EPAC-lung: European pooled analysis of the prognostic value of circulating tumour cells in small cell lung cancer

Victoria Foy, Colin R. Lindsay*, Alexandra Carmel, Fabiola Fernandez-Gutierrez, Matthew G. Krebs, Lynsey Priest, Mathew Carter, Harry J.M. Groen, T. Jeroen Hiltermann, Antonella de Luca, Francoise Farace, Benjamin Besse, Leon Terstappen, Elisabetta Rossi, Alessandro Morabito, Francesco Perrone, Andrew Renehan, Corinne Faivre-Finn, Nicola Normanno, Caroline DiveFiona Blackhall, Stefan Michiels

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
86 Downloads (Pure)


Background: Circulating tumour cell (CTC) number is an independent prognostic factor in patients with small cell lung cancer (SCLC) but there is no consensus on the CTC threshold for prognostic significance. We undertook a pooled analysis of individual patient data to clinically validate CTC enumeration and threshold for prognostication. Methods: Four European cancer centres, experienced in CellSearch CTC enumeration for SCLC provided pseudo anonymised data for patients who had undergone pre-treatment CTC count. Data was collated, and Cox regression models, stratified by centre, explored the relationship between CTC count and survival. The added value of incorporating CTCs into clinico-pathological models was investigated using likelihood ratio tests. Results: A total of 367 patient records were evaluated. A one-unit increase in log-transformed CTC counts corresponded to an estimated hazard ratio (HR) of 1.24 (95% CI: 1.19-1.29, P<0.0001) for progression free survival (PFS) and 1.23 (95% CI: 1.18-1.28, P<0.0001) for overall survival (OS). CTC count of ≥15 or ≥50 was significantly associated with an increased risk of progression (CTC ≥15: HR 3.20, 95% CI: 2.50-4.09, P<0.001; CTC ≥50: HR 2.56, 95% CI: 2.01-3.25, P<0.001) and an increased risk of death (CTC ≥15: HR 2.90, 95% CI: 2.28-3.70, P<0.001; CTC ≥50: HR 2.47, 95% CI: 1.95-3.13, P<0.001). There was no significant inter-centre heterogeneity observed. Addition of CTC count to clinico-pathological models as a continuous log-transformed variable, offers further prognostic value (both likelihood ratio P<0.001 for OS and PFS). Conclusions: Higher pre-treatment CTC counts are a negative independent prognostic factor in SCLC when considered as a continuous variable or dichotomised counts of ≥15 or ≥50. Incorporating CTC counts, as a continuous variable, improves clinic-pathological prognostic models.

Original languageEnglish
Pages (from-to)1653-1665
Number of pages13
JournalTranslational Lung Cancer Research
Issue number4
Publication statusPublished - Apr 2021


  • Biomarker
  • Circulating tumour cells (CTCs)
  • Liquid biopsies
  • Meta-analysis
  • Prognostic models
  • Small cell lung cancer (SCLC)


Dive into the research topics of 'EPAC-lung: European pooled analysis of the prognostic value of circulating tumour cells in small cell lung cancer'. Together they form a unique fingerprint.

Cite this