19 results on '"Boussageon M"'
Search Results
2. Maladies auto-immunes et immunothérapies: Autoimmune diseases and immunotherapies
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Duruisseaux, M., Boussageon, M., Lafitte, C., Pierret, T., Grigoriu, B., and Greillier, L.
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- 2023
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3. Données de vie réelle d’efficacité et de sécurité de la radiothérapie en condition stéréotaxique sans preuve de nodules pulmonaires suspects : sept ans d’expérience au sein des hospices civils de Lyon
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Pierret, T., primary, Lapierre, A., additional, Eker, E., additional, Le Bon, M., additional, Mornex, F., additional, Deberne, M., additional, Kiakouama, L., additional, Chumbi Flores, W., additional, Couraud, S., additional, Gerinière, L., additional, Souquet, P., additional, Locatelli-Sanchez, M., additional, Duruisseaux, M., additional, Lafitte, C., additional, and Boussageon, M., additional
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- 2024
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4. 1341P NRAS mutated non-small cell lung cancer (NSCLC) patients: Characteristics and outcomes
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Dehem, A., primary, Mazieres, J., additional, Chour, A., additional, Guisier, F., additional, Ferreira, M., additional, Boussageon, M., additional, Girard, N., additional, Moro-Sibilot, D., additional, Cadranel, J., additional, Zalcman, G., additional, Ricordel, C., additional, Wislez, M., additional, Munck, C., additional, Poulet, C-H., additional, Gauvain, C., additional, Descarpentries, C., additional, Wasielewski, E., additional, Cortot, A.B., additional, and Baldacci, S., additional
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- 2021
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5. 147P Non-small cell lung cancer: Artificial intelligence enables the identification of survival signatures complementary to an Immunologically active gene expression signature involving previous therapies
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Saintigny, P., Iriso, P., Afshar, M., Attignon, V.K., Auclair, J., Boulahfa, J., Boussageon, M., Fayette, J., Foy, J-P., Karabajakian, A., Kindermans, M., Lamkhioued, M., Lantuejoul, S., Michon, L., Ortiz-Cuaran, S., Parmentier, F., Pérol, M., Swalduz, A., and Turcat, T.
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- 2023
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6. Évolution de l’état nutritionnel de 579 résidents de 9 établissements d’hébergement pour personnes âgées dépendantes (EHPAD) avant/après confinement
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Desport, J.C., primary, Villemonteix, C., additional, Boussageon, M., additional, Guitard, M., additional, Humbert, L., additional, Ballussaud, C., additional, Varrier, C., additional, Fayemendy, P., additional, and Jésus, P., additional
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- 2021
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7. Comment réduire la quantité de déchets en EHPAD : exemple d'un diagnostic et d'une démarche d'accompagnement coordonnés par LINUT
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André, B., Villemonteix, C., Desport, Jean-Claude, De Magalhaes, S., Guitard, M., Boussageon, M., Balussaud, C., Service d'Hépato-Gastro-Entérologie et Nutrition [CHU Limoges], CHU Limoges, Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), and Grelier, Elisabeth
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[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2018
8. P1.01-116 Early Immune-Related Adverse Events Under PD-1/PD-L1 Inhibitors Predict Better Progression-Free Survival in NSCLC
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Boussageon, M., primary, Ortiz-Cuaran, S., additional, Chabaud, S., additional, Pérol, D., additional, Avrillon, V., additional, Mastroianni, B., additional, Fayette, J., additional, Ghiringhelli, F., additional, Neidhardt, E., additional, Swalduz, A., additional, Paulus, V., additional, Kaderbhai, C., additional, Fumet, J., additional, Saintigny, P., additional, and Perol, M., additional
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- 2019
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9. Survival of bronchopulmonary cancers according to radon exposure.
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Dessemon J, Perol O, Chauvel C, Noelle H, Coudon T, Grassot L, Foray N, Belladame E, Fayette J, Fournie F, Swalduz A, Neidhart EM, Saintigny P, Tabutin M, Boussageon M, Gomez F, Avrillon V, Perol M, Charbotel B, and Fervers B
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- Humans, Case-Control Studies, Environmental Exposure adverse effects, Air Pollution, Indoor, Radon adverse effects, Radon analysis, Lung Neoplasms
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Introduction: Residential exposure is estimated to be responsible for nearly 10% of lung cancers in 2015 in France, making it the second leading cause, after tobacco. The Auvergne-Rhône-Alpes region, in the southwest of France, is particularly affected by this exposure as 30% of the population lives in areas with medium or high radon potential. This study aimed to investigate the impact of radon exposure on the survival of lung cancer patients., Methods: In this single-center study, patients with a histologically confirmed diagnosis of lung cancer, and newly managed, were prospectively included between 2014 and 2020. Univariate and multivariate survival analyses were carried out using a non-proportional risk survival model to consider variations in risk over time., Results: A total of 1,477 patients were included in the analysis. In the multivariate analysis and after adjustment for covariates, radon exposure was not statistically associated with survival of bronchopulmonary cancers (HR = 0.82 [0.54-1.23], HR = 0.92 [0.72-1.18], HR = 0.95 [0.76-1.19] at 1, 3, and 5 years, respectively, for patients residing in category 2 municipalities; HR = 0.87 [0.66-1.16], HR = 0.92 [0.76-1.10], and HR = 0.89 [0.75-1.06] at 1, 3, and 5 years, respectively, for patients residing in category 3 municipalities)., Discussion: Although radon exposure is known to increase the risk of lung cancer, in the present study, no significant association was found between radon exposure and survival of bronchopulmonary cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Dessemon, Perol, Chauvel, Noelle, Coudon, Grassot, Foray, Belladame, Fayette, Fournie, Swalduz, Neidhart, Saintigny, Tabutin, Boussageon, Gomez, Avrillon, Perol, Charbotel and Fervers.)
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- 2024
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10. Characterization of 164 patients with NRAS mutated non-small cell lung cancer (NSCLC).
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Dehem A, Mazieres J, Chour A, Guisier F, Ferreira M, Boussageon M, Girard N, Moro-Sibilot D, Cadranel J, Zalcman G, Ricordel C, Wislez M, Munck C, Poulet C, Gauvain C, Descarpentries C, Wasielewski E, Cortot AB, and Baldacci S
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- Male, Humans, Middle Aged, Female, Mutation, Codon, Retrospective Studies, Membrane Proteins genetics, GTP Phosphohydrolases genetics, GTP Phosphohydrolases therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology, Adenocarcinoma genetics
- Abstract
Background: NRAS mutations are observed in less than 1% of non-small cell lung cancer (NSCLC). Clinical data regarding this rare subset of lung cancer are scarce and response to systemic treatment such as chemotherapy or immune checkpoint inhibitors (ICI) has never been reported., Methods: All consecutive patients with an NRAS mutated NSCLC, diagnosed between August 2014 and November 2020 in 14 French centers, were included. Clinical and molecular data were collected and reviewed from medical records., Results: Out of the 164 included patients, 106 (64.6%) were men, 150 (91.5%) were current or former smokers, and 104 (63.4%) had stage IV NSCLC at diagnosis. The median age was 62 years, and the most frequent histology was adenocarcinoma (81.7%). NRAS activating mutations were mostly found in codon 61 (70%), while codon 12 and 13 alterations were observed in 16.5% and 4.9% of patients, respectively. Programmed death ligand-1 expression level <1%/1-49%/≥50% were respectively found in 30.8%/27.1%/42.1% of tumors. With a median follow-up of 12.5 months, median overall survival (OS) of stage IV patients was 15.3 months (95% CI 9.9-27.6). No significant difference in OS was found according to the type of mutation (codon 61 vs. other), HR = 1.12 (95% CI 0.65-1.95). Among stage IV patients treated with platinum-based doublet (n = 66), ICI (n = 48), or combination of both (n = 10), objective response rate, and median progression free survival were respectively 45% and 5.8 months, 35% and 6.9 months, 70% and 8.6 months., Conclusion: NRAS mutated NSCLC are characterized by a high frequency of smoking history and codon 61 mutations. Further studies are needed to confirm the encouraging outcome of immunotherapy in combination with chemotherapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Simon Baldacci reports institutional funding for the present study for data storage and data management from Lille University Hospital; and financial support for manuscript writing from Edimark SAS. Julien Mazieres reports grants from AstraZeneca, Roche, Pierre Fabre; and financial support for participation to boards and for expertise from Merck, AstraZeneca, BMS, MSD, Roche, Novartis, Daiichi, and Pfizer. Jacques Cadranel reports grants for translational research and academic trial from AbbVie, Pfizer, and Sanofi; and financial and non-financial support for participation to boards of experts, presentations, educational events and attending meetings (ASCO and ESMO) from AMGEN, AstraZeneca, Boehringer Ingelheim, Daiichi, Jansen, MSD, Novartis, Pfizer, Takeda, Sanofi. Marion Ferreira reports non-financial support for meeting attending from AstraZeneca. Clotilde Descarpentries reports financial support for participation to presentation and to scientific committee from AstraZeneca. Camille Munck reports financial support for participation to presentation and expert bord from Sanofi and Novartis. Agathe Dehem, Florian Guisier, Maxime Boussageon, Denis Moro-Sibilot, Gérard Zalcman, Nicolas Girard, Marie Wislez, Eric Wasielewski, Ali Chour, Charles Ricordel, Claire Poulet, Clément Gauvain, and Alexis B. Cortot, declare that they have no known conflicts of interest that could have appeared to influence the work reported in this paper.., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2023
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11. Radiomics combined with transcriptomics to predict response to immunotherapy from patients treated with PD-1/PD-L1 inhibitors for advanced NSCLC.
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Bouhamama A, Leporq B, Faraz K, Foy JP, Boussageon M, Pérol M, Ortiz-Cuaran S, Ghiringhelli F, Saintigny P, Beuf O, and Pilleul F
- Abstract
Introduction: In this study, we aim to build radiomics and multiomics models based on transcriptomics and radiomics to predict the response from patients treated with the PD-L1 inhibitor., Materials and Methods: One hundred and ninety-five patients treated with PD-1/PD-L1 inhibitors were included. For all patients, 342 radiomic features were extracted from pretreatment computed tomography scans. The training set was built with 110 patients treated at the Léon Bérard Cancer Center. An independent validation cohort was built with the 85 patients treated in Dijon. The two sets were dichotomized into two classes, patients with disease control and those considered non-responders, in order to predict the disease control at 3 months. Various models were trained with different feature selection methods, and different classifiers were evaluated to build the models. In a second exploratory step, we used transcriptomics to enrich the database and develop a multiomic signature of response to immunotherapy in a 54-patient subgroup. Finally, we considered the HOT/COLD status. We first trained a radiomic model to predict the HOT/COLD status and then prototyped a hybrid model integrating radiomics and the HOT/COLD status to predict the response to immunotherapy., Results: Radiomic signature for 3 months' progression-free survival (PFS) classification: The most predictive model had an area under the receiver operating characteristic curve (AUROC) of 0.94 on the training set and 0.65 on the external validation set. This model was obtained with the t -test selection method and with a support vector machine (SVM) classifier. Multiomic signature for PFS classification: The most predictive model had an AUROC of 0.95 on the training set and 0.99 on the validation set. Radiomic model to predict the HOT/COLD status: the most predictive model had an AUROC of 0.93 on the training set and 0.86 on the validation set. HOT/COLD radiomic hybrid model for PFS classification: the most predictive model had an AUROC of 0.93 on the training set and 0.90 on the validation set., Conclusion: In conclusion, radiomics could be used to predict the response to immunotherapy in non-small-cell lung cancer patients. The use of transcriptomics or the HOT/COLD status, together with radiomics, may improve the working of the prediction models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bouhamama, Leporq, Faraz, Foy, Boussageon, Pérol, Ortiz-Cuaran, Ghiringhelli, Saintigny, Beuf and Pilleul.)
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- 2023
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12. Occupational asbestos exposure and survival among lung cancer patients.
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Noelle H, Pérol O, Pérol M, Avrillon V, Belladame E, Fayette J, Fournié F, Swalduz A, Dessemon J, Blay JY, Neidhardt EM, Saintigny P, Tabutin M, Boussageon M, Praud D, Charbotel B, and Fervers B
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- Humans, Carcinogens, Smoking adverse effects, Lung Neoplasms diagnosis, Asbestos adverse effects, Occupational Exposure adverse effects, Occupational Diseases diagnosis
- Abstract
Objective: This study investigated the association between occupational asbestos exposure (OAE) and survival in patients with histologically confirmed lung cancer (LC)., Methods: This monocentric study was conducted in the Comprehensive Cancer Centre Léon Bérard, Lyon, France. A systematic screening has been in place since 2014 for occupational exposure to carcinogens using a self-assessment questionnaire sent to all patients newly diagnosed with histologically confirmed LC identified through the multidisciplinary LC board from 2014 to 2019. When the physician suspected a work-related exposure from the questionnaire including job history, an occupational cancer consultation was carried out to detail carcinogen exposures and assess if the LC was work-related. Demographics, clinical characteristics and survival data were extracted from medical records. The association between asbestos exposure and overall survival (hazard ratio and 95% confidence intervals) was estimated by Cox proportional hazards regression., Results: Overall, 702 patients were eligible to the present study, including 180 patients with OAE. In the crude analysis, LCs assessed as moderately or highly attributable to OAE were associated with decreased overall survival (HR = 1.32, 95 %CI 1.04-1.67) compared to LC without OAE or with a low degree of imputability to OAE (median follow-up 28.8 months). After adjustment for confounding (age at diagnosis, smoking status, stage, brain metastasis at diagnosis, and histology), the association of OAE with overall survival was no longer statistically significant (HR = 1.21, 95 %CI 0.94-1.56)., Conclusion: Overall survival in occupationally asbestos exposed LC patients may be decreased in comparison with non-exposed LC patients, warranting further investigations in larger studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2023
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13. Correction to: First-Line Treatment of Advanced Non-Small-Cell Lung Cancer with Immune-Checkpoint Inhibitors: New Combinations and Long-Term Data.
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Boussageon M, Swalduz A, Chouaïd C, and Bylicki O
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- 2023
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14. Immunologically active phenotype by gene expression profiling is associated with clinical benefit from PD-1/PD-L1 inhibitors in real-world head and neck and lung cancer patients.
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Foy JP, Karabajakian A, Ortiz-Cuaran S, Boussageon M, Michon L, Bouaoud J, Fekiri D, Robert M, Baffert KA, Hervé G, Quilhot P, Attignon V, Girod A, Chaine A, Benassarou M, Zrounba P, Caux C, Ghiringhelli F, Lantuejoul S, Crozes C, Brochériou I, Pérol M, Fayette J, Bertolus C, and Saintigny P
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- B7-H1 Antigen, Cetuximab therapeutic use, Gene Expression Profiling, Humans, Immune Checkpoint Inhibitors, Phenotype, Programmed Cell Death 1 Receptor therapeutic use, Squamous Cell Carcinoma of Head and Neck drug therapy, Squamous Cell Carcinoma of Head and Neck genetics, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms pathology
- Abstract
Introduction: Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours., Methods: Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours. Validation of the 'HOT' score was done in 40 HNSCC and 992 NSCLC. Stability of the 'HOT' score was tested in paired HNSCC samples from diagnostic biopsies versus surgically resected specimens, untreated versus recurrent samples, and pre-versus post-cetuximab samples in a total of 76 patients. The association between the 'HOT' score with overall survival (OS) and progression-free survival (PFS) was tested in 184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors., Results: A 27-gene expression based 'HOT' score was correlated with: (i) PD-L1 and IDO1 expression, (ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance when comparing diagnostic biopsies and surgically resected specimens was higher than in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score was associated with an improved OS and PFS in multivariate analysis., Conclusion: The 'HOT' score is a simple and robust approach to identify real-world patients with HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2022
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15. Datasets for gene expression profiles of head and neck squamous cell carcinoma and lung cancer treated or not by PD1/PD-L1 inhibitors.
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Foy JP, Karabajakian A, Ortiz-Cuaran S, Boussageon M, Michon L, Bouaoud J, Fekiri D, Robert M, Baffert KA, Hervé G, Quilhot P, Attignon V, Girod A, Chaine A, Benassarou M, Zrounba P, Caux C, Ghiringhelli F, Lantuejoul S, Crozes C, Brochériou I, Pérol M, Fayette J, Bertolus C, and Saintigny P
- Abstract
Identification of tumors harboring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. In this context, we generated targeted gene expression profiles in three and two independent cohorts of patients with HNSCC or NSCLC respectively, treated or not by PD-1/PD-L1 inhibitors. Notably, we generated two datasets including 102 and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors. Clinical information, including detailed survival raw data, is available for each patient, allowing to test association between gene expression data and patient survival (overall and progression-free survival). Moreover, we also generated gene expression datasets of 27 paired HNSCC samples from diagnostic biopsies and versus surgically resected specimens as well as 33 paired HNSCC samples at initial diagnosis (untreated) and at recurrence. Those datasets may allow to test the stability of a given biomarker across paired samples., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PS is a member of HTG Diagnostics Scientific Advisory Board and receives research grants from HTG Diagnostics, Inivata, ArcherDx, Bristol-Myers Squibb, Roche Molecular Diagnostics, Roche, AstraZeneca, Novartis, Bristol-Myers Squibb Foundation and Illumina; JF reports grants, personal fees and non-financial support from Bristol-Myers Squibb, personal fees and non-financial support from MSD, personal fees from Merck, personal fees and non-financial support from Astrazeneca, personal fees from Rakuten, personal fees from Biogen and personal fees from Innate Pharma; SL received advisory board honoraria from AbbVie, AstraZeneca, Bayer, Bristol-Myers Squibb, Merck Sharp and Dohme, Takeda, Roche/Genentech; FG reports personal grants consultancy for Roche, AstraZeneca, and payments for development of educational presentations for Roche, Servier, Amgen, Merck. All remaining authors have declared no conflicts of interest., (© 2022 The Authors.)
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- 2022
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16. Epithelial-to-mesenchymal transition promotes immune escape by inducing CD70 in non-small cell lung cancer.
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Ortiz-Cuaran S, Swalduz A, Foy JP, Marteau S, Morel AP, Fauvet F, De Souza G, Michon L, Boussageon M, Gadot N, Godefroy M, Léon S, Tortereau A, Mourksi NE, Leonce C, Albaret MA, Dongre A, Vanbervliet B, Robert M, Tonon L, Pommier RM, Hofman V, Attignon V, Boyault S, Audoynaud C, Auclair J, Bouquet F, Wang Q, Ménétrier-Caux C, Pérol M, Caux C, Hofman P, Lantuejoul S, Puisieux A, and Saintigny P
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- CD27 Ligand genetics, CD27 Ligand metabolism, Cell Line, Tumor, Epithelial-Mesenchymal Transition genetics, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Ligands, Tumor Microenvironment, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms pathology
- Abstract
Introduction: Epithelial-to-mesenchymal transition (EMT) is associated with tumor aggressiveness, drug resistance, and poor survival in non-small cell lung cancer (NSCLC) and other cancers. The identification of immune-checkpoint ligands (ICPLs) associated with NSCLCs that display a mesenchymal phenotype (mNSCLC) could help to define subgroups of patients who may benefit from treatment strategies using immunotherapy., Methods: We evaluated ICPL expression in silico in 130 NSCLC cell lines. In vitro, CRISPR/Cas9-mediated knockdown and lentiviral expression were used to assess the impact of ZEB1 expression on CD70. Gene expression profiles of lung cancer samples from the TCGA (n = 1018) and a dataset from MD Anderson Cancer Center (n = 275) were analyzed. Independent validation was performed by immunohistochemistry and targeted-RNA sequencing in 154 NSCLC whole sections, including a large cohort of pulmonary sarcomatoid carcinomas (SC, n = 55)., Results: We uncover that the expression of CD70, a regulatory ligand from the tumor necrosis factor ligand family, is enriched in mNSCLC in vitro models. Mechanistically, the EMT-inducer ZEB1 impacted CD70 expression and fostered increased activity of the CD70 promoter. CD70 overexpression was also evidenced in mNSCLC patient tumor samples and was particularly enriched in SC, a lung cancer subtype associated with poor prognosis. In these tumors, CD70 expression was associated with decreased CD3
+ and CD8+ T-cell infiltration and increased T-cell exhaustion markers., Conclusion: Our results provide evidence on the pivotal roles of CD70 and ZEB1 in immune escape in mNSCLC, suggesting that EMT might promote cancer progression and metastasis by not only increasing cancer cell plasticity but also reprogramming the immune response in the local tumor microenvironment., Competing Interests: Conflict of interest statement SO–C: None. AS: Honoraria for Advisory Boards: Roche, Bristol-Myers Squibb, Takeda Symposiums: Roche, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Pfizer, Takeda. JPF: None. SM: None. APM: None. FF: None. MB: None. AD: None. CL: None. MR: None. NM: None. LM: None. MG: None. SL: None. AT: None. LT: None. SB: None. RMP: None. MAA: None. GDS: None. VH: None. NG: None. VA: None. CA: None. JA: None. BV: None. FB: Current employee at F. Hoffman La Roche. CMC: None. QW: None. MP: None. CC: None. PH: None. SL: consultant fees from MSD, BMS, Astra Zeneca, Abbvie, Bayer, Takeda. AP: None. PS: Research funding from Astra-Zeneca, Roche, Genentech BMS, Novartis and HTG Molecular Diagnostics. Scientific Advisory Board member of HTG Molecular Diagnostics., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
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17. First-Line Treatment of Advanced Non-Small-Cell Lung Cancer with Immune-Checkpoint Inhibitors: New Combinations and Long-Term Data.
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Boussageon M, Swalduz A, Chouaïd C, and Bylicki O
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- Aged, B7-H1 Antigen metabolism, ErbB Receptors therapeutic use, Humans, Immune Checkpoint Inhibitors, Nivolumab therapeutic use, Receptor Protein-Tyrosine Kinases therapeutic use, Brain Neoplasms, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
- Abstract
Treatment of metastatic non-small-cell lung cancers (NSCLCs) has long been based on cytotoxic chemotherapy. Immune checkpoint inhibitors (ICIs), notably monoclonal antibodies directed against programmed cell death protein-1 (PD-1) or its ligand (PD-L1), have transformed therapeutic standards in thoracic oncology. These ICIs are now the reference first-line therapy, and numerous phase III trials have established their efficacy in treatment-naïve patients. First-line pembrolizumab monotherapy was validated for patients with ≥ 50% of tumor cells expressing PD-L1 and, in the USA, for patients with ≥ 1% PD-L1 positivity. More recently, cemiplimab as monotherapy was also validated for patients whose tumors expressed ≥ 50% PD-L1. Several ICIs (pembrolizumab, atezolizumab, nivolumab, and recently durvalumab) in combination with chemotherapy achieved overall survival gains among "all comers", compared with chemotherapy alone. The results were more contrasting for paired immunotherapies combining anti-PD-L1 and anti-cytotoxic T-lymphocyte antigen-4 agents, with the benefit/risk balance not yet fully established. Recently, nivolumab-ipilimumab and two chemotherapy cycles limited patient exposure to chemotherapy and obtained positive results compared with the latter alone. However, those phase III trials included selected patients in good general condition and without active brain metastases. Little is known about immunotherapy and combination immunotherapy-chemotherapy efficacies in never-smokers or patients with tumors harboring an epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation. In this review, we report our analysis of the main results available on first-line ICI use, as monotherapy or combined or in combination with chemotherapy, to treat metastatic NSCLCs in general and also for specific populations: the elderly, never-smokers, patients with brain metastases, and those with an EGFR mutation or ALK translocation., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2022
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18. The safety and efficacy of erlotinib and ramucirumab combination in EGFR-mutant non-small-cell lung cancer.
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Boussageon M, Swalduz A, and Pérol M
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- Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols adverse effects, ErbB Receptors genetics, Erlotinib Hydrochloride adverse effects, Humans, Mutation, Protein Kinase Inhibitors adverse effects, Ramucirumab, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics
- Abstract
Introduction: EGFR-tyrosine kinase inhibitors (TKIs) changed the natural history of EGFR -mutant advanced NSCLC patients, but acquired resistance is inevitable. New strategies are being tested to overcome or prevent the emergence of resistance mechanisms to first-line TKIs, among which combinations of TKIs with antiangiogenic agents., Areas Covered: We performed a literature search for preclinical and clinical data on the interplay and dual inhibition of EGFR/VEGF pathways, particularly in EGFR -mutant NSCLC. We then focused on RELAY, a placebo-controlled phase 3 trial evaluating ramucirumab combined to erlotinib in treatment-naïve advanced EGFR -mutant NSCLC patients. This article aims to summarize efficacy and safety of the ramucirumab-erlotinib combination in this setting., Expert Opinion: RELAY confirmed the clinical relevance of combining EGFR and VEGF(R)-targeting therapies, previously investigated in smaller phase 2-3 trials of erlotinib and bevacizumab. However, the meaningful PFS benefit observed in the ramucirumab + erlotinib arm is counterbalanced by the toxicity profile of ramucirumab and the need for bimonthly infusions. Pending OS results are, therefore, critical to assess the real benefit from this combination, especially as first-line osimertinib has improved survival in EGFR -mutant NSCLC patients and will probably remain the pivotal EGFR-TKI in this setting. However, its heterogeneous efficacy across subgroups paves the way for osimertinib-based combinations, which are being investigated in ongoing trials.
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- 2021
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19. Response to the Combination of Osimertinib, Dabrafenib, and Trametinib in Leptomeningitis From EGFR -Mutant NSCLC With Acquired BRAF V600E Mutation: A Case Report.
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Valet O, Swalduz A, Boussageon M, Buisson A, Avrillon V, Mastroïanni B, and Pérol M
- Abstract
Molecular sequencing after highly potent targeted gene inhibitors have suggested resistant tumors can display substantial heterogeneity. Among these various mechanisms of resistance, secondary mutations on targetable oncogenes have been identified. BRAF V600E, as a bypass mechanism on disease progression while receiving osimertinib therapy, has been reported in 3% of EGFR- mutated patients. Few case reports described the efficacy of the association of osimertinib and dabrafenib plus trametinib. Here, we report, for the first time, a case of a patient treated with this association, with a prolonged response on leptomeningeal metastasis. We also provide a comprehensive overview of the available literature on the efficacy and tolerance of this association., (© 2021 The Authors.)
- Published
- 2021
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