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Journal Articles The Lancet Respiratory Medicine Year : 2020

Circulating tumour cells as a potential biomarker for lung cancer screening: a prospective cohort study

Charles-Hugo Marquette (1) , Jacques Boutros (2) , Jonathan Benzaquen (1) , Marion Ferreira (3) , Jean Pastre (4) , Christophe M. Pison (5) , Bernard Padovani (6) , Faiza Bettayeb (7) , Vincent Fallet (8) , Nicolas Guibert (9) , Damien Basille (10, 11) , Marius I. Ilie (1) , Véronique Hofman (1) , Paul Hofman (1) , Dominique Israël-Biet (12) , François Chabot (13) , Anne Guillaumot (14) , Gaetan Deslée (15) , Jeanne-Marie Perotin (16) , Sandra Dury (15) , Hervé Mal (17) , Armelle Marceau (18) , Romain Kessler (19) , Jean-Michel Vergnon (20) , Carole Pelissier (21) , Fabrice Di Palma (22) , Antoine Cuvelier (23) , Maxime Patout (23) , Arnaud Bourdin (24, 25) , Anne Sophie Gamez (26) , Claire Andréjak (27, 11) , Claire Poulet , Géraldine François (28) , Vincent Jounieaux (27, 11) , Nicolas Roche , Stéphane Jouneau (29) , Graziella Brinchault (30) , Philippe Bonniaud (31) , Ayoub Zouak , Arnaud Scherpereel (32) , Simon Baldacci (33) , Alexis Cortot (33) , Jean François Mornex , François Steenhouwer , Sylvie Leroy (6) , Jean-Philippe Berthet (34) , Eric Fontas (35) , Julie Bulsei (36) , Coralie Cruzel , Johanna Pradelli (37) , Maureen Fontaine (38) , Charlotte Maniel , Jennifer Griffonnet , Catherine Butori (6) , Eric Selva (6) , Michel Poudenx (1) , Bernard Aguilaniu (39) , Gilbert Ferreti , François Arbib (40) , Amandine Briault (28) , Anne-Claire Toffart (41) , Raissa Dahalani , Marie Destors (42) , Pascal Chanez (43) , Laurent Greillier (44) , Philippe Astoul (45) , Fabrice Barlesi (46) , Jean-Yves Gaubert (47) , Julien Mazières (48) , Sylvain Marchand-Adam (49) , Jacques Cadranel (50) , Nouha Chaabane , Armine Izadifar , Lise Rosencher (8) , Anne-Marie Ruppert (8) , Thibault Vieira (8) , Nathalie Mathiot (51)
1 COMUE UCA - COMUE Université Côte d'Azur (2015-2019)
2 IRCAN - Institut de Recherche sur le Cancer et le Vieillissement
3 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
4 HEGP - Hôpital Européen Georges Pompidou [APHP]
5 Département de médecine aiguë spécialisée
6 CHU Nice - Centre Hospitalier Universitaire de Nice
7 CHU Marseille
8 CHU Tenon [AP-HP]
9 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
10 CHU Amiens-Picardie
11 AGIR - Agents infectieux, résistance et chimiothérapie - UR UPJV 4294
12 Service de Pneumologie A, Centre de Compétences des Maladies Pulmonaires Rares,
13 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
14 Service de Pneumologie [CHRU Nancy]
15 CHU Reims - Hôpital universitaire Robert Debré [Reims]
16 PERPMP - Plasticité de l'épithélium respiratoire dans les conditions normales et pathologiques - UMR-S 903
17 APHP Service de Pneumologie B
18 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
19 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
20 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
21 UMRESTTE UMR T9405 - Unité Mixte de Recherche Epidémiologique et de Surveillance Transport Travail Environnement
22 Contraintes mécaniques et tissu osseux
23 Service de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen]
24 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
25 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
26 Département pneumologie et addictologie [Montpellier]
27 Service de Pneumologie et Réanimation
28 UL - Université de Lorraine
29 Service de pneumologie
30 Centre de Ressource et de Compétences de la Mucoviscidose [CHU Rennes]
31 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
32 OncoThAI - Thérapies Assistées par Lasers et Immunothérapies pour l'Oncologie - U 1189
33 SIRIC-ONCOLille - Site de Recherche Intégrée en Cancérologie
34 Service de chirurgie thoracique et cardio-vasculaire
35 CHU - Hôpital Cimiez [Nice]
36 Unité de Recherche Clinique en Economie de la Santé d'Ile-de-France
37 UNS UFR Médecine - Université Nice Sophia Antipolis - Faculté de Médecine
38 LNC - Laboratoire de Neurosciences Cognitives [Marseille]
39 HYLAB : Physiologie de l'exercice et interprétation clinique
40 Clinique de pneumologie
41 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
42 UGA UFRM - Université Grenoble Alpes - UFR Médecine
43 AMU - Aix Marseille Université
44 Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
45 Division d'oncologie thoracique, Département des maladies pulmonaires
46 APHM - Assistance Publique - Hôpitaux de Marseille
47 Department of Radiology
48 Service Pneumologie-Allergologie [CHU Toulouse]
49 PRPA - Pathologies Respiratoires : Protéolyse et Aérosolthérapie
50 Interactions cellulaires tumorales et leur environnement et réponse aux agents anti-cancéreux
51 GRC 4 - Theranoscan - Groupe de recherche clinique Biomarqueurs Théranostiques des Cancers Bronchiques Non à Petites Cellules
Faiza Bettayeb
  • Function : Author
Vincent Fallet
  • Function : Author
Paul Hofman
  • Function : Author
  • PersonId : 860820
Claire Poulet
  • Function : Author
Nicolas Roche
  • Function : Author
Stéphane Jouneau
  • Function : Author
  • PersonId : 946800
Ayoub Zouak
  • Function : Author
Jean François Mornex
  • Function : Author
François Steenhouwer
  • Function : Author
Coralie Cruzel
  • Function : Author
Charlotte Maniel
  • Function : Author
Jennifer Griffonnet
  • Function : Author
Gilbert Ferreti
  • Function : Author
Raissa Dahalani
  • Function : Author
Marie Destors
  • Function : Author
  • PersonId : 963113
Fabrice Barlesi
Nouha Chaabane
  • Function : Author
Armine Izadifar
  • Function : Author
Lise Rosencher
  • Function : Author

Abstract

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.
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Dates and versions

hal-02897076 , version 1 (01-08-2020)

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Charles-Hugo Marquette, Jacques Boutros, Jonathan Benzaquen, Marion Ferreira, Jean Pastre, et al.. Circulating tumour cells as a potential biomarker for lung cancer screening: a prospective cohort study. The Lancet Respiratory Medicine, 2020, 8 (7), pp.709-716. ⟨10.1016/S2213-2600(20)30081-3⟩. ⟨hal-02897076⟩
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