TY - JOUR
T1 - EPAC-lung
T2 - European pooled analysis of the prognostic value of circulating tumour cells in small cell lung cancer
AU - Foy, Victoria
AU - Lindsay, Colin R.
AU - Carmel, Alexandra
AU - Fernandez-Gutierrez, Fabiola
AU - Krebs, Matthew G.
AU - Priest, Lynsey
AU - Carter, Mathew
AU - Groen, Harry J.M.
AU - Hiltermann, T. Jeroen
AU - de Luca, Antonella
AU - Farace, Francoise
AU - Besse, Benjamin
AU - Terstappen, Leon
AU - Rossi, Elisabetta
AU - Morabito, Alessandro
AU - Perrone, Francesco
AU - Renehan, Andrew
AU - Faivre-Finn, Corinne
AU - Normanno, Nicola
AU - Dive, Caroline
AU - Blackhall, Fiona
AU - Michiels, Stefan
N1 - Funding Information:
The authors would like to thank all the patients who took the time to participate in this research at a time when they had other priorities. Funding: Dr. Lindsay was supported by the European Society for Medical Oncology (translational research fellowship – no grant number applicable) with the aid of a grant from Hoffman-La Roche and the International Association for the Study of Lung Cancer (no grant number applicable). CRL also received support as a recipient of the grant DUERTECC/EURONCO (Diplome Universitaire Européen de Recherche Translationelle et Clinique en Cancerologie - no grant number applicable). VF was funded via a Clinical Pharmacology Fellowship educational grant from CRUK and AstraZeneca (C147/A12328). The authors at the Gustave Roussy are grateful for the research support of the Fondation de France (grant no 201300038317), the Fondation ARC pour la Recherche sur le Cancer (grant no 20131200417), Innovative Medicines Initiative 11th Call CANCER ID (IMI-JU-11-2013, 115749), Institute National du Cancer (PRT-K14-032), Agence Nationale de la Recherche (ANR-CE17-0006-01) and the Ligue Contre Le Cancer (meta-analysis platform). This work was also supported by Cancer Research UK via funding to the CRUK Manchester Institute (Grant number A25254) and the CRUK Lung Cancer Centre of Excellence (Grant number A20465). Sample collection was undertaken as part of the CONVERT trial (Concurrent Once-daily Vs. twice daily RadioTherapy), and the ChemoRes trial (Molecular mechanisms underlying chemotherapy resistance, therapeutic escape, efficacy, and toxicity-Improving knowledge of treatment resistance in patients with lung cancer). This work was supported by the National Institute for Health research (NIHR) Manchester BRC, and the NIHR Christie Research Facility, and the Manchester MRC Single Cell Research Centre (MR/M008908/1). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. This project was also supported by funds from the Italian Ministry of Health through an intramural grant (M 2/1) of the Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale.
Funding Information:
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure forms (available at http://dx.doi. org/10.21037/tlcr-20-1061). Dr. CRL reports personal fees from Amgen, personal fees from copartners, outside the submitted work. Dr. CRL was supported by the European Society for Medical Oncology (translational research fellowship – no grant number applicable) with the aid of a grant from Hoffman-La Roche and the International Association for the Study of Lung Cancer (no grant number applicable). CRL also received support as a recipient of the grant DUERTECC/EURONCO (Diplome Universitaire Européen de Recherche Translationelle et Clinique en Cancerologie - no grant number applicable). Dr. VF was funded via a Clinical Pharmacology Fellowship educational grant from CRUK and AstraZeneca (C147/A12328). Dr. MGK reports personal fees from Janssen, personal fees from Roche, personal fees from Bayer, personal fees from Seattle Genetics, outside the submitted work. Dr. Groen reports grants from Cancer-ID project, outside the submitted work. Dr. BB reports grants from Abbvie, grants from Amgen, grants from AstraZeneca, grants from Biogen, grants from Blueprint Medicines, grants from BMS, grants from Celgène, grants from Eli-Lilly, grants from GSK, grants from Ignyta, grants from ISPEN, grants from Merck KGaA, grants from MSD, grants from Nektar, grants from Onxeo, grants from Pfizer, grants from Pharma Mar, grants from Sanofi, grants from Spectrum Pharmaceuticals, grants from Takeda, grants from Tiziana Pharma, outside the submitted work. Dr. AM reports personal fees from ROCHE, personal fees from ASTRAZENECA, personal fees from BOEHRINGER, from Pfizer, from BMS, from MSD, from TAKEDA, outside the submitted work. Dr. FP reports grants, personal fees and non-financial support from Bayer, personal fees from Sandoz, grants and personal fees from Incyte, personal fees from Celgene, grants and personal fees from Astra Zeneca, personal fees from Pierre Fabre, personal fees from Janssen Cilag, grants from Roche, grants from Pfizer, outside the submitted work. Dr. CFF reports grants and other from AstraZeneca, grants and other from Elekta, outside the submitted work. Dr. CD reports grants from AstraZeneca, grants from NIHR Manchester Biomedical Research Centre, during the conduct of the study; grants and personal fees from AstraZeneca, grants from Amgen, grants from Angle PLC, grants from Astex Pharmaceuticals, grants from Bayer, grants and personal fees from Biocartis, grants from Bioven, grants from BMS, grants from Boehringer Ingelheim, grants from Celgene, grants and non-financial support from Clearbridge Biomedics, grants from GSK, grants from Menarini Diagnostics, grants and personal fees from Merck KGaA, grants from Novartis, grants from Roche, grants from Taiho Oncology, non-financial support from Thermofisher, outside the submitted work. Dr. SM reports personal fees from Statistical advice: IDDI, Janssen CilagÐ personal fees from Independent Data Monitoring Committee member: Hexal, Steba, IQVIA, Roche, Sensorion, Biophytis, Servier, Yuhan, outside the submitted work. Dr. NN serves as an unpaid editorial board member of the Translational Lung Cancer Research from Sep 2019 to Sep 2021. The authors have no other conflicts of interest to declare.
Funding Information:
Dr. Lindsay was supported by the European Society for Medical Oncology (translational research fellowship - no grant number applicable) with the aid of a grant from Hoffman-La Roche and the International Association for the Study of Lung Cancer (no grant number applicable). CRL also received support as a recipient of the grant DUERTECC/EURONCO (Diplome Universitaire Europ?en de Recherche Translationelle et Clinique en Cancerologie - no grant number applicable). VF was funded via a Clinical Pharmacology Fellowship educational grant from CRUK and AstraZeneca (C147/A12328). The authors at the Gustave Roussy are grateful for the research support of the Fondation de France (grant no 201300038317), the Fondation ARC pour la Recherche sur le Cancer (grant no 20131200417), Innovative Medicines Initiative 11th Call CANCER ID (IMI-JU-11-2013, 115749), Institute National du Cancer (PRT-K14-032), Agence Nationale de la Recherche (ANR-CE17-0006-01) and the Ligue Contre Le Cancer (meta-analysis platform). This work was also supported by Cancer Research UK via funding to the CRUK Manchester Institute (Grant number A25254) and the CRUK Lung Cancer Centre of Excellence (Grant number A20465). Sample collection was undertaken as part of the CONVERT trial (Concurrent Once-daily Vs. twice daily RadioTherapy), and the ChemoRes trial (Molecular mechanisms underlying chemotherapy resistance, therapeutic escape, efficacy, and toxicity- Improving knowledge of treatment resistance in patients with lung cancer). This work was supported by the National Institute for Health research (NIHR) Manchester BRC, and the NIHR Christie Research Facility, and the Manchester MRC Single Cell Research Centre (MR/M008908/1). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. This project was also supported by funds from the Italian Ministry of Health through an intramural grant (M 2/1) of the Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale.
Publisher Copyright:
© Translational Lung Cancer Research. All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Biomarker
KW - Circulating tumour cells (CTCs)
KW - Liquid biopsies
KW - Meta-analysis
KW - Prognostic models
KW - Small cell lung cancer (SCLC)
UR - http://www.scopus.com/inward/record.url?scp=85105478967&partnerID=8YFLogxK
U2 - 10.21037/tlcr-20-1061
DO - 10.21037/tlcr-20-1061
M3 - Article
AN - SCOPUS:85105478967
SN - 2218-6751
VL - 10
SP - 1653
EP - 1665
JO - Translational Lung Cancer Research
JF - Translational Lung Cancer Research
IS - 4
ER -
