PMID- 33545389 OWN - NLM STAT- MEDLINE DCOM- 20210524 LR - 20210524 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 16 IP - 5 DP - 2021 May TI - Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC. PG - 807-816 LID - S1556-0864(21)01664-6 [pii] LID - 10.1016/j.jtho.2021.01.1617 [doi] AB - INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CI - Copyright (c) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved. FAU - Ilie, Marius AU - Ilie M AD - Laboratory of Clinical and Experimental Pathology, FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France; Hospital-Related Biobank (BB-0033-00025), FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France; Institute of Research on Cancer and Ageing of Nice (IRCAN), CNRS, INSERM, FHU OncoAge, Universite Cote d'Azur, Nice, France. FAU - Mazieres, Julien AU - Mazieres J AD - Department of Pulmonology, Centre Hospitalier Universitaire Toulouse, Institut Universitaire du Cancer, Universite Paul Sabatier, Toulouse, France. FAU - Chamorey, Emmanuel AU - Chamorey E AD - Biostatistics Unit, Antoine Lacassagne Comprehensive Cancer Center, Nice, France. FAU - Heeke, Simon AU - Heeke S AD - Laboratory of Clinical and Experimental Pathology, FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France; Hospital-Related Biobank (BB-0033-00025), FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France; Institute of Research on Cancer and Ageing of Nice (IRCAN), CNRS, INSERM, FHU OncoAge, Universite Cote d'Azur, Nice, France; Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Benzaquen, Jonathan AU - Benzaquen J AD - Institute of Research on Cancer and Ageing of Nice (IRCAN), CNRS, INSERM, FHU OncoAge, Universite Cote d'Azur, Nice, France; Department of Pulmonary Medicine and Oncology, FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France. FAU - Thamphya, Brice AU - Thamphya B AD - Biostatistics Unit, Antoine Lacassagne Comprehensive Cancer Center, Nice, France. FAU - Boutros, Jacques AU - Boutros J AD - Department of Pulmonary Medicine and Oncology, FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France. FAU - Tiotiu, Angelica AU - Tiotiu A AD - Department of Pulmonology, Centre Hospitalier Regional Universitaire de Nancy, Nancy, France; Development, Adaptation and Disadvantage, Cardio-Respiratory Regulations and Motor Control, Universite de Lorraine, Nancy, France. FAU - Fayada, Julien AU - Fayada J AD - Hospital-Related Biobank (BB-0033-00025), FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France. FAU - Cadranel, Jacques AU - Cadranel J AD - Department of Pulmonology, APHP, Hopital Tenon and GRC04 Theranoscan, Sorbonne Universite, Paris, France. FAU - Poudenx, Michel AU - Poudenx M AD - Department of Pulmonary Medicine and Oncology, FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France; Department of Oncology, Centre Antoine Lacassagne, Nice, France. FAU - Moro-Sibilot, Denis AU - Moro-Sibilot D AD - Thoracic Oncology Unit, Centre hospitalier universitaire Grenoble-Alpes, Grenoble, France. FAU - Barlesi, Fabrice AU - Barlesi F AD - Centre d'Essais Precoces en Cancerologie de Marseille CLIP(2), Aix Marseille University, CNRS, INSERM, CRCM, APHM, Marseille, France; Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France. FAU - Thariat, Juliette AU - Thariat J AD - Department of Radiation Therapy, Centre Francois Baclesse-ARCHADE, Universite de Caen Normandie, Caen, France. FAU - Clement-Duchene, Christelle AU - Clement-Duchene C AD - Oncology Department, Institut de Cancerologie de Lorraine, Nancy, France. FAU - Tomasini, Pascale AU - Tomasini P AD - Centre d'Essais Precoces en Cancerologie de Marseille CLIP(2), Aix Marseille University, CNRS, INSERM, CRCM, APHM, Marseille, France. FAU - Hofman, Veronique AU - Hofman V AD - Laboratory of Clinical and Experimental Pathology, FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France; Hospital-Related Biobank (BB-0033-00025), FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France; Institute of Research on Cancer and Ageing of Nice (IRCAN), CNRS, INSERM, FHU OncoAge, Universite Cote d'Azur, Nice, France. FAU - Marquette, Charles-Hugo AU - Marquette CH AD - Institute of Research on Cancer and Ageing of Nice (IRCAN), CNRS, INSERM, FHU OncoAge, Universite Cote d'Azur, Nice, France; Department of Pulmonary Medicine and Oncology, FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France. FAU - Hofman, Paul AU - Hofman P AD - Laboratory of Clinical and Experimental Pathology, FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France; Hospital-Related Biobank (BB-0033-00025), FHU OncoAge, Centre Hospitalier Universitaire de Nice, Universite Cote d'Azur, Nice, France; Institute of Research on Cancer and Ageing of Nice (IRCAN), CNRS, INSERM, FHU OncoAge, Universite Cote d'Azur, Nice, France. Electronic address: hofman.p@chu-nice.fr. CN - STALKLUNG01 Study Consortium Investigators LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20210203 PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Anaplastic Lymphoma Kinase/genetics MH - Gene Rearrangement MH - Humans MH - In Situ Hybridization, Fluorescence MH - *Lung Neoplasms/drug therapy/genetics MH - *Neoplastic Cells, Circulating MH - Prospective Studies MH - Receptor Protein-Tyrosine Kinases/genetics OTO - NOTNLM OT - ALK OT - CTCs OT - FISH OT - Immunocytochemistry OT - Lung adenocarcinoma FIR - Israel-Biet, Dominique IR - Israel-Biet D IRAD- Hopital Europeen Georges Pompidou. FIR - Pison, Christophe IR - Pison C IRAD- Hopital Universitaire de Grenoble. FIR - Moro-Sibilot, Denis IR - Moro-Sibilot D IRAD- Hopital Universitaire de Grenoble. FIR - Lantuejoul, Sylvie IR - Lantuejoul S IRAD- Hopital Universitaire de Grenoble. FIR - Stephanov, Olivier IR - Stephanov O IRAD- Hopital Universitaire de Grenoble. FIR - Juliette, Meyzenc IR - Juliette M IRAD- Hopital Universitaire de Grenoble. FIR - Mendozat, Christophe IR - Mendozat C IRAD- Hopital Universitaire de Grenoble. FIR - Zaidi, Manel IR - Zaidi M IRAD- Hopital Universitaire de Grenoble. FIR - Coulouvrat, Sandra IR - Coulouvrat S FIR - Col, Edwige IR - Col E IRAD- Hopital Universitaire de Grenoble. FIR - Chanez, Pascal IR - Chanez P IRAD- APHM Hopitaux Universitaires de Marseille. FIR - Greillier, Laurent IR - Greillier L IRAD- APHM Hopitaux Universitaires de Marseille. FIR - Tomasini, Pascale IR - Tomasini P IRAD- APHM Hopitaux Universitaires de Marseille. FIR - Barlesi, Fabrice IR - Barlesi F IRAD- APHM Hopitaux Universitaires de Marseille. FIR - Mascaux, Celine IR - Mascaux C IRAD- APHM Hopitaux Universitaires de Marseille. FIR - Jourdan, Sandrine IR - Jourdan S IRAD- APHM Hopitaux Universitaires de Marseille. FIR - Roger, Aurelie IR - Roger A IRAD- APHM Hopitaux Universitaires de Marseille. FIR - Biemar, Julie IR - Biemar J IRAD- APHM Hopitaux Universitaires de Marseille. FIR - Randriamampionona, Rondro IR - Randriamampionona R IRAD- APHM Hopitaux Universitaires de Marseille. FIR - Chabot, Francois IR - Chabot F IRAD- Hopital Universitaire de Nancy. FIR - Tiotiu, Angelica IR - Tiotiu A IRAD- Hopital Universitaire de Nancy. FIR - Clement-Duchene, Christelle IR - Clement-Duchene C IRAD- Hopital Universitaire de Nancy. FIR - Vignaud, Jean-Michel IR - Vignaud JM IRAD- Hopital Universitaire de Nancy. FIR - Lacomme, Stephanie IR - Lacomme S IRAD- Hopital Universitaire de Nancy. FIR - Lomazzi, Sandra IR - Lomazzi S IRAD- Hopital Universitaire de Nancy. FIR - Laurent, Carine IR - Laurent C IRAD- Institut de Cancerologie de Lorraine. FIR - Bulsei, Xavier IR - Bulsei X IRAD- Institut de Cancerologie de Lorraine. FIR - Bischoff, Laura IR - Bischoff L IRAD- Institut de Cancerologie de Lorraine. FIR - Rakotonirina, Raymond IR - Rakotonirina R IRAD- Institut de Cancerologie de Lorraine. FIR - Layouni, Mehdi IR - Layouni M IRAD- Institut de Cancerologie de Lorraine. FIR - Deslee, Gaetan IR - Deslee G IRAD- Hopital Universitaire de Reims. FIR - Mal, Herve IR - Mal H IRAD- Hopital Bichat. FIR - Kessler, Romain IR - Kessler R IRAD- Hopital Universitaire de Strasbourg. FIR - Vergnon, Jean-Michel IR - Vergnon JM IRAD- Hopital Universitaire de St Etienne. FIR - Pelissier, Isabelle IR - Pelissier I IRAD- Hopital Universitaire de St Etienne. FIR - Cuvelier, Antoine IR - Cuvelier A IRAD- Hopital Universitaire de Rouen. FIR - Bourdin, Arnaud IR - Bourdin A IRAD- Hopital Universitaire de Montpellier. FIR - Jounieaux, Vincent IR - Jounieaux V IRAD- Hopital Universitaire d'Amiens. FIR - Roche, Nicolas IR - Roche N IRAD- Hopital Cochin. FIR - Jouneau, Stephane IR - Jouneau S IRAD- Hopital Universitaire de Rennes. FIR - Bonniaud, Philippe IR - Bonniaud P IRAD- Hopital Universitaire de Dijon. FIR - Scherpereel, Arnaud IR - Scherpereel A IRAD- Hopital Universitaire de Lille. FIR - Mornex, Jean Francois IR - Mornex JF IRAD- Hopital Universitaire de Lyon. FIR - Steenhouwer, Francois IR - Steenhouwer F IRAD- Hopital de Roubaix. FIR - Leroy, Sylvie IR - Leroy S IRAD- Centre Hospitalier Universitaire de Nice. FIR - Marquette, Charles Hugo IR - Marquette CH IRAD- Centre Hospitalier Universitaire de Nice. FIR - Benzaquen, Jonathan IR - Benzaquen J IRAD- Centre Hospitalier Universitaire de Nice. FIR - Mazzette, Andrea IR - Mazzette A IRAD- Centre Hospitalier Universitaire de Nice. FIR - Padovani, Bernard IR - Padovani B IRAD- Centre Hospitalier Universitaire de Nice. FIR - Hofman, Paul IR - Hofman P IRAD- Centre Hospitalier Universitaire de Nice. FIR - Ilie, Marius IR - Ilie M IRAD- Centre Hospitalier Universitaire de Nice. FIR - Hofman, Veronique IR - Hofman V IRAD- Centre Hospitalier Universitaire de Nice. FIR - Fayada, Julien IR - Fayada J IRAD- Centre Hospitalier Universitaire de Nice. FIR - Long-Mira, Elodie IR - Long-Mira E IRAD- Centre Hospitalier Universitaire de Nice. FIR - Lassalle, Sandra IR - Lassalle S IRAD- Centre Hospitalier Universitaire de Nice. FIR - Pradelli, Johanna IR - Pradelli J IRAD- Centre Hospitalier Universitaire de Nice. FIR - Martinez, Estelle IR - Martinez E IRAD- Centre Hospitalier Universitaire de Nice. FIR - Habault, Marine IR - Habault M IRAD- Centre Hospitalier Universitaire de Nice. FIR - Bonnard, Melanie IR - Bonnard M IRAD- Centre Hospitalier Universitaire de Nice. FIR - Moutarde, Julie IR - Moutarde J IRAD- Centre Hospitalier Universitaire de Nice. FIR - Yatimi, Rachida IR - Yatimi R IRAD- Centre Hospitalier Universitaire de Nice. FIR - Labsi, Hakima IR - Labsi H IRAD- Centre Hospitalier Universitaire de Nice. FIR - Gazoppi, Loic IR - Gazoppi L IRAD- Centre Hospitalier Universitaire de Nice. FIR - Lpce, Tumorotheque IR - Lpce T IRAD- Centre Hospitalier Universitaire de Nice. FIR - Griffonnet, Jennifer IR - Griffonnet J IRAD- Centre Hospitalier Universitaire de Nice. FIR - Fontaine, Maureen IR - Fontaine M IRAD- Centre Hospitalier Universitaire de Nice. FIR - Guillemart, Ariane IR - Guillemart A IRAD- Centre Hospitalier Universitaire de Nice. FIR - Butori, Catherine IR - Butori C IRAD- Centre Hospitalier Universitaire de Nice. FIR - Selva, Eric IR - Selva E IRAD- Centre Hospitalier Universitaire de Nice. FIR - Poudenx, Michel IR - Poudenx M IRAD- Centre Antoine Lacassagne de Nice. FIR - Otto, Josiane IR - Otto J IRAD- Centre Antoine Lacassagne de Nice. FIR - Hebert, Christophe IR - Hebert C IRAD- Centre Antoine Lacassagne de Nice. FIR - Botchiellini, Delphine IR - Botchiellini D IRAD- Centre Antoine Lacassagne de Nice. FIR - Boudouf, Soukaina IR - Boudouf S IRAD- Centre Antoine Lacassagne de Nice. FIR - Menier, Margaux IR - Menier M IRAD- Centre Antoine Lacassagne de Nice. FIR - Occeli, Estelle IR - Occeli E IRAD- Centre Antoine Lacassagne de Nice. FIR - Bellentani, Sophie IR - Bellentani S IRAD- Centre Antoine Lacassagne de Nice. FIR - Pion, Carine IR - Pion C IRAD- Centre Antoine Lacassagne de Nice. FIR - Fournier, Elodie IR - Fournier E IRAD- Centre Antoine Lacassagne de Nice. FIR - Thariat, Juliette IR - Thariat J IRAD- Centre Francois BACLESSE a Caen. FIR - Gervais, Radj IR - Gervais R IRAD- Centre Francois BACLESSE a Caen. FIR - Hamond, Karim IR - Hamond K IRAD- Centre Francois BACLESSE a Caen. FIR - Marchand-Adam, Sylvain IR - Marchand-Adam S IRAD- Hopital Universitaire de Tours. FIR - Plantier, Laurent IR - Plantier L IRAD- Hopital Universitaire de Tours. FIR - Fajolle, Gaelle IR - Fajolle G IRAD- Hopital Universitaire de Tours. FIR - Rayez, Melanie IR - Rayez M IRAD- Hopital Universitaire de Tours. FIR - Cadranel, Jacques IR - Cadranel J IRAD- Hopital Tenon. FIR - Fallet, Vincent IR - Fallet V IRAD- Hopital Tenon. FIR - Wislez, Marie IR - Wislez M IRAD- Hopital Tenon. FIR - Antoine, Martine IR - Antoine M IRAD- Hopital Tenon. FIR - Cote, Jean-Francois IR - Cote JF IRAD- Hopital Tenon. FIR - Chaabane, Nouha IR - Chaabane N IRAD- Hopital Tenon. FIR - Ruppert, Anne Marie IR - Ruppert AM IRAD- Hopital Tenon. FIR - Bertrand, Eliane IR - Bertrand E IRAD- Hopital Tenon. FIR - Rodenas, Anita IR - Rodenas A IRAD- Hopital Tenon. FIR - Pontdeme, Gwenaelle IR - Pontdeme G IRAD- Hopital Tenon. FIR - Mathiot, Nathalie IR - Mathiot N IRAD- Hopital Tenon. FIR - Ribert, Tamazouzt IR - Ribert T IRAD- Hopital Tenon. FIR - Mazieres, Julien IR - Mazieres J IRAD- Hopital Universitaire de Toulouse. FIR - Guibert, Nicolas IR - Guibert N IRAD- Hopital Universitaire de Toulouse. FIR - Rouviere, Damien IR - Rouviere D IRAD- Hopital Universitaire de Toulouse. FIR - Bousquet, Emilie IR - Bousquet E IRAD- Hopital Universitaire de Toulouse. FIR - Bigay-Game, Laurence IR - Bigay-Game L IRAD- Hopital Universitaire de Toulouse. FIR - Hermant, Christophe IR - Hermant C IRAD- Hopital Universitaire de Toulouse. FIR - Plat, Gavin IR - Plat G IRAD- Hopital Universitaire de Toulouse. FIR - Rouquette, Isabelle IR - Rouquette I IRAD- Hopital Universitaire de Toulouse. FIR - Evrard, Solene IR - Evrard S IRAD- Hopital Universitaire de Toulouse. FIR - Gouin, Sandrine IR - Gouin S IRAD- Hopital Universitaire de Toulouse. FIR - Clermont, Estelle Taranchon IR - Clermont ET IRAD- Hopital Universitaire de Toulouse. FIR - Dormoy, Inge IR - Dormoy I IRAD- Hopital Universitaire de Toulouse. FIR - Coulomb, Christelle IR - Coulomb C IRAD- Hopital Universitaire de Toulouse. FIR - Pradine, Anne IR - Pradine A IRAD- Hopital Universitaire de Toulouse. FIR - Lambert, Veronique IR - Lambert V IRAD- Hopital Universitaire de Toulouse. FIR - Laborde, Lilian IR - Laborde L IRAD- Institut Paoli-Calmettes de Marseille. FIR - Castelnau, Olivier IR - Castelnau O IRAD- Institut Tzanck de St Laurent du Var. EDAT- 2021/02/06 06:00 MHDA- 2021/05/25 06:00 CRDT- 2021/02/05 20:11 PHST- 2020/09/30 00:00 [received] PHST- 2021/01/18 00:00 [revised] PHST- 2021/01/22 00:00 [accepted] PHST- 2021/02/06 06:00 [pubmed] PHST- 2021/05/25 06:00 [medline] PHST- 2021/02/05 20:11 [entrez] AID - S1556-0864(21)01664-6 [pii] AID - 10.1016/j.jtho.2021.01.1617 [doi] PST - ppublish SO - J Thorac Oncol. 2021 May;16(5):807-816. doi: 10.1016/j.jtho.2021.01.1617. Epub 2021 Feb 3.