TY - JOUR
T1 - Leukapheresis increases circulating tumour cell yield in non-small cell lung cancer, counts related to tumour response and survival
AU - Tamminga, Menno
AU - Andree, Kiki C.
AU - van den Bos, Hilda
AU - Hiltermann, T. Jeroen N.
AU - Mentink, Anouk
AU - Spierings, Diana C.J.
AU - Lansdorp, Peter
AU - Timens, Wim
AU - Schuuring, Ed
AU - Terstappen, Leon W.M.M.
AU - Groen, Harry J.M.
N1 - Funding Information:
The authors are part of the CANCER-ID consortium, which has received support from the Innovative Medicines Initiative (IMI) Joint Undertaking under grant agreement no. 115749. Additional funding from the Dutch cancer funds (KWF subsidy no. 10491 from 2016) was received. Funding sources had no influence on data gathering, analysing, interpreting or the writing and publishing of the manuscript.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - Background: Circulating tumour cells (CTCs) can be used to monitor cancer longitudinally, but their use in non-small cell lung cancer (NSCLC) is limited due to low numbers in the peripheral blood. Through diagnostic leukapheresis (DLA) CTCs can be obtained from larger blood volumes.Methods: Patients with all stages of NSCLC were selected. One total body blood volume was screened by DLA before and after treatment. Peripheral blood was drawn pre- and post DLA for CTC enumeration by CellSearch. CTCs were detected in the DLA product (volume equalling 2 × 108 leucocytes) and after leucocyte depletion (RosetteSep, 9 mL DLA product). Single-cell, whole-genome sequencing was performed on isolated CTCs.Results: Fifty-six patients were included. Before treatment, CTCs were more often detected in DLA (32/55, 58%) than in the peripheral blood (pre-DLA: 18/55, 33%; post DLA: 13/55, 23%, both at p < 0.01). CTCs per 7.5 mL DLA product were median 9.2 times (interquartile range = 5.6–24.0) higher than CTCs in 7.5 mL blood. RosetteSEP did not significantly improve CTC detection (pretreatment: 34/55, 62%, post treatment: 16/34, 47%) and CTCs per mL even decreased compared to DLA (p = 0.04). Patients with advanced-stage disease with DLA-CTC after treatment showed fewer tumour responses and shorter progression-free survival (PFS) than those without DLA-CTC (median PFS, 2.0 vs 12.0 months, p < 0.01). DLA-CTC persistence after treatment was independent of clinical factors associated with shorter PFS (hazard ratio (HR) = 5.8, 95% confidence interval (CI), 1.4–35.5, p = 0.02). All evaluable CTCs showed aneuploidy.Conclusions: DLA detected nine times more CTCs than in the peripheral blood. The sustained presence of CTCs in DLA after treatment was associated with therapy failure and shortened PFS. Trial registration: The study was approved by the Medical Ethical Committee (NL55754.042.15) and was registered in the Dutch trial register (NL5423).
AB - Background: Circulating tumour cells (CTCs) can be used to monitor cancer longitudinally, but their use in non-small cell lung cancer (NSCLC) is limited due to low numbers in the peripheral blood. Through diagnostic leukapheresis (DLA) CTCs can be obtained from larger blood volumes.Methods: Patients with all stages of NSCLC were selected. One total body blood volume was screened by DLA before and after treatment. Peripheral blood was drawn pre- and post DLA for CTC enumeration by CellSearch. CTCs were detected in the DLA product (volume equalling 2 × 108 leucocytes) and after leucocyte depletion (RosetteSep, 9 mL DLA product). Single-cell, whole-genome sequencing was performed on isolated CTCs.Results: Fifty-six patients were included. Before treatment, CTCs were more often detected in DLA (32/55, 58%) than in the peripheral blood (pre-DLA: 18/55, 33%; post DLA: 13/55, 23%, both at p < 0.01). CTCs per 7.5 mL DLA product were median 9.2 times (interquartile range = 5.6–24.0) higher than CTCs in 7.5 mL blood. RosetteSEP did not significantly improve CTC detection (pretreatment: 34/55, 62%, post treatment: 16/34, 47%) and CTCs per mL even decreased compared to DLA (p = 0.04). Patients with advanced-stage disease with DLA-CTC after treatment showed fewer tumour responses and shorter progression-free survival (PFS) than those without DLA-CTC (median PFS, 2.0 vs 12.0 months, p < 0.01). DLA-CTC persistence after treatment was independent of clinical factors associated with shorter PFS (hazard ratio (HR) = 5.8, 95% confidence interval (CI), 1.4–35.5, p = 0.02). All evaluable CTCs showed aneuploidy.Conclusions: DLA detected nine times more CTCs than in the peripheral blood. The sustained presence of CTCs in DLA after treatment was associated with therapy failure and shortened PFS. Trial registration: The study was approved by the Medical Ethical Committee (NL55754.042.15) and was registered in the Dutch trial register (NL5423).
KW - 2023 OA procedure
UR - http://www.scopus.com/inward/record.url?scp=85120319054&partnerID=8YFLogxK
U2 - 10.1038/s41416-021-01634-0
DO - 10.1038/s41416-021-01634-0
M3 - Article
AN - SCOPUS:85120319054
SN - 0007-0920
VL - 126
SP - 409
EP - 418
JO - British journal of cancer
JF - British journal of cancer
ER -
