TY - JOUR
T1 - Circulating tumour cells as a potential biomarker for lung cancer screening
T2 - a prospective cohort study
AU - Marquette, Charles Hugo
AU - Boutros, Jacques
AU - Benzaquen, Jonathan
AU - Ferreira, Marion
AU - Pastre, Jean
AU - Pison, Christophe
AU - Padovani, Bernard
AU - Bettayeb, Faiza
AU - Fallet, Vincent
AU - Guibert, Nicolas
AU - Basille, Damien
AU - Ilie, Marius
AU - Hofman, Véronique
AU - Hofman, Paul
AU - ISRAEL-BIET, Dominique
AU - CHABOT, François
AU - GUILLAUMOT, Anne
AU - DESLEE, Gaetan
AU - PEROTIN, Jeanne Marie
AU - DURY, Sandra
AU - MAL, Hervé
AU - MARCEAU, Armelle
AU - Kessler, Romain
AU - Vergnon, Jean Michel
AU - Pelissier, Carole
AU - Di Palma, Fabrice
AU - Cuvelier, Antoine
AU - PATOUT, Maxime
AU - Bourdin, Arnaud
AU - GAMEZ, Anne Sophie
AU - ANDREJAK, Claire
AU - POULET, Claire
AU - FRANCOIS, Géraldine
AU - Jounieaux, Vincent
AU - Roche, Nicolas
AU - Jouneau, Stéphane
AU - Brinchault, Graziella
AU - Bonniaud, Philippe
AU - ZOUAK, Ayoub
AU - Scherpereel, Arnaud
AU - BALDACCI, Simon
AU - CORTOT, Alexis
AU - Mornex, Jean François
AU - Steenhouwer, François
AU - LEROY, Sylvie
AU - BERTHET, Jean Philippe
AU - FONTAS, Eric
AU - BULSEI, Julie
AU - CRUZEL, Coralie
AU - Pradelli, Johanna
AU - Fontaine, Maureen
AU - MANIEL, Charlotte
AU - Griffonnet, Jennifer
AU - BUTORI, Catherine
AU - SELVA, Eric
AU - POUDENX, Michel
AU - AguilanIu, Bernard
AU - Ferreti, Gilbert
AU - Arbib, François
AU - Briault, Amandine
AU - Toffart, Anne Claire
AU - Dahalani, Raissa
AU - Destors, Marie
AU - Chanez, Pascal
AU - GREILLIER, Laurent
AU - ASTOUL, Philippe
AU - BARLESI, Fabrice
AU - GAUBERT, Jean Yves
AU - Mazières, Julien
AU - Marchand-Adam, Sylvain
AU - Cadranel, Jacques
AU - CHAABANE, Nouha
AU - IZADIFAR, Armine
AU - ROSENCHER, Lise
AU - RUPPERT, Anne Marie
AU - VIEIRA, Thibault
AU - MATHIOT, Nathalie
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Background: Lung cancer screening with low-dose chest CT (LDCT) reduces the mortality of eligible individuals. Blood signatures might act as a standalone screening tool, refine the selection of patients at risk, or help to classify undetermined nodules detected on LDCT. We previously showed that circulating tumour cells (CTCs) could be detected, using the isolation by size of epithelial tumour cell technique (ISET), long before the cancer was diagnosed radiologically. We aimed to test whether CTCs could be used as a biomarker for lung cancer screening. Methods: We did a prospective, multicentre, cohort study in 21 French university centres. Participants had to be eligible for lung cancer screening as per National Lung Screening Trial criteria and have chronic obstructive pulmonary disease with a fixed airflow limitation defined as post-bronchodilator FEV1/FVC ratio of less than 0·7. Any cancer, other than basocellular skin carcinomas, detected within the previous 5 years was the main exclusion criterion. Participants had three screening rounds at 1-year intervals (T0 [baseline], T1, and T2), which involved LDCT, clinical examination, and a blood test for CTCs detection. Participants and investigators were masked to the results of CTC detection, and cytopathologists were masked to clinical and radiological findings. Our primary objective was to test the diagnostic performance of CTC detection using the ISET technique in lung cancer screening, compared with cancers diagnosed by final pathology, or follow up if pathology was unavailable as the gold standard. This study is registered with ClinicalTrials.gov identifier, number NCT02500693. Findings: Between Oct 30, 2015, and Feb 2, 2017, we enrolled 614 participants, predominantly men (437 [71%]), aged 65·1 years (SD 6·5), and heavy smokers (52·7 pack-years [SD 21·5]). 81 (13%) participants dropped out between baseline and T1, and 56 (11%) did between T1 and T2. Nodules were detected on 178 (29%) of 614 baseline LDCTs. 19 participants (3%) were diagnosed with a prevalent lung cancer at T0 and 19 were diagnosed with incident lung cancer (15 (3%) of 533 at T1 and four (1%) of 477 at T2). Extrapulmonary cancers were diagnosed in 27 (4%) of participants. Overall 28 (2%) of 1187 blood samples were not analysable. At baseline, the sensitivity of CTC detection for lung cancer detection was 26·3% (95% CI 11·8–48·8). ISET was unable to predict lung cancer or extrapulmonary cancer development. Interpretation: CTC detection using ISET is not suitable for lung cancer screening. Funding: French Government, Conseil Départemental 06, Fondation UNICE, Fondation Aveni, Fondation de France, Ligue Contre le Cancer-Comité des Alpes-Maritimes, ARC (Canc'Air Genexposomics), Claire de Divonne-Pollner, Enca Faidhi, Basil Faidhi, Fabienne Mourou, Michel Mourou, Leonid Fridlyand, cogs4cancer, and the Fondation Masikini.
AB - Background: Lung cancer screening with low-dose chest CT (LDCT) reduces the mortality of eligible individuals. Blood signatures might act as a standalone screening tool, refine the selection of patients at risk, or help to classify undetermined nodules detected on LDCT. We previously showed that circulating tumour cells (CTCs) could be detected, using the isolation by size of epithelial tumour cell technique (ISET), long before the cancer was diagnosed radiologically. We aimed to test whether CTCs could be used as a biomarker for lung cancer screening. Methods: We did a prospective, multicentre, cohort study in 21 French university centres. Participants had to be eligible for lung cancer screening as per National Lung Screening Trial criteria and have chronic obstructive pulmonary disease with a fixed airflow limitation defined as post-bronchodilator FEV1/FVC ratio of less than 0·7. Any cancer, other than basocellular skin carcinomas, detected within the previous 5 years was the main exclusion criterion. Participants had three screening rounds at 1-year intervals (T0 [baseline], T1, and T2), which involved LDCT, clinical examination, and a blood test for CTCs detection. Participants and investigators were masked to the results of CTC detection, and cytopathologists were masked to clinical and radiological findings. Our primary objective was to test the diagnostic performance of CTC detection using the ISET technique in lung cancer screening, compared with cancers diagnosed by final pathology, or follow up if pathology was unavailable as the gold standard. This study is registered with ClinicalTrials.gov identifier, number NCT02500693. Findings: Between Oct 30, 2015, and Feb 2, 2017, we enrolled 614 participants, predominantly men (437 [71%]), aged 65·1 years (SD 6·5), and heavy smokers (52·7 pack-years [SD 21·5]). 81 (13%) participants dropped out between baseline and T1, and 56 (11%) did between T1 and T2. Nodules were detected on 178 (29%) of 614 baseline LDCTs. 19 participants (3%) were diagnosed with a prevalent lung cancer at T0 and 19 were diagnosed with incident lung cancer (15 (3%) of 533 at T1 and four (1%) of 477 at T2). Extrapulmonary cancers were diagnosed in 27 (4%) of participants. Overall 28 (2%) of 1187 blood samples were not analysable. At baseline, the sensitivity of CTC detection for lung cancer detection was 26·3% (95% CI 11·8–48·8). ISET was unable to predict lung cancer or extrapulmonary cancer development. Interpretation: CTC detection using ISET is not suitable for lung cancer screening. Funding: French Government, Conseil Départemental 06, Fondation UNICE, Fondation Aveni, Fondation de France, Ligue Contre le Cancer-Comité des Alpes-Maritimes, ARC (Canc'Air Genexposomics), Claire de Divonne-Pollner, Enca Faidhi, Basil Faidhi, Fabienne Mourou, Michel Mourou, Leonid Fridlyand, cogs4cancer, and the Fondation Masikini.
UR - http://www.scopus.com/inward/record.url?scp=85087410368&partnerID=8YFLogxK
U2 - 10.1016/S2213-2600(20)30081-3
DO - 10.1016/S2213-2600(20)30081-3
M3 - Article
C2 - 32649919
AN - SCOPUS:85087410368
SN - 2213-2600
VL - 8
SP - 709
EP - 716
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
IS - 7
ER -