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

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