Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC.
ALK
CTCs
FISH
Immunocytochemistry
Lung adenocarcinoma
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN: 1556-1380
Titre abrégé: J Thorac Oncol
Pays: United States
ID NLM: 101274235
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
30
09
2020
revised:
18
01
2021
accepted:
22
01
2021
pubmed:
6
2
2021
medline:
25
5
2021
entrez:
5
2
2021
Statut:
ppublish
Résumé
Patients with advanced-stage NSCLC whose tumors harbor an ALK gene rearrangement benefit from treatment with multiple ALK inhibitors (ALKi). Approximately 30% of tumor biopsy samples contain insufficient tissue for successful ALK molecular characterization. This study evaluated the added value of analyzing circulating tumor cells (CTCs) as a surrogate to ALK tissue analysis and as a function of the response to ALKi. We conducted a multicenter, prospective observational study (NCT02372448) of 203 patients with stage IIIB/IV NSCLC across nine French centers, of whom 81 were ALK positive (immunohistochemistry or fluorescence in situ hybridization [FISH]) and 122 ALK negative on paraffin-embedded tissue specimens. Blood samples were collected at baseline and at 6 and 12 weeks after ALKi initiation or at disease progression. ALK gene rearrangement was evaluated with CTCs using immunocytochemistry and FISH analysis after enrichment using a filtration method. At baseline, there was a high concordance between the detection of an ALK rearrangement in the tumor tissue and in CTCs as determined by immunocytochemistry (sensitivity, 94.4%; specificity 89.4%). The performance was lower for the FISH analysis (sensitivity, 35.6%; specificity, 56.9%). No significant association between the baseline levels or the dynamic change of CTCs and overall survival (hazard ratio = 0.59, 95% confidence interval: 0.24-1.5, p = 0.244) or progression-free survival (hazard ratio = 0.84, 95% confidence interval: 0.44-1.6, p = 0.591) was observed in the patients with ALK-positive NSCLC. CTCs can be used as a complementary tool to a tissue biopsy for the detection of ALK rearrangements. Longitudinal analyses of CTCs revealed promise for real-time patient monitoring and improved delivery of molecularly guided therapy in this population.
Identifiants
pubmed: 33545389
pii: S1556-0864(21)01664-6
doi: 10.1016/j.jtho.2021.01.1617
pii:
doi:
Substances chimiques
Anaplastic Lymphoma Kinase
EC 2.7.10.1
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Multicenter Study
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
807-816Investigateurs
Dominique Israel-Biet
(D)
Christophe Pison
(C)
Denis Moro-Sibilot
(D)
Sylvie Lantuejoul
(S)
Olivier Stephanov
(O)
Meyzenc Juliette
(M)
Christophe Mendozat
(C)
Manel Zaidi
(M)
Sandra Coulouvrat
(S)
Edwige Col
(E)
Pascal Chanez
(P)
Laurent Greillier
(L)
Pascale Tomasini
(P)
Fabrice Barlesi
(F)
Céline Mascaux
(C)
Sandrine Jourdan
(S)
Aurélie Roger
(A)
Julie Biemar
(J)
Rondro Randriamampionona
(R)
François Chabot
(F)
Angélica Tiotiu
(A)
Christelle Clement-Duchene
(C)
Jean-Michel Vignaud
(JM)
Stéphanie Lacomme
(S)
Sandra Lomazzi
(S)
Carine Laurent
(C)
Xavier Bulsei
(X)
Laura Bischoff
(L)
Raymond Rakotonirina
(R)
Mehdi Layouni
(M)
Gaëtan Deslee
(G)
Hervé Mal
(H)
Romain Kessler
(R)
Jean-Michel Vergnon
(JM)
Isabelle Pelissier
(I)
Antoine Cuvelier
(A)
Arnaud Bourdin
(A)
Vincent Jounieaux
(V)
Nicolas Roche
(N)
Stéphane Jouneau
(S)
Philippe Bonniaud
(P)
Arnaud Scherpereel
(A)
Jean François Mornex
(JF)
François Steenhouwer
(F)
Sylvie Leroy
(S)
Charles Hugo Marquette
(CH)
Jonathan Benzaquen
(J)
Andrea Mazzette
(A)
Bernard Padovani
(B)
Paul Hofman
(P)
Marius Ilié
(M)
Véronique Hofman
(V)
Julien Fayada
(J)
Elodie Long-Mira
(E)
Sandra Lassalle
(S)
Johanna Pradelli
(J)
Estelle Martinez
(E)
Marine Habault
(M)
Mélanie Bonnard
(M)
Julie Moutarde
(J)
Rachida Yatimi
(R)
Hakima Labsi
(H)
Loïc Gazoppi
(L)
Tumorothèque Lpce
(T)
Jennifer Griffonnet
(J)
Maureen Fontaine
(M)
Ariane Guillemart
(A)
Catherine Butori
(C)
Eric Selva
(E)
Michel Poudenx
(M)
Josiane Otto
(J)
Christophe Hebert
(C)
Delphine Botchiellini
(D)
Soukaina Boudouf
(S)
Margaux Menier
(M)
Estelle Occeli
(E)
Sophie Bellentani
(S)
Carine Pion
(C)
Elodie Fournier
(E)
Juliette Thariat
(J)
Radj Gervais
(R)
Karim Hamond
(K)
Sylvain Marchand-Adam
(S)
Laurent Plantier
(L)
Gaelle Fajolle
(G)
Mélanie Rayez
(M)
Jacques Cadranel
(J)
Vincent Fallet
(V)
Marie Wislez
(M)
Martine Antoine
(M)
Jean-François Cote
(JF)
Nouha Chaabane
(N)
Anne Marie Ruppert
(AM)
Eliane Bertrand
(E)
Anita Rodenas
(A)
Gwenaëlle Pontdeme
(G)
Nathalie Mathiot
(N)
Tamazouzt Ribert
(T)
Julien Mazières
(J)
Nicolas Guibert
(N)
Damien Rouviere
(D)
Emilie Bousquet
(E)
Laurence Bigay-Game
(L)
Christophe Hermant
(C)
Gavin Plat
(G)
Isabelle Rouquette
(I)
Solène Evrard
(S)
Sandrine Gouin
(S)
Estelle Taranchon Clermont
(ET)
Inge Dormoy
(I)
Christelle Coulomb
(C)
Anne Pradine
(A)
Véronique Lambert
(V)
Lilian Laborde
(L)
Olivier Castelnau
(O)
Informations de copyright
Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.