EPAC-lung: pooled analysis of circulating tumour cells in advanced non-small cell lung cancer

C. R. Lindsay, F. H. Blackhall, A. Carmel, F. Fernandez-Gutierrez, P. Gazzaniga, H. J.M. Groen, T. J.N. Hiltermann, M. G. Krebs, S. Loges, R. López-López, L. Muinelo-Romay, K. Pantel, L. Priest, S. Riethdorf, E. Rossi, L. Terstappen, H. Wikman, J. C. Soria, F. Farace, A. Renehan & 3 others C. Dive, B. Besse, S. Michiels

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Introduction: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data. Methods: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices. Results: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p < 0·001; ≥5 CTCs: HR = 2.21, p < 0·001) and overall survival (≥2 CTCs: HR = 2·18, p < 0·001; ≥5 CTCs: HR = 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p < 0·001; ≥2 CTCs p < 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs. Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models.

Original languageEnglish
Pages (from-to)60-68
Number of pages9
JournalEuropean journal of cancer
Volume117
Early online date27 Jun 2019
DOIs
Publication statusPublished - Aug 2019

Fingerprint

Circulating Neoplastic Cells
Non-Small Cell Lung Carcinoma
Lung
Cell Count
Survival
Disease-Free Survival
erythromycin propionate-N-acetylcysteinate
Proportional Hazards Models
Cell Survival

Keywords

  • Circulating tumour cells
  • CTCs
  • KRAS
  • Lung cancer
  • Non-small cell

Cite this

Lindsay, C. R., Blackhall, F. H., Carmel, A., Fernandez-Gutierrez, F., Gazzaniga, P., Groen, H. J. M., ... Michiels, S. (2019). EPAC-lung: pooled analysis of circulating tumour cells in advanced non-small cell lung cancer. European journal of cancer, 117, 60-68. https://doi.org/10.1016/j.ejca.2019.04.019
Lindsay, C. R. ; Blackhall, F. H. ; Carmel, A. ; Fernandez-Gutierrez, F. ; Gazzaniga, P. ; Groen, H. J.M. ; Hiltermann, T. J.N. ; Krebs, M. G. ; Loges, S. ; López-López, R. ; Muinelo-Romay, L. ; Pantel, K. ; Priest, L. ; Riethdorf, S. ; Rossi, E. ; Terstappen, L. ; Wikman, H. ; Soria, J. C. ; Farace, F. ; Renehan, A. ; Dive, C. ; Besse, B. ; Michiels, S. / EPAC-lung : pooled analysis of circulating tumour cells in advanced non-small cell lung cancer. In: European journal of cancer. 2019 ; Vol. 117. pp. 60-68.
@article{51645334e2794e03bd760813d557602f,
title = "EPAC-lung: pooled analysis of circulating tumour cells in advanced non-small cell lung cancer",
abstract = "Introduction: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data. Methods: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices. Results: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p < 0·001; ≥5 CTCs: HR = 2.21, p < 0·001) and overall survival (≥2 CTCs: HR = 2·18, p < 0·001; ≥5 CTCs: HR = 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p < 0·001; ≥2 CTCs p < 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs. Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models.",
keywords = "Circulating tumour cells, CTCs, KRAS, Lung cancer, Non-small cell",
author = "Lindsay, {C. R.} and Blackhall, {F. H.} and A. Carmel and F. Fernandez-Gutierrez and P. Gazzaniga and Groen, {H. J.M.} and Hiltermann, {T. J.N.} and Krebs, {M. G.} and S. Loges and R. L{\'o}pez-L{\'o}pez and L. Muinelo-Romay and K. Pantel and L. Priest and S. Riethdorf and E. Rossi and L. Terstappen and H. Wikman and Soria, {J. C.} and F. Farace and A. Renehan and C. Dive and B. Besse and S. Michiels",
year = "2019",
month = "8",
doi = "10.1016/j.ejca.2019.04.019",
language = "English",
volume = "117",
pages = "60--68",
journal = "European journal of cancer",
issn = "0959-8049",
publisher = "Elsevier",

}

Lindsay, CR, Blackhall, FH, Carmel, A, Fernandez-Gutierrez, F, Gazzaniga, P, Groen, HJM, Hiltermann, TJN, Krebs, MG, Loges, S, López-López, R, Muinelo-Romay, L, Pantel, K, Priest, L, Riethdorf, S, Rossi, E, Terstappen, L, Wikman, H, Soria, JC, Farace, F, Renehan, A, Dive, C, Besse, B & Michiels, S 2019, 'EPAC-lung: pooled analysis of circulating tumour cells in advanced non-small cell lung cancer' European journal of cancer, vol. 117, pp. 60-68. https://doi.org/10.1016/j.ejca.2019.04.019

EPAC-lung : pooled analysis of circulating tumour cells in advanced non-small cell lung cancer. / Lindsay, C. R.; Blackhall, F. H.; Carmel, A.; Fernandez-Gutierrez, F.; Gazzaniga, P.; Groen, H. J.M.; Hiltermann, T. J.N.; Krebs, M. G.; Loges, S.; López-López, R.; Muinelo-Romay, L.; Pantel, K.; Priest, L.; Riethdorf, S.; Rossi, E.; Terstappen, L.; Wikman, H.; Soria, J. C.; Farace, F.; Renehan, A.; Dive, C.; Besse, B.; Michiels, S.

In: European journal of cancer, Vol. 117, 08.2019, p. 60-68.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - EPAC-lung

T2 - pooled analysis of circulating tumour cells in advanced non-small cell lung cancer

AU - Lindsay, C. R.

AU - Blackhall, F. H.

AU - Carmel, A.

AU - Fernandez-Gutierrez, F.

AU - Gazzaniga, P.

AU - Groen, H. J.M.

AU - Hiltermann, T. J.N.

AU - Krebs, M. G.

AU - Loges, S.

AU - López-López, R.

AU - Muinelo-Romay, L.

AU - Pantel, K.

AU - Priest, L.

AU - Riethdorf, S.

AU - Rossi, E.

AU - Terstappen, L.

AU - Wikman, H.

AU - Soria, J. C.

AU - Farace, F.

AU - Renehan, A.

AU - Dive, C.

AU - Besse, B.

AU - Michiels, S.

PY - 2019/8

Y1 - 2019/8

N2 - Introduction: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data. Methods: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices. Results: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p < 0·001; ≥5 CTCs: HR = 2.21, p < 0·001) and overall survival (≥2 CTCs: HR = 2·18, p < 0·001; ≥5 CTCs: HR = 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p < 0·001; ≥2 CTCs p < 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs. Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models.

AB - Introduction: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data. Methods: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices. Results: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p < 0·001; ≥5 CTCs: HR = 2.21, p < 0·001) and overall survival (≥2 CTCs: HR = 2·18, p < 0·001; ≥5 CTCs: HR = 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p < 0·001; ≥2 CTCs p < 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs. Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models.

KW - Circulating tumour cells

KW - CTCs

KW - KRAS

KW - Lung cancer

KW - Non-small cell

U2 - 10.1016/j.ejca.2019.04.019

DO - 10.1016/j.ejca.2019.04.019

M3 - Article

VL - 117

SP - 60

EP - 68

JO - European journal of cancer

JF - European journal of cancer

SN - 0959-8049

ER -

Lindsay CR, Blackhall FH, Carmel A, Fernandez-Gutierrez F, Gazzaniga P, Groen HJM et al. EPAC-lung: pooled analysis of circulating tumour cells in advanced non-small cell lung cancer. European journal of cancer. 2019 Aug;117:60-68. https://doi.org/10.1016/j.ejca.2019.04.019