An Observational Study of Circulating Tumor Cells and (18)F-FDG PET Uptake in Patients with Treatment-Naive Non-Small Cell Lung Cancer

INTRODUCTION: We investigated the relationship of circulating tumor cells (CTCs) in non-small cell lung cancer (NSCLC) with tumor glucose metabolism as defined by (18)F-fluorodeoxyglucose (FDG) uptake since both have been associated with patient prognosis. MATERIALS & METHODS: We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM) independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or “HD-CTCs”). We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis. RESULTS: We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0–3.6) and median maximum standardized uptake value (SUV(max)) was 7.2 (IQR 3.7–15.5). More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71) or in stage I disease (27 of 43). HD-CTCs were weakly correlated with partial volume corrected tumor SUV(max) (r = 0.27, p-value = 0.03) and not correlated with tumor diameter (r = 0.07; p-value = 0.60). For a given partial volume corrected SUV(max) or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease. CONCLUSIONS: CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.