Release of circulating tumor cells during surgery for non-small cell lung cancer: are they what they appear to be?

Menno Tamminga*, Sanne de Wit, C. Wauwer, van der, Hilda Bos, van den, Joost Franciscus Swennenhuis, Theo. J. Klinkenberg, T. Jeroen N. Hiltermann, K.C. Andree, Diana.C.J. Spierings, Peter, M. Lansdorp, Anke Berg, van den, Wim Timens, L.W.M.M. Terstappen, Harry J.M. Groen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose: Tumor cells from lung cancer patients are expelled from the primary tumor into the blood, but difficult to detect in the peripheral circulation. We studied the release of circulating tumor cells (CTC) during surgery to test the hypothesis that CTC counts are influenced by hemodynamic changes (caused by surgical approach) and manipulation. Experimental Design: Patients undergoing video-assisted thoracic surgery (VATS) or open surgery for (suspected) primary lung cancer were included. Blood samples were taken before surgery (T0) from the radial artery (RA), from both the RA and pulmonary vein (PV) when the PV was located (T1) and when either the pulmonary artery (T2 open) or the PV (T2 VATS) was dissected. The CTC were enumerated using the CellSearch system. Single-cell whole genome sequencing was performed on isolated CTC for aneuploidy. Results: CTC were detected in 58/138 samples (42%) of 31 patients. CTC were more often detected in the PV (70%) compared to the RA (22%, p<0.01) and in higher counts (p<0.01). After surgery, the RA but not the PV showed less often CTC (p=0.02). Type of surgery did not influence CTC release. Only 6/496 isolated CTC showed aneuploidy, despite matched primary tumor tissue being aneuploid. Euploid so-called CTC had a different morphology than aneuploid. Conclusion: CTC defined by CellSearch were identified more often and in higher numbers in the PV compared to the RA, suggesting central clearance. The majority of cells in the PV were normal epithelial cells and outnumbered CTC. Release of CTC was not influenced by surgical approach.
Original languageEnglish
JournalClinical cancer research
DOIs
Publication statusE-pub ahead of print/First online - 26 Nov 2019

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Circulating Neoplastic Cells
Non-Small Cell Lung Carcinoma
Pulmonary Veins
Radial Artery
Aneuploidy
Video-Assisted Thoracic Surgery
Lung Neoplasms
Neoplasms
Pulmonary Artery

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Tamminga, M., de Wit, S., Wauwer, van der, C., Bos, van den, H., Swennenhuis, J. F., Klinkenberg, T. J., ... Groen, H. J. M. (2019). Release of circulating tumor cells during surgery for non-small cell lung cancer: are they what they appear to be? Clinical cancer research. https://doi.org/10.1158/1078-0432.CCR-19-2541
Tamminga, Menno ; de Wit, Sanne ; Wauwer, van der, C. ; Bos, van den, Hilda ; Swennenhuis, Joost Franciscus ; Klinkenberg, Theo. J. ; Hiltermann, T. Jeroen N. ; Andree, K.C. ; Spierings, Diana.C.J. ; Lansdorp, Peter, M. ; Berg, van den, Anke ; Timens, Wim ; Terstappen, L.W.M.M. ; Groen, Harry J.M. / Release of circulating tumor cells during surgery for non-small cell lung cancer : are they what they appear to be?. In: Clinical cancer research. 2019.
@article{2447854e982e46f18aa08fd0f13dc54b,
title = "Release of circulating tumor cells during surgery for non-small cell lung cancer: are they what they appear to be?",
abstract = "Purpose: Tumor cells from lung cancer patients are expelled from the primary tumor into the blood, but difficult to detect in the peripheral circulation. We studied the release of circulating tumor cells (CTC) during surgery to test the hypothesis that CTC counts are influenced by hemodynamic changes (caused by surgical approach) and manipulation. Experimental Design: Patients undergoing video-assisted thoracic surgery (VATS) or open surgery for (suspected) primary lung cancer were included. Blood samples were taken before surgery (T0) from the radial artery (RA), from both the RA and pulmonary vein (PV) when the PV was located (T1) and when either the pulmonary artery (T2 open) or the PV (T2 VATS) was dissected. The CTC were enumerated using the CellSearch system. Single-cell whole genome sequencing was performed on isolated CTC for aneuploidy. Results: CTC were detected in 58/138 samples (42{\%}) of 31 patients. CTC were more often detected in the PV (70{\%}) compared to the RA (22{\%}, p<0.01) and in higher counts (p<0.01). After surgery, the RA but not the PV showed less often CTC (p=0.02). Type of surgery did not influence CTC release. Only 6/496 isolated CTC showed aneuploidy, despite matched primary tumor tissue being aneuploid. Euploid so-called CTC had a different morphology than aneuploid. Conclusion: CTC defined by CellSearch were identified more often and in higher numbers in the PV compared to the RA, suggesting central clearance. The majority of cells in the PV were normal epithelial cells and outnumbered CTC. Release of CTC was not influenced by surgical approach.",
author = "Menno Tamminga and {de Wit}, Sanne and {Wauwer, van der}, C. and {Bos, van den}, Hilda and Swennenhuis, {Joost Franciscus} and Klinkenberg, {Theo. J.} and Hiltermann, {T. Jeroen N.} and K.C. Andree and Diana.C.J. Spierings and Lansdorp, {Peter, M.} and {Berg, van den}, Anke and Wim Timens and L.W.M.M. Terstappen and Groen, {Harry J.M.}",
year = "2019",
month = "11",
day = "26",
doi = "10.1158/1078-0432.CCR-19-2541",
language = "English",
journal = "Clinical cancer research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",

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Tamminga, M, de Wit, S, Wauwer, van der, C, Bos, van den, H, Swennenhuis, JF, Klinkenberg, TJ, Hiltermann, TJN, Andree, KC, Spierings, DCJ, Lansdorp, PM, Berg, van den, A, Timens, W, Terstappen, LWMM & Groen, HJM 2019, 'Release of circulating tumor cells during surgery for non-small cell lung cancer: are they what they appear to be?', Clinical cancer research. https://doi.org/10.1158/1078-0432.CCR-19-2541

Release of circulating tumor cells during surgery for non-small cell lung cancer : are they what they appear to be? / Tamminga, Menno; de Wit, Sanne; Wauwer, van der, C.; Bos, van den, Hilda; Swennenhuis, Joost Franciscus; Klinkenberg, Theo. J.; Hiltermann, T. Jeroen N.; Andree, K.C.; Spierings, Diana.C.J.; Lansdorp, Peter, M.; Berg, van den, Anke ; Timens, Wim; Terstappen, L.W.M.M.; Groen, Harry J.M.

In: Clinical cancer research, 26.11.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Release of circulating tumor cells during surgery for non-small cell lung cancer

T2 - are they what they appear to be?

AU - Tamminga, Menno

AU - de Wit, Sanne

AU - Wauwer, van der, C.

AU - Bos, van den, Hilda

AU - Swennenhuis, Joost Franciscus

AU - Klinkenberg, Theo. J.

AU - Hiltermann, T. Jeroen N.

AU - Andree, K.C.

AU - Spierings, Diana.C.J.

AU - Lansdorp, Peter, M.

AU - Berg, van den, Anke

AU - Timens, Wim

AU - Terstappen, L.W.M.M.

AU - Groen, Harry J.M.

PY - 2019/11/26

Y1 - 2019/11/26

N2 - Purpose: Tumor cells from lung cancer patients are expelled from the primary tumor into the blood, but difficult to detect in the peripheral circulation. We studied the release of circulating tumor cells (CTC) during surgery to test the hypothesis that CTC counts are influenced by hemodynamic changes (caused by surgical approach) and manipulation. Experimental Design: Patients undergoing video-assisted thoracic surgery (VATS) or open surgery for (suspected) primary lung cancer were included. Blood samples were taken before surgery (T0) from the radial artery (RA), from both the RA and pulmonary vein (PV) when the PV was located (T1) and when either the pulmonary artery (T2 open) or the PV (T2 VATS) was dissected. The CTC were enumerated using the CellSearch system. Single-cell whole genome sequencing was performed on isolated CTC for aneuploidy. Results: CTC were detected in 58/138 samples (42%) of 31 patients. CTC were more often detected in the PV (70%) compared to the RA (22%, p<0.01) and in higher counts (p<0.01). After surgery, the RA but not the PV showed less often CTC (p=0.02). Type of surgery did not influence CTC release. Only 6/496 isolated CTC showed aneuploidy, despite matched primary tumor tissue being aneuploid. Euploid so-called CTC had a different morphology than aneuploid. Conclusion: CTC defined by CellSearch were identified more often and in higher numbers in the PV compared to the RA, suggesting central clearance. The majority of cells in the PV were normal epithelial cells and outnumbered CTC. Release of CTC was not influenced by surgical approach.

AB - Purpose: Tumor cells from lung cancer patients are expelled from the primary tumor into the blood, but difficult to detect in the peripheral circulation. We studied the release of circulating tumor cells (CTC) during surgery to test the hypothesis that CTC counts are influenced by hemodynamic changes (caused by surgical approach) and manipulation. Experimental Design: Patients undergoing video-assisted thoracic surgery (VATS) or open surgery for (suspected) primary lung cancer were included. Blood samples were taken before surgery (T0) from the radial artery (RA), from both the RA and pulmonary vein (PV) when the PV was located (T1) and when either the pulmonary artery (T2 open) or the PV (T2 VATS) was dissected. The CTC were enumerated using the CellSearch system. Single-cell whole genome sequencing was performed on isolated CTC for aneuploidy. Results: CTC were detected in 58/138 samples (42%) of 31 patients. CTC were more often detected in the PV (70%) compared to the RA (22%, p<0.01) and in higher counts (p<0.01). After surgery, the RA but not the PV showed less often CTC (p=0.02). Type of surgery did not influence CTC release. Only 6/496 isolated CTC showed aneuploidy, despite matched primary tumor tissue being aneuploid. Euploid so-called CTC had a different morphology than aneuploid. Conclusion: CTC defined by CellSearch were identified more often and in higher numbers in the PV compared to the RA, suggesting central clearance. The majority of cells in the PV were normal epithelial cells and outnumbered CTC. Release of CTC was not influenced by surgical approach.

U2 - 10.1158/1078-0432.CCR-19-2541

DO - 10.1158/1078-0432.CCR-19-2541

M3 - Article

JO - Clinical cancer research

JF - Clinical cancer research

SN - 1078-0432

ER -