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1. An Experimental Study of an Autonomous Heat Removal System Based on an Organic Rankine Cycle for an Advanced Nuclear Power Plant

Author: Nicolas Tauveron, Guillaume Lhermet, Benoît Payebien, Nadia Caney, and Franck Morin
Subjects: safety, organic rankine cycle, safety condenser, autonomous system, Technology
Abstract: The present study focuses on the recovery of waste heat in an autonomous safety system designed for advanced nuclear reactors. The system primarily relies on passive safety condensers, which are increasingly integrated into the design of advanced Pressurized Water Reactors (PWRs). These condensers are typically immersed in large water tanks that serve as heat sinks and are placed at sufficient heights to ensure natural circulation. Such a heat removal system can operate for an extended period, depending on the size of the tank. This research is driven by the potential to recover part of the energy stored in the boiling water volume, using it as a heat source for an Organic Rankine Cycle (ORC) system via an immersed heat exchanger. The electricity generated by the ORC engine can be used to power the system components, thereby making it self-sufficient. In particular, a pump replenishes the water tank, ensuring core cooling for a duration no longer limited by the water volume in the tank. An experimental test setup, including a boiling water pool and an ORC engine with an electrical output of approximately several hundred watts, along with an immersed evaporator, was constructed at CEA (Grenoble, France). Several test campaigns were conducted on the experimental test bench, exploring different configurations: two distinct ORC working fluids, cold source temperature variation effects, and relative positioning of the submerged evaporator and heat source within the water tank impact. These tests demonstrated the reliability of the system. The results were also used to validate both the ORC condenser and evaporator models. This article presents this innovative system, which has recently been patented. Moreover, to the best of our knowledge, the investigated configuration of an ORC that includes an immersed evaporator is original.
Published: 2024
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2. Neoadjuvant durvalumab for resectable non-small-cell lung cancer (NSCLC): results from a multicenter study (IFCT-1601 IONESCO)

Author: Julien Mazières, Diane Damotte, Virginie Westeel, Gérard Zalcman, Franck Morin, Marie-Ange Massiani, Jalal Assouad, Marie Wislez, Martine Antoine, Armelle Lavole, Olivier Carre, Thomas Egenod, Raffaele Caliandro, Catherine Dubos-Arvis, Gaelle Jeannin, Olivier Molinier, Alexandra Langlais, Francoise Le Pimpec Barthes, Laurent Brouchet, and Bernard Milleron
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background The IONESCO (IFCT-1601) trial assessed the feasibility of neoadjuvant durvalumab, for early-stage resectable non-small-cell lung cancer (NSCLC).Methods In a multicenter, single-arm, phase II trial, patients with IB (≥4 cm)-IIIA, non-N2, resectable NSCLC received three doses of durvalumab (750 mg every 2 weeks) and underwent surgery between 2 and 14 days after the last infusion. The primary endpoint was the complete surgical resection rate. Secondary endpoints included tumor response rate, major histopathological response (MPR: ≤10% remaining viable tumor cells), disease-free survival (DFS), overall survival (OS), durvalumab-related safety, and 90-day postoperative mortality (NCT03030131).Results Forty-six patients were eligible (median age 60.9 years); 67% were male, 98% were smokers, and 41% had squamous cell carcinoma. Regarding tumor response, 9% had a partial response, 78% had stable disease, and 13% had progressive disease. Among the operated patients (n=43), 41 achieved complete resection (89%, 95% CI 80.1% to 98.1%)), and eight achieved MPR (19%). The 12-month median OS and DFS rates were 89% (95% CI 75.8% to 95.3%) and 78% (95% CI 63.4% to 87.7%), respectively (n=46). The median follow-up was 28.4 months (12.8–41.1). All patients in whom MPR was achieved were disease-free at 12 months compared to only 11% of those with >10% residual tumor cells (p=0.04). No durvalumab-related serious or grade 3–5 events were reported. The unexpected 90-day postoperative mortality of four patients led to premature study termination. None of these four deaths was considered secondary to direct durvalumab-related toxicity.Conclusions Neoadjuvant durvalumab given as monotherapy was associated with an 89% complete resection rate and an MPR of 19%. Despite an unexpectedly high rate of postoperative deaths, which prevented us from completing the trial, we were able to show a significant association between MPR and DFS.
Published: 2022
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3. A Recent Advance on Partial Evaporating Organic Rankine Cycle: Experimental Results on an Axial Turbine

Author: Guillaume Lhermet, Nicolas Tauveron, Nadia Caney, Quentin Blondel, and Franck Morin
Subjects: organic Rankine cycle (ORC), partial evaporating organic Rankine cycle (PEORC), wet-to-dry cycle, axial turbine, dry fluid, Technology
Abstract: The organic Rankine cycle (ORC) technology is an efficient way to convert low-grade heat from renewable sources or waste heat for power generation. The partial evaporating organic Rankine cycle (PEORC) can be considered as a promising alternative as it can offer a higher utilization of the heat source. An experimental investigation of a small ORC system used in full or partial evaporation mode is performed. First characterized in superheated mode, which corresponds to standard ORC behavior, a semi-empirical correlative approach involving traditional non-dimensional turbomachinery parameters (specific speed, pressure ratio) can accurately describe one-phase turbine performance. In a second step, two-phase behavior is experimentally investigated. The efficiency loss caused by the two-phase inlet condition is quantified and considered acceptable. The turbine two-phase operation allows for an increase in the amount of recovered heat source. The ability to operate in two phases provides a new degree of flexibility when designing a PEORC. The semi-empirical correlative approach is then completed to take into account the partially evaporated turbine inlet condition. The qualitative description and the quantitative correlations in the one-phase and two-phase modes were applied to different pure working fluids (Novec649TM, HFE7000 and HFE7100) as well as to a zeotropic mixture (Novec649TM/HFE7000).
Published: 2022
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4. Outcomes of Patients With Advanced NSCLC From the Intergroupe Francophone de Cancérologie Thoracique Biomarkers France Study by KRAS Mutation Subtypes

Author: Anne-Marie Ruppert, MD, PhD, Michèle Beau-Faller, MD, PhD, Didier Debieuvre, MD, L’Houcine Ouafik, MD, PhD, Virginie Westeel, MD PhD, Isabelle Rouquette, MD, Julien Mazières, MD, PhD, Pierre-Paul Bringuier, MD, Isabelle Monnet, MD, Fabienne Escande, MD, Charles Ricordel, MD, Jean-Philippe Merlio, MD, PDh, Henri Janicot, MD, Antoinette Lemoine, MD, PhD, Pascal Foucher, MD, Michel Poudenx, MD, Franck Morin, MSc, Alexandra Langlais, MSc, Pierre-Jean Souquet, MD, PhD, Fabrice Barlesi, MD, PhD, and Marie Wislez, MD, PhD
Subjects: KRAS mutation, Non–small cell lung cancer, NSCLC, Prognosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Introduction: KRAS mutations are detected in 20% to 30% of NSCLC. However, KRAS mutation subtypes may differently influence the outcome of patients with advanced NSCLC. Methods: In the Biomarkers France study, 4894 KRAS mutations (26.2%) were detected in 4634 patients from the 17,664 enrolled patients with NSCLC. Survival and treatment data on noncurative stage III to IV NSCLC were available for 901 patients. First- and second-line treatment effects on progression-free survival and overall survival were analyzed according to the KRAS mutations subtype. Results: Over 95% of patients with KRAS mutation were smokers or former smokers who were white (99.5%), presenting with adenocarcinoma (82.5%). The most common KRAS mutation subtype was G12C (374 patients; 41.5%), followed by G12V (168; 18.6%), G12D (131; 14.5%), G12A (62; 6.9%), G13C (45; 5.0%), G13D (31; 3.4%), and others (10; 1%). Approximately 21% of patients had transition mutation and 68.2% had a transversion mutation. G12D and transition mutations were predominant in never-smokers. The median overall survival for patients with KRAS-mutated NSCLC was 8.1 months (95% confidence interval [CI]: 7.5–9.5), without any differences according to the different KRAS subtypes mutations. The median progression-free survival was 4.6 months (95% CI: 4.2–5.1) for first-line treatment and 4.8 months (95% CI: 4.3–6.8) for second-line treatment, without any differences according to the different KRAS subtypes mutations. Conclusions: KRAS mutation subtypes influenced neither treatment responses nor outcomes. The KRAS G12C mutation was detected in 41.5% of patients, who are now eligible for potent and specific G12C inhibitors.
Published: 2020
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5. Development and Validation of a Simplified Prognostic Score in SCLC

Author: Elodie Negre, MD, Amandine Coffy, BSc, Alexandra Langlais, BSc, Jean-Pierre Daures, MD, PhD, Armelle Lavole, MD, Elisabeth Quoix, MD, PhD, Olivier Molinier, MD, Laurent Greillier, MD, PhD, Clarisse Audigier-Valette, MD, Denis Moro-Sibilot, MD, PhD, Virginie Westeel, MD, PhD, Franck Morin, PhD, Benoît Roch, MD, and Jean-Louis Pujol, MD, PhD
Subjects: Small cell lung cancer, Prognosis, Prognostic score, Chemotherapy, Serum markers, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Introduction: This study aimed at generating a new simplified prognostic score (SPS) using common clinical and biological variables to discriminate a limited number of subgroups of patients with SCLC differing by their overall survival (OS). Methods: The SPS was developed exploring the Montpellier University Hospital retrospective database of 401 patients over a 16-year period. All patients had received etoposide - platinum-based chemotherapy as first-line treatment. The SPS development took into account significant determinants of OS in the Cox model, weighted by their regression β coefficients. Validation of the consequent SPS has been done separately in a combined population of 213 patients accrued from two different published trials (NCT03059667 and NCT00930891). Results: The significant independent determinants of OS included the following: (1) American Joint Committee on Cancer TNM stage IV (hazard ratio [HR]: 2.52; 95% confidence interval [CI]: 1.91–3.33); (2) Eastern Cooperative Oncology Group performance status greater than 1 (HR: 2.27; 95% CI: 1.79–2.87); (3) the presence of liver metastases (HR: 1.66; 95% CI: 1.29–2.15); and (4) neutrophil-to-lymphocyte ratio greater than 4 (HR: 1.39; 95% CI: 1.11–1.92). The SPS generated with these four variables, segregated three groups (good, intermediate, and poor prognosis) with respective median OS of 26.9 months (95% CI: 20.1–38.9), 11.5 months (95% CI: 9.8–13.0), and 6.8 months (95% CI: 5.8–8.3; log-rank p < 10–4). Harrell's C statistic estimate was 0.68 ± 0.012, suggesting goodness of calibration. In the validation cohort, the SPS segregated the aforementioned three subgroups in a nearly similar manner, with respective median OS: 27.2, 12.3, and 8.6 months (log-rank p < 10–3; Harrell’s C statistic: 0.58 ± 0.02). Conclusions: The SPS is easy to calculate in real-life practice and efficiently discriminates three populations with different prognoses. This study deserves further validation of this score in patients with SCLC receiving immunochemotherapy.
Published: 2020
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6. Study and Evaluation of Innovative Fuel Handling Systems for Sodium-Cooled Fast Reactors: Fuel Handling Route Optimization

Author: Franck Dechelette, Franck Morin, Guy Laffont, Gilles Rodriguez, Emmanuel Sanseigne, Sébastien Christin, Xavier Mognot, and Aurélien Morcillo
Subjects: Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract: The research for technological improvement and innovation in sodium-cooled fast reactor is a matter of concern in fuel handling systems in a view to perform a better load factor of the reactor thanks to a quicker fuelling/defueling process. An optimized fuel handling route will also limit its investment cost. In that field, CEA has engaged some innovation study either of complete FHR or on the optimization of some specific components. This paper presents the study of three SFR fuel handling route fully described and compared to a reference FHR option. In those three FHR, two use a gas corridor to transfer spent and fresh fuel assembly and the third uses two casks with a sodium pot to evacuate and load an assembly in parallel. All of them are designed for the ASTRID reactor (1500 MWth) but can be extrapolated to power reactors and are compatible with the mutualisation of one FHS coupled with two reactors. These three concepts are then intercompared and evaluated with the reference FHR according to four criteria: performances, risk assessment, investment cost, and qualification time. This analysis reveals that the “mixed way” FHR presents interesting solutions mainly in terms of design simplicity and time reduction. Therefore its study will be pursued for ASTRID as an alternative option.
Published: 2014
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7. Combination of Trastuzumab, Pertuzumab, and Docetaxel in Patients With Advanced Non–Small-Cell Lung Cancer Harboring HER2 Mutations: Results From the IFCT-1703 R2D2 Trial

Author: Julien Mazieres, Claire Lafitte, Charles Ricordel, Laurent Greillier, Elodie Negre, Gérard Zalcman, Charlotte Domblides, Jeannick Madelaine, Jaafar Bennouna, Céline Mascaux, Denis Moro-Sibilot, François Pinquie, Alexis B. Cortot, Josiane Otto, Jacques Cadranel, Alexandra Langlais, Franck Morin, Virginie Westeel, Benjamin Besse, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Services de Pneumologie, Exploration Fonctionnelle Respiratoire et Cardiologie (Hôpital Louis Pradel), Hospices Civils de Lyon (HCL), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), 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), 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)-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), Multidisciplinary Oncology and Therapeutic Innovations Unit, Hôpital Nord [CHU - APHM], Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), Service d’oncologie thoracique et essais précoces [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Foch [Suresnes], Service de Pneumologie [Strasbourg], Université de Strasbourg (UNISTRA)-Nouvel Hôpital Civil, Hospices Civils de Strasbourg, CHU de Grenoble-Alpes, Université Côte d'Azur (UCA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Groupe de recherche clinique Biomarqueurs Théranostiques des Cancers Bronchiques Non à Petites Cellules (GRC 4 - Theranoscan), Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Gustave Roussy (IGR), and Département de médecine oncologique [Gustave Roussy]
Subjects: MESH: Aged, MESH: Docetaxel, Cancer Research, MESH: Humans, MESH: Middle Aged, MESH: Mutation, MESH: Survival Rate, MESH: Non-Randomized Controlled Trials as Topic, MESH: Adult, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Follow-Up Studies, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Male, MESH: Prognosis, MESH: Lung Neoplasms, MESH: Receptor, ErbB-2, MESH: Antineoplastic Combined Chemotherapy Protocols, MESH: Aged, 80 and over, Oncology, MESH: Antibodies, Monoclonal, Humanized, MESH: Trastuzumab, MESH: Female, MESH: Carcinoma, Non-Small-Cell Lung
Abstract: PURPOSE HER2 exon 20 insertions and point mutations are oncogenic drivers found in 1%-2% of patients with non–small-cell lung cancer (NSCLC). No targeted therapy is approved for this subset of patients. We prospectively evaluated the effectiveness of the combination of two antibodies against human epidermal growth factor 2 (HER2 [HER2] trastuzumab and pertuzumab with docetaxel; trastuzumab and pertuzumab) and docetaxel. METHODS The IFCT 1703-R2D2 trial is a multicenter, nonrandomized phase II study. Patients with HER2-mutated, advanced NSCLC who progressed after ≥ 1 platinum-based treatment were enrolled. Patients received pertuzumab at a loading dose of 840 mg and 420 mg thereafter; trastuzumab at an 8 mg/kg loading dose and 6 mg/kg thereafter; and docetaxel at a dose of 75 mg/m2 every 3 weeks. The primary outcome was the objective response rate (ORR). Other end points included the duration of response, progression-free survival, and safety ( NCT03845270 ). RESULTS Forty-five patients were enrolled and treated. The median age was 64.5 years (range, 31-84 years), 35% were smokers, 72% were females, 15% had an Eastern Cooperative Oncology Group performance status of 2, and 30% had brain metastases. The objective response rate was 29% (n = 13), and 58% had stable disease (n = 26). The median progression-free survival was 6.8 months (95% CI, 4.0 to 8.5). The median duration of response in patients with a confirmed response (n = 13) was 11 months (95% CI, 2.9 to 14.9). Grade 3/4 treatment-related adverse events were observed in 64% of the patients. No patient discontinued treatment because of toxicity. The most frequent grade ≥ 3 treatment-related adverse events were neutropenia (33%), diarrhea (13%), and anemia (9%). CONCLUSION Triple therapy with trastuzumab, pertuzumab, and docetaxel is feasible and effective for HER2-mutated pretreated advanced NSCLC. These results highlight the effectiveness of the HER2 antibody-based strategy, which should be considered for these patients.
Published: 2022

8. FP09.05 Driver Oncogenic Alterations and Indoor Radon in NSCLC Patients From the IFCT Biomarker Cohort: Bioradon France Study

Author: Virginie Westeel, David Planchard, Isabelle Monnet, L'Houcine Ouafik, Alexandra Langlais, C. Vignaud, Isabelle Rouquette, Jean-Philippe Merlio, K. Leuraud, Charles Ricordel, Didier Debieuvre, Jean Mosser, Benjamin Besse, Fabrice Barlesi, Jose Carlos Benitez, Dominique Laurier, Fabienne Escande, G. Ielsch, Edouard Auclin, Franck Morin, Laura Mezquita, Department of Medical Oncology [Barcelona, Spain], Hospital del Mar [Barcelona, Spain], Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), 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), Bureau d'étude et d'expertise du radon (IRSN/PSE-ENV/SEREN/BERAD), Service d'expertise et d'étude en radioprotection des populations et de la radioactivité dans l'environnement (IRSN/PSE-ENV/SEREN), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), CHU Bordeaux [Bordeaux], Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), CHU Pontchaillou [Rennes], Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de Transfert d’Oncologie Biologique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHI Créteil, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Ouafik, L'Houcine
Subjects: Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, business.industry, Prevention, chemistry.chemical_element, Radon, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risky Behaviors, chemistry, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Cohort, medicine, Biomarker (medicine), business, Family History
Abstract: International audience; Those with FH of LC were more likely to be obese regardless of demographic factors, and less likely to exercise 2+ times per week (Table). Those with FH of LC were more likely to have received 10+ imaging scans and to have been exposed to hydrocarbons compared to those without FH (Table). There were no reported differences in any other occupational or home exposures, including asbestos and radon in those with v. without FH of LC (Table). Conclusion: FH of LC is associated with higher-risk behaviors that increase the likelihood of developing both lung and other cancers. As such, FH can be used in cancer prevention and control programs to identify higher-risk patients and educate patients that FH of lung cancer is associated with risk-increasing behaviors that are nonetheless modifiable.
Published: 2021

9. First-line afatinib plus cetuximab for EGFR-mutant non–small cell lung cancer: Results from the randomized phase II IFCT-1503 ACE-lung study

Author: Franck Morin, Judith Raimbourg, Didier Debieuvre, Denis Moro-Sibilot, Elisabeth Quoix, Hugues Morel, Elodie Amour, Olivier Molinier, José Hureaux, Etienne Giroux-Leprieur, Isabelle Rault, Alexis B. Cortot, Benjamin Huret, Josiane Otto, Aldo Renault, L. Moreau, Anne Madroszyk, Sandrine Charpentier, Marc G. Denis, Eric Pichon, Henri Berard, Jacques Cadranel, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Le Mans (CH Le Mans), CHU Strasbourg, Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CHU Amiens-Picardie, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC René Gauducheau, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Université Bretagne Loire (UBL), Hôpitaux Civils de Colmar, Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bristol-Myers Squibb, BMS, Pfizer, AstraZeneca, Merck, Novartis, Roche, Meso Scale Diagnostics, MSD, Boehringer Ingelheim, Takeda Pharmaceutical Company, TPC, and nonfinancial support from MSD, Takeda, and AbbVie outside the submitted work. E. Pichon reports nonfinancial support from Takeda, personal fees from Roche and AstraZeneca, and nonfinancial support from BMS outside the submitted work. B. Huret reports personal fees from Roche, AstraZeneca, BMS, and Boehringher Ingelheim outside the submitted work. M.G. Denis reports grants and personal fees from AstraZeneca and Takeda, grants from BluePrint Medicines, and personal fees from BMS, Boehringer Ingelheim, Roche Diagnostics, and Amgen outside the submitted work. J. Cadranel reports personal fees from BI, grants and personal fees from AstraZeneca, Pfizer, and Novartis, and personal fees from Roche, MSD, BMS, and Takeda outside the submitted work. No disclosures were reported by the other authors., A.B. Cortot reports grants from Boeringher-Ingelheim during the conduct of the study, as well as personal fees and nonfinancial support from AstraZeneca and Pfizer, grants, personal fees, and nonfinancial support from Roche and Novartis, personal fees and nonfinancial support from MSD, BMS, and Takeda, and grants from Merck, outside the submitted work. A. Madroszyk reports other support from Boehringer and MSD during the conduct of the study, as well as other support from Roche, Pfizer, AstraZeneca, BMS, and Prostrakan outside the submitted work. E. Giroux-Leprieur reports grants, personal fees, and nonfinancial support from AstraZeneca, Bristol Myers Squibb, and Roche, personal fees and nonfinancial support from Boehringer Ingelheim, MSD, and Takeda, and personal fees from Novartis outside the submitted work. O. Molinier reports personal fees from AstraZeneca, MSD, BMS, Amgen, Takeda, and Menarini outside the submitted work. E. Quoix reports grants from Boehringer Ingelheim and Ligue Nationale contre le Cancer during the conduct of the study, as well as personal fees and other from BMS and Chugai, other from Roche and Takeda, and personal fees from Novartis outside the submitted work. H. Bérard reports other from MSD, Roche, and Novartis outside the submitted work. D. Moro-Sibilot reports grants, personal fees, and nonfinancial support from Boehringer Ingelheim, Roche, BMS, Pfizer, AstraZeneca, and Merck, as well as personal fees, Medical writing assistance was provided by Dr Sarah Hopwood (Scinopsis, France), funded by IFCT. We thank the participating patients and their families as well as the study teams involved in the trial, the clinical research assistants, study coordinators, and IFCT operations staff. We thank the staff of the department of Biochemistry, CHU de Nantes. We also thank all the participating investigators: Dr Anne Madroszyk (institut Paoli Calmette, Marseille), Dr Etienne Giroux-Leprieur (hôpital Ambroise Paré, Boulogne), Dr Olivier Molinier (CHG, Le Mans), Pr Elisabeth Quoix (NHC, Strasbourg), Pr Jacques Cadranel (hôpital Tenon, Paris), Dr Henri Bérard (HIA Sainte-Anne, Toulon), Dr Josiane Otto (centre Antoine Lacassagne, Nice), Dr Isabelle Rault (CH, Saint Quentin), Pr Denis Moro-Sibilot (CHU, Grenoble), Pr Alexis B. Cortot (hôpital Calmette, Lille), Dr Judith Raimbourg (Institut de Cancérologie de l’Ouest, Nantes), Dr José Hureaux (CHU Angers), Lionel Moreau (CH Colmar), Dr Didier Debieuvre (GHRMSA, Mulhouse), Dr Hugues Morel (CHR, Orléans), Dr Valérie Gounant (hôpital Bichat, Paris), Dr Ludovic Doucet (hôpital Saint-Louis, Paris), Dr Aldo Renault (CHG, Pau), Dr Eric Pichon (CHU, Tours), Dr Benjamin Huret (hôpital privé, Villeneuve d’Asq), Dr Nadine Dohollou (Polyclinique Bordeaux Nord), Dr Clarisse Audigier-Valette (CHI, Toulon), Dr Chantal Decroisette (CH, Annecy), Dr Mathilde Cabart (Institut Bergonié, Bordeaux), Dr Patrick Merle (CHU, Clermont-Ferrand), Dr Catherine Becht (clinique du Parc, Castelnau le Lez), and Dr Luc Odier (CH, Villefranche sur Saône)., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Oncology, Cancer Research, medicine.medical_specialty, medicine.drug_class, Afatinib, [SDV.CAN]Life Sciences [q-bio]/Cancer, EGFR Gene Mutation, Tyrosine-kinase inhibitor, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Epidermal growth factor receptor, Adverse effect, Lung cancer, 030304 developmental biology, 0303 health sciences, Cetuximab, biology, business.industry, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, biology.protein, business, medicine.drug
Abstract: Purpose: Double inhibition of epidermal growth factor receptor (EGFR) using a tyrosine kinase inhibitor plus a monoclonal antibody may be a novel treatment strategy for non–small cell lung cancer (NSCLC). We assessed the efficacy and toxicity of afatinib + cetuximab versus afatinib alone in the first-line treatment of advanced EGFR-mutant NSCLC. Patients and Methods: In this phase II, randomized, open-label study, patients with stage III/IV EGFR-positive NSCLC were randomly assigned (1:1) to receive afatinib (group A) or afatinib + cetuximab (group A + C). Oral afatinib 40 mg was given once daily; cetuximab 250 mg/m² was administered intravenously on day 15 of cycle 1, then every 2 weeks at 500 mg/m² for 6 months. The primary endpoint was time to treatment failure (TTF) rate at 9 months. Exploratory analysis of EGFR circulating tumor DNA in plasma was performed. Results: Between June 2016 and November 2018, 59 patients were included in group A and 58 in group A + C. The study was ended early after a futility analysis was performed. The percentage of patients without treatment failure at 9 months was similar for both groups (59.3% for group A vs. 64.9% for group A + C), and median TTF was 11.1 (95% CI, 8.5–14.1) and 12.9 (9.2–14.5) months, respectively. Other endpoints, including progression-free survival and overall survival, also showed no improvement with the combination versus afatinib alone. There was a slight numerical increase in grade ≥3 adverse events in group A + C. Allele frequency of the EGFR gene mutation in circulating tumor DNA at baseline was associated with shorter PFS, regardless of the treatment received. Conclusions: These results suggest that addition of cetuximab to afatinib does not warrant further investigation in treatment-naïve advanced EGFR-mutant NSCLC.
Published: 2021

10. Circulating Tumor DNA as a Prognostic Determinant in Small Cell Lung Cancer Patients Receiving Atezolizumab

Author: Denis Moro-Sibilot, Guillaume Herbreteau, Olivier Molinier, José Hureaux, Patrick Merle, Jeannick Madelaine, Audrey Rabeau, J. Otto, Florian Guisier, Clarisse Audigier-Valette, Lionel Uwer, Valérie Gounant, Aldo Renault, Marc G. Denis, Laurent Greillier, Jean-Louis Pujol, Alexandra Langlais, Franck Morin, Pierre-Jean Souquet, Delphine Carmier, Centre hospitalier universitaire de Nantes (CHU Nantes), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Grenoble, Service de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de pneumologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d’oncologie thoracique et essais précoces [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Clermont-Ferrand, Centre Hospitalier Le Mans (CH Le Mans), Centre hospitalier de Pau, Service de pneumologie [Toulouse], CHU Toulouse [Toulouse]-Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Herrada, Anthony, and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Oncology, atezolizumab, medicine.medical_specialty, medicine.medical_treatment, lcsh:Medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease_cause, Article, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Atezolizumab, Internal medicine, medicine, RB1, Progression-free survival, TP53, 030304 developmental biology, 0303 health sciences, Chemotherapy, Mutation, business.industry, lcsh:R, SCLC, General Medicine, Immunotherapy, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, ctDNA, NOTCH, 3. Good health, Clinical trial, 030220 oncology & carcinogenesis, Non small cell, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, mutation, business
Abstract: Background: The IFCT-1603 trial evaluated atezolizumab in small cell lung cancer (SCLC). The purpose of the present study was to determine whether circulating tumor DNA (ctDNA), prospectively collected at treatment initiation, was associated with the prognosis of SCLC, and whether it identified patients who benefited from atezolizumab. Methods: 68 patients were included in this study: 46 patients were treated with atezolizumab and 22 with conventional chemotherapy. Circulating DNA was extracted from plasma and NGS (Next Generation Sequencing) looked for mutations in the TP53, RB1, NOTCH1, NOTCH2, and NOTCH3 genes. ctDNA was detectable when at least one somatic mutation was identified, and its relative abundance was quantified by the variant allele fraction (VAF) of the most represented mutation. Results: We found that 49/68 patients (70.6%) had detectable baseline ctDNA. The most frequently identified mutations were TP53 (32/49, 65.3%) and RB1 (25/49, 51.0%). Patients with detectable ctDNA had a significantly lower disease control rate at week 6 compared with patients with no detectable ctDNA, regardless of the nature of the treatment. Detection of ctDNA was associated with a poor OS prognosis. The detection of ctDNA at a relative abundance greater than the median value was significantly associated with poor overall survival (OS) and progression free survival (PFS). Interestingly, the benefit in overall survival (OS) associated with low ctDNA was more pronounced in patients treated with atezolizumab than in patients receiving chemotherapy. Among patients whose relative ctDNA abundance was below the median, those treated with atezolizumab tended to have higher OS than those in the chemotherapy arm. Conclusion: ctDNA is strongly associated with the prognosis of SCLC patients treated with second-line immunotherapy. Its analysis seems justified for future SCLC clinical trials.
Published: 2020

11. Outcomes of Patients With Advanced NSCLC From the Intergroupe Francophone de Cancérologie Thoracique Biomarkers France Study by KRAS Mutation Subtypes

Author: Fabrice Barlesi, H. Janicot, Pierre-Jean Souquet, Didier Debieuvre, Michel Poudenx, Virginie Westeel, Julien Mazieres, Michèle Beau-Faller, M. Wislez, Isabelle Monnet, Fabienne Escande, Pierre-Paul Bringuier, L'Houcine Ouafik, Pascal Foucher, Alexandra Langlais, Isabelle Rouquette, Jean-Philippe Merlio, Antoinette Lemoine, Anne-Marie Ruppert, Franck Morin, Charles Ricordel, Groupe de recherche clinique Biomarqueurs Théranostiques des Cancers Bronchiques Non à Petites Cellules (GRC 4 - Theranoscan), Sorbonne Université (SU), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Biochimie et Biologie Moléculaire [Strasbourg] (HUS), Les Hôpitaux Universitaires de Strasbourg (HUS), Univ Strasbourg, INSERM, IRFAC, UMR S1113, F-67200 Strasbourg, France, Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Pneumologie-Allergologie [CHU Toulouse], Pôle Clinique des Voies respiratoires [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL), Centre Hospitalier Intercommunal de Créteil (CHIC), Laboratoire de Biochimie et Biologie Moléculaire [CHRU Lille] (Pôle de Biologie Pathologie Génétique), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Rennes (CHU Rennes), INSERM U1053, Université Bordeaux, Bordeaux, France., Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, INSERM UMR S1193, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), AstraZeneca, Roche, 2011-038, Institut National Du Cancer, France, Novartis, France, Ouafik, L'Houcine, Theranoscan [CHU Tenon] (GRC 4), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité pneumologie et oncologie thoracique [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pneumologie [CHU Toulouse], Groupement hospitalier lyon Est (Hospices Civils de Lyon), INSERM U1242, Université Rennes 1, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)
Subjects: Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, endocrine system diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease_cause, NSCLC, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Non-small cell lung cancer, Internal medicine, medicine, Overall survival, Non–small cell lung cancer, Stage (cooking), neoplasms, 030304 developmental biology, 0303 health sciences, Mutation, Transition (genetics), business.industry, KRAS mutation, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Confidence interval, digestive system diseases, 3. Good health, respiratory tract diseases, 030220 oncology & carcinogenesis, Adenocarcinoma, Original Article, KRAS, business, Kras mutation
Abstract: Introduction KRAS mutations are detected in 20% to 30% of NSCLC. However, KRAS mutation subtypes may differently influence the outcome of patients with advanced NSCLC. Methods In the Biomarkers France study, 4894 KRAS mutations (26.2%) were detected in 4634 patients from the 17,664 enrolled patients with NSCLC. Survival and treatment data on noncurative stage III to IV NSCLC were available for 901 patients. First- and second-line treatment effects on progression-free survival and overall survival were analyzed according to the KRAS mutations subtype. Results Over 95% of patients with KRAS mutation were smokers or former smokers who were white (99.5%), presenting with adenocarcinoma (82.5%). The most common KRAS mutation subtype was G12C (374 patients; 41.5%), followed by G12V (168; 18.6%), G12D (131; 14.5%), G12A (62; 6.9%), G13C (45; 5.0%), G13D (31; 3.4%), and others (10; 1%). Approximately 21% of patients had transition mutation and 68.2% had a transversion mutation. G12D and transition mutations were predominant in never-smokers. The median overall survival for patients with KRAS-mutated NSCLC was 8.1 months (95% confidence interval [CI]: 7.5–9.5), without any differences according to the different KRAS subtypes mutations. The median progression-free survival was 4.6 months (95% CI: 4.2–5.1) for first-line treatment and 4.8 months (95% CI: 4.3–6.8) for second-line treatment, without any differences according to the different KRAS subtypes mutations. Conclusions KRAS mutation subtypes influenced neither treatment responses nor outcomes. The KRAS G12C mutation was detected in 41.5% of patients, who are now eligible for potent and specific G12C inhibitors.
Published: 2020

12. Lorlatinib for advanced ALK and ROS1+non-small cell lung cancer (NSCLC): Efficacy and treatment sequences in the IFCT-1803 LORLATU expanded access program (EAP) cohort

Author: Julien Mazieres, Bertrand Mennecier, Jacques Cadranel, Hélène Doubre, Renaud Descourt, Pascale Dubray-Longeras, P. Missy, Denis Moro-Sibilot, Sophie Schneider, Franck Morin, Virginie Westeel, Benjamin Besse, Michael Duruisseaux, J. Otto, Simon Baldacci, Nicolas Girard, Sigolene Galland-Girodet, Virginie Avrillon, Charles Ricordel, Isabelle Monnet, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Léon Bérard [Lyon], Prédicteurs moléculaires et nouvelles cibles en oncologie (PMNCO), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Sorbonne Université - Faculté de médecine Pitié Salpétrière, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pneumologie [CHI Créteil], CHI Créteil, Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Curie [Paris], IFCT, Pharmaceutical/Biotech Company, Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de médecine [CHU Pitié Salpétrière], Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Cancer Research, medicine.drug_class, business.industry, non-small cell lung cancer (NSCLC), [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease, Lorlatinib, Tyrosine-kinase inhibitor, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Oncology, Refractory, 030220 oncology & carcinogenesis, Expanded access, Cohort, Cancer research, medicine, ROS1, business, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract: 9615 Background: Lorlatinib, a third-generation tyrosine kinase inhibitor targeting ALK and ROS1, has been made available in France starting October 2015 through an EAP for advanced, refractory, ALK+ NSCLC after the failure of chemotherapy and TKIs. Besides the landmark, multi-cohort phase II trial that assessed lorlatinib in ALK+ NSCLC, real-life evidence regarding the efficacy and safety, as well as treatment sequences including lorlatinib, is lacking. Methods: We report the cohort of consecutive patients with advanced, refractory, ALK or ROS1+ NSCLC enrolled in the French EAP of lorlatinib from October 2015 to October 2019. Data were collected from medical records by French Cooperative Thoracic Intergroup (IFCT) research study assistants on site. Primary endpoint was progression-free survival. Results: 200 patients were included: 143 (71.5%) ALK+, 57 (28.5%) ROS1+, 87 (44%) men, 127 (66%) never-smokers, and 167 (85%) stage IV disease. Mean age was 59 years. At the time of initiation of lorlatinib, 146 (74%) patients had Central Nervous System (CNS) disease (78 % for ALK+, 63% for ROS1+), 131 (76%) were PS 0/1. Lorlatinib was delivered as 2nd/3rd/4th/5th+ line in 3%/17%/27%/53%of ALK+ patients and in 30%/30%/16%/24%of ROS1+ patients, respectively. 150 (75%), 185 (93%), 138 (69%), and 80 (40%) patients had received prior chemotherapy, crizotinib, 2nd generation TKIs, and brain radiotherapy, respectively. Median PFS and OS from the initiation of lorlatinib were 11.8 (95% CI 7.3-14.6) months and NR (95% CI 18.6-NR) months, respectively for ALK+ patients and 7.6 (95% CI 6.2-10.2) months and 20.9 (95% CI 10.0-NR) months, respectively for ROS1+ patients. ORR and DCR were 46.2% (95% CI 37.6-54.7) and 86.2% (95% CI 80.2-92.1), respectively for ALK+ patients and 47.1% (95% CI 33.4-60.8) and 88.2% (95% CI 79.4-97.1), respectively for ROS1+ patients. CNS ORR was 41.7% (95% CI 33.3-50.1) and 37.7% (95% CI 24.7-50.8), respectively. With a median follow-up of 15.6 (95% CI 14.0-17.6) months, progression under lorlatinib treatment was observed in 71 (50%) ALK+ patients and 35 (61%) ROS1+ patients, and CNS progression in 24 (34%) and 8 (23%) patients, respectively. The safety profile of lorlatinib was consistent with published data. Conclusions: These real-life results confirmed lorlatinib as a major treatment option for patients with advanced refractory ALK or ROS1+ NSCLC.
Published: 2020

13. Development and Validation of a Simplified Prognostic Score in SCLC

Author: D. Moro-Sibilot, Jean-Louis Pujol, Olivier Molinier, Jean-Pierre Daurès, Laurent Greillier, Benoît Roch, Franck Morin, Armelle Lavolé, Alexandra Langlais, Elodie Negre, Elisabeth Quoix, Virginie Westeel, Clarisse Audigier-Valette, and Amandine Coffy
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.medical_treatment, Population, lcsh:RC254-282, Serum markers, Prognostic score, Internal medicine, medicine, Chemotherapy, education, Etoposide, education.field_of_study, Small cell lung cancer, Proportional hazards model, business.industry, Hazard ratio, Cancer, University hospital, medicine.disease, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Oncology, Original Article, business, medicine.drug
Abstract: Introduction: This study aimed at generating a new simplified prognostic score (SPS) using common clinical and biological variables to discriminate a limited number of subgroups of patients with SCLC differing by their overall survival (OS). Methods: The SPS was developed exploring the Montpellier University Hospital retrospective database of 401 patients over a 16-year period. All patients had received etoposide - platinum-based chemotherapy as first-line treatment. The SPS development took into account significant determinants of OS in the Cox model, weighted by their regression β coefficients. Validation of the consequent SPS has been done separately in a combined population of 213 patients accrued from two different published trials (NCT03059667 and NCT00930891). Results: The significant independent determinants of OS included the following: (1) American Joint Committee on Cancer TNM stage IV (hazard ratio [HR]: 2.52; 95% confidence interval [CI]: 1.91–3.33); (2) Eastern Cooperative Oncology Group performance status greater than 1 (HR: 2.27; 95% CI: 1.79–2.87); (3) the presence of liver metastases (HR: 1.66; 95% CI: 1.29–2.15); and (4) neutrophil-to-lymphocyte ratio greater than 4 (HR: 1.39; 95% CI: 1.11–1.92). The SPS generated with these four variables, segregated three groups (good, intermediate, and poor prognosis) with respective median OS of 26.9 months (95% CI: 20.1–38.9), 11.5 months (95% CI: 9.8–13.0), and 6.8 months (95% CI: 5.8–8.3; log-rank p < 10–4). Harrell's C statistic estimate was 0.68 ± 0.012, suggesting goodness of calibration. In the validation cohort, the SPS segregated the aforementioned three subgroups in a nearly similar manner, with respective median OS: 27.2, 12.3, and 8.6 months (log-rank p < 10–3; Harrell’s C statistic: 0.58 ± 0.02). Conclusions: The SPS is easy to calculate in real-life practice and efficiently discriminates three populations with different prognoses. This study deserves further validation of this score in patients with SCLC receiving immunochemotherapy.
Published: 2020

14. Independent prognostic value of ultra-sensitive quantification of tumor pre-treatment T790M subclones in EGFR mutated non-small cell lung cancer (NSCLC) treated by first/second generation TKI, depends on variant allele frequency (VAF): Results of the French cooperative thoracic intergroup (IFCT) biomarkers France project

Author: Franck Morin, Hélène Blons, Fabienne Escande, Denis Moro-Sibilot, Alexandra Langlais, Charlotte Leduc, L'Houcine Ouafik, Antoinette Lemoine, Roger Lacave, Samia Melaabi, P. Missy, Jean-Philippe Merlio, Jacques Cadranel, Fabrice Barlesi, Pierre-Paul Bringuier, Michèle Beau-Faller, Paul Hofman, Marc G. Denis, Erwan Pencreach, Florence de Fraipont, Laboratoire de Biochimie et de Biologie Moléculaire, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Service de Pneumologie, Nouvel Hôpital Civil, Université de Strasbourg, Strasbourg, Service de Biochimie (HEGP - Biochimie), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM U1209, Institute for Advanced Biosciences, Laboratoire de Biochimie et Biologie Moléculaire (LILLE - Biochimie et Biol Moléculaire), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), INSERM UMR S1193, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Laboratoire de Biochimie et Plateforme de Génétique Moléculaire des Cancers [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Biopathologie [Institut Curie, Paris], Institut Curie [Paris], Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Unité d'Oncologie Thoracique-Pneumologie, CHU de Grenoble, INSERM U823, Grenoble, France., Centre Hospitalier Universitaire [Grenoble] (CHU), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Université Nice Sophia Antipolis (1965 - 2019) (UNS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ouafik, L'Houcine, Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Institut national de recherches archéologiques préventives (Inrap), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département de pathologie [Hôpital Haut Lévêque], CHU Bordeaux [Bordeaux]-CHU Bordeaux [Bordeaux], Département de biologie intégrée, CHU Grenoble-Hôpital Michallon, Microenvironnement et Physiopathologie de la Differenciation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Transfert d’Oncologie Biologique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Laboratoire de Biochimie, Unit of Pharmacogenomics, Department of Genetics, Amplitude Systèmes, Clinique de pneumologie, CHU Grenoble, Oncologie multidisciplinaire et innovations thérapeutiques [Hôpital Nord - APHM], École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [APHP], Institut Curie, Service de pneumologie et réanimation [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Institut Régional du Cancer-Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), École pratique des hautes études (EPHE), Aix Marseille Université (AMU)- Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), and Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)
Subjects: 0301 basic medicine, Oncology, Male, Cancer Research, Lung Neoplasms, [SDV]Life Sciences [q-bio], non-small cell lung cancer (NSCLC), T790M, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Digital polymerase chain reaction, Variant allele frequency (VAF), ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hazard ratio, Variant allele, Middle Aged, Prognosis, 3. Good health, ErbB Receptors, Survival Rate, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Female, France, Droplet digital PCR (ddPCR), Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, Adenocarcinoma of Lung, Non-small cell lung cancer (NSCLC), [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Biomarkers, Tumor, Humans, Clinical significance, Protein Kinase Inhibitors, Aged, Retrospective Studies, business.industry, Proportional hazards model, medicine.disease, Confidence interval, respiratory tract diseases, 030104 developmental biology, Drug Resistance, Neoplasm, Mutation, Carcinoma, Large Cell, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, EGFR mutation, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: T790M mutations inEGFR-mutated non-small cell lung cancer (NSCLC) account for nearly 50% of acquired resistance mechanisms to EGFR-TKIs. Earlier studies suggested that tumor T790M could also be detected in TKI-naïve EGFR-mutated NSCLC. The aim of the study is to assess the prevalence and clinical significance of quantification of tumor pre-treatment T790M subclones.We analyzed 366 EGFR-mutated NSCLC patients of the real-life IFCT Biomarkers France study with available pre-treatment formalin-fixed paraffin-embedded (FFPE) tumor DNA before treatment by first/second-generation EGFR-TKI. We used ultra-sensitive Droplet Digital Polymerase Chain Reaction (ddPCR) QX200 (BIO-RAD®, Hercules, CA, USA). All samples were tested in duplicate.ddPCR identified T790M in 19/240 specimens (8%). T790M-positive and T790M-negative populations were not different for clinical baseline characteristics. T790M Variant Allele Frequency (VAF) was 0.01% 0.1%, 0.1% 1%, 1% 10%, and10% in five (26.3%), six (31.6%), six (31.6%), and two (10.5%) patients, respectively. T790M VAF was0.1% in 11/13 (84%) patients with rapid (3 months) or usual progression (3-20 months) compared to 0/3 with low progression (20 months) (p = 0.02). In a Cox model, T790M mutation positivity was correlated with overall survival (OS) and progression-free survival (PFS) for 10%VAF1% (hazard ratio [HR] = 2.83, 95% confidence interval [CI] 1.13-7.07, p = 0.03; HR=3.62, 95%CI 1.43-4.92, p = 0.007, respectively) and for VAF10% (HR = 19.14, 95%CI 4.35-84.26, p 0.001; HR = 17.89, 95%CI 2.21-144.86, p = 0.007, respectively).Ultra-sensitive detection of tumor T790M mutation concerned 8% of EGFR-mutated TKI-naïve NSCLC patients and has a negative prognostic value only for T790M VAF over 1%.
Published: 2020

15. Role of the YAP-1 Transcriptional Target cIAP2 in the Differential Susceptibility to Chemotherapy of Non-Small-Cell Lung Cancer (NSCLC) Patients with Tumor RASSF1A Gene Methylation from the Phase 3 IFCT-0002 Trial

Author: Alexandra Langlais, Laurence Bigay-Game, Emmanuel Bergot, Elisabeth Quoix, Guénaëlle Levallet, Fatéméh Dubois, Jean-Louis Pujol, Elodie Maille, Martine Antoine, Franck Morin, Virginie Westeel, Julien Hoflack, Maureen Keller, Gérard Zalcman, Armelle Lavolé, Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Département de Pathologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Œstrogènes, reproduction, cancer (OeReCa), Normandie Université (NU)-Normandie Université (NU), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de pneumologie [CHU Caen], Service de pneumologie, CHU Strasbourg-Hopital Civil, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d’oncologie thoracique et essais précoces [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Toulouse [Toulouse], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Couteau, Florence, Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Cancer Research, medicine.medical_treatment, non-small cell lung cancer (NSCLC), [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, lcsh:RC254-282, Article, 03 medical and health sciences, chemistry.chemical_compound, paclitaxel, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Gene silencing, Lung cancer, 030304 developmental biology, 0303 health sciences, Chemotherapy, Gene knockdown, DNA methylation, business.industry, RASSF1A, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Gemcitabine, 3. Good health, Oncology, Paclitaxel, chemistry, non-small-cell lung cancer, 030220 oncology & carcinogenesis, Cancer research, IAP2, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], business, medicine.drug
Abstract: RASSF1 gene methylation predicts longer disease-free survival (DFS) and overall survival (OS) in patients with early-stage non-small-cell lung cancer treated using paclitaxel-based neo-adjuvant chemotherapy compared to patients receiving a gemcitabine-based regimen, according to the randomized Phase 3 IFCT (Intergroupe Francophone de Canc&eacute, rologie Thoracique)-0002 trial. To better understand these results, this study used four human bronchial epithelial cell (HBEC) models (HBEC-3, HBEC-3-RasV12, A549, and H1299) and modulated the expression of RASSF1A or YAP-1. Wound-healing, invasion, proliferation and apoptosis assays were then carried out and the expression of YAP-1 transcriptional targets was quantified using a quantitative polymerase chain reaction. This study reports herein that gemcitabine synergizes with RASSF1A, silencing to increase the IAP-2 expression, which in turn not only interferes with cell proliferation but also promotes cell migration. This contributes to the aggressive behavior of RASSF1A-depleted cells, as confirmed by a combined knockdown of IAP-2 and RASSF1A. Conversely, paclitaxel does not increase the IAP-2 expression but limits the invasiveness of RASSF1A-depleted cells, presumably by rescuing microtubule stabilization. Overall, these data provide a functional insight that supports the prognostic value of RASSF1 gene methylation on survival of early-stage lung cancer patients receiving perioperative paclitaxel-based treatment compared to gemcitabine-based treatment, identifying IAP-2 as a novel biomarker indicative of YAP-1-mediated modulation of chemo-sensitivity in lung cancer.
Published: 2019

16. Clinical outcomes of non–small-cell lung cancer patients with BRAF mutations: results from the French Cooperative Thoracic Intergroup biomarkers France study

Author: P. Missy, Franck Morin, Faraj Al Freijat, Jean-Philippe Merlio, Fabrice Barlesi, Hervé Lena, Alexandra Langlais, David Planchard, Clara Fontaine-Deraluelle, Didier Debieuvre, S. Couraud, Pierre-Paul Bringuier, Clarisse Audigier-Valette, L. Moreau, Michèle Beau-Faller, Pierre-Jean Souquet, Remi Veillon, Jean Mosser, Virginie Westeel, Alain Morel, L'Houcine Ouafik, Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 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), Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Louis Pasteur [Colmar] (CH Colmar), Laboratoire de Biochimie et de Biologie Moléculaire, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Pontchailloux [Rennes], Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de Transfert d’Oncologie Biologique, APHM, Hôpital Nord, Hôpital Nord [CHU - APHM], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Institut Gustave Roussy (IGR), National Cancer Institute, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Hospices Civils de Lyon (HCL), Assistance Publique - Hôpitaux de Marseille (APHM), Service de pneumologie, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Département de biologie de la tumeur, CH Colmar, Hôpital Pontchaillou, Equipe 4, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de Transfert d’Oncologie Biologique, Service de Pneumologie, Hôpital Jean Minjoz, Hôpital Sainte-Musse, Pôle chirurgical et interventionnel [Gustave Roussy], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire régional de Besançon (CHRU Besançon), Innate immunity and Immunotherapy (CRCINA - Département INCIT - Equipe 7), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, Lung Neoplasms, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Disease, medicine.disease_cause, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Molecular Targeted Therapy, Prospective cohort study, education.field_of_study, Middle Aged, Chemotherapy regimen, Progression-Free Survival, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, France, KRAS, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Population, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, BRAF, Oncogenic driver, 03 medical and health sciences, Internal medicine, medicine, Humans, Chemotherapy, Lung cancer, education, Protein Kinase Inhibitors, neoplasms, Aged, business.industry, Non–small-cell lung cancer, medicine.disease, digestive system diseases, respiratory tract diseases, 030104 developmental biology, Case-Control Studies, Mutation, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, V600E
Abstract: International audience; Introduction - Patients with stage IV non-small-cell lung cancer (NSCLC) and BRAF V600 mutations may benefit from targeted therapies. Chemotherapy outcomes are little known in this population. Methods - The French Cooperative Thoracic Intergroup (IFCT) Biomarkers France study was a national prospective cohort study aiming to describe the molecular characteristics and clinical outcome of all consecutive NSCLC patients (N = 17,664) screened for molecular alterations. We used this data set to set up a case-control analysis. Cases had stage IV BRAF-mutated (BRAF-MT) NSCLC, whereas controls had NSCLC that was wild-type for EGFR, KRAS, HER2, BRAF, PIK3CA and ALK. Each case was matched for sex, age at diagnosis and smoking status to two controls randomly selected. Results - Overall, 83 cases with BRAF mutant disease (66.3% V600E) were matched to 166 controls. Five cases received tyrosine kinase inhibition in the first-line and 16 in the second-line. All others were treated with standard chemotherapy. There was no significant difference in first-line and second-line progression-free survival (PFS) between the groups, as well as in the disease control rate, BRAF mutation was not found to be prognostic of overall survival. We found no significant difference in outcome between the treatment types used in first-line or second-line in patients with BRAF-MT disease compared with controls nor between BRAF V600E or non-V600E compared with controls. Conclusions - BRAF mutation is not a strong prognostic factor in NSCLC. Although taxan-based therapy shows poorest PFS in first-line, no chemotherapy regimen was associated with prognosis.
Published: 2019

17. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial

Author: Julien Mazieres, Pascal Do, Gérard Zalcman, O. Bylicki, Jacques Cadranel, Sylvie Lantuejoul, Franck Morin, Florian Guisier, Laurent Greillier, David Planchard, Olivier Molinier, Clarisse Audigier-Valette, Didier Debieuvre, Catherine Ligeza-poisson, M. Locatelli-Sanchez, Romain Corre, Delphine Carmier, Thierry Urban, Isabelle Monnet, Denis Moro-Sibilot, E. Amour, Arnaud Scherpereel, Sandrine Hiret, Séverine Fraboulet-Moreau, Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), and Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)
Subjects: Adult, Male, Mesothelioma, 0301 basic medicine, medicine.medical_specialty, Lung Neoplasms, Combination therapy, Pleural Neoplasms, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Ipilimumab, Gastroenterology, law.invention, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Prospective Studies, education, Aged, Aged, 80 and over, education.field_of_study, Chemotherapy, business.industry, Mesothelioma, Malignant, Middle Aged, medicine.disease, 3. Good health, respiratory tract diseases, Nivolumab, 030104 developmental biology, Pemetrexed, Oncology, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business, medicine.drug
Abstract: There is no recommended therapy for malignant pleural mesothelioma that has progressed after first-line pemetrexed and platinum-based chemotherapy. Disease control has been less than 30% in all previous studies of second-line drugs. Preliminary results have suggested that anti-programmed cell death 1 (PD-1) monoclonal antibody could be efficacious in these patients. We thus aimed to prospectively assess the anti-PD-1 monoclonal antibody alone or in combination with anti-cytotoxic T-lymphocyte protein 4 (CTLA-4) antibody in patients with malignant pleural mesothelioma.This multicentre randomised, non-comparative, open-label, phase 2 trial was done at 21 hospitals in France. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, histologically proven malignant pleural mesothelioma progressing after first-line or second-line pemetrexed and platinum-based treatments, measurable disease by CT, and life expectancy greater than 12 weeks. Patients were randomly allocated (1:1) to receive intravenous nivolumab (3 mg/kg bodyweight) every 2 weeks, or intravenous nivolumab (3 mg/kg every 2 weeks) plus intravenous ipilimumab (1 mg/kg every 6 weeks), given until progression or unacceptable toxicity. Central randomisation was stratified by histology (epithelioid vs non-epithelioid), treatment line (second line vs third line), and chemosensitivity to previous treatment (progression ≥3 months vs3 months after pemetrexed treatment) and used a minimisation method with a 0·8 random factor. The primary outcome was the proportion of patients who achieved 12-week disease control, assessed by masked independent central review; the primary endpoint would be met if disease control was achieved in at least 40% of patients. The primary endpoint was assessed in the first 108 eligible patients. Efficacy analyses were also done in the intention-to-treat population and safety analyses were done in all patients who received at least one dose of their assigned treatment. This trial is registered at ClinicalTrials.gov, number NCT02716272.Between March 24 and August 25, 2016, 125 eligible patients were recruited and assigned to either nivolumab (n=63) or nivolumab plus ipilimumab (n=62). In the first 108 eligible patients, 12-week disease control was achieved by 24 (44%; 95% CI 31-58) of 54 patients in the nivolumab group and 27 (50%; 37-63) of 54 patients in the nivolumab plus ipilimumab group. In the intention-to-treat population, 12-week disease control was achieved by 25 (40%; 28-52) of 63 patients in the nivolumab group and 32 (52%; 39-64) of 62 patients in the combination group. Nine (14%) of 63 patients in the nivolumab group and 16 (26%) of 61 patients in the combination group had grade 3-4 toxicities. The most frequent grade 3 adverse events were asthenia (one [2%] in the nivolumab group vs three [5%] in the combination group), asymptomatic increase in aspartate aminotransferase or alanine aminotransferase (none vs four [7%] of each), and asymptomatic lipase increase (two [3%] vs one [2%]). No patients had toxicities leading to death in the nivolumab group, whereas three (5%) of 62 in the combination group did (one fulminant hepatitis, one encephalitis, and one acute kidney failure).Anti-PD-1 nivolumab monotherapy or nivolumab plus anti-CTLA-4 ipilimumab combination therapy both showed promising activity in relapsed patients with malignant pleural mesothelioma, without unexpected toxicity. These regimens require confirmation in larger clinical trials.French Cooperative Thoracic Intergroup.
Published: 2019

18. MST1/Hippo promoter gene methylation predicts poor survival in patients with malignant pleural mesothelioma in the IFCT-GFPC-0701 MAPS Phase 3 trial

Author: Laurent Greillier, Romain Corre, Olivier Molinier, Isabelle Monnet, Valérie Gounant, Denis Moro-Sibilot, Alexandra Langlais, Vincent Hanoux, Emmanuel Bergot, Elodie Maille, Christian Creveuil, Gérard Zalcman, Arnaud Scherpereel, Guénaëlle Levallet, Franck Morin, Solenn Brosseau, Clarisse Audigier-Valette, Julien Mazieres, Claire Danel, Jacques Margery, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de pneumologie [CHU Caen], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Œstrogènes, reproduction, cancer (OeReCa), Normandie Université (NU)-Normandie Université (NU), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Département d'Anatomo-Pathologie [Hôpital Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], 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), Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Le Mans (CH Le Mans), CHU Pontchaillou [Rennes], Service de Pneumologie [CHI Créteil], CHI Créteil, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, CIC Hôpital Bichat, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, Institut Curie [Paris], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Couteau, Florence, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Mesothelioma, Cancer Research, Lung Neoplasms, Bevacizumab, Pleural Neoplasms, Apoptosis, Cell Cycle Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, Protein Serine-Threonine Kinases, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Article, Prognostic markers, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Proto-Oncogene Proteins, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Hippo Signaling Pathway, Neoplasm Invasiveness, Promoter Regions, Genetic, Cell Proliferation, Cisplatin, Hippo signaling pathway, Hepatocyte Growth Factor, Cell growth, business.industry, Mesothelioma, Malignant, Nuclear Proteins, Methylation, DNA Methylation, medicine.disease, 3. Good health, Pemetrexed, Oncology, 030220 oncology & carcinogenesis, DNA methylation, Cancer research, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], business, Transcription Factors, medicine.drug
Abstract: CERVOXY; International audience; Background: The Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS/NCT00651456) phase 3 trial demonstrated the superiority of bevacizumab plus pemetrexed–cisplatin triplet over chemotherapy alone in 448 malignant pleural mesothelioma (MPM) patients. Here, we evaluated the prognostic role of Hippo pathway gene promoter methylation.Methods: Promoter methylations were assayed using methylation-specific polymerase chain reaction in samples from 223 MAPS patients, evaluating their prognostic value for overall survival (OS) and disease-free survival in univariate and multivariate analyses. MST1 inactivation effects on invasion, soft agar growth, apoptosis, proliferation, and YAP/TAZ activation were investigated in human mesothelial cell lines.Results: STK4 (MST1) gene promoter methylation was detected in 19/223 patients tested (8.5%), predicting poorer OS in univariate and multivariate analyses (adjusted HR: 1.78, 95% CI (1.09–2.93), p = 0.022). Internal validation by bootstrap resampling supported this prognostic impact. MST1 inactivation reduced cellular basal apoptotic activity while increasing proliferation, invasion, and soft agar or in suspension growth, resulting in nuclear YAP accumulation, yet TAZ cytoplasmic retention in mesothelial cell lines. YAP silencing decreased invasion of MST1-depleted mesothelial cell lines.Conclusions: MST1/hippo kinase expression loss is predictive of poor prognosis in MPM patients, leading to nuclear YAP accumulation and electing YAP as a putative target for therapeutic intervention in human MPM.
Published: 2019

19. Second- or third-line nivolumab (Nivo) versus nivo plus ipilimumab (Ipi) in malignant pleural mesothelioma (MPM) patients: Results of the IFCT-1501 MAPS2 randomized phase II trial

Author: Julien Mazieres, Denis Moro-Sibilot, Pascal Do, David Planchard, Catherine Ligeza-poisson, Luc Thiberville, O. Bylicki, E. Amour, Clarisse Audigier-Valette, Arnaud Scherpereel, Franck Morin, Romain Corre, Olivier Molinier, Thierry Urban, M. Locatelli-Sanchez, Gérard Zalcman, Laurent Greillier, Isabelle Monnet, Service de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Breton, Céline, Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Ipilimumab, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Clinical endpoint, Medicine, ComputingMilieux_MISCELLANEOUS, business.industry, Pleural mesothelioma, Disease control, 3. Good health, Surgery, [SDV] Life Sciences [q-bio], 030104 developmental biology, Pemetrexed, Oncology, Third line, 030220 oncology & carcinogenesis, Nivolumab, business, medicine.drug
Abstract: LBA8507 Background: To date, no treatment is recommended in MPM pts progressing after 1st-line pemetrexed-platinum doublet. Disease control rate (DCR) is nd-line setting. Preliminary results suggested possible activity of anti-PD-1 mAb in 2nd/3rd-line, opposed to single agent anti-CTLA-4 mAb. Therefore anti-PD1 mAb efficacy deserves confirmation, and anti-PD-1 + anti-CTLA-4 combination value is currently unknown in MPM. Methods: In this multicenter randomized non comparative phase 2 trial, eligible pts had age>18, PS 0-1, histologically proven MPM relapsing after 1 or 2 prior lines including pemetrexed/platinum doublet, measurable disease. Randomized pts (1:1) received Nivo 3 mg/kg q2w, or Nivo 3 mg/kg q2w + Ipi 1 mg/kg q6w, until progression or unacceptable toxicity. Primary endpoint was DCR at 12 weeks with a blinded independent central review (BICR). 114 patients were to be randomized (with 108 eligible), with one-step Fleming procedure, H0 P40%, with 95% power, 5% one-sided a-risk: ≥17 failure-free pts had to be observed at 12 weeks in either arm, to conclude to the activity of the corresponding regimen. Results: From March to August 2016, 125 pts were enrolled in 21 centers. Males: 80%, median age: 71.8 years (range 32.5-88.1), PS 1: 62.4%, epithelioid 83.2%, 1 previous line: 69.6%; 70% of pts received ≥ 3 cycles of either treatment. Twelve weeks-DCR assessed by BICR in the first 108 eligible pts was 42.6% [IC95%: 29.4-55.8%] with Nivo (n=23/54), and 51.9% [38.5-65.2%] with Nivo+Ipi (n=28/54). ORR was 16.7% [6.7%-26.6%] with Nivo (n=9/54), and 25.9% [14.2-37.6%] with Nivo+Ipi (n=14/54). All grade/G3-4 toxicities were slightly increased in the combo arm (86.9%/16.4%) vs Nivo alone (77.8%/9.5%); 3 treatment-related deaths were observed in the combo arm (1 metabolic encephalopathy, 1 fulminant hepatitis, 1 acute renal failure). Full QoL, PFS and OS data will be presented at 2017 ASCO meeting. Conclusions: Both Nivo and Nivo+Ipi arms reached their endpoint in 2nd/3rd-line MPM pts, suggesting that immunotherapy may provide new options for these pts. Clinical trial information: NCT02716272.
Published: 2017

20. Association between lung cancer somatic mutations and occupational exposure in never-smokers

Author: Christophe, Paris, Pascal, Do, Bénédicte, Mastroianni, Adrien, Dixmier, Patrick, Dumont, Eric, Pichon, Christos, Chouaid, Bruno, Coudert, Pascal, Foucher, Séverine, Fraboulet, Myriam, Locatelli-Sanchez, Nathalie, Baize, Eric, Dansin, Lionel, Moreau, Michel, Vincent, Pascale, Missy, Franck, Morin, Denis, Moro-Sibilot, Sébastien, Couraud, Etienne, Suc, Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional d'Orléans (CHRO), Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Pneumologie (CRETEIL - Pneumologie), CHI Créteil, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Service de chirurgie cardio-vasculaire et thoracique (CHU Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Foch [Suresnes], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, CH Colmar, INSAVALOR, Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon, Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Unité d'Oncologie Thoracique-Pneumologie, CHU de Grenoble, INSERM U823, Grenoble, France., Centre Hospitalier Universitaire [Grenoble] (CHU), Boehringer Ingelheim, Pfizer, AstraZeneca, Roche, Eli Lilly and Company, Pierre Fabre, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Université de Lille-UNICANCER, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Male, Proto-Oncogene Proteins B-raf, Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Pathology, Lung Neoplasms, Receptor, ErbB-2, Adenocarcinoma, medicine.disease_cause, Asbestos, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Occupational Exposure, Internal medicine, Biomarkers, Tumor, Humans, Medicine, Prospective Studies, Risk factor, Lung cancer, Prospective cohort study, Carcinogen, Aged, Aged, 80 and over, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, business.industry, Smoking, Middle Aged, medicine.disease, 3. Good health, ErbB Receptors, Logistic Models, 030228 respiratory system, 030220 oncology & carcinogenesis, Mutation, Female, France, KRAS, business, Gasoline, Cohort study
Abstract: Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.
Published: 2017

21. Safeguarding the future of independent, academic clinical cancer research in Europe for the benefit of patients

Author: Anastassia Negrouk, Eva Carrasco, Richard Marais, Denis Lacombe, Rudolf Maibach, Fatima Cardoso, Rolf A Stahel, Joan Maurel, Franck Morin, Enrique Aranda, University of Zurich, and Negrouk, Anastassia
Subjects: 0301 basic medicine, Cancer Research, media_common.quotation_subject, Translational research, 610 Medicine & health, Disease, Safeguarding, academic research, 03 medical and health sciences, 0302 clinical medicine, independent investigator, Added value, media_common.cataloged_instance, Medicine, cancer, Quality (business), 1306 Cancer Research, European union, independent research, media_common, Original Research, business.industry, legal framework, Clinical trial, Editorial, 030104 developmental biology, Clinical research, Oncology, 030220 oncology & carcinogenesis, 10032 Clinic for Oncology and Hematology, Cancer research, 2730 Oncology, business
Abstract: Cancer is a complex disease that is constantly evolving. It is now the most common cause of death in Europe after cardiovascular diseases. There are inequalities among European countries, potentially unsustainable healthcare systems impacting quality of cancer care and increasing number of patients with cancer with rare conditions. Clinical and translational research are the backbone in establishing scientific advances as novel treatments and advancing progress to the benefit of patients. Commercially sponsored clinical trials are responsible for developing new medicines that can treat various disease areas, including cancer. It is important to note, however, that these clinical trials only assess the viability of compounds that are chosen by a commercial entity that funds the entire process. By their design and focus, these trials need to fulfil commercial interests and market expectations, which do not always coincide with patients’ needs. As soon or even before novel treatments and compounds obtain formal market authorisation, academia will take these existing and new medicines to further conduct research in order to optimise their use, develop new combinations and with a strong focus on the patients and their needs. Established standard of care most commonly relies on clinical cancer research stemming from non-commercial entities, cooperative groups or academic clinical research. This article provides a consensus on the definition of academic research, illustrates its added value and suggests and calls to European Union institutions to support this type of research for the benefit of patients.
Published: 2017

22. Reply to the letter to the editor ‘Flaws in the trial design of IFCT-0802’ by Gyawali et al

Author: J.L. Pujol, G. Zalcman, Franck Morin, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, CHU Caen, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)
Subjects: Male, medicine.medical_specialty, Lung Neoplasms, Letter to the editor, Bevacizumab, Angiogenesis Inhibitors, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, business.industry, General surgery, Hematology, Small Cell Lung Carcinoma, Surgery, Oncology, 030220 oncology & carcinogenesis, Female, business, medicine.drug
Abstract: International audience
Published: 2015

23. Randomized phase II–III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial†

Author: Julien Mazieres, P.-J. Souquet, G. Jeannin, J. Tredaniel, P. Dumont, H. Le Caer, Gérard Zalcman, F. Vaylet, L. Petit, C. Dayen, B. Coudert, Virginie Westeel, M. Poudenx, P. Barre, F. Goutorbe, H. Monnot, P. Deguiral, C. Raspaud, S. Schneider, P. Chatellain, A. Lavole, A. Dixmier, D. Coëtmeur, D. Moro-Sibilot, J. Dauba, R. Gervais, E. Pichon, H. Berard, J.P. Oster, Olivier Molinier, Pierre-Jean Lamy, P. Mourlanette, Franck Morin, Fabrice Barlesi, Luc Thiberville, M. Zaegel, Yves Martinet, M. Derollez, J-P. Duhamel, Elisabeth Quoix, P. Romand, A. Renault, A. Langlais, H. Laize, Pascal Foucher, Debra S. Herman, H. Doubre, Jean-Louis Pujol, S. Dehette, J-P. Gury, N. Baize, P. Fournel, Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Strasbourg, Centre Hospitalier Le Mans (CH Le Mans), Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Oncologie multidisciplinaire et innovations thérapeutiques [Hôpital Nord - APHM], Aix Marseille Université (AMU)- Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM), Centre Hospitalier de la Dracénie [Draguignan], Clinique de pneumologie, CHU Grenoble, Institut de Cancérologie Lucien Neuwirth, CHU Saint-Etienne, CH Colmar, Centre Hospitalier Alpes Léman (CHAL), Centre hospitalier Jean Rougier, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Pierre Bérégovoy [Nevers], Centre hospitalier de Pau, Centre hospitalier de Saint-Quentin, Institut Régional du Cancer, Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Oncology, Lung Neoplasms, Time Factors, anti-angiogenesis therapy, medicine.medical_treatment, Angiogenesis Inhibitors, Kaplan-Meier Estimate, chemotherapy, Gastroenterology, 0302 clinical medicine, Risk Factors, Antineoplastic Combined Chemotherapy Protocols, Clinical endpoint, small-cell lung cancer, Etoposide, 0303 health sciences, Hazard ratio, Induction Chemotherapy, Hematology, Middle Aged, Chemotherapy regimen, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Disease Progression, Female, France, medicine.drug, Adult, medicine.medical_specialty, Randomization, Bevacizumab, [SDV.CAN]Life Sciences [q-bio]/Cancer, bevacizumab, Disease-Free Survival, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Lung cancer, Cyclophosphamide, Aged, Epirubicin, Proportional Hazards Models, 030304 developmental biology, Chemotherapy, business.industry, Induction chemotherapy, medicine.disease, Small Cell Lung Carcinoma, Cisplatin, business
Abstract: IFCT study administering 7.5 mg/kg Bevacizumab plus chemotherapy after chemotherapy induction did not improve outcomes in extensive SCLC patients. Background This randomized phase II–III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC). Patients and methods Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle. Results In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers. Conclusion Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.
Published: 2015

24. BioCAST/IFCT-1002: epidemiological and molecular features of lung cancer in never-smokers

Author: Sébastien, Couraud, Pierre-Jean, Souquet, Christophe, Paris, Pascal, Dô, Hélène, Doubre, Eric, Pichon, Adrien, Dixmier, Isabelle, Monnet, Bénédicte, Etienne-Mastroianni, Michel, Vincent, Jean, Trédaniel, Marielle, Perrichon, Pascal, Foucher, Bruno, Coudert, Denis, Moro-Sibilot, Eric, Dansin, Stéphanie, Labonne, Pascale, Missy, Franck, Morin, Hélène, Blanché, Gérard, Zalcman, Laurence, Bigay-Game, Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Hôpital Foch [Suresnes], Centre Hospitalier Régional d'Orléans (CHRO), Centre Hospitalier Intercommunal de Créteil (CHIC), Centre de Mise en Forme des Matériaux (CEMEF), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Unité de cancérologie thoracique [ESPIC Groupe hospitalier Paris Saint-Joseph], Université Paris Descartes - Paris 5 (UPD5)-Groupe Hospitalier Paris Saint Joseph, Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER, Epidémiologie et Biostatistique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Fondation Jean Dausset CEPH, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional d'Orléans (CHR), Centre National de la Recherche Scientifique (CNRS)-PSL Research University (PSL)-MINES ParisTech - École nationale supérieure des mines de Paris, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Center Oscar Lambret, CRLCC Oscar Lambret, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Mines Paris - PSL (École nationale supérieure des mines de Paris), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-UNICANCER
Subjects: Male, Lung Neoplasms, Passive smoking, Receptor, ErbB-2, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Risk Factors, Surveys and Questionnaires, Epidemiology, Anaplastic Lymphoma Kinase, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Smoking, Nuclear Proteins, Middle Aged, 3. Good health, ErbB Receptors, Occupational Diseases, [STAT]Statistics [stat], 030220 oncology & carcinogenesis, Biomarker (medicine), Female, France, KRAS, Proto-Oncogene Proteins B-raf, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Sex Factors, Occupational Exposure, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Risk factor, Lung cancer, Pathological, Aged, 030304 developmental biology, business.industry, Receptor Protein-Tyrosine Kinases, medicine.disease, Surgery, Carcinogens, Tobacco Smoke Pollution, Observational study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Biomarkers, Transcription Factors
Abstract: Lung cancer in never-smokers (LCINS) (fewer than 100 cigarettes in lifetime) is considered as a distinct entity and harbours an original molecular profile. However, the epidemiological and molecular features of LCINS in Europe remain poorly understood.All consecutive newly diagnosed LCINS patients were included in this prospective observational study by 75 participating centres during a 14-month period. Each patient completed a detailed questionnaire about risk factor exposure. Biomarker and pathological analyses were also collected. We report the main descriptive overall results with a focus on sex differences.384 patients were included: 65 men and 319 women. 66% had been exposed to passive smoking (significantly higher among women). Definite exposure to main occupational carcinogens was significantly higher in men (35%versus8% in women). A targetable molecular alteration was found in 73% of patients (without any significant sex difference):EGFRin 51%,ALKin 8%,KRASin 6%,HER2in 3%,BRAFin 3%,PI3KCAin less than 1%, and multiple in 2%.We present the largest and most comprehensive LCINS analysis in a European population. Physicians should track occupational exposure in men (35%), and a somatic molecular alteration in both sexes (73%).
Published: 2015

25. No impact of passive smoke on the somatic profile of lung cancers in never-smokers

Author: Didier Debieuvre, Laurent Cellerin, Jean-François Mornex, P. Missy, Pierre-Jean Souquet, Bernard Duvert, Sébastien Couraud, Jacques Cadranel, N. Baize, Patrick Dumont, Marie Coudurier, Bruno Taviot, Jacques Margery, Franck Morin, Elisabeth Quoix, Gérard Zalcman, L. Moreau, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Service de pneumologie, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Hôpitaux Civils Colmar, Centre Hospitalier de Chauny, Partenaires INRAE, Hôpital d'instruction des Armées Percy, Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), Centre Hospitalier Montélimar, CH Montélimar, Service de Pneumologie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Médical, Centre Hospitalier de Chambéry (C.H.de Chambéry), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Intergroupe Français de Cancérologie Thoracique, Rétrovirus et Pathologie Comparée, Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)
Subjects: Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Pathology, Passive smoking, Lung, business.industry, [SDV]Life Sciences [q-bio], medicine.disease_cause, medicine.disease, Passive Smoke Exposure, respiratory tract diseases, medicine.anatomical_structure, Internal medicine, Cohort, medicine, Biomarker (medicine), KRAS, Mutation frequency, business, Lung cancer, neoplasms
Abstract: EGFR and HER2 mutations and ALK rearrangement are known to be related to lung cancer in never-smokers, while KRAS, BRAF and PIK3CA mutations are typically observed among smokers. There is still debate surrounding whether never-smokers exposed to passive smoke exhibit a “smoker-like” somatic profile compared with unexposed never-smokers.Passive smoke exposure was assessed in the French BioCAST/IFCT-1002 never-smoker lung cancer cohort and routine molecular profiles analyses were compiled.Of the 384 patients recruited into BioCAST, 319 were tested for at least one biomarker and provided data relating to passive smoking. Overall, 219 (66%) reported having been exposed to passive smoking. No significant difference was observed between mutation frequency and passive smoke exposure (EGFR mutation: 46% in never exposed versus 41% in ever exposed; KRAS: 7% versus 7%; ALK: 13% versus 11%; HER2: 4% versus 5%; BRAF: 6% versus 5%; PIK3CA: 4% versus 2%). We observed a nonsignificant trend for a negative association between EGFR mutation and cumulative duration of passive smoke exposure. No association was found for other biomarkers.There is no clear association between passive smoke exposure and somatic profile in lifelong, never-smoker lung cancer.
Published: 2015

26. High-energy chirped- and divided-pulse Sagnac femtosecond fiber amplifier

Author: Patrick Georges, Khanh-Linh Mai, Marc Hanna, Franck Morin, Clemens Hönninger, Florent Guichard, Eric Mottay, Yoann Zaouter, Amplitude Systèmes, Laboratoire Charles Fabry / Lasers, Laboratoire Charles Fabry (LCF), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)
Subjects: Physics, High energy, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], business.industry, Amplifier, Atomic and Molecular Physics, and Optics, Power (physics), Pulse (physics), Optics, Phase noise, Femtosecond, Optoelectronics, business, Scaling, Circular polarization
Abstract: International audience; We report on the generation of 1.1-mJ, 300-fs pulses at 50 kHz by implementing an amplifier architecture whereby four stretched pulse replicas are created in the temporal and spatial domains, allowing pulse energy scaling by the same factor. The whole spatiotemporal coherent combining geometry is passive, avoiding the need for active electronic stabilization loop systems. The combining efficiency remains above 90% at all power levels.
Published: 2015

27. Study and Evaluation of Innovative Fuel Handling Systems for Sodium-Cooled Fast Reactors: Fuel Handling Route Optimization

Author: Sebastien Christin, Emmanuel Sanseigne, Aurelien Morcillo, Guy Laffont, Xavier Mognot, Franck Dechelette, Gilles Rodriguez, Franck Morin, Service de Technologie des Composants et des Procédés (STCP), Département Technologie Nucléaire (DTN), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Service d'Etudes des Systèmes Innovants (SESI), and Département Etude des Réacteurs (DER)
Subjects: Engineering, Waste management, Article Subject, business.industry, Process (engineering), 020209 energy, 02 engineering and technology, 7. Clean energy, 01 natural sciences, Load factor, 010305 fluids & plasmas, Power (physics), [CHIM.GENI]Chemical Sciences/Chemical engineering, Nuclear Energy and Engineering, 0103 physical sciences, Limit (music), 0202 electrical engineering, electronic engineering, information engineering, Investment cost, lcsh:Electrical engineering. Electronics. Nuclear engineering, Energy source, business, Process engineering, lcsh:TK1-9971
Abstract: International audience; The research for technological improvement and innovation in sodium-cooled fast reactor is a matter of concern in fuel handling systems in a view to perform a better load factor of the reactor thanks to a quicker fuelling/defueling process. An optimized fuel handling route will also limit its investment cost. In that field, CEA has engaged some innovation study either of complete FHR or on the optimization of some specific components. This paper presents the study of three SFR fuel handling route fully described and compared to a reference FHR option. In those three FHR, two use a gas corridor to transfer spent and fresh fuel assembly and the third uses two casks with a sodium pot to evacuate and load an assembly in parallel. All of them are designed for the ASTRID reactor (1500MWth) but can be extrapolated to power reactors and are compatible with the mutualisation of one FHS coupled with two reactors. These three concepts are then intercompared and evaluated with the reference FHR according to four criteria: performances, risk assessment, investment cost, and qualification time. This analysis reveals that the "mixed way" FHR presents interesting solutions mainly in terms of design simplicity and time reduction. Therefore its study will be pursued for ASTRID as an alternative option.
Published: 2014

28. Rare EGFR exon 18 and exon 20 mutations in non-small-cell lung cancer on 10 117 patients: a multicentre observational study by the French ERMETIC-IFCT network

Author: Hélène Blons, Benjamin Besse, Jérôme Solassol, Michèle Legrain, Isabelle Rouquette, P. de Cremoux, Ivan Bièche, Anne-Claire Voegeli, Pascale Tomasini, Jacques Cadranel, Marie Wislez, F. De Fraipont, Laurence Baudrin, Fabienne Escande, Jean-Luc Prétet, Elisabeth Quoix, E. Favre-Guillevin, Nathalie Prim, Franck Morin, Roger Lacave, Ludovic Lacroix, A.-M. Ruppert, Isabelle Nanni-Metellus, Sarab Lizard, Anne Cayre, Gérard Zalcman, Michèle Beau-Faller, Progression tumorale et microenvironnement. Approches translationnelles et épidémiologie, Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Institut Régional du Cancer-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), CHU Strasbourg, CHU Tenon [APHP], CHU Marseille, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), CHU Toulouse [Toulouse], Institut Curie, Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), CHU Grenoble, Hôpital René HUGUENIN (Saint-Cloud), CHU Clermont-Ferrand, CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie et réanimation [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Theranoscan, Université Pierre et Marie Curie - Paris 6 (UPMC), Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Curie [Paris], Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Régional du Cancer-Université de Strasbourg (UNISTRA)-CHU Strasbourg-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Lung Neoplasms/drug therapy/*genetics/mortality, Drug Resistance, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease_cause, Disease-Free Survival, Exon, Young Adult, Protein Kinase Inhibitors/pharmacology/therapeutic use, Gene Frequency, Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics/mortality, 80 and over, Medicine, Humans, Epidermal growth factor receptor, Antineoplastic Agents/pharmacology/therapeutic use, Lung cancer, Allele frequency, Genetic Association Studies, Aged, Proportional Hazards Models, Mutation, biology, Neoplasm/genetics, business.industry, Cancer, Hematology, Original Articles, Exons, Middle Aged, medicine.disease, Molecular biology, Adenocarcinoma/drug therapy/*genetics/mortality, respiratory tract diseases, 3. Good health, Epidermal Growth Factor/antagonists & inhibitors/*genetics, Oncology, Cancer research, biology.protein, Adenocarcinoma, Female, business, Receptor
Abstract: International audience; BACKGROUND: There is scarce data available about epidermal growth factor receptor (EGFR) mutations other than common exon 19 deletions and exon 21 (L858R) mutations. PATIENTS AND METHODS: EGFR exon 18 and/or exon 20 mutations were collected from 10 117 non-small-cell lung cancer (NSCLC) samples analysed at 15 French National Cancer Institute (INCa)-platforms of the ERMETIC-IFCT network. RESULTS: Between 2008 and 2011, 1047 (10%) samples were EGFR-mutated, 102 (10%) with rare mutations: 41 (4%) in exon 18, 49 (5%) in exon 20, and 12 (1%) with other EGFR mutations. Exon 20 mutations were related to never-smoker status, when compared with exon 18 mutations (P \textless 0.001). Median overall survival (OS) of metastatic disease was 21 months [95% confidence interval (CI) 12-24], worse in smokers than in non-smoker patients with exon 20 mutations (12 versus 21 months; hazard ratio [HR] for death 0.27, 95% CI 0.08-0.87, P = 0.03). Under EGFR-tyrosine kinase inhibitors (TKIs), median OS was 14 months (95% CI 6-21); disease control rate was better for complex mutations (6 of 7, 86%) than for single mutations (16 of 40, 40%) (P = 0.03). CONCLUSIONS: Rare EGFR-mutated NSCLCs are heterogeneous, with resistance of distal exon 20 insertions and better sensitivity of exon 18 or complex mutations to EGFR-TKIs, probably requiring individual assessment.
Published: 2014

29. Energy scaling of a nonlinear compression setup using passive coherent combining

Author: Patrick Georges, Marc Hanna, Yoann Zaouter, Clemens Hönninger, Florent Guichard, Frédéric Druon, Franck Morin, Eric Mottay, Laboratoire Charles Fabry / Lasers, Laboratoire Charles Fabry (LCF), Université Paris-Sud - Paris 11 (UP11)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS), and Amplitude Systèmes
Subjects: Physics, Optical amplifier, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], business.industry, Amplifier, 02 engineering and technology, 021001 nanoscience & nanotechnology, 01 natural sciences, Atomic and Molecular Physics, and Optics, 010309 optics, Nonlinear system, Optics, Modulation, Pulse compression, 0103 physical sciences, Femtosecond, 0210 nano-technology, Self-phase modulation, business, Energy (signal processing)
Abstract: International audience; Passive spatial and temporal coherent combining schemes are implemented to scale the output energy of a nonlinear temporal compression setup. By generating 32 replicas of the incident femtosecond pulses, the output of a highenergy fiber chirped-pulse amplifier can be compressed using self-phase modulation in a large-mode-area rod-type fiber at peak-power levels well beyond the self-focusing power. We demonstrate the generation of 71 fs 7.5 μJ pulses at 100 kHz repetition rate, corresponding to a peak power of 86 MW.
Published: 2013

30. Passive coherent combination of two ultrafast rod type fiber chirped pulse amplifiers

Author: Marc Hanna, Yoann Zaouter, Clemens Hönninger, Eric Mottay, Patrick Georges, Franck Morin, Louis Daniault, Dimitris N. Papadopoulos, Frédéric Druon, Amplitude Systèmes, Laboratoire Charles Fabry / Lasers, Laboratoire Charles Fabry (LCF), and Université Paris-Sud - Paris 11 (UP11)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: High energy, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], Materials science, business.industry, Relative power, Pulse amplifiers, 02 engineering and technology, 01 natural sciences, Atomic and Molecular Physics, and Optics, 010309 optics, 020210 optoelectronics & photonics, Optics, Robustness (computer science), 0103 physical sciences, Femtosecond, Phase noise, 0202 electrical engineering, electronic engineering, information engineering, business, Ultrashort pulse, Photonic-crystal fiber
Abstract: International audience; Using passive coherent beam combining of two ultrafast fiber amplifiers, we demonstrate the generation of high temporal quality 300 fs and 650 μJ pulses corresponding to 60 W of average power at a repetition rate of 92 kHz. Furthermore, at 2 MHz of repetition rate record coherent combining average powers of 135 W before and 105 W after compression are measured. A combining efficiency higher than 90% is maintained over the whole range of output powers and repetition rates investigated demonstrating the efficiency and robustness of the passive combining technique. The measured pulse-to-pulse relative power fluctuation at high energy is 2%, indicating that the system is essentially immune to environmental phase noise. We believe the passive combining method to be an attractive approach for compact multi-GW peak power femtosecond fiber-based sources.
Published: 2012

31. Frequency Conversion from IR to UV of High Peak Power Ultrafast Fiber Amplifier

Author: Eric Mottay, Mario Tonin, Clemens Hönninger, Y. Zaouter, R. Maleck, Patrick Georges, Marc Hanna, Franck Morin, Amplitude Systèmes, Laboratoire Charles Fabry / Lasers, Laboratoire Charles Fabry (LCF), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)
Subjects: High peak, Materials science, business.industry, Second-harmonic generation, 02 engineering and technology, 021001 nanoscience & nanotechnology, 01 natural sciences, 7. Clean energy, Power (physics), 010309 optics, Optics, Frequency conversion, 0103 physical sciences, Fiber amplifier, High harmonic generation, 0210 nano-technology, business, Ultrashort pulse, Photonic-crystal fiber
Abstract: We report the frequency conversion from IR to UV of a high peak power ultrashort pulse fiber amplifier based on the use of a state of the art rod type fibre.
Published: 2012

32. De la lumière infrarouge pour guider les biopsies de la prostate

Author: Didier Vray, N. Grenier, Aurélie Laidevant, Patrick Georges, O. Messineo, Jean-Marc Dinten, Franck Morin, Mathieu Debourdeau, Frédéric Druon, Lena Herve, An Nguyen-Dinh, Jérôme Boutet, Marc Hanna, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Imagerie Ultrasonore, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Vermon S.A., Laboratoire Charles Fabry / Lasers, Laboratoire Charles Fabry (LCF), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS), Imagerie moléculaire et fonctionnelle: de la physiologie à la thérapie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Centre National de la Recherche Scientifique (CNRS), Laboratoire de l'intégration, du matériau au système (IMS), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS), and Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SPI.ACOU]Engineering Sciences [physics]/Acoustics [physics.class-ph], 0303 health sciences, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Labex CELYA, Biomedical Engineering, Biophysics, Laser, reseauₙational, 01 natural sciences, 010309 optics, 03 medical and health sciences, Imagerie Ultrasonore, 0103 physical sciences, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, categₘixte, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: Resume Une methode permettant de combiner imagerie optique et ultrasonore sur une sonde endorectale pourrait permettre d’ameliorer la detection precoce du cancer de la prostate. Les ultrasons fournissent une information morphologique alors que l’optique permet de localiser des tumeurs marquees par un traceur fluorescent. Le projet PROSTAFLUO a permis de developper une telle sonde. Le protocole consiste a injecter dans l’organe des traceurs fluorescents, elements biologiques et chimiques fixant un fluorophore sur les zones tumorales. Une illumination laser dans le proche infrarouge balaye la zone a investiguer generant une fluorescence au niveau des zones tumorales marquees. Cette derniere est captee par des fibres optiques et une methode permet de localiser les tumeurs en 3D. Leur position est alors superposee dans une image morphologique en ultrasons a partir de laquelle on dirige precisement l’outil de biopsie vers la zone tumorale fluorescente. La sonde a ete validee sur un fantome representatif des proprietes optiques et ultrasonore d’une prostate humaine ainsi que sur petit animal.
Published: 2011

33. Ultrashort pulse laser surgery of the cornea and the sclera

Author: Cord L. Arnold, Patrick Georges, Caroline Crotti, Michèle Savoldelli, Antoine Courjaud, Donald A. Peyrot, Karsten Plamann, Marc Hanna, Florent Aptel, Jean-Marc Legeais, Eric Mottay, Frédéric Druon, Franck Morin, Florent Deloison, Valeria Nuzzo, Laboratoire d'optique appliquée (LOA), École Nationale Supérieure de Techniques Avancées (ENSTA Paris)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Service d'Ophtalmologie [Hôpital Edouard Herriot - HCL]], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Amplitude Systèmes, Laboratoire Charles Fabry de l'Institut d'Optique / Elsa, Laboratoire Charles Fabry de l'Institut d'Optique (LCFIO), Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11), Laboratoire Biotechnologie et Œil, Université Paris Descartes - Paris 5 (UPD5)-Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-École Nationale Supérieure de Techniques Avancées (ENSTA Paris), Université Paris-Sud - Paris 11 (UP11)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'optique appliquée ( LOA ), École Nationale Supérieure de Techniques Avancées ( Univ. Paris-Saclay, ENSTA ParisTech ) -École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Laboratoire Charles Fabry de l'Institut d'Optique ( LCFIO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut d'Optique Graduate School ( IOGS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut d'Optique Graduate School ( IOGS ) -Centre National de la Recherche Scientifique ( CNRS ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpital Hôtel-Dieu [Paris]
Subjects: Laser surgery, medicine.medical_specialty, Materials science, genetic structures, medicine.medical_treatment, 01 natural sciences, law.invention, 010309 optics, 03 medical and health sciences, 0302 clinical medicine, Optics, law, Fiber laser, Cornea, Refractive surgery, 0103 physical sciences, PACS 87.80.-y, 42.66.Ct, 87.64.Ee, 42.62.Be, medicine, Eye surgery, Ultrashort pulse laser, [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], [ PHYS.PHYS.PHYS-OPTICS ] Physics [physics]/Physics [physics]/Optics [physics.optics], business.industry, Laser, Atomic and Molecular Physics, and Optics, eye diseases, Electronic, Optical and Magnetic Materials, Surgery, medicine.anatomical_structure, 030221 ophthalmology & optometry, sense organs, business, Ultrashort pulse
Abstract: International audience; The strongly localized interaction process of ultrashort laser pulses with tissue makes femtosecond lasers a powerful tool for eye surgery. These lasers are now routinely used in refractive surgery and other forms of surgery of the anterior segment of the eye. Several clinical laser systems also offer options for corneal grafting and the potential use of ultrashort pulse lasers in glaucoma surgery has been the object of several recent studies which have shown promising results. While devices aimed for interventions in clear tissue may be based on available solid state or fibre laser technology, the development of tools for surgery in more strongly scattering tissue has to account for the compromised tissular transparency and requires the development of optimized laser sources. The present paper focuses on surgery of clear and pathological cornea as well as sclera. It aims to give an overview over typical medical indications for ultrashort pulse laser surgery, the optics of the tissues involved, the available laser technology, the laser–tissue interaction process, and possible future developments.
Published: 2010

34. Mid-Infrared Supercontinuum Generation in Lead-Bismuth-Gallium Oxide Glass Photonic Crystal Fiber

Author: Dariusz Pysz, Nicolas Ducros, Frédéric Druon, Alexis Labruyere, Marc Hanna, Ryszard Buczynski, Sébastien Février, Patrick Georges, Ryszard Stepien, Franck Morin, PHOTONIQUE, XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Charles Fabry de l'Institut d'Optique / Elsa, Laboratoire Charles Fabry de l'Institut d'Optique (LCFIO), Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11), Faculty of physics-Optics department, and University of Warsaw (UW)
Subjects: Optical fiber, Materials science, business.industry, Oxide, Nonlinear optics, 02 engineering and technology, 01 natural sciences, Particle detector, law.invention, Supercontinuum, 010309 optics, chemistry.chemical_compound, 020210 optoelectronics & photonics, Optics, Gallium oxide, chemistry, law, 0103 physical sciences, 0202 electrical engineering, electronic engineering, information engineering, Optoelectronics, business, Photonic crystal, Photonic-crystal fiber
Abstract: Supercontinuum generation from visible up to 2.8 µm is demonstrated in a highly nonlinear heavy metal oxide glass photonic crystal fiber. Numerical modelling suggests that the supercontinuum can be extended to 4 µm.
Published: 2010

35. Dual-pumping scheme for high-energy femtosecond Er-doped fiber laser at 1.6 µm

Author: Franck Morin, Patrick Georges, Frédéric Druon, Marc Hanna, Laboratoire Charles Fabry de l'Institut d'Optique / Elsa, Laboratoire Charles Fabry de l'Institut d'Optique (LCFIO), Université Paris-Sud - Paris 11 (UP11)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS), and ANR-06-TECSAN-0025,GRECO,Greffes de cornée automatisées par laser femtoseconde optimisé et système de contrôle aberrométrique(2006)
Subjects: High energy, Materials science, business.industry, Doping, chemistry.chemical_element, 02 engineering and technology, 01 natural sciences, Light scattering, 010309 optics, Optical pumping, Erbium, 020210 optoelectronics & photonics, Optics, chemistry, Fiber laser, 0103 physical sciences, Femtosecond, 0202 electrical engineering, electronic engineering, information engineering, Optoelectronics, Stimulated emission, business
Abstract: We present the first microjoule-class sub-picosecond erbium-doped fiber laser at 1600 nm, and demonstrate the generation of 2.2 µJ, 650 fs pulses at 100 kHz. Dual-pumping schemes at 980 and/or 1550 nm are investigated.
Published: 2010

36. Mid-IR Supercontinuum in a Fluorozirconate Fiber Pumped by a Femtosecond CPA System at 1.6µm

Author: Frédéric Druon, Nicolas Ducros, Patrick Georges, Marc Hanna, Sébastien Février, Alexis Labruyere, Franck Morin, PHOTONIQUE, XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Charles Fabry de l'Institut d'Optique / Elsa, Laboratoire Charles Fabry de l'Institut d'Optique (LCFIO), and Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Optical fiber, Materials science, Fiber nonlinear optics, business.industry, Glass fiber, Ultrafast optics, 02 engineering and technology, 021001 nanoscience & nanotechnology, 01 natural sciences, Supercontinuum, law.invention, 010309 optics, Optics, law, 0103 physical sciences, Femtosecond, Optoelectronics, 0210 nano-technology, business, Self-phase modulation, Photonic-crystal fiber
Abstract: Mid-IR supercontinuum is demonstrated in a step index fluorozirconate glass fiber pumped by a CPA system emitting 500 fs pulses at 1.6 µm. Output power up to 60 mW is obtained over the supercontinuum bandwidth.
Published: 2010

37. Frequency conversion from near-infrared to mid-infrared in highly nonlinear optical fibres

Author: Alexis Labruyere, Franck Morin, Dariusz Pysz, Frédéric Druon, Marc Hanna, Nicolas Ducros, John Canning, Kevin Cook, Sébastien Février, Georges Humbert, Ryszard Buczynski, Ryszard Stepien, Patrick Georges, PHOTONIQUE, XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Charles Fabry de l'Institut d'Optique / Elsa, Laboratoire Charles Fabry de l'Institut d'Optique (LCFIO), Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11), Faculty of physics-Optics department, and University of Warsaw (UW)
Subjects: Materials science, Optical fiber, business.industry, Nonlinear optics, Physics::Optics, 02 engineering and technology, 021001 nanoscience & nanotechnology, 01 natural sciences, law.invention, 010309 optics, symbols.namesake, Raman laser, Optics, Fiber Bragg grating, law, 0103 physical sciences, symbols, 0210 nano-technology, Raman spectroscopy, business, Ultrashort pulse, Raman scattering, Photonic-crystal fiber
Abstract: International audience; Chalcogenide or heavy metal oxide glasses are well known for their good transparency in the mid-infrared (MIR) domain as well as their high nonlinear refractive index (n2) tens to hundreds times higher than that of silica. We have investigated the nonlinear frequency conversion processes, based upon either stimulated Raman scattering (SRS) or soliton fission and soliton self-frequency shift (SSFS) in fibres made up with such highly nonlinear infrared transmitting glasses. First, SRS has been investigated in a chalcogenide As2S3 step index fibre. In the single pass configuration, under quasi continuous wave 1550 nm pumping, Raman cascade up to the forth Stokes order has been obtained in a 3 m long piece of fibre. The possibility to build a Raman laser thanks to in-fibre written Bragg gratings has also been investigated. A 5 dB Bragg grating has been written successfully in the core. Then, nonlinear frequency conversion in ultra-short pulse regime has been studied in a heavy metal oxide (lead-bismuth-gallium ternary system) glass photonic crystal fibre. Broadband radiation, from 800 nm up to 2.8 μm, has been obtained by pumping an 8 cm long piece of fibre at 1600 nm in sub-picosecond pulsed regime. The nonlinear frequency conversion process was assessed by numerical modelling taking into account the actual fibre cross-section as well as the measured linear and nonlinear parameters and was found to be due to soliton fission and Raman-induced SSFS.
Published: 2010

38. Ultrashort-pulse laser eye surgery uses fiber technology at 1.6 microns

Author: Karsten Plamann, Marc Hanna, Florent Deloison, Michèle Savoldelli, Valeria Nuzzo, Franck Morin, Eric Mottay, Florent Aptel, Caroline Crotti, Cord L. Arnold, Jean-Marc Legeais, Donald A. Peyrot, Frédéric Druon, A. Courjaud, Patrick Georges, Laboratoire d'optique appliquée (LOA), École Nationale Supérieure de Techniques Avancées (ENSTA Paris)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), School of Engineering and Applied Physics of Havard University, Harvard University [Cambridge], Service d'Ophtalmologie [Hôpital Edouard Herriot - HCL]], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Amplitude Systèmes, Laboratoire Charles Fabry de l'Institut d'Optique / Elsa, Laboratoire Charles Fabry de l'Institut d'Optique (LCFIO), Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Université Paris-Sud - Paris 11 (UP11), Laboratoire Biotechnologie et Œil, Université Paris Descartes - Paris 5 (UPD5)-Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'optique appliquée ( LOA ), École Nationale Supérieure de Techniques Avancées ( Univ. Paris-Saclay, ENSTA ParisTech ) -École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Physics, Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Laboratoire Charles Fabry de l'Institut d'Optique ( LCFIO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut d'Optique Graduate School ( IOGS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut d'Optique Graduate School ( IOGS ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ) -Hôpital Hôtel-Dieu [Paris], Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-École Nationale Supérieure de Techniques Avancées (ENSTA Paris), and Université Paris-Sud - Paris 11 (UP11)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [PHYS.PHYS.PHYS-OPTICS]Physics [physics]/Physics [physics]/Optics [physics.optics], Materials science, [ PHYS.PHYS.PHYS-OPTICS ] Physics [physics]/Physics [physics]/Optics [physics.optics], genetic structures, business.industry, medicine.medical_treatment, Laser, 01 natural sciences, eye diseases, law.invention, 010309 optics, 03 medical and health sciences, 0302 clinical medicine, Optics, law, 0103 physical sciences, 030221 ophthalmology & optometry, medicine, Glaucoma surgery, Fiber, Eye surgery, sense organs, business, Ultrashort pulse laser
Abstract: International audience; New, compact, and wavelength-optimized ultrashort-pulse laser systems may facilitate corneal grafting and enable new forms of glaucoma surgery.
Published: 2009

39. Deliverable 3.2: 50-W, 300-fs, >1-MHz laser for seeding an Yb:YAG amplifier

Author: Franck Morin and Clemens Hoenninger
Subjects: High Productivity USP laser-based Micro-machining, High Power, 7. Clean energy
Abstract: Thanks to the combined use of chirp pulse amplification and large-mode-area fibers, the Satsuma fiber amplifier platform is able to deliver short pulse duration (40µJ) within a small footprint. In this work package, Amplitude Systemes had to optimise the Satsuma for seeding an Yb:YAG thin disk amplifier.

40. PCN97 COST EFFECTIVENESS OF ERLOTINIB TREATMENT GIVEN BY A CLINICALLY BASED APPROACH AND AN EGFR/KRAS TESTING-GUIDED APPROACH ADVANCED IN NON SMALL-CELL LUNG CANCER: A PROSPECTIVE MULTICENTRIC FRENCH STUDY (ERMETIC)

Author: B Coudert, C Daniel, Anne Madroszyk, S Friard, Jacques Cadranel, JP Pignon, Christos Chouaid, J Madeleine, Isabelle Borget, G Danton, Eric Dansin, Elisabeth Quoix, and Franck Morin
Subjects: Oncology, medicine.medical_specialty, business.industry, Cost effectiveness, Health Policy, Public Health, Environmental and Occupational Health, medicine.disease_cause, medicine.disease, Internal medicine, Medicine, KRAS, Erlotinib, Non small cell, business, Lung cancer, medicine.drug
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41. P3-118: IFCT-0301 randomized phase II trial of gefitinib, gemcitabine or docetaxel in Performance Status (PS) 2 or 3 non-small cell lung cancer (NSCLC) patients: analysis of the clinical impact of comorbidities and tumour burden

Author: Fabien Vaylet, Valérie Gounant, Denis Moro-Sibilot, Jeanne-Marie Bréchot, Bernard Lebeau, Franck Morin, Fabrice Barlesi, Jean-François Morère, Thierry Urban, and Virginie Westeel
Subjects: Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Performance status, business.industry, non-small cell lung cancer (NSCLC), medicine.disease, Gemcitabine, Gefitinib, Docetaxel, Internal medicine, medicine, business, medicine.drug
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42. Customized adjuvant phase II trial in patients with non-small-cell lung cancer: IFCT-0801 TASTE.

Author: Wislez M, Barlesi F, Besse B, Mazières J, Merle P, Cadranel J, Audigier-Valette C, Moro-Sibilot D, Gautier-Felizot L, Goupil F, Renault A, Quoix E, Souquet PJ, Madroszyck A, Corre R, Pérol D, Morin F, Zalcman G, and Soria JC
Subjects: Adult, Aged, Carcinoma, Non-Small-Cell Lung enzymology, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung surgery, Chemotherapy, Adjuvant, Cisplatin administration & dosage, DNA-Binding Proteins metabolism, Endonucleases metabolism, Female, Glutamates administration & dosage, Guanine administration & dosage, Guanine analogs & derivatives, Humans, Lung Neoplasms enzymology, Lung Neoplasms pathology, Lung Neoplasms surgery, Male, Middle Aged, Pemetrexed, Prospective Studies, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
Abstract: Purpose: Surgical resection plus adjuvant platinum-based chemotherapy is considered standard care for stage II to III non-small-cell lung cancer (NSCLC), but its efficacy is limited, and it involves toxic risks, justifying patient-tailored treatment. Excision repair cross-complementation group 1 (ERCC1) was shown to predict cisplatin-based chemotherapy response; EGFR mutations were predictive of epidermal growth factor receptor inhibition response., Patients and Methods: This prospective randomized phase II trial enrolled 150 patients with completely resected non-squamous cell stage II or IIIA (non-N2) tumors. Patients in the control arm (n = 74) were treated with four standard-dose courses of cisplatin plus pemetrexed (CP). In the customized treatment arm (n = 76), patients with activated EGFR mutations received erlotinib 150 mg for 1 year; ERCC1-negative patients received four CP courses, whereas ERCC1-positive patients underwent follow-up. The trial sought to demonstrate the feasibility of customized adjuvant chemotherapy based on timely biomarker analysis within a 2-month postsurgery delay. Secondary objectives were tolerability, compliance with adjuvant therapy, and biomarker distribution., Results: In arm A, all patients received CP; in arm B, seven received erlotinib, 53 were administered CP, and 16 underwent follow-up. Median erlotinib exposure was 344 days. Of the 127 patients allocated to CP, 82% received four cycles with good tolerability. The overall success rate of the trial (ie, percentage of patients with complete biomarker status able to start adjuvant treatment within 2 months of surgery) was 80%., Conclusion: The primary end point of the trial was met, demonstrating the feasibility of a national biology-driven trial in the adjuvant NSCLC setting. Nevertheless, the phase III part was canceled because of the unreliability of the ERCC1 immunohistochemical readouts.
Published: 2014
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