Positive correlation between postoperative tumor recurrence and changes in circulating tumor cell counts in pulmonary venous blood (pvCTC) during surgical manipulation in non-small cell lung cancer

Background: In non-small cell lung cancer (NSCLC), circulating tumor cells (CTC) are shed and circulate to the peripheral blood through the pulmonary vein. Previously, CTC count in pulmonary venous blood (pvCTC) was shown to significantly increase after surgical manipulation. Therefore, we assessed the correlation between the changes in the pvCTC count (Delta pvCTC) and clinical outcomes. Methods: Consecutive patients with peripheral-type, NSCLC, who underwent lobectomy or bi-lobectomy through open thoracotomy, were enrolled prospectively. Before and after lobectomy, 2.5 mL of blood was drawn from the associated lobar pulmonary vein (PV), and was served for the quantitative evaluation of CTC using the CellSearch (R) system. The cut-off point of Delta pvCTC was determined according to clinical outcomes and Delta pvCTC using receiver operation characteristic (ROC) curve. Then the correlation between Delta pvCTC and clinical outcomes was evaluated by Kaplan-Meier analyses and log-rank test. In addition, the correlation between Delta pvCTC and perioperative variables was assessed. Results: A total of 30 patients were enrolled, tumor recurrence occurred in 11 patients over a median follow-up of 64.4 months. Of these, 7 patients had distant metastasis and 4 had local recurrence. The median Delta pvCTC was 49 cells/2.5 mL, and pvCTC-count was increased during surgical manipulation in 24 patients (80%). We divided patients into two groups based on Delta pvCTC with the cut-off value as 119 cells/2.5 mL according to ROC curve. Significant shorter time to distant metastasis (TDM) (P=0.0123) was observed in high Delta pvCTC group (Delta pvCTC >= 119 cells/2.5 mL) than low Delta pvCTC group (.pvCTC < 119 cells/2.5mL). Neither disease-free survival (DFS) nor overall survival (OS) was significantly correlated with Delta pvCTC. Conclusions: Increasing pvCTC count during surgical manipulation was significantly correlated with postoperative distant metastasis in completely resected NSCLC patients. Significant shorter TDM was observed in patient with high Delta pvCTC group.