Search

Supplementary Table S1: Best response rates for primary tumors and metastases in 67 patients (ITT population) treated with bevacizumab plus paclitaxel and carboplatin

Appendix Methods and Materials, Tables 1-4, Figures 1-3. Appendix Table 1: Characteristics of patients at baseline Appendix Table 2: Best response rates for primary tumors and metastases in 24 patients treated with second-line bevacizumab plus erlotinib Appendix Table 3: PFS, OS, and response rates according to EGFR mutation status in 24 patients treated with second-line bevacizumab plus erlotinib Appendix Table 4: Overview of AEs in 24 patients treated with second-line bevacizumab plus erlotinib Appendix Figure 1. Response rates for patients treated with second-line bevacizumab plus erlotinib. Appendix Figure 2. Waterfall plots of best overall response for patients treated with second-line bevacizumab plus erlotinib. Appendix Figure 3. Kaplan-Meier curves for second-line treatment with bevacizumab plus erlotinib.

Purpose: The phase II prospective, noncomparative BRAIN study (NCT00800202) investigated efficacy and safety of bevacizumab in chemotherapy-naïve or pretreated patients with non–small cell lung cancer (NSCLC) and asymptomatic untreated brain metastases to provide data in this previously unexplored subgroup.Experimental Design: Patients with stage IV nonsquamous NSCLC, Eastern Cooperative Oncology Group performance status 0–1, and untreated, asymptomatic brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin (area under the curve ×6) and paclitaxel (200 mg/m2) every 3 weeks (B + CP), or second-line bevacizumab plus erlotinib (150 mg/d; B + E). Six-month progression-free survival (PFS) was the primary endpoint. The trial could be stopped if there were more than three (B + CP) or more than two (B + E) intracranial hemorrhages.Results: In first-line B + CP cohort (n = 67), 6-month PFS rate was 56.5% with a median PFS of 6.7 months [95% confidence interval (CI), 5.7–7.1] and median overall survival (OS) of 16.0 months. Investigator-assessed overall response rate (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions. Because of low enrolment (n = 24), efficacy results for the second-line B + E cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3 months (95% CI, 3.0–8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse events were comparable with previous trials of bevacizumab. One grade 1 intracranial hemorrhage occurred and resolved without sequelae.Conclusions: The BRAIN study demonstrates encouraging efficacy and acceptable safety of bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and asymptomatic, untreated brain metastases. Clin Cancer Res; 21(8); 1896–903. ©2015 AACR.

BackgroundSurvivors of severe-to-critical coronavirus disease 2019 (COVID-19) may have functional impairment, radiological sequelae and persistent symptoms requiring prolonged follow-up. This pragmatic study aimed to describe their clinical follow-up and determine their respiratory recovery trajectories, and the factors that could influence them and their health-related quality of life.MethodsAdults hospitalised for severe-to-critical COVID-19 were evaluated at 3 months and up to 12 months post-hospital discharge in this prospective, multicentre, cohort study.ResultsAmong 485 enrolled participants, 293 (60%) were reassessed at 6 months and 163 (35%) at 12 months; 89 (51%) and 47 (27%) of the 173 participants initially managed with standard oxygen were reassessed at 6 and 12 months, respectively. At 3 months, 34%, 70% and 56% of the participants had a restrictive lung defect, impaired diffusing capacity of the lung for carbon monoxide (DLCO) and significant radiological sequelae, respectively. During extended follow-up, bothDLCOand forced vital capacity percentage predicted increased by means of +4 points at 6 months and +6 points at 12 months. Sex, body mass index, chronic respiratory disease, immunosuppression, pneumonia extent or corticosteroid use during acute COVID-19 and prolonged invasive mechanical ventilation (IMV) were associated withDLCOat 3 months, but not its trajectory thereafter. Among 475 (98%) patients with at least one chest computed tomography scan during follow-up, 196 (41%) had significant sequelae on their last images.ConclusionsAlthough pulmonary function and radiological abnormalities improved up to 1 year post-acute COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up.

Objectives Immunohistochemistry (IHC) is considered as a screening method for ALK rearrangement thanks to its excellent sensitivity. Strong marking on immunohistochemistry give the go-ahead to start ALK tyrosine kinase inhibitors (ALK TKI). Lack of therapeutic response may then lead to the suspicion of molecular alterations other than ALK rearrangements. Methods We present a patient with strong ALK and PD-L1 positive IHC expression lung sarcomatoid carcinoma with initial life-threatening disease progression after beginning ALK TKI. We also review the literature to summarize ALK amplification clinical features and therapeutic management in lung cancers. Results Fluorescence in situ Hybridization (FISH) revealed ALK amplification on the initial anatomopathological samples. Lack of ALK rearrangement and strong PD-L1 positive IHC expression led to the initiation of immune checkpoint inhibitor (ICI) as a second line of treatment, with an excellent response. Conclusion We demonstrated that IHC positive test, in these cases, must be interpreted with caution. FISH analysis has to be recommended to confirm IHC results in case of unusual phenotype, such as smoker or lung cancer other than adenocarcinoma. Although lung carcinoma with ALK rearrangement seems to be not sensitive to ICI, further investigations should be conducted on other types of ALK molecular alterations. ALK amplifications, as observed in the present case, should not be an impediment to taking into account the PD-L1 marking for the initiation of treatment by immunotherapy.

Resume Le cancer bronchique (CB) est la premiere cause de mortalite par cancer dans le monde et en France avec plus de 30 000 deces par an. L’arret du tabac est la mesure la plus efficace pour limiter l’epidemie du CB, mais est aussi un element important dans la prise en charge des patients atteints de CB quel que soit le stade. Dans les cancers localises, la poursuite du tabac est associee a une diminution de la survie par augmentation du risque de recidive et de developper un deuxieme cancer. En periode peri-operatoire, le sevrage tabagique permet de limiter les complications infectieuses et la duree d’hospitalisation. Quel que soit le stade du cancer, le sevrage permet d’ameliorer la dyspnee, l’appetit ainsi que de reduire l’asthenie ; ceci se traduit par une amelioration de la qualite de vie. Le tabac entraine une addiction forte avec une dependance physique, psychologique et comportementale. La substitution nicotinique et la varenicline sont indiquees en cas de dependance physique a la nicotine. La cigarette electronique peut etre consideree comme un outil d’aide au sevrage tabagique. Les therapies cognitives et comportementales permettent d’aider le fumeur a se debarrasser de son comportement, et elles ont une place dans la prevention de la rechute. © 2020 SPLF. Publie par Elsevier Masson SAS. Tous droits reserves.

International audience; The setting up of an advanced practice nursing activity to monitor patients with severe or very severe pneumonia associated with Severe Acute Respiratory Syndrome Coronavirus 2, is a reponse to the population's new health care needs and a massive influx of patients. The skills of the advanced practice nurse are mobilised in this context in order to carry out prevention missions and screening for potential sequelae which could lead to chronic respiratory failure.; L'IPA dans le suivi respiratoire post-Covid-19 Résumé : La mise en place d'une activité de pratique avancée infirmière pour le suivi des patients atteints de formes sévères ou très sévères de pneumonie à severe acute respiratory syndrome coronavirus 2 permet de répondre aux besoins de santé nouveaux d'une population et à l'afflux

Resume Ces dernieres annees ont vu l’emergence d’une nouvelle classification histologique des cancers pulmonaires integrant des donnees moleculaires. Des alterations moleculaires agissant comme des drivers oncogeniques et conferant une sensibilite a des traitements cibles sont recherchees dans les CBNPC diagnostiques a un stade avance. Ces therapies adaptees transforment le pronostic des patients. Si certaines cibles sont bien connues comme EGFR, KRAS, ALK, ROS, HER2 et BRAF mais pas toujours associees a un succes therapeutique (KRAS), d’autres nombreuses mais peu frequentes font l’objet de tests recents comme pour la voie MET (mutation de l’exon 14 et amplification), et les rearrangements de RET, NRG1, et NTRK. S’il existe certaines correspondances cliniques, morphologiques et phenotypiques avec le type d’alterations moleculaires, celles-ci n’ont que valeur d’orientation et ces tests doivent etre pratiques chez tous les patients presentant un CBNPC non epidermoide de stade avance. Le carcinome epidermoide reste toujours le parent pauvre de cette strategie moleculaire, mais est le candidat des therapies immunitaires meme si le biomarqueur predictif : molecule, cellule ou signature immunitaire, ou charge mutationnelle n’est pas defini. Enfin, nombre d’entites rares caracterisees par une anomalie moleculaire specifique diagnostique sont decrites dans le thorax, parfois communes a d’autres organes, mais ne beneficient pas d’un traitement cible.

Resume En France, le nombre de deces lies au tabac est estime a 73 000/an, dont 44 000 par cancer et plus de 20 000 par cancer bronchique (CB). L’arret du tabac est la mesure la plus efficace pour limiter l’epidemie du CB mais est aussi un element important dans la prise en charge des patients atteints de CB quel que soit le stade. Dans les cancers localises, la poursuite du tabac est associee a une diminution de la survie par augmentation du risque de recidive et de developper un deuxieme cancer. En periode peri-operatoire, le sevrage tabagique permet de limiter les complications infectieuses et la duree d’hospitalisation. Quel que soit le stade du cancer, le sevrage permet d’ameliorer la dyspnee, l’appetit et de reduire l’asthenie ; ceci se traduit par une amelioration de la qualite de vie. Le tabac entraine une addiction forte avec une dependance physique, psychologique et comportementale. La substitution nicotinique et la varenicline sont indiquees en cas de dependance physique a la nicotine. Les therapies cognitives - comportementales permettent d’aider le fumeur a se debarrasser de son comportement, ont une place dans la prevention de la rechute.

The setting up of an advanced practice nursing activity to monitor patients with severe or very severe pneumonia associated with Severe Acute Respiratory Syndrome Coronavirus 2, is a reponse to the population's new health care needs and a massive influx of patients. The skills of the advanced practice nurse are mobilised in this context in order to carry out prevention missions and screening for potential sequelae which could lead to chronic respiratory failure.

Risk factors and prevention of lung cancer. In France, lung cancer is the leading cause of death from cancer with more than 30,000 deaths per year. The vast majority (85%) of lung cancer are due to tobacco and the duration of smoking has a greater impact than the amount smoked. Passive smoking increases the risk of lung cancer and is responsible for around 25% of lung cancers in non-smokers in France. The risk of lung cancer linked to cannabis smoke hasn't been demonstrated, but is suspected. Other carcinogens found in certain workplaces, such as asbestos, or in the environment, such as radon in granite soils and urban air pollution, increase the risk of lung cancer. The maximum benefit on lung cancer mortality reduction should be obtained by combining smoking cessation and lung cancer screening by chest CT. Lung cancer screening has shown its effectiveness, but is currently not recommended in France. Measures to promote smoking cessation are known and include public health measures to de-normalize tobacco (neutral packaging, ban on advertising, significant increase in its price) and treatments that have been shown to be effective in smoking cessation: nicotine replacement therapy, varenicline and cognitive behavioral therapy.Facteurs de risque et prévention des cancers du poumon. En France, le cancer du poumon est la première cause de mortalité par cancer, avec plus de 30 000 décès par an. La très grande majorité (85 %) des cancers du poumon sont dus au tabac. La durée du tabagisme a un impact plus important que la quantité fumée. Le tabagisme passif augmente aussi le risque de cancer du poumon et serait responsable d’environ 25 % des cancers du non-fumeur en France. Le risque de cancer du poumon lié à la fumée de cannabis n’est à ce jour pas démontré mais est suspecté. D’autres cancérogènes trouvés dans certains lieux de travail, tels que l’amiante, ou dans l’environnement, tel que le radon des sols granitiques, et la pollution de l’air des villes peuvent augmenter le risque de cancer du poumon. Le bénéfice maximal sur la réduction de la mortalité par cancer du poumon pourrait être observé par le sevrage tabagique et le dépistage par scanner thoracique. Le dépistage a montré son efficacité, mais n’est pas à ce jour recommandé en France. Les mesures pour favoriser le sevrage tabagique comportent les mesures de santé publique pour dénormaliser le tabac (paquet neutre, interdiction de la publicité, augmentation importante de son prix) et les traitements qui ont démontré leur efficacité dans le sevrage tabagique : la substitution nicotinique, la varénicline et les thérapies cognitives et comportementales.

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.

International audience

Purpose The aim of this study was to compare the effectiveness of chest X-ray to that of thoracic computed tomography (CT) for the detection of the causes of secondary spontaneous pneumothorax (SP). Methods A prospective cohort of patients with SP was studied. All chest X-ray and CT examinations of the patients were reviewed retrospectively by an expert radiologist blinded to clinical data. The concordance between the CT examination and chest X-ray was assessed using the Cohen Kappa coefficient (κ), based on a bootstrap resampling method. Results A total of 105 patients with SP were included. There were 78 men and 27 women, with a mean age of 34.5 years ± 14.2 (SD) (range: 16–87 years). Of these, 44/105 (41%) patients had primary SP and 61/105 (59%) had secondary SP due to emphysema (47/61; 77%), tuberculosis (3/61, 5%), lymphangioleiomyomatosis (3/61; 5%), lung cancer (2/61, 3%) or other causes (6/61; 10%). Apart from pneumothorax, CT showed abnormal findings in 85/105 (81%) patients and chest X-ray in 29/105 (28%). Clinically relevant abnormalities were detected on 62/105 (59%) CT examinations. The concordance between chest X-ray and CT was fair for detecting emphysema (κ = 0.39; 95% CI: 0.2420–0.55), moderate for a mass or nodule (κ = 0.60; 95% CI: 0.28–0.90), fair for alveolar opacities (κ = 0.39; 95% CI: −0.02–1.00), and slight for interstitial syndrome (κ = 0.20; 95% CI: −0.02–0.85). Conclusion Chest X-ray is not sufficient for detecting the cause of secondary SP. As the detection of the cause of secondary SP may alter the therapeutic approach and long-term follow-up in patients with SP, the usefulness of a systematic CT examination should be assessed in a prospective trial.

Purpose To compare imaging findings on thoracic computed tomography (CT) examination in patients with primary spontaneous pneumothorax (SP), depending on their tobacco and/or cannabis consumption. Materials and methods A total of 83 patients who had thoracic CT for primary SP were prospectively included. There were 65 men and 18 women with a median age of 33 years (IQR: 27; 44 years). The patients were further categorized into three groups according to their smoking habits. Thirteen patients were non-smokers, 38 were tobacco only smokers and 32 were tobacco and cannabis smokers. CT examinations were retrospectively reviewed for the presence of blebs, centrilobular and paraseptal emphysema and lung nodules in each group for comparison. Results Emphysema was detected in 43/85 patients (51.8%), including 1/13 patients (7.7%) in the non-smoking group, 19/38 patients (50%) in the tobacco only group and 23/32 patients (71.9%) in the tobacco and cannabis smokers, with no difference between tobacco only and tobacco and cannabis smokers. No differences in type and location of emphysema was found between tobacco only and tobacco and cannabis smokers. Tobacco and cannabis smokers with emphysema were significantly younger than tobacco only smokers with emphysema (35 vs. 46 years, respectively) (P = 0.009). Conclusion The prevalence of emphysema visible on CT is not different between tobacco and tobacco/cannabis smokers, however, it occurs at a younger age in tobacco and cannabis smokers. This result suggests that cannabis, when added to tobacco, may lead to emphysema at a younger age.

Introduction Immune checkpoint inhibitors (ICIs) have improved cancer prognosis but have not been evaluated specifically in sarcomatoid carcinoma (SC), a rare lung cancer subtype with poor prognosis. As such, our study sought to retrospectively assess the efficacy of ICI in SC. Methods All consecutive patients with centrally confirmed SC treated using ICI as a second-line treatment or beyond between 2011 and 2017 were enrolled. Programmed death-ligand 1 (PD-L1) tumor expression was assessed using immunohistochemistry (SP263 clone) and the tumor mutational burden (TMB) with the Foundation One panel. TMB was considered high if it was greater than or equal to 10 mutations per megabase. Results Overall, 37 patients with SC were evaluated, predominantly men (73%) with a median age of 63.2 years (36.8–79.7) and who were current or former smokers (94.6%). Immunotherapy (nivolumab, 86.5% of cases) was given as a second-line treatment in 54% of the patients and as third-line treatment or beyond in 46% of the patients. The objective response rate was 40.5% and disease control rate was 64.8%, regardless of PD-L1 status. Median overall survival was 12.7 months (range: 0.3–45.7). One-third of patients exhibited early progression. The median PD-L1 expression was 70% (0–100). There was a trend toward higher PD-L1 expression in responsive diseases, with an objective response rate of 58.8% in patients with PD-L1+ and 0% in the one patient with PD-L1- (p = 0.44). The median TMB was 18 (4–39) mutations per megabase, with 87.5% of the cases displaying a high TMB. There was a trend toward higher TMB in responders versus stable or progressive diseases (p = 0.2). Conclusions Patients with SC exhibited high response rates and prolonged overall survival under ICI treatment. These data support the prospective investigation of ICI in patients with SC who are under first-line treatment.

Smoking is a public health issue, especially during the perioperative period. Tobacco increases the risk of hospital mortality by 20% and major postoperative complications by 40%. Active smoking is associated with respiratory complications particularly bronchospasm and pneumonia, but also all surgical complications as scar infections, local thrombosis, suture release and delayed bone healing. The perioperative period is an opportunity to stop smoking. Smoking cessation should always be recommended, regardless of the surgery and the date of intervention. All health professionals, doctors, surgeons, anesthetists, but also nurses and physiotherapists, must inform smokers of the benefits of stopping smoking, offer them a dedicated support and a personalized follow-up. Tobacco consultation and the prescription of nicotine replacement increase the rate of smoking cessation. Stopping smoking reduces perioperative complications and is associated with health benefits that increase with time.

Objective In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN). Methods All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24. Results Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms. Conclusion Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate.

Introduction Les consequences a long terme des formes severes de pneumonie a SARS-CoV-2 (COVID-19) restent meconnues mais le risque de sequelles pulmonaires, de handicap fonctionnel, notamment respiratoire, d’impact psychologique et d’alteration de la qualite de vie des patients semble indeniable. Methodes RE 2 COVERI est une etude de cohorte observationnelle multicentrique (14 centres) francaise visant a inclure 625 participants. Les criteres d’inclusion sont: âge ≥ 18 ans; PCR SARS-CoV-2 positive ou TDM typique de COVID-19 au diagnostic; infection COVID-19 severe (hospitalisation ≥ 7 jours et oxygenotherapie ≥ 3L/min) ou tres severe (SDRA necessitant le recours a la ventilation mecanique pendant au moins 48 h). L’objectif principal de l’etude est de determiner la trajectoire de recuperation de la fonction respiratoire (spirometrie, plethysmographie, diffusion du monoxyde de carbone) des pneumonies COVID-19 severes ou tres severes (evaluation a M3, M6 et M12). Les objectifs secondaires sont de: determiner la trajectoire de recuperation et la proportion de patients presentant des anomalies en termes de capacite d’exercice (test de marche, test du lever de chaise), de lesions pulmonaires (scanner thoracique) et de force musculaire (hand grip et pinch test; mesure de la force des muscles respiratoires); determiner les relations entre les alterations fonctionnelles, la capacite d’exercice et l’etendue initiale des lesions; evaluer la dyspnee et les autres symptomes residuels, la fatigue, l’anxiete et la depression, le stress post-traumatique et l’impact sur la qualite de vie; comparer les alterations fonctionnelles et de la capacite d’exercice selon la severite clinique initiale, en tenant compte de l’impact des comorbidites et des therapeutiques et interventions proposees, tant initialement que secondairement; evaluer la consommation de soins de sante chez les patients severes ou tres severes, en mettant l’accent sur l’utilisation des soins de rehabilitation. Cette etude a recu un soutien financier de la Fondation du Souffle dans le cadre de l’appel a projet “SARSCohorte-Covid2020”. Resultats Les resultats preliminaires de cette etude (evaluation a M3 et M6) seront presentes lors du congres. Conclusion Nos resultats devraient permettre de preciser les facteurs influencant la recuperation a distance d’une forme severe a tres severe de pneumonie a SARS-CoV-2 et de preciser quels patients justifient d’une attention et d’un suivi particuliers.

Introduction Le Pembrolizumab est indique dans le cancer bronchique non a petites cellules (CBNPC) en 1re ligne pour les tumeurs exprimant PD-L1 ≥ 50 %. Le taux de reponse etait de 45 % dans l’essai d’enregistrement [1] . Les enjeux medico-economiques de la place de l’immunotherapie sont importants. L’objectif de notre etude est de rechercher des facteurs predictifs cliniques, biologiques, histologiques, moleculaires et radiologiques de reponse au Pembrolizumab en 1re ligne dans les CBNPC. Methodes Etude retrospective monocentrique incluant 65 patients ayant recu du Pembrolizumab en 1re ligne entre aout 2017 et octobre 2019. Le critere de jugement principal etait la reponse au Pembrolizumab a la premiere evaluation. Les criteres de jugement secondaires etaient la survie sans progression (SSP) et la survie globale (SG). Resultats Parmi les 65 patients inclus, 36 (55,3 %) presentaient une reponse partielle ou stabilite et 9 (13,8 %) etaient decedes a la 1re evaluation. La mediane de suivi etait de 5,8 mois (3 jours–28,6 mois). La mediane de SSP etait de 3,6 mois (IC95 % 2,03–5,73) et celle de SG etait de 7,46 mois (IC95 % 4,73–13,5). En analyse multivariee, le facteur predictif de reponse etait le PS a 0/1 [Odd Ratio (OR) 0,37 (Intervalle de confiance (IC) 95 % 0,03–1,00) : Variable Importance (VI) = 0,94]. Les facteurs predictifs de non reponse etaient: stade IV [OR 3,49 (IC95 % 1,00–53,05) : VI = 0,96], CRP > 50 mg/l [OR 1,20 (IC95 % 0,97–14,43) : VI = 0,91], monocytes > 650/mm3 [OR 1,87 (IC95 % 1,00–18,25) : VI = 0,83], NLR ≥ 5 [OR 1,49 (IC95 % 0,95–10,17) : VI = 0,78], mutation KRAS [OR 1,13 (IC95 % 0,93–7,14) : VI = 0,82], nombre de sites metastatiques > 2 [OR 1,65 (IC95 % 1,00–17,31) : VI = 0,82] et un RECIST important [OR1,04 (IC95 % 1,00–1,32) : VI = 0,77]. De meme pour la SSP et la SG, le facteur de bon pronostic etait le PS 0/1, les facteurs de mauvais pronostic etaient un NLR ≥ 5, la CRP > 50 mg/l et la mutation KRAS : avec en plus pour la SSP, le stade IV et un nombre de sites metastatiques > 2. Conclusion Cette etude suggere que le PS 0/1, une inflammation plus legere et un faible « tumor burden » sont des facteurs predictifs de reponse a l’immunotherapie.

Resume Le cancer du poumon est la premiere cause de mortalite par cancer dans le monde et en France avec plus de 30 000 deces par an. L’arret du tabac est la mesure la plus efficace pour limiter l’epidemie du cancer du poumon, mais est aussi un element important dans la prise en charge des patients atteints de cancer du poumon quel que soit le stade. Dans les cancers localises, la poursuite du tabac est associee a une diminution de la survie par augmentation du risque de recidive et de developper un deuxieme cancer. En periode peri-operatoire, le sevrage tabagique permet de limiter les complications infectieuses et la duree d’hospitalisation. Quel que soit le stade du cancer, le sevrage permet d’ameliorer la dyspnee, l’appetit ainsi que de reduire l’asthenie ; ceci se traduit par une amelioration de la qualite de vie. Le tabac entraine une addiction forte avec une dependance physique, psychologique et comportementale. La substitution nicotinique et la varenicline sont indiquees en cas de dependance physique a la nicotine. La cigarette electronique peut etre consideree comme un outil d’aide au sevrage tabagique. Les therapies cognitives et comportementales permettent d’aider le fumeur a se debarrasser de son comportement, et elles ont une place dans la prevention de la rechute. © 2021 SPLF. Publie par Elsevier Masson SAS. Tous droits reserves.

Resume Les essais controles randomises (ECR) constituent la reference pour evaluer l’efficacite d’une intervention. Le developpement clinique du medicament s’est aligne a cette methodologie pour l’obtention d’une autorisation de mise sur le marche en imposant la realisation successive d’essais de phase I, II et III. Neanmoins, face a l’augmentation des couts humains et financiers et a la necessite de maintenir le niveau de remuneration des actionnaires de l’industrie pharmaceutique, les essais combines de phase I/II et II/III ont ete proposes afin de raccourcir la duree du developpement et de diminuer les couts. Par ailleurs, l’irruption de la medecine de precision issue de la recherche d’un couple biomarqueur predictif/therapie ciblee a rendu ethiquement difficile la poursuite des ECR dans cette situation et a permis de developper des nouveaux schemas d’essais therapeutiques comme les essais stratifies, basket, umbrella, adaptatifs et strategiques. Ces nouveaux schemas ont permis l’acces rapide a des AMM pour des maladies rares (dabrafenib+trimetinib/BRAFV600, crizotinib/ROS) mais ils ont egalement ete utilises dans le developpement initial de certaines immunotherapies. Leurs inconvenients sont : la multiplicite des bras ; la complexite de l’analyse statistique ; l’absence d’evaluation de l’effet de la molecule ciblee en population generale ; le faible effectif des malades inclus avec un risque d’ignorer des evenements indesirables rares ; l’absence de comparaison a un traitement de reference et finalement l’absence d’evaluation de l’impact du traitement sur la survie globale.

Resume Ces dernieres annees ont vu la decouverte dans les CBNPC d’alterations moleculaires agissant comme « drivers » oncogeniques et conferant une sensibilite a des traitements cibles, definissant ainsi l’addiction oncogenique. Ces progres concernent principalement les CBPNC non-epidermoides. Certaines anomalies donnent acces a des traitements pour lesquels une AMM est disponible. Il s’agit des mutations d’EGFR, de BRAF, des rearrangements d’ALK, et de ROS1. D’autres biomarqueurs anciens font toujours l’objet d’essais therapeutiques, et d’autres emergents sont prometteurs (mutations KRAS, HER2, PIK3CA, anomalies moleculaires de la voie MET) (amplifications du gene et mutations des sites d’epissage de l’exon 14), rearrangements de RET (et de NTRK). Plus recemment ont ete mis en evidence des biomarqueurs refletant l’etat d’activation du systeme immunitaire, predictifs de la sensibilite a certaines immunotherapies par inhibiteurs des points de controle (anti-PD1 ou anti-PD-L1). Ainsi, l’etude de l’expression de PD-L1 va devenir systematique car conditionnant des AMM de premiere et de deuxieme ligne. Il faut donc rechercher systematiquement les mutations d’EGFR, BRAF, KRAS, le rearrangement ALK et la surexpression de PD-L1 ; en cas de negativite de ceux-ci, sont ou devraient etre recherchees les anomalies de MET, ROS1, RET, NTRK.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly named Churg-Strauss syndrome, is a small-vessel necrotizing vasculitis associated with eosinophilia and asthma. Glucocorticoids (GCs) usually control the disease, but relapses and GC-dependant asthma are frequent, leading to potential biological therapy use. Objectives: We examined off-label biological therapy use for relapsing/refractory EGPA. Methods: Remission was defined as the absence of asthma and vasculitis manifestations with a prednisone dose ≤5 mg/day, and partial response as the absence of manifestations requiring prednisone dose between 6 and 10 mg/day. Results: One hundred and eigteen patients (66 men, 52 women; median age 50.5 years) were included. Fifty (42%) patients received rituximab (RTX), 38 (32%) mepolizumab (MEPO), and 30 (26%) omalizumab (OMA). Previous treatments were: oral GCs (98%), methylprednisolone infusions (51%), azathioprine (68%), cyclophosphamide (47%), methotrexate (30%), mycophenolate mofetil (8%). At inclusion, median (interquartile range) BVAS in the RTX, OMA and MEPO groups were 8 (4.5-13), 2 (1.5-4) and 2 (2-5), respectively, median (IQR) daily GCs dose were 20 mg/day (15-40), 20 mg/day (10-37.5), 10 mg/day (7.5-20). GC-dependant asthma was found in 39 (78%) of the RTX group, 36 (95%) in the MEPO group and 28 (93%) in the OMA group. After median follow-up of 22.8 months (IQR 10-47), remissions, partial responses and therapeutic failures, respectively, were noted in 50%, 16% and 34% for RTX recipients, 17%, 38% and 45% for the OMA group and 84%, 3% and 13% for the MEPO group. Median BVAS dropped to 0 at 6 and 12 months and at last follow-up in all groups. A GC-sparing effect seemed more important with RTX and MEPO. Median GCs dose decreased from the baseline 20 mg/day to 8.5 at 6 months, 7.5 at 12 months and 5 at last follow-up in the RTX group, from 20 mg/day to 12 at 6 months, 10 at 12 months and 10 at last follow-up in the OMA group, and from 10 mg/day to 5 at 6 months, 3 at 12 months and 5 at last follow-up in the MEPO group. In the MEPO group, no difference was noted between patients receiving 100 mg and those 300 mg monthly.Nine (18%) patients stopped RTX because of refractory disease, and 12 (24%) experienced adverse events, including severe infections in 5. Thirteen (43%) stopped OMA because of severe infusion reaction in one and refractory disease in 12, and 4 (13%) patients receiving OMA experienced adverse events. Three (8%) patients stopped MEPO because of adverse events in 2 (one severe infusion reaction and one because of paresthesia), because of pregnancy in one. Seven (18%) additional patients receiving MEPO experienced adverse events, mainly asthenia. Conclusion: The results suggest that RTX may be effective in 50% of patients with vasculitis relapses related to EGPA, with an acceptable safety profile, while MEPO is highly effective with a good GCs-sparing effect and safety profile in patients with steroid-dependant asthma. Disclosure of Interests: Alice Canzian: None declared, Nils Venhoff: None declared, Silvia Sartorelli: None declared, Anne Marie Ruppert: None declared, Matthieu Groh: None declared, Camille Taille: None declared, Virginie Rieu: None declared, Perrine Smets: None declared, Francois Maurier: None declared, Nicolas Girszyn: None declared, Maxime Samson: None declared, Claire De Moreuil: None declared, Gregory Pugnet: None declared, Xavier Delbrel: None declared, Jean-Emmanuel Kahn: None declared, Xavier Puechal: None declared, Giacomo Emmi: None declared, Loic Guillevin: None declared, Lorenzo Dagna Consultant for: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Sanofi-Genzyme, and SOBI., Jens Thiel: None declared, Augusto Vaglio: None declared, Benjamin Terrier: None declared

International audience; Calpain 1 is a proinflammatory calcium-activated cysteine protease, which can be partly externalized. Extracellular calpains limit inflammatory processes and promote tissue repair, through cell proliferation and migration. Toll like receptor (TLR) 2 has been identified as a target of extracellular calpains in lymphocytes. The aim was to investigate the externalization of calpain 1 and the release of soluble TLR2 during tumor progression of pulmonary lepidic predominant adenocarcinoma (LPA). Extracellular calpain 1, soluble fragment of TLR2 and cytokines were analyzed by ELISA in bronchoalveolar lavage fluid (BALF) supernatants from patients with LPA (n = 68). Source of calpain was analyzed by immunohistochemistry and soluble TLR2 by flow cytometry on polymorphonuclear neutrophils (PMN) and human lung cancer cell lines. Extracellular calpain 1, secreted by tumor cells, was associated to tumor progression, neutrophilic inflammation, with a poor prognostic factor on survival (P = 0.003). TLR2 was expressed on PMN and tumor cells and decreased after calpain exposure. Soluble fragment of TLR2 in BALF supernatants was correlated to the extracellular calpain 1 concentration (r = 0.624; P < 0.001), and its high level was associated with tumor progression and a pro-inflammatory environment. Extracellular calpain 1 secreted by tumor cells, could participate in inflammatory microenvironment and tumor progression through TLR2 in LPA.

Summary Background Despite recent progress, non-small cell lung cancer (NSCLC) first-line treatment remains a platinum-based doublet in most cases. No guidelines exist beyond third line. Chemotherapy rechallenge is an option, but little data is available in NSCLC. Our study aims to describe patients who underwent chemotherapy rechallenge while assessing its efficacy and safety. Methods Consecutive patients with advanced-stage NSCLC receiving first-line treatment in Tenon hospital in 2011 were included, with a 5-year follow-up. Patients were analyzed according to chemotherapy rechallenge or not. Chemotherapy rechallenge was defined as re-initiation of a previously administered chemotherapy agent at any point in the treatment sequence, with at least one treatment regimen between first use and rechallenge. Results Of 149 patients, 18 underwent chemotherapy rechallenge (12%). They were younger (56 vs. 61 years, P = 0.04), mostly women (61% vs. 30%, P = 0.02), with lepidic adenocarcinoma (23% vs. 3.5%, P = 0.03), a better general state of health (100% performance status 0–1 vs. 74%, P = 0.04), and fewer cardiovascular comorbidities (16% vs. 42%, P = 0.04). They were more likely to have received a receptor tyrosine kinase inhibitor treatment (89% vs. 43%, P = 0.0003). Progression-free survival was longer at first use than at rechallenge (median 9.2 vs. 2.7 months, P = 0.002). No increased toxicity was observed at rechallenge compared to first use. Finally, a subsequent line of treatment was given after rechallenge in 61% of the patients. Conclusion Patients eligible for chemotherapy rechallenge were those with good prognostic factors. Chemotherapy rechallenge may provide a well-tolerated additional line of treatment, with decreased efficacy compared to its first application.

Introduction Organisation d’un bilan post-COVID a 3 mois de l’hospitalisation des patients ayant presente une atteinte respiratoire severe ou tres severe de COVID-19 en pneumologie et/ou en reanimation a l’hopital Tenon a Paris. Methodes Selon les recommandations de la SPLF [1] , mise en place en hopital de jour par le trinome IDEC/IPA, AMA et medecin d’un bilan comprenant un examen clinique (IDEC/IPA, medecin), un scanner thoracique sans injection, des EFR, un ECG et un bilan biologique. Recueil standardise des donnees. Inclusion dans l’etude RE2COVERI (cohorte de suivi des patients COVID-19 severes et tres severes) et suivis a j90 pour l’etude CORIMUNO (fin de suivi d’une etude comparant anti-Il6 vs traitement standard). Resultats Deux cent deux patients ont ete hospitalises pour COVID-19, dont 22 sont decedes. Ont ete contactes 145 patients ambulatoires. Le bilan a ete realise pour 89 (61 %) patients entre le 15/06/2020 et le 21/08/2020. Resultats preliminaires : la cohorte comportait 63 (71 %) hommes, l’âge moyen etait de 61 ans (SD 9,3), l’IMC moyen etait de 28 (SD 4) kg/m2. Le bilan realise trouvait une persistance de la dyspnee mMRC1 (35,2 %) ou mMRC2 (20,4 %), de la toux (13,6 %), de l’asthenie (35,6 %). Le scanner montrait la persistance des lesions entre 10 et 25 % chez 23,6 % des patients et > 25 % chez 4,5 % des patients. Aux EFR, 13,8 % patients presentaient un trouble ventilatoire obstructif et 33,9 % un trouble ventilatoire restrictif. La DLCO etait abaissee chez 48.1 % des patients. Ce bilan a permis d’inclure 43 (48 %) patients dans l’etude RE2COVERI et de realiser 32 suivis a j90 pour l’etude CORIMUNO. Trente-trois (37 %) patients seront revus pour un nouveau controle a 6 mois. Conclusion Cette organisation a ete possible suite a la mobilisation rapide des equipes medicales, paramedicales et AMA dans un delai restreint. Le bilan realise pour ces patients etait rassurant dans deux-tiers des cas. Seul un tiers des patients sera revu a 6 mois. Neanmoins, 38 % des patients hospitalises pour COVID-19 en pneumologie sont perdus de vus.

International audience; Non–small-cell lung cancer (NSCLC) is the most common non-acquired immune deficiency syndrome-related malignancy responsible for death. Mutational status is crucial for choosing treatment of advanced NSCLC, yet no data is available on the frequency of epidermal growth factor receptor (EGFR) and Kirsten ras (KRAS) mutations and their impact on NSCLC in human immunodeficiency virus (HIV)-infected patients (HIV-NSCLC).All consecutive HIV-NSCLC patients diagnosed between June 1996 and August 2013 at two Paris university hospitals were reviewed, with tumor samples analyzed for EGFR and KRAS mutational status.Overall, 63 tumor samples were analyzed out of 73HIV-NSCLC cases, with 63% of advanced NSCLC. There were 60 non-squamous and nine squamous cell carcinomas, with EGFR and KRAS mutations identified in two (3.3%) and seven (11.5%) tumors, respectively. The proportion of KRAS mutations was 29% if solely the more sensitive molecular techniques were considered. The two patients with advanced adenocarcinoma harboring EGFR mutations exhibited lasting partial response to EGFR-tyrosine kinase inhibitors. Overall survival for patients with advanced NSCLC were >30 months for those with EGFR mutations

Recently, developments of therapies that target abnormally activated signaling pathways are increasing for patients with non-small cell lung cancer. EGFR mutations are found in about 10% of lung cancers, especially in adenocarcinoma, women and non-smokers. Three EGFR inhibitors (erlotinib, gefitinib and afatinib) received a European marketing authorization for up to first line treatment of EGFR mutated NSCLC. Effectiveness of EGFR inhibitors is higher than conventional chemotherapy. Third generation EGFR inhibitors (rociletinib, AZD9291) are effective for patients who develop a resistance mutation such as T790M resistance mutation; they obtained temporary authorization for use in France in 2015. The EML4-ALK translocation is found in about 5% of NSCLC and more particularly in adenocarcinoma of young non-smoking patients. Crizotinib is a new therapeutic standard in ALK translocated NSCLC in second line. Ceritinib is a 2nd generation ALK inhibitor which received a European marketing authorization for up to treatment of ALK translocated NSCLC after progression with crizotinib. INCA supports ACSe program evaluating the efficacy of crizotinib in NSCLC amplified for MET or translocated for ROS1 and ACSe program evaluating the efficacy of vemurafenib in tumors non melanoma mutated V600E BRAF. The role of other biomarkers such as KRAS, BRAF, HER2 and PI3KCA mutations remains to be defined in NSCLC.

Resume Le bilan initial doit repondre a quatre imperatifs : apprecier l’etat clinique, obtenir une preuve diagnostique, definir le stade cTNM et, en cas de resecabilite, l'operabilite du patient. Les modalites du bilan locoregional basees sur les recommandations nationales et internationales sont resumees. L'examen clinique reste essentiel. Le scanner thoracique avec injection de produit de contraste iode est systematique, sauf contre-indication. La taille de la tumeur, son extension pleurale, parietale, endobronchique et mediastinale directe doivent etre precisees. Les performances du scanner pour predire l'envahissement ganglionnaire mediastinal sont mediocres (sensibilite [Se] = 61 % et specificite [Sp] = 79 %). La tomographie par emission de positons-tomodensitometrie (TEP-TDM) n'est pas indiquee en 1re intention, mais elle est indispensable chez un patient potentiellement eligible a un traitement curatif. Ses performances pour definir le statut mediastinal sont meilleures (Se = 80 % et Sp = 80-90 %). En l'absence d'un envahissement mediastinal massif, des explorations invasives sont indiquees en cas de ganglion ≥ 10 mm ou infracentimetrique fixant le fluorodesoxyglucose (FDG) ou devant la presence d'une adenopathie hilaire, d'une tumeur centrale ou > 3 cm. L’echoendoscopie bronchique et/ou œsophagienne est realisee en 1re intention, avant la mediastinoscopie. Les stades III doivent etre classes en potentiellement resecables, non resecables, potentiellement resecables avec risque de resection incomplete. Le respect des recommandations et une organisation adequate optimisent la prise en charge.

Resume Les cellules inflammatoires et immunitaires, les fibroblastes et les cellules endotheliales forment le micro-environnement de la tumeur. L'immunite innee favorise l'inflammation et constitue la premiere ligne de defense non specifique contre les agents pathogenes ou les cellules ≪ transformees ≫. Elle se compose principalement des mastocytes, des macrophages, des neutrophiles et des cellules naturelles tueuses NK (Natural Killer). L'inflammation chronique est le lit du cancer. De nombreuses maladies inflammatoires chroniques sont associees a un surrisque de cancer. En ce qui concerne le cancer du poumon, l'inflammation chronique observee au cours de la BPCO, de l'emphyseme ou de la fibrose pulmonaire idiopathique est associee au developpement d'un cancer bronchique. Dans cet article, nous presentons les effets proet antitumoraux de l'inflammation liee au systeme immunitaire inne dans le cancer bronchique. La place du systeme immunitaire specifique est decrite dans un autre chapitre. Au cours de la progression tumorale, les cellules cancereuses vont pouvoir utiliser et/ou contourner les signaux issus des cellules inflammatoires afin de favoriser la proliferation tumorale, l'invasion tissulaire et la formation de metastases. Il n'y a pas d'agents therapeutiques disponibles qui ciblent specifiquement l'inflammation.

Resume Il n'y a pas de bonne definition de l'innovation therapeutique. Dans le domaine du cancer du poumon, il semble bien que ce soit la quantite de vie gagnee qui definisse le mieux l'innovation therapeutique pour le grand public comme pour les professionnels de sante. Les medicaments doivent subir un developpement long et multi-etape pour arriver jusqu’a leur autorisation de mise sur le marche (AMM). Ce developpement est tres couteux pour les industriels, et l'innovation therapeutique pese lourd economiquement pour la societe, du fait du remboursement des traitements. Le concept de therapeutique ciblee couplee a son biomarqueur predictif a permis de rationaliser et de raccourcir les delais d'obtention des AMM, mais le nivolumab, anticorps anti-PD1, a obtenu tres rapidement son AMM dans le traitement des carcinomes epidermoides, sans la necessite d'un biomarqueur predictif. Les agences de regulation ont egalement mis en place des procedures d’evaluation acceleree des molecules, comme les AMM conditionnelles. L'explosion des techniques de biologie moleculaire a aussi permis de decouvrir un grand nombre d'addictions oncogeniques rares, mais parfois partagees par differents cancers, menant a de nouvelles sortes d'essais therapeutiques de type basket, afin d'en evaluer l'efficacite. Finalement, la France propose des dispositifs reglementaires uniques a travers ses autorisations temporaires d'utilisation (ATU) et recommandations temporaires d'utilisation (RTU) pour offrir a tous – ou presque – un acces aux innovations therapeutiques.

Resume L'incidence et la mortalite par cancer chez les personnes vivant avec le VIH (PVVIH) ont evolue depuis les annees 1990 : le VIH ne represente plus qu'un quart des deces dans cette population. Cette evolution est liee a l’emergence de combinaisons antiretrovirales tres actives, ayant permis d'allonger l'esperance de vie des patients et de diminuer les complications liees au virus. Les cancers sont de ce fait devenus la premiere cause de mortalite. Du fait de l'immunodepression et du tabagisme important, le risque de cancer broncho-pulmonaire (CBP) est deux a trois fois plus eleve que celui de la population generale. Il est le plus frequent des cancers non classant sida et represente la premiere cause de deces par cancer. L’âge de survenue chez les PVVIH est plus jeune, et le pronostic plus mauvais. Le traitement du CBP chez les PVVIH est plus complexe que dans la population generale, en raison d'interactions medicamenteuses avec les antiretroviraux (ARV), de l'agressivite tumorale et de comorbidites particulieres. Une meilleure connaissance de la biologie moleculaire, l'immunotherapie et le depistage sont des axes de recherche majeurs pour ameliorer la survie des PVVIH atteintes de CBP. Pour toutes ces raisons, l'inclusion dans les essais therapeutiques dedies constitue une priorite.

Introduction L’immunotherapie est recemment devenue un standard therapeutique des CBNPC localement avances et metastatiques. Des etudes recentes suggerent que la RT pourrait stimuler la reponse immunitaire antitumorale. L’objectif de cette etude etait d’evaluer l’impact d’une RT prealable ou concomitante a une immunotherapie dans les CBNPC metastatiques. Methodes Cette etude retrospective monocentrique concerne 194 CBNPC metastatiques diagnostiques dans un CHU entre 01/2015 et 08/2018 et traites par un anti-PD1. Le critere de jugement principal etait la survie sans progression (SSP) a partir du debut de l’immunotherapie. Les criteres secondaires etaient la survie globale a partir du debut de l’immunotherapie (SG) et la tolerance. Resultats Au total, 65 patients (pts) avaient recu une RT prealable ou concomitante a l’immunotherapie (RT + ) et 129 n’en avaient pas recu (RT − ). Les patients RT+ presentaient davantage de sites metastatiques (p = 0,015), de metastases osseuses (p Conclusion La RT prealable ou concomitante a l’immunotherapie semble etre un facteur de bon pronostic sur la SSP et la SG chez les pts traites par immunotherapie dans les CBNPC metastatiques. Des etudes prospectives sont en cours pour confirmer cet impact.

Introduction MNNG HOS transforming gene (MET) abnormalities such as amplification and exon 14 mutations may be responsive to targeted therapies. They are prevalent in lung sarcomatoid carcinomas (LSCs) and must be diagnosed as efficiently as possible. Hypothetically, c-MET overexpression by immunohistochemistry (IHC) may prove effective as a screening test for MET abnormalities. Methods Tissue samples were obtained from consecutive patients with a resected LSC in four oncologic centers. IHC was performed using the SP44 antibody (Ventana, Tucson, Arizona) and evaluated using the MetMab score and H-score. Fluorescence in situ hybridization was applied with the dual color probe set from Zytovision (Clinisciences, Nanterre, France). True MET amplification was diagnosed when MET gene copy number was 5 or greater and the ratio between MET gene copy number and chromosome 7 number was greater than 2. All MET exon 14 alterations including those affecting splice sites occurring within splice donor and acceptor sites were detected in the routine molecular testing on genetic platforms. Results A total of 81 LSCs were included. Fourteen (17%) exhibited positive IHC using the MetMab score and 15 (18.5%) using the H-score. MET amplification was detected in six tumors (8.5%) and MET exon 14 mutation in five (6%). A weak positive correlation between IHC and fluorescence in situ hybridization was found (r = 0.27, p = 0.0001). IHC sensitivity for MET amplification was 50%, with a specificity of 83%, positive predictive value of 21.4%, and negative predictive value of 94.7%. IHC sensitivity for MET exon 14 mutations was 20%, with a specificity of 83%, positive predictive value of 7%, and negative predictive value of 94%. Conclusion IHC is not a relevant screening tool for MET abnormalities in LSC.

Anaplastic lymphoma kinase (ALK) translocations are a validated molecular target in non-small cell lung cancer (NSCLC). ALK translocations result in the expression of a chimeric protein, exhibiting a constitutive ALK kinase activation, involved in cell proliferation, invasion and loss of apoptosis (1). ALK translocations are found in 4–7% of NSCLC, particularly in adenocarcinomas and in non-smokers (1). According to FDA and EMEA, standard first-line therapy for advanced ALK translocated NSCLC is crizotinib, a multi-target MET, ALK and ROS1 inhibitor (1,2). The use of second generation ALK inhibitors, such as ceritinib or alectinib, was initially validated at progression (3-5). More recently, these second generation ALK inhibitors were evaluated in first-line treatment. This year, ceritinib received FDA and EMEA approval in the first-line treatment for advanced ALK translocated NSCLC after the results of a phase III trial comparing ceritinib to platinum - pemetrexed chemotherapy with a benefit on progression-free survival of 16.6 vs. 8.1 months (6). Several clinical trials are underway comparing head to head different ALK inhibitors in phase III trials in ALK naive patients, as brigatinib vs. crizotinib (NCT02737501) or lorlatinib vs. crizotinib (NCT03052608).

Purpose: The phase II prospective, noncomparative BRAIN study (NCT00800202) investigated efficacy and safety of bevacizumab in chemotherapy-naïve or pretreated patients with non–small cell lung cancer (NSCLC) and asymptomatic untreated brain metastases to provide data in this previously unexplored subgroup. Experimental Design: Patients with stage IV nonsquamous NSCLC, Eastern Cooperative Oncology Group performance status 0–1, and untreated, asymptomatic brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin (area under the curve ×6) and paclitaxel (200 mg/m2) every 3 weeks (B + CP), or second-line bevacizumab plus erlotinib (150 mg/d; B + E). Six-month progression-free survival (PFS) was the primary endpoint. The trial could be stopped if there were more than three (B + CP) or more than two (B + E) intracranial hemorrhages. Results: In first-line B + CP cohort (n = 67), 6-month PFS rate was 56.5% with a median PFS of 6.7 months [95% confidence interval (CI), 5.7–7.1] and median overall survival (OS) of 16.0 months. Investigator-assessed overall response rate (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions. Because of low enrolment (n = 24), efficacy results for the second-line B + E cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3 months (95% CI, 3.0–8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse events were comparable with previous trials of bevacizumab. One grade 1 intracranial hemorrhage occurred and resolved without sequelae. Conclusions: The BRAIN study demonstrates encouraging efficacy and acceptable safety of bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and asymptomatic, untreated brain metastases. Clin Cancer Res; 21(8); 1896–903. ©2015 AACR.

Lung cancer (LC) is a major public health issue because of its frequency, but especially because of the severity of this disease. The epidemiology has changed with an increased incidence in non-smokers and women. The ATS/ERS/IASLC classification of adenocarcinomas was modified in 2011, and they are now the most frequent histological subtype. More than half the cases of LC are diagnosed at the metastatic stage. Biopsies must provide tissue samples that are quantitatively large enough and of a good enough quality for diagnosis and to search for biomarkers. When the cancer seems to be localized, precise staging must be obtained. Treatment is based on the TNM classification. In localized stages, lobectomy associated with lymph node dissection is the standard therapy. Intraoperative chemotherapy improves survival in case of lymph node infiltration. Stereotactic radiation therapy and radiofrequency can be considered as specific cases. In cases with local progression, treatment is more controversial. In the presence of metastases, the goal is not a cure, but improving survival and quality of life. Numerous advances have been made with personalized treatment, (in particular in relation to the histological type and oncogenic addiction in tumors, access to new drugs, and improved management). Clinical research in thoracic cancer is very active. The fight against tobacco should remain a priority.

Resume Le cancer broncho-pulmonaire (CBP) reste un probleme majeur de sante publique du fait de la frequence et surtout de la gravite de la maladie. L’epidemiologie s’est modifiee avec une augmentation d’incidence chez les non-fumeurs et les femmes. La classification ATS/ERS/IASLC des adenocarcinomes a ete modifiee en 2011. C’est aujourd’hui le sous-type histologique le plus frequent. Plus de la moitie des CBP sont diagnostiques au stade metastatique. Le preleveur doit obtenir des prelevements quantitativement et qualitativement adequats pour le diagnostic et la recherche de biomarqueurs. Lorsque le cancer est a priori localise, un staging precis doit etre realise. Le traitement depend du TNM. Dans les stades localises, la lobectomie associee au curage reste le standard. La chimiotherapie peri-operatoire ameliore la survie en cas d’atteinte ganglionnaire. La radiotherapie stereotaxique et la radiofrequence sont des options pouvant etre discutees dans certains cas precis. Dans les stades localement avances, le traitement est plus controverse. Dans les stades metastatiques, l’objectif n’est pas la guerison mais l’amelioration de la survie et la qualite de vie du patient. De nombreux progres ont ete faits avec une personnalisation du traitement (en particulier sur le type histologique et sur les addictions oncogeniques de la tumeur), la mise a disposition de nouvelles drogues et le developpement de la maintenance. La recherche clinique en oncologie thoracique est tres active. La lutte contre le tabagisme doit rester une priorite.

Resume Au cours de l’infection au virus de l’immunodeficience humaine (VIH), le sida etait responsable de la majorite des deces avant 1996 mais, depuis l’introduction des therapeutiques antiretrovirales, les causes de mortalite ont beaucoup evolue. En 2010, 75 % des deces sont secondaires a des maladies non-classant sida et les cancers constituent la plus grande proportion de cas. Le cancer du poumon est le plus frequent, en termes d’incidence mais egalement de mortalite. Il presente certaines particularites par rapport a la population generale : il existe un exces de risque, en raison d’une plus grande exposition au tabagisme mais aussi probablement en raison de l’immunodepression. L’âge de survenue est plus jeune, et le pronostic est plus mauvais que dans la population generale. La difficulte de prise en charge est liee d’une part a l’agressivite particuliere de la tumeur et d’autre part aux comorbidites de ces patients et aux interactions potentielles entre les anticancereux et les therapies antiretrovirales. Un essai therapeutique de phase II (IFCT-CHIVA 1001) est en cours au niveau national.

Introduction Au cours du traitement des cancers bronchiques non a petites cellules (CBNPC) de stade avance, certains patients (pts) vont recevoir la reintroduction d’un traitement par chimiotherapie (R-CT). L’objectif de ce travail etait de decrire la frequence des R-CT, son efficacite et sa tolerance ainsi que les facteurs associes a cette pratique. Methodes Cohorte retrospective exhaustive monocentrique dans un service d’oncologie thoracique universitaire incluant tous les CBNPC de stade avance (stade IV ou stade IIIB non accessible a un traitement chirurgical ou par radiotherapie), recevant une 1 re ligne de traitement en 2011. Les donnees cliniques (âge, sexe, histoire tabagique, performans status [PS], comorbidites), histologiques (dont sous-type d’adenocarcinome), la survie sans progression (SSP) et la tolerance etaient recueillies. La R-CT etait definie par la reintroduction en n-ieme ligne d’une CT deja utilisee, avec au moins une ligne therapeutique differente entre la primo-utilisation et la R-CT. Resultats Sur 149 patients, 18 avaient eu une R-CT. Certains patients ( n = 5) ayant eu deux R-CT differentes, on denombrait en tout 23 R-CT. Les R-CT les plus frequentes comportaient un doublet a base de sel de platine ( n = 8) et du pemetrexed ( n = 7). Les pts avec R-CT etaient plus jeunes (56 vs 61 ans, p = 0,04), en meilleur etat general (PS 0–1 100 % vs 74 %, p = 0,04), avec moins de comorbidites cardiovasculaires (16 % vs 42 %, p = 0,04). Il y avait une predominance feminine (61 % vs 30 %, p = 0,02), et plus d’adenocarcinomes lepidiques (23 % vs 3 %, p = 0,04). Ils avaient plus souvent recu un traitement par inhibiteur de recepteur a tyrosine kinase (89 % vs 43 %, p = 0,0003), independamment de la presence ou non d’une addiction oncogenique. La SSP etait plus courte a la reintroduction qu’a la primo-prescription (mediane 2,6 vs 8,9 mois, p = 0,002). Il n’y avait pas d’exces de toxicite (toxicites grade 3 ou 4 : n = 7 (30 %) lors de la primo-utilisation vs n = 5 (24 %) lors de la reintroduction). Une ligne de traitement ulterieure a la R-CT etait possible dans 61 % des cas ( n = 14/23). Conclusion La R-CT est proposee a 12 % de nos malades. Elle semble bien toleree et permet d’acceder a une ligne supplementaire de traitement.

Introduction La granulomatose eosinophilique avec polyangeite (GEPA), anciennement syndrome de Churg–Strauss, est une vascularite necrosante caracterisee par la presence d’un asthme hypereosinophilique. Le traitement standard repose sur les glucocorticoides (GCs) associees ou non a des immunosuppresseurs conventionnels. Cependant, des rechutes et/ou des manifestations refractaires peuvent survenir, notamment un asthme cortico-dependant. Nous avons etudie l’utilisation hors-AMM des biotherapies pour le traitement des GEPA refractaires ou en rechute. Patients et methodes Etude retrospective, multicentrique europeenne, ayant inclut les patients atteints de GEPArepondant aux criteres ACR et/ou a la definition de la Conference de consensus de Chapel Hill. La remission etait definie par l’absence de manifestations actives de vascularite (BVAS = 0) ou d’asthme symptomatique et une dose de prednisone ≤5 mg/jour. La reponse partiale etait definie par un score BVAS = 0, l’absence d’asthme symptomatique et une dose de GCs >5 et ≤ 10 mg/jour. Resultats Cent dix-huit patients ont ete inclus (66 hommes, âge moyen 50,5 ans). Cinquante(42 %) patients ont recu du rituximab (RTX), 38 (32 %) du mepolizumab (MEPO) et 30 (26 %) de l’omalizumab (OMA). Les traitements precedemment recus etaient : GCs oraux (98 %), bolus de methylprednisolone (51 %), azathioprine (68 %), cyclophosphamide (47 %), methotrexate (30 %), mycophenolate mofetil (8 %). A la mise sous biotherapies, le BVAS median (IQR) dans les groupes traites par RTX, OMA et MEPO etait, respectivement, de 8 (4,5–13), 2 (1,5–4) et 2 (2–5), et la dose mediane (IQR) de prednisone etait respectivement de 20 mg/jour (15–40), 20 mg/j (10–37,5) et 10 mg/j (7,5–20). Un asthme mal controle etait retrouve chez 31 (62 %) patients du groupe RTX, tandis que 28 (93 %) du groupe OMA et 36 (95 %) du groupe MEPO avait un asthme cortico-dependant. Apres un suivi median de 22,8 mois (IQR 10-47), les remissions, les reponses partielles et les echecs etaient observes dans 50 %, 16 % et 34 % dans le groupe traite par RTX, respectivement, 17 %, 38 % et 45 % dans le groupe traite par OMA, et 84 %, 3 % et 13 % dans le groupe traite par MEPO. Le BVAS median baissait a 0 a 6 et 12 mois et au dernier suivi dans tous les groupes. Un effet d’epargne cortisonique plus important etait observe avec le RTX et le MEPO. La dose mediane de prednisone baissait de 20 mg/j a l’inclusion a 8,5 a 6 mois, 7,5 a 12 mois et 5 au dernier suivi dans le groupe RTX, de 20 mg/j a 12 a 6 mois, 10 a 12 mois et 10 au dernier suivi dans le groupe OMA, et de 10 mg/j a 5 a 6 mois, 3 a 12 mois et 5 au dernier suivi dans le groupe MEPO. Concernant la posologie de MEPO, nous n’avons pas observe des differences entre les patients traites par une dose mensuelle de 100 mg et ceux recevant une dose de 300 mg. Neuf (18 %) patients ont arrete le RTX en raison d’un echec et 12 (24 %) ont eu des effets indesirables, notamment des infections severes chez 5. Treize (43 %) patients ont arrete l’OMA, en raison d’une reaction severe chez un patient et d’un echec chez 12, et 4 (13 %) patients ont eu des effets indesirables. Enfin, 3 (8 %) patients ont arrete le MEPO en raison d’effets indesirables chez 2 (une reaction severe apres l’infusion et une paresthesie) et d’une grossesse chez une patiente. Sept (18 %) patients traites par MEPO ont developpe des effets indesirables moderes, principalement de l’asthenie. Conclusion Les resultats de cette etude montrent que le rituximab peut etre efficace chez 50 % des patients en rechute de leur vascularite, avec un profil de tolerance satisfaisant. Le mepolizumab semble etre tres efficace quant a lui chez les patients avec une asthme cortico-dependant, avec un important effet d’epargne cortisonique et une bonne tolerance. L’omalizumab ne semble pas etre une alternative satisfaisante a l’ere des anti-interleukine-5.