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2. Transcriptomics profiling of the non-small cell lung cancer microenvironment across disease stages reveals dual immune cell-type behaviors.

Author

Hurtado, Marcelo, Khajavi, Leila, Essabbar, Abdelmounim, Kammer, Michael, Xie, Ting, Coullomb, Alexis, Pradines, Anne, Casanova, Anne, Kruczynski, Anna, Gouin, Sandrine, Clermont, Estelle, Boutillet, Léa, Senosain, Maria Fernanda, Zou, Yong, Zhao, Shillin, Burq, Prosper, Mahfoudi, Abderrahim, Besse, Jerome, Launay, Pierre, and Passioukov, Alexandre

Subjects
TRANSCRIPTION factors, KILLER cells, NON-small-cell lung carcinoma, CELL populations, DISEASE progression
Abstract

Background: Lung cancer is the leading cause of cancer death worldwide, with poor survival despite recent therapeutic advances. A better understanding of the complexity of the tumor microenvironment is needed to improve patients' outcome. Methods: We applied a computational immunology approach (involving immune cell proportion estimation by deconvolution, transcription factor activity inference, pathways and immune scores estimations) in order to characterize bulk transcriptomics of 62 primary lung adenocarcinoma (LUAD) samples from patients across disease stages. Focusing specifically on early stage samples, we validated our findings using an independent LUAD cohort with 70 bulk RNAseq and 15 scRNAseq datasets and on TCGA datasets. Results: Through our methodology and feature integration pipeline, we identified groups of immune cells related to disease stage as well as potential immune response or evasion and survival. More specifically, we reported a duality in the behavior of immune cells, notably natural killer (NK) cells, which was shown to be associated with survival and could be relevant for immune response or evasion. These distinct NK cell populations were further characterized using scRNAseq data, showing potential differences in their cytotoxic activity. Conclusion: The dual profile of several immune cells, most notably T-cell populations, have been discussed in the context of diseases such as cancer. Here, we report the duality of NK cells which should be taken into account in conjunction with other immune cell populations and behaviors in predicting prognosis, immune response or evasion. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC

Author

Israel-Biet, Dominique, Pison, Christophe, Moro-Sibilot, Denis, Lantuejoul, Sylvie, Stephanov, Olivier, Juliette, Meyzenc, Mendozat, Christophe, Zaidi, Manel, Coulouvrat, Sandra, Col, Edwige, Chanez, Pascal, Greillier, Laurent, Tomasini, Pascale, Barlesi, Fabrice, Mascaux, Céline, Jourdan, Sandrine, Roger, Aurélie, Biemar, Julie, Randriamampionona, Rondro, Chabot, François, Tiotiu, Angélica, Clement-Duchene, Christelle, Vignaud, Jean-Michel, Lacomme, Stéphanie, Lomazzi, Sandra, Laurent, Carine, Bulsei, Xavier, Bischoff, Laura, Rakotonirina, Raymond, Layouni, Mehdi, Deslee, Gaëtan, Mal, Hervé, Kessler, Romain, Vergnon, Jean-Michel, Pelissier, Isabelle, Cuvelier, Antoine, Bourdin, Arnaud, Jounieaux, Vincent, Roche, Nicolas, Jouneau, Stéphane, Bonniaud, Philippe, Scherpereel, Arnaud, Mornex, Jean François, Steenhouwer, François, Leroy, Sylvie, Marquette, Charles Hugo, Benzaquen, Jonathan, Mazzette, Andrea, Padovani, Bernard, Hofman, Paul, Ilié, Marius, Hofman, Véronique, Fayada, Julien, Long-Mira, Elodie, Lassalle, Sandra, Pradelli, Johanna, Martinez, Estelle, Habault, Marine, Bonnard, Mélanie, Moutarde, Julie, Yatimi, Rachida, Labsi, Hakima, Gazoppi, Loïc, Lpce, Tumorothèque, Griffonnet, Jennifer, Fontaine, Maureen, Guillemart, Ariane, Butori, Catherine, Selva, Eric, Poudenx, Michel, Otto, Josiane, Hebert, Christophe, Botchiellini, Delphine, Boudouf, Soukaina, Menier, Margaux, Occeli, Estelle, Bellentani, Sophie, Pion, Carine, Fournier, Elodie, Thariat, Juliette, Gervais, Radj, Hamond, Karim, Marchand-Adam, Sylvain, Plantier, Laurent, Fajolle, Gaelle, Rayez, Mélanie, Cadranel, Jacques, Fallet, Vincent, Wislez, Marie, Antoine, Martine, Cote, Jean-François, Chaabane, Nouha, Ruppert, Anne Marie, Bertrand, Eliane, Rodenas, Anita, Pontdeme, Gwenaëlle, Mathiot, Nathalie, Ribert, Tamazouzt, Mazières, Julien, Guibert, Nicolas, Rouviere, Damien, Bousquet, Emilie, Bigay-Game, Laurence, Hermant, Christophe, Plat, Gavin, Rouquette, Isabelle, Evrard, Solène, Gouin, Sandrine, Clermont, Estelle Taranchon, Dormoy, Inge, Coulomb, Christelle, Pradine, Anne, Lambert, Véronique, Laborde, Lilian, Castelnau, Olivier, Chamorey, Emmanuel, Heeke, Simon, Thamphya, Brice, Boutros, Jacques, Clément-Duchêne, Christelle, and Marquette, Charles-Hugo

Published
2021
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5. Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study

Author

Ilié, Marius, Mazières, Julien, Chamorey, Emmanuel, Heeke, Simon, Benzaquen, Jonathan, Thamphya, Brice, Boutros, Jacques, Tiotiu, Angélica, Fayada, Julien, Cadranel, Jacques, Poudenx, Michel, Moro-Sibilot, Denis, Barlesi, Fabrice, Thariat, Juliette, Clément-Duchêne, Christelle, Tomasini, Pascale, Hofman, Véronique, Marquette, Charles-Hugo, Hofman, Paul, Israel-Biet, Dominique, Pison, Christophe, Lantuejoul, Sylvie, Stephanov, Olivier, Juliette, Meyzenc, Mendozat, Christophe, Zaidi, Manel, Coulouvrat, Sandra, Col, Edwige, Chanez, Pascal, Greillier, Laurent, Mascaux, Céline, Jourdan, Sandrine, Roger, Aurélie, Biemar, Julie, Randriamampionona, Rondro, Chabot, François, Vignaud, Jean-Michel, Lacomme, Stéphanie, Lomazzi, Sandra, Laurent, Carine, Bulsei, Xavier, Bischoff, Laura, Rakotonirina, Raymond, Layouni, Mehdi, Deslee, Gaëtan, Mal, Hervé, Kessler, Romain, Vergnon, Jean-Michel, Pelissier, Isabelle, Cuvelier, Antoine, Bourdin, Arnaud, Jounieaux, Vincent, Roche, Nicolas, Jouneau, Stéphane, Bonniaud, Philippe, Scherpereel, Arnaud, Mornex, Jean François, Steenhouwer, François, Leroy, Sylvie, Marquette, Charles Hugo, Mazzette, Andrea, Padovani, Bernard, Long-Mira, Elodie, Lassalle, Sandra, Pradelli, Johanna, Martinez, Estelle, Habault, Marine, Bonnard, Mélanie, Moutarde, Julie, Yatimi, Rachida, Labsi, Hakima, Gazoppi, Loïc, Lpce, Tumorothèque, Griffonnet, Jennifer, Fontaine, Maureen, Guillemart, Ariane, Butori, Catherine, Selva, Eric, Otto, Josiane, Hebert, Christophe, Botchiellini, Delphine, Boudouf, Soukaina, Menier, Margaux, Occeli, Estelle, Bellentani, Sophie, Pion, Carine, Fournier, Elodie, Gervais, Radj, Hamond, Karim, Marchand-Adam, Sylvain, Plantier, Laurent, Fajolle, Gaelle, Rayez, Mélanie, Fallet, Vincent, Wislez, Marie, Antoine, Martine, Cote, Jean-François, Chaabane, Nouha, Ruppert, Anne Marie, Bertrand, Eliane, Rodenas, Anita, Pontdeme, Gwenaëlle, Mathiot, Nathalie, Ribert, Tamazouzt, Guibert, Nicolas, Rouviere, Damien, Bousquet, Emilie, Bigay-Game, Laurence, Hermant, Christophe, Plat, Gavin, Rouquette, Isabelle, Evrard, Solène, Gouin, Sandrine, Clermont, Estelle Taranchon, Dormoy, Inge, Coulomb, Christelle, Pradine, Anne, Lambert, Véronique, Laborde, Lilian, Castelnau, Olivier, University of Manchester [Manchester], Hôpital du Sacré-Coeur de Montréal, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Yonsei University College of Medicine [Séoul, Corée du Sud], August Pi i Sunyer Biomedical Research Institute - IDIBAPS [Barcelona, Spain], Hospital de la Santa Creu i Sant Pau, University Hospitals Leuven [Leuven], National and Kapodistrian University of Athens (NKUA), Odense University Hospital (OUH), Oregon Health and Science University [Portland] (OHSU), Kyushu University, Hacettepe University = Hacettepe Üniversitesi, University of Copenhagen = Københavns Universitet (UCPH), University of Groningen [Groningen], Abbvie Inc. [North Chicago], Asklepios Klinikum Uckermark GmbH, Méthodes computationnelles pour la prise en charge thérapeutique en oncologie : Optimisation des stratégies par modélisation mécaniste et statistique (COMPO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Cancérologie de Marseille (CRCM), and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut Paoli-Calmettes

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, medicine.medical_treatment, CELL LUNG-CANCER, Population, Peripheral edema, Phases of clinical research, [SDV.CAN]Life Sciences [q-bio]/Cancer, Delta-like protein 3, Rovalpituzumab tesirine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, DRUG, education, ComputingMilieux_MISCELLANEOUS, Chemotherapy, education.field_of_study, Small cell lung cancer, business.industry, Hazard ratio, Confidence interval, 030104 developmental biology, 030220 oncology & carcinogenesis, Topotecan, medicine.symptom, business, medicine.drug
Abstract

INTRODUCTION: DLL3, an atypical Notch ligand, is expressed in SCLC tumors but is not detectable in normal adult tissues. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate containing a DLL3-targeting antibody tethered to a cytotoxic agent pyrrolobenzodiazepine by means of a protease-cleavable linker. The efficacy and safety of Rova-T compared with topotecan as second-line therapy in patients with SCLC expressing high levels of DLL3 (DLL3-high) was evaluated. METHODS: The TAHOE study was an open-label, two-to-one randomized, phase 3 study comparing Rova-T with topotecan as second-line therapy in DLL3-high advanced or metastatic SCLC. Rova-T (0.3 mg/kg) was administered intravenously on day 1 of a 42-day cycle for two cycles, with two additional cycles available to patients who met protocol-defined criteria for continued dosing. Topotecan (1.5 mg/m2) was administered intravenously on days 1 to 5 of a 21-day cycle. The primary end point was overall survival (OS). RESULTS: Patients randomized to Rova-T (n = 296) and topotecan (n = 148) were included in the efficacy analyses. The median age was 64 years, and 77% had the extensive disease at initial diagnosis. The median OS (95% confidence interval) was 6.3 months (5.6-7.3) in the Rova-T arm and 8.6 months (7.7-10.1) in the topotecan arm (hazard ratio, 1.46 [95% confidence interval: 1.17-1.82]). An independent data monitoring committee recommended that enrollment be discontinued because of the shorter OS observed with Rova-T compared with topotecan. Safety profiles for both drugs were consistent with previous reports. CONCLUSIONS: Compared with topotecan, which is the current standard second-line chemotherapy, Rova-T exhibited an inferior OS and higher rates of serosal effusions, photosensitivity reaction, and peripheral edema in patients with SCLC. A considerable unmet therapeutic need remains in this population. ispartof: JOURNAL OF THORACIC ONCOLOGY vol:16 issue:9 pages:1547-1558 ispartof: location:United States status: published

Published
2021
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6. Prospective Multicenter Validation of the Detection of ALK Rearrangements of Circulating Tumor Cells for Noninvasive Longitudinal Management of Patients With Advanced NSCLC

Author

Ilié, Marius, primary, Mazières, Julien, additional, Chamorey, Emmanuel, additional, Heeke, Simon, additional, Benzaquen, Jonathan, additional, Thamphya, Brice, additional, Boutros, Jacques, additional, Tiotiu, Angélica, additional, Fayada, Julien, additional, Cadranel, Jacques, additional, Poudenx, Michel, additional, Moro-Sibilot, Denis, additional, Barlesi, Fabrice, additional, Thariat, Juliette, additional, Clément-Duchêne, Christelle, additional, Tomasini, Pascale, additional, Hofman, Véronique, additional, Marquette, Charles-Hugo, additional, Hofman, Paul, additional, Israel-Biet, Dominique, additional, Pison, Christophe, additional, Lantuejoul, Sylvie, additional, Stephanov, Olivier, additional, Juliette, Meyzenc, additional, Mendozat, Christophe, additional, Zaidi, Manel, additional, Coulouvrat, Sandra, additional, Col, Edwige, additional, Chanez, Pascal, additional, Greillier, Laurent, additional, Mascaux, Céline, additional, Jourdan, Sandrine, additional, Roger, Aurélie, additional, Biemar, Julie, additional, Randriamampionona, Rondro, additional, Chabot, François, additional, Clement-Duchene, Christelle, additional, Vignaud, Jean-Michel, additional, Lacomme, Stéphanie, additional, Lomazzi, Sandra, additional, Laurent, Carine, additional, Bulsei, Xavier, additional, Bischoff, Laura, additional, Rakotonirina, Raymond, additional, Layouni, Mehdi, additional, Deslee, Gaëtan, additional, Mal, Hervé, additional, Kessler, Romain, additional, Vergnon, Jean-Michel, additional, Pelissier, Isabelle, additional, Cuvelier, Antoine, additional, Bourdin, Arnaud, additional, Jounieaux, Vincent, additional, Roche, Nicolas, additional, Jouneau, Stéphane, additional, Bonniaud, Philippe, additional, Scherpereel, Arnaud, additional, Mornex, Jean François, additional, Steenhouwer, François, additional, Leroy, Sylvie, additional, Marquette, Charles Hugo, additional, Mazzette, Andrea, additional, Padovani, Bernard, additional, Ilié, Marius, additional, Long-Mira, Elodie, additional, Lassalle, Sandra, additional, Pradelli, Johanna, additional, Martinez, Estelle, additional, Habault, Marine, additional, Bonnard, Mélanie, additional, Moutarde, Julie, additional, Yatimi, Rachida, additional, Labsi, Hakima, additional, Gazoppi, Loïc, additional, Lpce, Tumorothèque, additional, Griffonnet, Jennifer, additional, Fontaine, Maureen, additional, Guillemart, Ariane, additional, Butori, Catherine, additional, Selva, Eric, additional, Otto, Josiane, additional, Hebert, Christophe, additional, Botchiellini, Delphine, additional, Boudouf, Soukaina, additional, Menier, Margaux, additional, Occeli, Estelle, additional, Bellentani, Sophie, additional, Pion, Carine, additional, Fournier, Elodie, additional, Gervais, Radj, additional, Hamond, Karim, additional, Marchand-Adam, Sylvain, additional, Plantier, Laurent, additional, Fajolle, Gaelle, additional, Rayez, Mélanie, additional, Fallet, Vincent, additional, Wislez, Marie, additional, Antoine, Martine, additional, Cote, Jean-François, additional, Chaabane, Nouha, additional, Ruppert, Anne Marie, additional, Bertrand, Eliane, additional, Rodenas, Anita, additional, Pontdeme, Gwenaëlle, additional, Mathiot, Nathalie, additional, Ribert, Tamazouzt, additional, Guibert, Nicolas, additional, Rouviere, Damien, additional, Bousquet, Emilie, additional, Bigay-Game, Laurence, additional, Hermant, Christophe, additional, Plat, Gavin, additional, Rouquette, Isabelle, additional, Evrard, Solène, additional, Gouin, Sandrine, additional, Clermont, Estelle Taranchon, additional, Dormoy, Inge, additional, Coulomb, Christelle, additional, Pradine, Anne, additional, Lambert, Véronique, additional, Laborde, Lilian, additional, and Castelnau, Olivier, additional

Published
2021
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9. Baseline circulating myeloid-derived suppressor cells and response to PD-1 inhibitor in non-small cell lung cancer patients.

Author

Delaunay, Myriam, primary, Guibert, Nicolas, additional, Lusque, Amellie, additional, Farella, Magali, additional, Boubekeur, Nadia, additional, Gouin, Sandrine, additional, Dormoy, Inge, additional, Fons, Pierre, additional, Esquerre, Michael, additional, Favre, Gilles, additional, Pradines, Anne, additional, and Mazieres, Julien, additional

Published
2018
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10. Monitoring PD-L1 expression on circulating tumor cells (CTCs) in patients with NSCLC treated with PD1 inhibitors.

Author

Guibert, Nicolas Marie, primary, Delaunay, Myriam, additional, Lusque, Amellie, additional, Gouin, Sandrine, additional, Boubekeur, Nadia, additional, Rouquette, Isabelle, additional, Clermont, Estelle, additional, Fourtoul, Aurélien, additional, Favre, Gilles, additional, Pradines, Anne, additional, and Mazieres, Julien, additional

Published
2018
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11. Alternative Processing of the U2 Small Nuclear RNA Produces a 19–22nt Fragment with Relevance for the Detection of Non-Small Cell Lung Cancer in Human Serum

Author

Mazières, Julien, primary, Catherinne, Caroline, additional, Delfour, Olivier, additional, Gouin, Sandrine, additional, Rouquette, Isabelle, additional, Delisle, Marie-Bernadette, additional, Prévot, Grégoire, additional, Escamilla, Roger, additional, Didier, Alain, additional, Persing, David H., additional, Bates, Mike, additional, and Michot, Bernard, additional

Published
2013
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12. Prospective multi-center validation of the detection of ALKrearrangements of circulating tumor cells for non-invasive longitudinal management of patients with advanced non-small cell lung cancer

Author

ILIE, Marius, MAZIÈRES, Julien, CHAMOREY, Emmanuel, HEEKE, Simon, BENZAQUEN, Jonathan, THAMPHYA, Brice, BOUTROS, Jacques, TIOTIU, Angelica, FAYADA, Julien, CADRANE, Jacques, POUDENX, Michel, MORO-SIBILOT, Denis, BARLESI, Fabrice, THARIAT, Juliette, CLEMENT-DUCHENE, Christelle, TOMASINI, Pascale, HOFMAN, Véronique, MARQUETTE, Charles-Hugo, HOFMAN, Paul, ISRAEL-BIET, Dominique, PISON, Christophe, MORO-SIBILOT, Denis, LANTUEJOUL, Sylvie, STEPHANOV, Olivier, Juliette, M.E.Y.Z.E.N.C., MENDOZAT, Christophe, ZAIDI, Manel, COULOUVRAT, Sandra, COL, Edwige, CHANEZ, Pascal, GREILLIER, Laurent, TOMASINI, Pascale, BARLESI, Fabrice, MASCAUX, Céline, JOURDAN, Sandrine, ROGER, Aurélie, BIEMAR, Julie, RANDRIAMAMPIONONA, Rondro, CHABOT, François, TIOTIU, Angélica, CLEMENT-DUCHENE, Christelle, Jean-Michel, V.I.G.N.A.U.D., LACOMME, Stéphanie, LOMAZZI, Sandra, LAURENT, Carine, BULSEI, Xavier, BISCHOFF, Laura, RAKOTONIRINA, Raymond, LAYOUNI, Mehdi, DESLEE, Gaëtan, MAL, Hervé, KESSLER, Romain, VERGNON, Jean-Michel, PELISSIER, Isabelle, CUVELIER, Antoine, BOURDIN, Arnaud, JOUNIEAUX, Vincent, ROCHE, Nicolas, JOUNEAU, Stéphane, BONNIAUD, SCHERPEREEL, Arnaud, MORNEX, Jean François, STEENHOUWER, François, LEROY, Sylvie, MARQUETTE, Charles Hugo, BENZAQUEN, Jonathan, MAZZETTE, Andrea, PADOVANI, Bernard, HOFMAN, Paul, ILIE, Marius, HOFMAN, Véronique, FAYADA, Julien, LONG-MIRA, Elodie, LASSALLE, Sandra, PRADELLI, Johanna, MARTINEZ, Estelle, HABAULT, Marine, BONNARD, Mélanie, MOUTARDE, Julie, YATIMI, Rachida, LABSI, Hakima, GAZOPPI, Loïc, LPCE, Tumorothèque, GRIFFONNET, Jennifer, FONTAINE, Maureen, GUILLEMART, Ariane, BUTORI, Catherine, SELVA, Eric, POUDENX, Michel, OTTO, Josiane, HEBERT, Christophe, BOTCHIELLINI, Delphine, BOUDOUF, Soukaina, MENIER, Margaux, OCCELI, Estelle, BELLENTANI, Sophie, PION, Carine, FOURNIER, Elodie, THARIAT, Juliette, GERVAIS, Radj, HAMOND, Karim, MARCHAND-ADAM, Sylvain, PLANTIER, Laurent, FAJOLLE, Gaelle, RAYEZ, Mélanie, CADRANEL, Jacques, FALLET, Vincent, WISLEZ, Marie, ANTOINE, Martine, COTE, Jean-François, CHAABANE, Nouha, RUPPERT, Anne Marsie, BERTRAND, Eliane, RODENAS, Anita, PONTDEME, Gwenaëlle, MATHIOT, Nathalie, RIBERT, Tamazouzt, MAZIÈRES, Julien, GUIBERT, Nicolas, ROUVIERE, Damien, BOUSQUET, Emilie, BIGAY-GAME, Laurence, HERMANT, Christophe, PLAT, Gavin, ROUQUETTE, Isabelle, EVRARD, Solène, GOUIN, Sandrine, TARANCHON CLERMONT, Estelle, DORMOY, Inge, COULOMB, Christelle, PRADINE, Anne, LAMBERT, Véronique, LABORDE, Lilian, and CASTELNAU, Olivier

Abstract

Patients with advanced-stage non-small cell lung cancer (NSCLC) whose tumors harbor an anaplastic lymphoma kinase (ALK) gene rearrangement benefit from treatment with multiple ALK inhibitors (ALKi). Approximately 30% of tumor biopsies contain insufficient tissue for successful ALKmolecular characterization. This study evaluated the added value of analyzing circulating tumor cells (CTCs) as a surrogate to ALKtissue analysis and as a function of the response to ALKi.

Published
2021
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