Abstract 3783: Circulating tumor cells measured in the pulmonary vein and the radial artery during surgery of non-small cell lung cancer
Authors: Tamminga Menno , Wit Sanne de , Swennenhuis Joost F. , Wauwer Caroline van de , Klinkenberg Theo J. , Hiltermann T. Jeroen , Groen Harry J. , Terstappen Leon W. M. 
Published: July 2017

Background: The number of circulating tumor cells (CTC) detected by the CellSearch system is low or absent in 7.5 mL of venous peripheral blood of metastatic and non-metastatic non-small cell lung cancer (NSCLC) patients. Our hypothesis is that CTC can be detected in the pulmonary vein draining the lobe containing the primary tumor before its removal and would be influenced by manipulation of the lobe during surgery.

Methods: Patients with early stage NSCLC undergoing open lobectomy were included. During surgery, blood was drawn centrally (pulmonary vein draining the lobe containing the tumor) and peripherally (radial artery) at two time points: directly after thoracotomy and identification of the draining pulmonary vein (T1) and just before closure of the draining pulmonary vein after manipulation, dissection and closure of the pulmonary artery (T2). EpCAM+ CTC were detected by CellSearch. The EpCAM+ CTC depleted sample was subsequently filtered through 5µm micosieves and fluorescently labeled for identification of EpCAM- CTC (DAPI+, Cytokeratin+ and CD45-).

Results: So far, three patients have been included. Remarkably, cell clumps were detected among EpCAM+ CTC at T1 in the pulmonary vein in all patients, and as well at T2 in patient #3. CTC in the pulmonary vein at T1 were morphologically different than those detected at T2 and in the arteries. Experiments to confirm malignancy of both subtypes of CTC are pending, using chromosome aneuploidy status and copy number variation analysis to compare them with the resected tumor.

Conclusion: In early stage NSCLC high amounts single and clumps of CTC are observed in the draining pulmonary vein during surgery. The amount measured in the radial artery is lower, indicating loss of CTC in the circulatory system before peripheral measurement. If the cells found really are CTC that are shed from the primary tumor during surgery, it will have clinical consequences for the surgery techniques used.

EpCAM+ and EpCAM- Circulating tumor cells found during surgery in non-small cell lung cancerPatient #1Patient #2Patient $3#CTC/7.5 mLEpCAM+EpCAM-EpCAM+EpCAM-EpCAM+EpCAM-Baseline (T0)NANANANA32Draining vein T1*8535*104*50130Draining Vein T2151911*10110Radial artery T1120500Radial artery T22101012Radial Artery T1+3NANANANA02Radial artery T1+5NANANANA05Radial artery T2+5NANANANA21*Presence of CTC clusters

Citation Format: Menno Tamminga, Sanne de Wit, Joost F. Swennenhuis, Caroline van de Wauwer, Theo J. Klinkenberg, T. Jeroen Hiltermann, Harry J. Groen, Leon W. M. Terstappen. Circulating tumor cells measured in the pulmonary vein and the radial artery during surgery of non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3783. doi:10.1158/1538-7445.AM2017-3783