Abstract

Abstract Background: The number of circulating tumor cells (CTCs) detected by the CellSearch system is usually low or absent in NSCLC, possibly by elimination of CTCs in the capillary system. Our hypothesis is that the number of CTCs will be higher in the pulmonary vein draining the primary tumor compared to peripheral blood vessels and is influenced by the manipulation of the tumor during surgery. Methods: In an ongoing study, patients with NSCLC undergoing open thoracotomy or video assisted surgery (VATS) lobectomy are included. During surgery, blood was drawn from the draining pulmonary vein (dv) of the lobe containing the tumor (T1,T2) and from the radial artery (ra) (T0,T1,T2). T0 was at start of surgery, T1 upon identification of the draining pulmonary vein and T2 right before the pulmonary vein was dissected. Dissection of the pulmonary artery occurred in open surgeries before, and in VATS after T2. EpCAM+ CTCs were detected by CellSearch and EpCAM- CTCs after filtration of the EpCAM depleted samples. EpCAM+ CTCs were isolated by FACS and analyzed for copy number variations (CNV) by single-cell whole genome sequencing and genomic alterations of EpCAM- CTC by FISH on the microsieves. Results: So far, 17 patients have been included, one with a benign inflammatory tumor (pt 8). CTC counts were higher in the pulmonary vein than in the distal artery, with CTC clumps observed in some patients (* in table). No consistent effect of manipulation could be determined. In patient 4 and 5, EpCAM+ CTCs from the vein showed CNVs aberrations, whereas in patient 6 CTCs in the radial artery were of normal epithelial origin. EpCAM- CTCs of patient 1 and 2 were of both tumor and normal origin. Conclusion: In NSCLC patients high amounts of single and clumps of EpCAM+ and EpCAM-CTCs were observed in the draining pulmonary vein during surgery. In contrast, the amount of CTCs measured in the radial artery is low (even after correction of blood flow from non-tumor vessels), suggesting loss of CTCs in the cardiac system. EpCAM+ and EpCAM- CTCs in the draining vein and the radial artery during surgeryDraining vein T1 (EpCAM+)Draining vein T1 (EpCAM-)Draining vein T2 (EpCAM+)Draining vein T2 (EpCAM-)radial artery T0 (EpCAM+)radial artery T0 (EpCAM-)radial artery T1 (EpCAM+)radial artery T1 (EpCAM-)Radial artery T2 (EpCAM+)Patient 185*3515NDND122Patient 210*41911NDND050Patient 350*130101*103*2000Patient 42117110000Patient 5127312231Patient 600050027210Patient 7>3000*>26000132000000Patient 8#017596*1000050Patient 9000001000Patient 10 Lower lobe73*255204*173NDND000Patient 10 Middle lobe1426016NDND000Patient 11NDND05NDNDNDND0Patient 121013NDND01NDPatient 13440400000Patient 10121102010NDPatient 102321000000Patient 10305>1000*>100001NDND0Patient 1042820*7NDND100 Citation Format: Menno Tamminga, S de Wit, Joost F. Swennenhuis, Ellen Heitzer, Michael Speicher, T. Jeroen N. Hiltermann, Ed M. Schuuring, Leon W.M. Terstappen, Harry J. Groen. Circulating tumor cells measured in the pulmonary vein and radial artery during surgery of non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5594.

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