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We report the case of a 55-year-old woman with pulmonary adenocarcinoma and bone metastases who was diagnosed with paraneoplastic secretion of the beta subunit of human chorionic gonadotropin (beta-HCG) while being screened for inclusion in a clinical trial. Immunohistochemistry analysis of a bone biopsy revealed strong staining of cancer cells with anti-beta HCG antibodies. Serial measurements of circulating Beta HCG seemed to be influenced by antineoplastic treatments, although they were not strictly associated with tumour evolution assessed by CT scans. Little is known about paraneoplastic secretion of beta HCG, although it has been found in 12% to 24% of non-small cell lung cancers. Usefulness of serial measurements of beta HCG for monitoring NSCLC has yet to be demonstrated, but its use as a criterion for inclusion in clinical trials needs to be questioned.

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor issued from the mesothelial surface of the pleural space. A previous exposure to asbestos is the main risk factor of mesothelioma. Clinical signs are most of the time late and unspecific. Chest CT-scan, a key imaging procedure, usually shows a (unilateral) pleurisy associated with pleural nodular thickening. PET-scan associated with CT-scan may help to differenciate MPM from pleural benign tumors but it is not recommended for the diagnosis of MPM, as well as chest resonance magnetic imaging and blood or pleural fluid biomarkers, including soluble mesothelin still under investigation. The diagnosis of MPM is based on histology using essentially immunohistochemistry on pleural biopsies best obtained by thoracoscopy. The treatment of MPM relies mostly on chemotherapy. Surgery, pleurectomy/decortication or extrapleural pneumonectomy, is not recommended outside a clinical trial, as well as adjuvant chest radiotherapy. Prophylactic irradiation of chest scars and drains, validated by the French guidelines in 2005, is however highly discussed at the international level. Finally, numerous research studies presently assess the value of targeted therapies and biomarkers in MPM, opening new perspectives in the management of this cancer.

To determine the diagnostic accuracy of pharmacokinetic parameters measured by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting the response of brain metastases to antineoplastic therapy in patients with lung cancer. Forty-four consecutive patients with lung cancer, harbouring 123 newly diagnosed brain metastases prospectively underwent conventional 3-T MRI at baseline (within 1 month before treatment), during the early (7–10 weeks) and midterm (5–7 months) post-treatment period. An additional DCE MRI sequence was performed during baseline and early post-treatment MRI to evaluate baseline pharmacokinetic parameters (K trans, k ep, v e, v p) and their early variation (∆K trans, ∆k ep, ∆v e, ∆v p). The objective response was judged by the volume variation of each metastasis from baseline to midterm MRI. ROC curve analysis determined the best DCE MRI parameter to predict the objective response. Baseline DCE MRI parameters were not associated with the objective response. Early ∆K trans, ∆v e and ∆v p were significantly associated with the objective response (p = 0.02, p = 0.001 and p = 0.02, respectively). The best predictor of objective response was ∆v e with an area under the curve of 0.93 [95% CI = 0.87, 0.99]. DCE MRI and early ∆v e may be a useful tool to predict the objective response of brain metastases in patients with lung cancer. • DCE MRI could predict the response of brain metastases from lung cancer • ∆v e was the best predictor of response • DCE MRI could be used to individualize patients’ follow-up

// Michael Duruisseaux 1 , Benjamin Besse 2 , Jacques Cadranel 3 , Maurice Perol 4 , Bertrand Mennecier 5 , Laurence Bigay-Game 6 , Renaud Descourt 7 , Eric Dansin 8 , Clarisse Audigier-Valette 9 , Lionel Moreau 10 , Jose Hureaux 11 , Remi Veillon 12 , Josiane Otto 13 , Anne Madroszyk-Flandin 14 , Alexis Cortot 15 , Francois Guichard 16 , Pascaline Boudou-Rouquette 17 , Alexandra Langlais 18 , Pascale Missy 19 , Franck Morin 19 , Denis Moro-Sibilot 1 1 Centre Hospitalier Universitaire Grenoble Alpes, Thoracic Oncology Unit, Chest Department, Grenoble, France 2 Medical Oncology Department, Gustave Roussy, Villejuif, France 3 Assistance Publique Hopitaux de Paris, Tenon Hospital, Chest Department, Paris, France 4 Leon-Berard Cancer Center, Lyon, France 5 Centre Hospitalier Universitaire de Strasbourg, Chest Department, Strasbourg, France 6 Larrey Hospital, Chest Department, Toulouse, France 7 Centre Hospitalier Universitaire de Brest, Brest, France 8 Oscar Lambret Cancer Center, Medical Oncology Department, Lille, France 9 Centre Hospitalier Sainte Musse, Chest Department, Toulon, France 10 Centre Hospitalier General de Colmar, Louis Pasteur Hospital, Chest Department, Colmar, France 11 Centre Hospitalier Universitaire d’Angers, Chest Department, Angers, France 12 Centre Hospitalier Universitaire de Bordeaux, Respiratory Disease Department, Pessac, France 13 Antoine Lacassagne Cancer Center, Nice, France 14 Paoli Calmettes Institute, Marseille, France 15 Centre Hospitalier Universitaire de Lille, Thoracic Oncology Unit, Lille, France 16 Medical Oncology Department, Polyclinique Bordeaux Nord Aquitaine, Bordeaux, France 17 Assistance Publique Hopitaux de Paris, Cochin-Port Royal Hospital, Medical Oncology Department, Paris, France 18 French Cooperative Thoracic Intergroup, Department of Biostatistics, Paris, France 19 French Cooperative Thoracic Intergroup, Clinical Research Unit, Paris, France Correspondence to: Denis Moro-Sibilot, email: DMoro-Sibilot@chu-grenoble.fr Keywords: lung cancer, ALK, crizotinib, ceritinib, alectinib Received: September 28, 2016 Accepted: January 10, 2017 Published: February 26, 2017 ABSTRACT Overall survival (OS) with the anaplastic lymphoma kinase (ALK) inhibitor (ALKi) crizotinib in a large population of unselected patients with ALK -positive non-small-cell lung cancer (NSCLC) is not documented. We sought to assess OS with crizotinib in unselected ALK -positive NSCLC patients and whether post-progression systemic treatments affect survival outcomes. ALK -positive NSCLC patients receiving crizotinib in French expanded access programs or as approved drug were enrolled. We collected clinical and survival data, RECIST-defined progressive disease (PD) and post-PD systemic treatment efficacy. We performed multivariable analysis of OS from crizotinib initiation and PD under crizotinib. At time of analysis, 209 (65.7%) of the 318 included patients had died. Median OS with crizotinib was 16.6 months. The line of crizotinib therapy did not impact survival outcomes. Of the 263 patients with PD, 105 received best supportive care, 74 subsequent drugs other than next-generation ALKi and 84 next-generation ALKi. Next-generation ALKi treatment correlated with better survival outcomes in multivariate analysis. These patients had a median post-PD survival of 25.0 months and median OS from metastatic disease diagnosis of 89.6 months. Unselected ALK -positive NSCLC patients achieve good survival outcomes with crizotinib therapy. Next-generation ALKi may provide survival improvement after PD under crizotinib.

Accessibility to cancer screening in France has been facilitated by the implementation of organised programs (breast cancer and colorectal cancer) and by national recommendations (cervical cancer). Personal motivation may also trigger participation in prostate cancer screening. This paper proposes an overview of attitudes toward cancer screening among the general population over a period of more than 10 years and the perception of this behaviour by general practitioners. It is noteworthy that although certain cancer screening programmes, such as for breast cancer, are widely established throughout the population, uptake of others, such as for colorectal or prostate cancer, is contingent on sociological factors and vulnerability. Monitoring of compliance is thus all the more important since participation may be more acutely affected by the impact of social conditions and vulnerability in the current critical economic climate.

International audience; The acquisition of a resistance EGFR mutation in exon 20 (T790M) occurs in half of the cases of secondary resistance to EGFR tyrosine kinase inhibitors (TKI), given in first-line treatment in advanced EGFR-mutated non-small cell lung cancers (NSCLC). Osimertinib (AZD9291, Tagrisso®) is a third-generation, irreversible EGFR TKI, active in case of T790M mutation. A large phase I trial showed the efficacy of osimertinib after failure of first-generation EGFR TKI (erlotinib, gefitinib), with response rate at 51% and up to 61% in case of T790M mutation. Progression-free survival was 9.6 months in case of T790M. Toxicity profile was acceptable, with mainly digestive (diarrhea) and skin (rash) side effects. Preliminary data from a phase II trial confirmed these efficacy and safety data. Screening of T790M mutation at the time of progression with TKI can be performed in circulating tumor DNA in plasma, with good diagnostic performances.; L’acquisition d’une mutation EGFR de résistance au niveau de l’exon 20 (T790M) est responsable de plus de la moitié des cas de résistance secondaire aux inhibiteurs de tyrosine kinase (ITK) de l’EGFR, prescrits en 1re ligne dans les cancers bronchiques non à petites cellules (CBNPC) de stade localement avancé ou métastatique, mutés EGFR. L’osimertinib (AZD9291, Tagrisso®) est un inhibiteur irréversible d’EGFR de 3e génération, actif en cas de mutations activatrices et mutation T790M. Un essai de phase I avec extension de cohorte a montré son efficacité après échec des ITK de l’EGFR de 1re génération (erlotinib, gefitinib), avec des taux de réponse de 51 %, et jusqu’à 61 % en cas de mutation T790M. La survie sans progression en cas de mutation T790M était de 9,6 mois. Le profil de toxicité est acceptable, avec essentiellement une toxicité digestive (diarrhées) et cutanée (rash). Des données préliminaires d’un essai de phase II ont confirmé ces résultats d’efficacité et de tolérance. La prescription d’osimertinib est conditionnée à la mise en évidence d’une mutation T790M dont la recherche au moment de la progression sous ITK peut être faite sur l’ADN tumoral circulant dans le plasma, avec des performances diagnostiques intéressantes ce qui en fait une alternative à la rebiopsie.

Objectives The receptor tyrosine kinase MET is essential to embryonic development and organ regeneration. Its deregulation is associated with tumorigenesis. While MET gene amplification and mutations leading to MET self-activation concern only a few patients, a high MET level has been found in about half of the non-small cell lung cancers (NSCLCs) tested. How this affects MET activation in tumors is unclear. Also uncertain is the prognostic value, in cancer, of a phenomenon well described in cell models: MET shedding, i.e. its cleavage by membrane proteases leading to release of a soluble fragment into the medium. Materials and methods A prospective cohort of 39 NSCLC patients was constituted at diagnosis or soon after. Normal tissues, tumor tissues, and blood samples were obtained. This allowed, for the same patient, synchronous determination of (i) the MET level in the tumor, (ii) receptor phosphorylation, and (iii) the concentration of soluble MET fragment (sMET) in the serum. Results After confirming the adequacy of an ELISA for measuring the serum level of sMET, we found no correlation between this level and the concentration of MET in tumors, as evaluated by immunohistochemistry and western blotting. Nevertheless, all but one tumor displaying a high MET level also displayed receptor phosphorylation, restricted to a small number of tumor cells. Conclusion Our results thus demonstrate that the serum level of sMET is not indicative of the amount of MET present in the tumor cells and cannot be used as a biomarker for therapeutic purposes. However, MET scoring of tumor biopsies could be a first step prior to determination of MET receptor activation in high-MET tumors.

The acquisition of a resistance EGFR mutation in exon 20 (T790M) occurs in half of the cases of secondary resistance to EGFR tyrosine kinase inhibitors (TKI), given in first-line treatment in advanced EGFR-mutated non-small cell lung cancers (NSCLC). Osimertinib (AZD9291, Tagrisso

The pulmonary sarcomatoid carcinoma (SC) represents less than 1% of non-small cell lung cancer (NSCLC). Its prognosis is worse than that of other histological subtypes, by its particular aggressiveness and resistance to conventional therapies (1,2). Therefore, alternative therapies are sought, via immunotherapy or targeting molecular abnormalities. Liu et al . performed in Asian patients whole exome sequencing of 10 samples from SC followed by targeted sequencing of a set of five key genes on a validation cohort with 26 samples (3). The first analysis of the 10 samples showed two samples with mutations at the splice sites of exon 14 of MET . Subsequent targeted mutation screening of all 36 tumors confirmed these 2 mutations and identified 6 additional tumors with DNA alterations leading to exon 14 skipping.

Resume L’aspergillose bronchopulmonaire allergique est une affection respiratoire qui touche 1 a 2 % des asthmatiques et jusqu’a 9 % des patients atteints de mucoviscidose. Les reactions immunes complexes font intervenir l’IgE mais aussi l’IgG, avec une activation des lymphocytes Th2 sur un epithelium prealablement active/lese. Le terrain genetique favorisant est essentiel a son installation, et des sensibilites associees a certains HLA-DR et -DQ, des polymorphismes sur le gene codant pour l’IL-4RA, la proteine A du surfactant ou des mutations du gene codant pour le CFTR ont probablement un role cle. Lorsque le diagnostic est etabli sur base de criteres, deux formes sont retenues : ABPA-seropositive et ABPA avec bronchectasies. Le traitement fait appel a la corticotherapie systemique et a l’itraconazole. Plusieurs etudes semblent montrer un role benefique de l’omalizumab, mais seules des etudes contre placebo permettront de preciser sa place dans cette indication.

Introduction L’ajout du bevacizumab a un doublet de chimiotherapie avec sels de platine (pCT-BEVA) en premiere ligne de traitement des cancers du poumon non a petites cellules (CBNPC) non-epidermoides avances permet un benefice en survie globale. Aucune donnee d’efficacite de la pCT-BEVA n’est disponible dans les CBNPC ALK+. Methodes L’etude IFCT-1302 CLINALK est une etude observationnelle, retrospective et multicentrique ayant inclus 318 patients avec un CBNPC ALK+ prouve, de stade III avance/IV, traites par crizotinib dans le cadre du programme ATU ou de l’AMM de 2e ligne. L’efficacite des traitements avant crizotinib etait collectee. Les donnees des patients traites en 1re ligne par un doublet de chimiotherapie avec cisplatine ou carboplatine (pCT) associe au pemetrexed ou au paclitaxel ou a la gemcitabine ont ete analysees. Les caracteristiques cliniques, le taux de reponse objective selon RECIST (TRO) et la survie sans progression (SSP) etaient comparees selon que du BEVA etait administre (pCT-BEVA) ou non (pCT). Un modele de Cox etait utilise pour determiner les variables cliniques (âge, sexe, tabac) et les traitements (BEVA, pemetrexed, gemcitabine, paclitaxel) associees a la SSP. Resultats Au total, 244 patients (pts) recevaient une 1re ligne par pCT dont 60 un traitement par pCT-BEVA (24,6 %). La chimiotherapie comportait du pemetrexed pour 180 pts (73,8 %), du paclitaxel pour 40 pts (16,4 %) et de la gemcitabine pour 24 pts (9,8 %). Le type de molecule de troisieme generation utilisee etait equilibree entre les groupes pCT-BEVA et pCT. Le groupe pCT-BEVA etait significativement plus jeune (mediane 53,6 vs. 58,6 ans, p = 0,01), avait plus frequemment une maladie metastatique au diagnostic (97 vs. 84,8 %, p = 0,01) et recevaient plus frequemment une maintenance (62 vs. 28 %, p Conclusion Un traitement par pCT-BEVA etait associe a un TRO superieur compare a un traitement par pCT. De plus, un traitement par pCT-BEVA etait associe a une meilleure SSP en analyse multivariee. Ces donnees suggerent que l’association pCT-BEVA serait une option therapeutique efficace apres echec des inhibiteurs d’ALK.

Introduction Les cancers bronchiques non a petites cellules (CBNPC) EGFR-mutes ou ALK-positifs sont caracterises par le recours aux inhibiteurs de tyrosine kinase (TKI) et au traitement local des oligo-progressions (TLOP). Le profil de progression tumorale determine le recours au TLOP ou le changement de traitement. L’objectif de cette etude etait de determiner le profil de progression sous TKI des CBNPC EGFR - ou ALK-positifs et d’etudier le recours a un TLOP. Methodes Les patients porteurs d’un CBNPC EGFR - ou ALK-positif identifies par la plateforme regionale de Lille entre 2009 et 2015 et pris en charge dans le Nord-Pas-de-Calais etaient inclus retrospectivement. Les donnees cliniques et radiologiques etaient recueillies dans le dossier medical. Le survie sans progression (SSP) et survie globale (SG) etaient estimees selon la methode de Kaplan-Meier et le test du Log Rank etait utilise pour les comparaisons. Le mode de progression tumorale sous TKI, le recours a un TLOP etait releve. Toute survenue d’effet flare etait notee et decrite. Resultats Au total, 347 patients mutes EGFR et 86 patients rearranges ALK ont ete inclus. La SG etait de 24 mois pour les mutes EGFR et de 36,37 mois pour les rearranges ALK. Un TKI a ete instaure 260 fois chez les mutes EGFR, 193 progressions relevees et la SSP etait de 10,6 mois. Chez les rearranges ALK, un TKI a ete instaure 72 fois avec 47 survenues de progression et la SSP etait de 10 mois. Les sites de progression les plus frequents chez les mutes EGFR etaient le poumon, l’os, la plevre, le cerveau, le mediastin et le foie et pour les rearranges ALK le cerveau, le poumon, la plevre, le foie, et l’os. Une oligo-progression etait constatee chez 46 (24 %) patients EGFR-mutes et 13 (28 %) patients ALK-positifs en progression. Chez 46 (78 %) des 59 patients presentant une oligo-pregression, un TLOP etait propose. Les 13 autres patients poursuivaient simplement le TKI. Tous ont poursuivi le TKI au-dela de cette oligo-progression. La SG des patients ayant poursuivi le TKI au-dela de la progression etait significativement plus longue que celle des autres patients (22,9 vs. 43,1 mois, p Conclusion Les CBNPC EGFR-mutes et ALK-rearranges n’ont pas le meme profil de progression sous TKI. La survenue d’une oligo-progression et la poursuite du TKI au-dela de la progression, le plus souvent apres recours a un TLOP, sont associes a un allongement de la SG.

In this article a French working party critically review the international literature to revise the definition, pathophysiology, treatment and cost of exacerbations of adult asthma. The various guidelines do not always provide a consistent definition of exacerbations of asthma. An exacerbation can be defined as deterioration of clinical and/or functional parameters lasting more than 24 hours, without return to baseline, requiring a change of treatment. No single clinical or functional criterion can be used as an early marker of an exacerbation. Innate and acquired immune mechanisms, modified by contact with infectious, irritant or allergenic agents, participate in the pathogenesis of exacerbations, which are accompanied by bronchial inflammation. In 2010, mortality is related to progression of exacerbations, often occurring before the patient seeks medical attention. The objective of treatment is to control asthma and prevent exacerbations. However, many factors can trigger exacerbations and often cannot be controlled. The efficacy of inhaled corticosteroids has been demonstrated on reduction of the number of exacerbations and the number of asthma-related deaths. This treatment is cost-effective, especially in terms of reduction of exacerbations.

Resume Certaines des innovations therapeutiques les plus marquantes en pneumologie au cours des dernieres annees incluent les traitements dits « cibles » utilises dans la lutte contre le cancer bronchique non a petites cellules. Parmi ces traitements, les inhibiteurs du recepteur de l’Epidermal Growth Factor (EGFR) occupent une place de choix. Qu’il s’agisse des inhibiteurs de l’activite tyrosine kinase du recepteur, gefitinib et erlotinib ou de l’anticorps monoclonal dirige contre le domaine extracellulaire d’EGFR, le cetuximab, ces nouveaux medicaments sont appeles a occuper une place grandissante dans notre pharmacopee. Cette synthese a pour but de detailler le role d’EGFR dans la cancerogenese bronchique, d’exposer les principales approches therapeutiques visant a en inhiber l’activite, d’en presenter les marqueurs d’activite ou de resistance et de discuter les principales etudes ayant evalue ces nouveaux traitements.

Objectif de l’etude Depuis 2014, plusieurs essais randomises ont montre la superiorite des inhibiteurs de checkpoint immunitaires, et notamment des anti PD-1, dans le traitement des cancers bronchiques non a petites cellules metastatiques, par rapport a la chimiotherapie. Ces patients recoivent souvent de maniere sequentielle rapprochee ou concomitante du nivolumab, un inhibiteur de PD-1, et une radiotherapie, souvent a visee symptomatique. Neanmoins, meme si les etudes precliniques suggerent une potentielle synergie entre les deux traitements, la tolerance de cette association est meconnue. Materiel et methode Nous avons analyse retrospectivement une large serie de patients atteints d’un cancer bronchique non a petites cellules metastatiques, traites dans trois centres francais et ayant recu une radiotherapie dans les six mois precedents et une injection de nivolumab les trois mois suivant ou en concomitance. Resultats Parmi les 104 patients inclus (37 femmes, 67 hommes, d’âge median 60,3 ans, 67 % d’indices de performance inferieur a 2, 93 % de fumeurs actifs ou sevres) et les 144 cibles irradiees incluses, des effets secondaires ont ete observes chez 62 patients (59,6 %), dont dix souffrant au moins d’une toxicite de grade III-IV. Pour neuf de ces dix patients, cette toxicite severe etait immuno-induite, en rapport avec les injections de nivolumab. Les taux de survie globale a 1 et 2 ans etaient respectivement de 48,8 % et 29,1 % et ceux de survie sans progression de 20,9 % et 10,1 %. Le delai d’administration de la radiotherapie avant ou pendant/apres le nivolumab, n’influencait pas les taux de survie ou la frequence des effets indesirables. La survie sans progression etait significativement plus longue pour les patients souffrant d’effets secondaires induits par le nivolumab (p = 0,038). Conclusion Il s’agit a ce jour de la serie retrospective la plus large evaluant specifiquement l’association de nivolumab et de radiotherapie chez les patients atteints de cancer bronchique non a petites cellules metastatiques. Cette combinaison therapeutique est bien toleree et ne semble pas etre associee a un surcroit d’effets indesirables.

e21077Background: Anti-PD-1 therapy with nivolumab has demonstrated improved overall survival (OS) in patients with non-small-cell-lung cancer (NSCLC). Indeed, since CheckMate 017 and 057 results, ...

Purpose To assess the incremental cost associated with the management of patients with primary non-squamous non-small cell lung cancer (NSCLC) with brain metastases at the time of diagnosis. Methods Data were extracted from the French Hospital medical information database (Programme de Medicalisation des Systemes d’Information (PMSI)). Patients with non-squamous NSCLC were identified through a diagnosis of lung cancer and a prescription of bevacizumab or pemetrexed. All such patients hospitalised with lung cancer for the first time in 2013 and with metastases identified at the first hospitalisation were eligible. Two cohorts were identified, one with brain metastases (group B: n=971) and one with metastases at other sites (group A: n=1529). For each patient, total in-hospital medical resource consumption associated with the initial hospitalisation in 2013 and with any follow-up stays in the following 24 months was documented. Costs were attributed from official French national tariffs and expressed in 2017 euros. Results The mean number of hospitalisations per patient in the 24-moth follow-up period was 17 in group A and 21 in group B. >99% of patients in both groups received chemotherapy. 58% of patients in group B and 13% in group A were managed by radiotherapy. 37% in group B and 24% in group A received palliative care. The associated cost was €2979 per patient-month for patients in group B and €2426 for patients in group A, representing a differential cost of €553 per month. Radiotherapy (+€164/month) and palliative care (+€130/month) were the principal drivers of the incremental cost. Conclusions The presence of brain metastases at the time of diagnosis of non-squamous NSCLC carries a significant burden, and ways of lowering this burden are needed.

Introduction Une maintenance (M) est la strategie habituellement realisee dans le traitement des cancers bronchiques non a petites cellules non epidermoides (CBNPCNE), apres une chimiotherapie d’induction (CT). Le benefice de la switch maintenance apparait plus grand pour les patients stables (MS) apres CT alors que la M de continuation est meilleure pour les patients en reponse objective (RO). Cet essai compare une strategie de M dependant de la reponse au doublet cisplatine (C) gemcitabine (G) : M par G pour les RO et M par pemetrexed (P) pour les MS, vs CP suivie de P, quelle que soit la reponse (RO et MS) apres la CT. Methodes Criteres d’inclusion : âge 18–70 ans, PS 0–1, CBNPCNE de stade IV en premiere ligne, naif de toute chimiotherapie, sans mutation EGFR ou translocation ALK connue, ineligible au bevacizumab. Randomisation 1 :1 entre CG 4 cycles puis M par G si RO et M par P si MS ou CP 4 cycles et M par P si MS ou RO. Objectif principal : survie globale (SG), objectifs secondaires : survie sans progression (SSP), RO, toxicites. Resultats Au total, 932 patients ont ete randomises entre 07/12 et 06/16 (CG : 467, CP : 465). Les caracteristiques des patients etaient homogenes entre les deux groupes. Au total, 255 patients (54,6 %) du groupe CG ont eu une M (G : 142, P : 113) et 274 (58,9 %) du groupe CP. Le nombre median de cycles de M etait de 5 pour CG et 4 pour P. La SG etait de 10,9 mois (m) pour CG vs 10,4 m pour CP ; HR ajuste 0,97 (IC95 % : 0,84–1,13, p = 0,72). La SSP etait de 5,0 m pour CG vs 4,7 m pour CP, HR ajuste 0,96 (IC95 % : 0,84–1,10). La RO apres la CT etait de 5,1 % pour CG vs 33,8 % pour CP. Les toxicites etaient celles attendues pendant la CT d’induction. Pendant la M, les toxicites hematologiques de grade ≥ 3 etaient de 28 % et 31 % des patients pour CG et CP respectivement : neutropenie febrile (2,4 % vs 1,1 %), anemie (9,4 % vs 11,7 %), thrombopenie (6,7 % vs 5,8 %). Aucune toxicite non hematologique de grade ≥ 3 n’etait constatee dans plus de 5 % des cas sauf l’asthenie (3,9 % CG vs 5,1 % CP). Conclusion L’adaptation de la strategie de maintenance a la reponse apres la CT d’induction n’apporte pas de benefice en termes de survie globale ou de survie sans progression.

The patient information and obtaining their consent before any therapeutic constitute a basis for medicine exercise. However, there are situations where the physician may be in default. In that case, concepts of benefit/risk balance, of clear and appropriate information, and of legal liability for medico-surgical staff takes all their magnitude. That was the case in our observation, with a 69 years old patient with history of smoking, presenting a suspicious lung opacity which will require, following an agreement by multidisciplinary meeting, an exploration by thoracotomy despite an acceptable but altered respiratory function, as a result of a post-smoking broncho-emphysema. The non-malignant character of the suspected lesion raise questions about the risks involved, the benefit/risk balance, and the legal risk scopes of the medicosurgical staff as defined in the Cancer programme framework.

The law specifies how a doctor may write a medical certifcate and how a patient or his beneficiaries can obtain his medical records. It's important for a doctor to know this rules. A 56 years old patient was referred to our hospital for pulmonary adenocarcinoma cT2N2M1, the clinical stage was IV. The patient underwent radiotherapy and chemotherapy. During the treatment, the relations with the family were difficult. The patient refuse to accept the doctors tell his son any information and get married with his companion in secret. After patient's death, the son and the wife asked for many medical certificates. The doctors turned down so the son asked for the patient medical records. This observation asks the question of the medical certificates: how and when write them, which are obligatories? Moreover, how should a patient or his beneficiaries obtain medical records?

Resume Introduction Le diagnostic etiologique d'une enteropathie exsudative est parfois difficile. Exceptionnellement, elle peut resulter d'une gene au retour veineux lie a une pericardite chronique constrictive qui peut etre paucisymptomatique. Exegese Nous presentons le cas d'une enteropathie exsudative ayant revele une pericardite chronique constrictive idiopathique. Conclusion Il faut savoir rechercher une pericardite chronique constrictive devant toute enteropathie exsudative inexpliquee. L'echocardiographie pouvant etre normale, le scanner thoracique ou l'imagerie par resonance magnetique nucleaire cardiaque puis le catheterisme cardiaque droit de confirmation doivent etre proposes en seconde intention devant toute enteropathie exsudative inexpliquee.

Background HER2 mutations have been identified as oncogenic drivers in lung cancers and are found in 1–2% of lung adenocarcinomas. There is, to date, no standard of care for these patients. We thus aim to study the therapeutic outcomes of patients harboring HER2 mutations and establish the efficacy of various drug regimens. Patients and methods This retrospective cohort study in European centers assessed patients with advanced non-small-cell lung cancer (NSCLC), a known HER2 exon-20 insertion, treated with chemotherapy and/or HER2-targeted drugs. Results We identified 101 eligible patients from 38 centers: median age 61 years (range: 30–87), 62.4% women, 60.4% never-smokers. All tumors were adenocarcinomas. Concomitant EGFR mutations, ALK translocations, and ROS translocations were observed in 5, 1, and 1 patients, respectively. The median number of treatment lines was 3 (range: 1–11). The median overall survival was 24 months. Overall response rate (ORR) and the median progression-free survival (PFS) with conventional chemotherapy (excluding targeted therapies) were 43.5% and 6 months in first-line (n = 93), and 10% and 4.3 months in second-line (n = 52) therapies. Sixty-five patients received HER2-targeted therapies: trastuzumab=57, neratinib=14, afatinib=9, lapatinib=5, T-DM1 = 1. ORR was 50.9% and PFS was 4.8 months with trastuzumab or T-DM1. Conclusion This series shows the chemosensitivity of HER2-driven NSCLC, and the potential interest of HER2-targeted agents. Our results should help to define the best therapeutic strategy for these patients and to orient future clinical trials.

Introduction: Treatment of Non-Small-Cell Lung Cancer (NSCLC) harboring an Epidermal Growth Factor Receptor (EGFR) mutation relies on EGFR tyrosine kinase inhibitors (TKI). However all patients treated with EGFR TKI eventually present tumor progression, because of mechanisms of resistance such as amplification of the met receptor gene. There is currently no data on cellular phenotypic changes of tumor cells induced by met amplification in this context. Objective: to determine whether met amplification triggers a more aggressive tumor phenotype in TKI resistant EGFR-mutated NSCLC. Methods: The proliferation and migration capacities were studied in HCC827 cell line, derived from a mutated EGFR NSCLC, and his daughter cell line HCC827 GR6 which is resistant to EGFR TKI through amplification of the met gene. Tumor growth of both strains was analyzed in a mouse model of ectopic xenograft. Results: in vitro, we found a similar proliferation in the two cell lines and a significant increase in migration and anchorage-independant growth in the met amplified cell line. Treatment with PHA-665752, a MET TKI, significantly reduced the migration advantage of met amplified cells. In vivo, we observed a significant increase in tumor growth with the met amplified cell line. In vivo results regarding the metastatic potential of the two cell lines and the impact of EGFR and MET TKI will be presented during the meeting. Conclusion: met amplification confers an aggressive phenotype to TKI resistant EGFR-mutated NSCLC. These results pave the way for an early use of MET inhibitors in association with EGFR TKI in order to prevent emergence of an aggressive tumor clone.

International audience; Various solid tumors including lung or gastric carcinomas display aberrant activation of the Met receptor which correlates with aggressive phenotypes and poor prognosis. Although downstream signaling of Met is well described, its integration at the transcriptional level is poorly understood. We demonstrate here that in cancer cells harboring met gene amplification, inhibition of Met activity with tyrosine kinase inhibitors or specific siRNA drastically decreased expression of ETV1, ETV4 and ETV5, three transcription factors constituting the PEA3 subgroup of the ETS family, while expression of the other members of the family were less or not affected. Similar link between Met activity and PEA3 factors expression was found in lung cancer cells displaying resistance to EGFR targeted therapy involving met gene amplification. Using silencing experiments, we demonstrate that the PEA3 factors are required for efficient migration and invasion mediated by Met, while other biological responses such as proliferation or unanchored growth remain unaffected. PEA3 overexpression or silencing revealed that they participated in the regulation of the MMP2 target gene involved in extracellular matrix remodeling. Our results demonstrated that PEA3-subgroup transcription factors are key players of the Met signaling integration involved in regulation of migration and invasiveness.

Resume Les resultats de la chirurgie seule ou associee a un traitement adjuvant, chimio- et/ou radiotherapie dans la prise en charge des cancers bronchiques non a petites cellules (CBNPC) stade III resecables sont decevants, avec des taux de survie a 5 ans generalement inferieurs a 20 % et de nombreuses recidives locales et a distance. Ils ont justifie de nombreuses etudes de phase II qui ont montre la faisabilite de la chimiotherapie et de la chimioradiotherapie neo-adjuvante avec des taux de reponses eleves et une toxicite acceptable. Les trois etudes de phase III de chimiotherapie d’induction ont abouti a des resultats contradictoires, deux d’entre elles ne portaient que sur de faibles effectifs et presentaient des biais methodologiques. Quant a la chimioradiotherapie preoperatoire, il n’existe pas actuellement d’essai de phase III publie, les etudes de phase II recentes privilegient un mode concomitant avec irradiation bifractionnee. Les nouveaux agents de therapeutique ciblee n’ont pour l’instant pas d’indication dans ce domaine. Dans le cas particulier des tumeurs resecables de l’apex envahissant la paroi, dites de Pancoast, la chimioradiotherapie neo-adjuvante suivie d’une resection chirurgicale est devenu le traitement recommande. La place de la chimiotherapie, de la radiotherapie et meme de la chirurgie dans le traitement des CBNPC stade III resecables reste a definir et l’inclusion des patients dans des essais cliniques randomises est conseillee.

Resume Introduction. – Les maladies inflammatoires chroniques de l’intestin se compliquent dans 10 a 30 % des cas d’anomalies hepatobiliaires. Parmi celles-ci, la steatose hepatique et les lithiases biliaires sont les plus frequentes dans la maladie de Crohn. A l’inverse, la peliose hepatique n’est qu’exceptionnellement decrite en association avec les maladies inflammatoires chroniques de l’intestin. Nous decrivons un cas de peliose hepatique compliquant une maladie de Crohn jusqu’alors meconnue. Exegese. – Une jeune femme âgee de 24 ans consultait pour une hepatomegalie et une alteration de l’etat general. L’interrogatoire retrouvait une diarrhee depuis trois mois et un episode de rectorragie. Il existait une lesion aphtoide de la langue. Le transit du grele mettait en evidence un aspect typique d’ileite terminale evocateur de maladie de Crohn. Le foie etait morphologiquement heterogene. La ponction–biopsie hepatique permettait de poser le diagnostic de peliose hepatique pour laquelle les autres causes etaient ecartees. Il s’agissait donc d’une peliose hepatique decouverte devant une hepatomegalie et associee a une maladie de Crohn meconnue. Conclusion. – L’association entre une maladie de Crohn et une peliose hepatique n’a ete qu‘exceptionnellement decrite. Il ne s’agit pas a priori d’un facteur de gravite des maladies inflammatoires chroniques de l’intestin. La signification physiopathologique de cette association est inconnue.

9003 Background: Benefit coming from maintenance treatment appears greater for switch maintenance in pts with disease stabilization (SD) while it might be larger for continuation maintenance in pts with objective response (OR). This study assessed a maintenance strategy conditioned by response to cisplatin-gemcitabine (CG): continuation maintenance with G for pts with OR and switch maintenance with pemetrexed (P) for pts with SD compared with a control arm using P continuation maintenance following cisplatin-pemetrexed (CP) induction regimen. Methods: Eligibility criteria included age 18-70 years, PS of 0-1, untreated stage IV NSQ NSCLC without EGFR mutation or ALK rearrangement, ineligibility to bevacizumab. Pts were randomized 1:1 to receive either experimental CG arm: CG (4 cycles) followed by G maintenance in case of OR followed by second-line P or switch maintenance with P for pts with SD, or standard CP arm: 4 cycles CP induction regimen followed by maintenance P. Overall survival (OS) was the primary endpoint; secondary endpoints included PFS, response rate and safety. Results: Between Jul 2012 and Jun 2016, 932 pts were randomized (CG: 467, CP: 465). Pts characteristics were balanced between the arms. 255 pts (54.6%) in the CG arm received maintenance treatment (G: 142, P: 113) while 274 pts (58.9%) received P maintenance in the CP arm. Median number of maintenance cycles was 5 for G and 4 for P in both arms. The OS adjusted HR was 0.97 (95% CI 0.84, 1.13; p=0.72); median OS: 10.9m CG vs. 10.4m CP. The HR for PFS was 0.96 (95% CI 0.84, 1.10; p=0.56); median PFS: 5.0m CG vs. 4.7m CP. Safety profile was as expected during induction chemotherapy. During maintenance, grade ≥3 hematological AEs occurred in 28% and 31% of pts in CG and CP, respectively, with febrile neutropenia (2.4% vs. 1.1%), anemia (9.4% vs. 11.7%), thrombocytopenia (6.7% vs. 5.8%). No grade ≥3 non-hematological AEs occurred in >5% of pts except for asthenia (3.9% CG vs. 5.1% CP). Conclusions: Adapting maintenance strategy according to response to induction chemotherapy does not improve patient outcome. Clinical trial information: NCT01631136.

Introduction: The determination of epidermal growth factor receptor (EGFR) mutation status is required to guide systemic treatment in patients with non small cell lung cancer (NSCLC). Patients and methods: In this retrospective cohort, we evaluated EGFR mutational status including the resistance-associated mutation T790M using SNapShot technology combined with fragment analysis, RT PCR or NGS in the cerebrospinal fluid (CSF) of NSCLC patients diagnosed with leptomeningeal metastasis (LM) between 2012 and 2016. Results: Among 23 patients with LM (11 females), an EGFR mutation was identified in the primary tumor in 13 cases (exon 19, n=7; exon 21, n=6) at diagnosis. EGFR status was not determined in 4 cases and not interpretable in 3 cases. Other mutations included 1 KRAS mutation, 1 ALK rearrangement, and 1 HER2 mutation. At the time of molecular CSF analysis, malignant cells were observed in the CSF of 23 patients. CSF molecular analysis results were obtained for all patients. The same mutation was found in the CSF in all 13 patients with initially confirmed EGFR-mutant tumors. A L858R mutation on exon 21 was identified in the CSF in one patient where the molecular analysis of the primary tumor was not interpretable. An EGFR T790M mutation was detected in the CSF of one patient without interpretable EGFR status in the primary tumor. In another patient, a EGFR mutation was detected where no malignant cells were observed using standard cytology. Molecular blood analyses were also performed at LM diagnosis in 4 patients, with a concordance between primary tumors and CSF analysis for all 4 patients (deletion exon 19=3, no EGFR mutation=1). Initial treatments for LM from EGFR-mutant NSCLC included first- or second-generation tyrosine kinase inhibitors (TKI, n=11), chemotherapy combined with targeted therapy (n=4), chemotherapy alone (n=1), immunotherapy (n=1) and intra-CSF liposomal cytarabine combined with systemic treatment (n=9) or alone (n=2), or intraCSF MTX combined with systemic treatment (n=1). Median overall was 4.9 months (range, 0.2-39.5) in the whole population and 6 months (range, 0.2-39.5) in patients with EGFR-mutant tumors. Conclusion: A very strong concordance of EGFR mutational status (100%) was observed between primary tumor and CSF in patients with LM from NSCLC. New informations on the molecular status were obtained for 2/23 patients. These results confirm the feasibility of detection of mutations in the CSF.

536 Background: The aim of EDIFICE surveys is to improve insight into the behavior of the French population with regard to cancer prevention and participation in screening programs. The colorectal cancer (CRC) screening program is in place and targets the 50-74-yr age group. CRC prevention also relies on increased awareness of known risk factors (behavioral [BRF] or non-behavioral [NBRF]). This analysis focuses on awareness of CRC risk factors among the lay population and physicians. Methods: The 4th nationwide observational survey was conducted by phone interviews using the quota method. A representative sample of 1463 individuals with no history of cancer (age, 40-75 yrs) was interviewed between June 12 and July 10, 2014. A mirror survey on a representative sample of 301 physicians was conducted between July 9 and August 8, 2014. Interviewees were asked to cite the five main RF for CRC. Results: Heredity/family history of CRC was widely cited by physicians but far less by laypersons (LP) (95.3% vs. 26.1%, P < 0.01). Digestive disorders, age, polyps and Crohn’s disease were also cited as NBRF by 38.2%, 22.9%, 15.3% and 12.3% of physicians, respectively. In comparison, these RF were very rarely cited by LP (5.4%, 1.5%, 1.7% and 0.1%, respectively, P < 0.01). Unhealthy-lifestyle RF were cited by 86.4% and 52.7% of physicians and LP, respectively (P < 0.01): poor eating habits, ranked first for both physicians and LP (80.1 vs 46.8%, P < 0.01), including unbalanced or excessively rich diet (52.8% vs. 41.2%, P < 0.01) and excessive quantities of red meat (12.6% vs. 2.2%, P < 0.01). Among unhealthy-lifestyle RF, after poor eating habits, physicians cited first tobacco (24.3%), then alcohol (19.9%), and lack of exercise (14.6%) as other BRF. These were cited by 12.2% (P < 0.01), 16.0% (NS) and 4.7% (P < 0.01) of LP, respectively. Overweight/obesity was cited by 19.6% of physicians but by only 1.8% of LP. Conclusions: Overall, there is a lower level of awareness of CRC risk factors in lay persons than in physicians. Physicians are generally aware that heredity/family history and unhealthy lifestyle are the major RF for CRC, in line with the widely recognized RF. In contrast, lay persons rank BRF highest, and notably those related to poor eating habits.

Introduction Le syndrome d’apnees–hypopnees obstructives du sommeil (SAHOS) est une maladie frequente qui a un impact sur de nombreuses pathologies. L’incidence et le risque de mortalite par cancer seraient influences, d’apres des etudes cliniques recentes, par le SAHOS. Aucune donnee n’est disponible a ce jour pour le cancer bronchopulmonaire. Methodes De juin 2014 a juin 2015, nous avons mene une etude prospective, observationnelle et bicentrique, proposant aux patients atteints de cancer bronchopulmonaire, un depistage de SAHOS par l’intermediaire d’un autoquestionnaire. En cas de suspicion clinique de SAHOS, les patients etaient invites a confirmer ce diagnostic, dans un premier temps, par la realisation en ambulatoire, d’un APNEALINK AIR puis, en fonction des resultats, d’une polygraphie ventilatoire ou d’une polysomnographie en laboratoire de sommeil. Resultats Cent treize patients ont ete inclus et ont repondu a l’autoquestionnaire. Quarante-six pour cent des patients jugent leur sommeil de mauvaise qualite. Le questionnaire est positif dans 63 % des cas. Vingt-quatre patients ont beneficie d’un APNEALINK AIR qui s’est avere positif chez 18 patients. Au total 6 patients ont eu un diagnostic de SAHOS par enregistrement en laboratoire de sommeil et 9 patients etaient deja connus porteur d’un SAHOS severe lors de l’inclusion. La survie globale a 2 ans est inferieure chez les patients avec un questionnaire positif (56 % versus 84 %), cependant de maniere non significative (p = 0,06). Le faible taux de participation des patients aux examens de confirmation diagnostique ne nous a pas permis de conclure sur l’impact reel du SAHOS sur le pronostic du cancer bronchique. Conclusion Les patients atteints de cancer bronchique ont, dans notre travail, un sommeil de mauvaise qualite avec une suspicion clinique forte de SAHOS. L’existence de symptomes compatibles avec des troubles respiratoires du sommeil pourrait etre associee a une plus grande severite de la maladie cancereuse.