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Diagnostic Leukapheresis Increases Circulating Tumor Cell Yield in Non-Small Cell Lung Cancer Patients, Which Correspond with Response and Survival

32 Pages Posted: 21 Nov 2019 Publication Status: Review Complete

See all articles by Menno Tamminga

Menno Tamminga

University of Groningen - Department of Pulmonary Diseases

Kiki c. Andree

University of Twente - Department of Medical Cell BioPhysics

Hilda Van den Bos

University of Groningen - European Research Institute for the Biology of Ageing (ERIBA)

T.Jeroen N. Hiltermann

University of Groningen - Department of Pulmonary Diseases

Anouk Mentink

University of Twente - Department of Medical Cell BioPhysics

Diana C.J. Spierings

University of Groningen - European Research Institute for the Biology of Ageing (ERIBA)

Peter Lansdorp

University of Groningen - European Research Institute for the Biology of Ageing (ERIBA)

W. Timens

University of Groningen - Department of Pathology and Medical Biology

Ed Schuuring

University of Groningen - Department of Pathology and Medical Biology

Leon W.M.M. Terstappen

University of Twente - Department of Medical Cell BioPhysics

Harry J.M. Groen

University of Groningen - Department of Pulmonary Diseases

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Abstract

Introduction: Circulating tumor cells (CTC) can be used to monitor malignant disease longitudinally, but their use in non-small cell lung cancer (NSCLC) is limited due to low numbers in peripheral blood. Through Diagnostic leukapheresis (DLA) CTC can be obtained from larger blood volumes. We studied CTC in DLA product of NSCLC patients before and after treatment.

Methods: One total blood volume was screened by DLA before and 1-3 months after treatment. Peripheral blood was drawn pre and post DLA for CTC enumeration by CellSearch. CTC were detected in DLA product directly (volume equaling 2×10^8 leukocytes) and after leukocyte depletion (RosetteSep, 9mL DLA product). Single cell whole genome sequencing was performed on isolated CTC.

Results: Before treatment, CTC were more often detected in DLA (32/55, 58%) compared to blood (pre: 18/55, 33%, p<0.01, post: 13/55, 23%, p<0.01). After treatment, number of patients with CTC were similar in DLA and peripheral blood (DLA: 14/34 ,41%, pre: 9/34, 26%, p=0.18, post: 7/34, 21%, p=0.02). CTC counts normalized to 7.5mL fluid remained higher in DLA (p<0.01). RosetteSEP non-significantly increased CTC detection (pretreatment: 34/55, 62%, post-treatment: 16/34, 47%) and counts per mL decreased (p=0.04) compared to DLA measurement. Change in DLA-CTC after treatment corresponded to response in 23/24 advanced stage patients (96%) and was associated with shorter progression free survival (median PFS=2 versus 12 months, p=0.02). All 25 isolated CTC showed aneuploidy.

Conclusions: CTC can be more readily found in DLA product. DLA-CTC in NSCLC patients are associated with response to treatment and survival.

Keywords: DLA, NSCLC, CTC, liquid biopsy, biomarker

Suggested Citation

Tamminga, Menno and Andree, Kiki c. and Van den Bos, Hilda and Hiltermann, T.Jeroen N. and Mentink, Anouk and Spierings, Diana C.J. and Lansdorp, Peter and Timens, W. and Schuuring, Ed and Terstappen, Leon W.M.M. and Groen, Harry J.M., Diagnostic Leukapheresis Increases Circulating Tumor Cell Yield in Non-Small Cell Lung Cancer Patients, Which Correspond with Response and Survival (November 19, 2019). Available at SSRN: https://ssrn.com/abstract=3490278 or http://dx.doi.org/10.2139/ssrn.3490278
This version of the paper has not been formally peer reviewed.

Menno Tamminga (Contact Author)

University of Groningen - Department of Pulmonary Diseases ( email )

Netherlands

Kiki c. Andree

University of Twente - Department of Medical Cell BioPhysics ( email )

Netherlands

Hilda Van den Bos

University of Groningen - European Research Institute for the Biology of Ageing (ERIBA) ( email )

Antonius Deusinglaan, 1
Building 3226
Groningen, 9713
Netherlands

T.Jeroen N. Hiltermann

University of Groningen - Department of Pulmonary Diseases ( email )

Netherlands

Anouk Mentink

University of Twente - Department of Medical Cell BioPhysics ( email )

Netherlands

Diana C.J. Spierings

University of Groningen - European Research Institute for the Biology of Ageing (ERIBA) ( email )

Antonius Deusinglaan, 1
Building 3226
Groningen, 9713
Netherlands

Peter Lansdorp

University of Groningen - European Research Institute for the Biology of Ageing (ERIBA) ( email )

Antonius Deusinglaan, 1
Building 3226
Groningen, 9713
Netherlands

W. Timens

University of Groningen - Department of Pathology and Medical Biology ( email )

Netherlands

Ed Schuuring

University of Groningen - Department of Pathology and Medical Biology ( email )

Netherlands

Leon W.M.M. Terstappen

University of Twente - Department of Medical Cell BioPhysics ( email )

Netherlands

Harry J.M. Groen

University of Groningen - Department of Pulmonary Diseases ( email )

Netherlands

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