Cancer

Introduction: The prognostic value of quantitative 18F-fluoro-2-deoxy-d-glucose (FDG) uptake on positron emission tomography (PET) is controversial in unselected patients with non-small cell lung cancer (NSCLC). We assessed the in vivo FDG uptake, measured as maximum pixel standardized uptake value (SUV max ), in stages I and II NSCLC for its prognostic value and association with in vitro quantitative morphology of tumor vitality. Methods: Prospective FDG-PET data were available in 91 consecutive patients operated for pathologic stages I and II NSCLC. Quantitative morphology was performed of tumor architecture, tumor cell density and immunohistochemical biomarkers for apoptosis (caspase-3), cell proliferation (Ki-67), hypoxia (HIF-1α), cellular pH regulation (carbonic anhydrase IX [CAIX]), and microvessel density (CD31). Results: SUV max ≥ median and SUV max partial volume corrected for lesion size (PVC SUV max ) ≥ median were associated with an increased risk of death in univariable analysis. After correcting for stage, tumor size and age in multivariable analysis, only PVC SUV max ≥ median remained significant. The strong significant association between tumor size and SUV max weakened after PVC, suggesting that an important amount of SUV max can be simply explained by tumor size, which is less in case for PVC SUV max that associates more to the tumor cell density. In multivariable logistic regression analysis, a PVC SUV max ≥ median could be explained by high Ki-67 and high-CAIX length density. Conclusion: PVC SUV max has a prognostic value in completely resected stages I and II NSCLC. A high-quantitative FDG uptake is associated with characteristics of tumor vitality such as high tumor cell density, high cell proliferation, and extracellular acidosis.