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International audience; INTRODUCTION: Molecular profile of resected stage I-II non-small cell lung cancer (NSCLC) would help refine prognosis and personalize induction or adjuvant strategies. We sought to report the molecular profile of resected stage I-II NSCLC and analyzed the impact of epidermal growth factor receptor (EGFR) mutations on outcomes in a Western population. PATIENTS AND METHODS: Surgical cases were identified from Biomarkers France study, a nationwide prospective study including NSCLC patients screened for EGFR, HER2, KRAS, BRAF, PIK3CA, ALK alterations from 2012 to 2013. Among surgical patients, clinical charts of the largest centers were reviewed in order to analyze the prognostic impact of EGFR mutations. RESULTS: In the BMF database (n = 17.636), surgical patients (n = 854) were characterized by a higher proportion of EGFR mutations than nonsurgical patients (12.9% vs. 10.2%, P = .025), while the other molecular alterations did not differ. The proportion of EGFR mutations was 27% in women undergoing surgery. In the study group (n = 293; EGFR wild type, n = 235; usual mutation, n = 50; rare mutation, n = 8), after a median follow-up of 67 months, 215 patients (74.4%) had not relapsed. No difference was found between EGFR-mutant and EGFR-wt tumors regarding recurrence site, disease-free survival, and overall survival. The 5-year disease-free survival and overall survival after surgical resection of stage I-II EGFR-mutated tumors were 65% and 75%, respectively. CONCLUSION: In resected stage I to II NSCLC, EGFR mutations were found in 12.9% of cases, associated with a 5-year overall survival of 75%, with no impact on recurrence site, disease-free survival, and overall survival.

PDF file - 344K, Supplementary methods, suppl. Figure 1 with with the specimens flow-chart, suppl. Figure 2 with the diagram of the clinical trial IFCT 0002 and sampling timepoints, suppl. Figure 4 with RASSF1A interactome, suppl. Table 1 & 2 with primers used in the study, suppl. Table 3 with all the molecular analyses in the bio-IFCT 0002 study, suppl. Table 4 comparing patients with or without molecular analyses, suppl. Table 5 with all the HRs and p-values forthe molecular and clinical variables in the final prognostic analysis

PDF file - 21K, Acknowledegements to IFCT staff (administrative and CRAs), to expert pathological panel, and list of investigators of the phase 3 clinical trial IFCT 0002

PDF file - 205K, Correlation between RASSF1 promoter gene methylation and RASSF1A protein expression by immunoblotting

Purpose: To evaluate prognostic and predictive molecular biomarkers in early-stage non–small cell lung carcinoma (NSCLC) receiving neoadjuvant chemotherapy.Experimental Design: The IFCT-0002 trial compared two neoadjuvant regimens in 528 stages I to II NSCLC patients. DNA extraction of snap-frozen surgical samples taken from 208 patients receiving gemcitabine-cisplatin or paclitaxel-carboplatin regimens allowed for the identification of 3p allelic imbalance, Ras association domain family 1A (RASSF1A) and death-associated protein kinase 1 (DAPK1) promoter methylation, and epidermal growth factor receptor, K-ras, and TP53 mutations. Multivariate analysis identified prognostic and predictive effects of molecular alterations. A Bootstrapping approach was used to assess stability of the prognostic models generating optimism corrected indexes.Results: RASSF1A methylation correlated significantly with shorter disease-free survival (DFS; adjusted HR = 1.88, 95% CI: 1.25–2.82, P = 0.0048) and shorter median overall survival (OS; adjusted HR = 2.01, 95% CI: 1.26–3.20, P = 0.020). A computed bootstrap resampling strategy led to a prognostic model, including RASSF1A, DAPK1, and tumor stage, dividing patients into three prognostic groups, with median OS ranging from 34 months for high-risk patients (HR for death = 3.85, 95% CI: 1.79–6.40) to more than 84 months for moderate (HR = 1.85, 95% CI: 0.97–3.52) and low-risk patients (reference group; P = 0.00044). In addition, RASSF1A methylation predicted longer DFS in patients treated with paclitaxel-carboplatin compared with gemcitabine-cisplatin (adjusted HR = 0.47, 95% CI: 0.23–0.97, Pinteraction = 0.042).Conclusions: Following neoadjuvant chemotherapy, RASSF1A methylation negatively impacted prognosis of early-stage NSCLC. Along with DAPK1 methylation and tumor stage, RASSF1A methylation allowed definition of three subgroups with strikingly different prognosis. Conversely, significantly longer DFS following paclitaxel-based neoadjuvant chemotherapy for patients whose tumors showed RASSF1A methylation suggested its predictive interest in stages I and II NSCLC. Clin Cancer Res; 18(10); 2976–86. ©2012 AACR.

BackgroundThe IONESCO (IFCT-1601) trial assessed the feasibility of neoadjuvant durvalumab, for early-stage resectable non-small-cell lung cancer (NSCLC).MethodsIn a multicenter, single-arm, phase II trial, patients with IB (≥4 cm)-IIIA, non-N2, resectable NSCLC received three doses of durvalumab (750 mg every 2 weeks) and underwent surgery between 2 and 14 days after the last infusion. The primary endpoint was the complete surgical resection rate. Secondary endpoints included tumor response rate, major histopathological response (MPR: ≤10% remaining viable tumor cells), disease-free survival (DFS), overall survival (OS), durvalumab-related safety, and 90-day postoperative mortality (NCT03030131).ResultsForty-six patients were eligible (median age 60.9 years); 67% were male, 98% were smokers, and 41% had squamous cell carcinoma. Regarding tumor response, 9% had a partial response, 78% had stable disease, and 13% had progressive disease. Among the operated patients (n=43), 41 achieved complete resection (89%, 95% CI 80.1% to 98.1%)), and eight achieved MPR (19%). The 12-month median OS and DFS rates were 89% (95% CI 75.8% to 95.3%) and 78% (95% CI 63.4% to 87.7%), respectively (n=46). The median follow-up was 28.4 months (12.8–41.1). All patients in whom MPR was achieved were disease-free at 12 months compared to only 11% of those with >10% residual tumor cells (p=0.04). No durvalumab-related serious or grade 3–5 events were reported. The unexpected 90-day postoperative mortality of four patients led to premature study termination. None of these four deaths was considered secondary to direct durvalumab-related toxicity.ConclusionsNeoadjuvant durvalumab given as monotherapy was associated with an 89% complete resection rate and an MPR of 19%. Despite an unexpectedly high rate of postoperative deaths, which prevented us from completing the trial, we were able to show a significant association between MPR and DFS.

Following the American National Lung Screening Trial results in 2011 a consortium of French experts met to edit a statement. Recent results of other randomized trials gave the opportunity for our group to meet again in order to edit updated guidelines. After literature review, we provide here a new update on lung cancer screening in France. Notably, in accordance with all international guidelines, the experts renew their recommendation in favor of individual screening for lung cancer in France as per the conditions laid out in this document. In addition, the experts recommend the very rapid organization and funding of prospective studies, which, if conclusive, will enable the deployment of lung cancer screening organized at the national level.

Even after resection of early-stage non-small-cell lung cancer (NSCLC), patients have a high risk of developing recurrence and second primary lung cancer. We aimed to assess efficacy of a follow-up approach including clinic visits, chest x-rays, chest CT scans, and fibre-optic bronchoscopy versus clinical visits and chest x-rays after surgery for resectable NSCLC.In this multicentre, open-label, randomised, phase 3 trial (IFCT-0302), patients aged 18 years or older and after complete resection of pathological stage I-IIIA NSCLC according to the sixth edition of the TNM classification were enrolled within 8 weeks of resection from 122 hospitals and tertiary centres in France. Patients were randomly assigned (1:1) to CT-based follow-up (clinic visits, chest x-rays, thoraco-abdominal CT scans, and fibre-optic bronchoscopy for non-adenocarcinoma histology) or minimal follow-up (visits and chest x-rays) after surgery for NSCLC, by means of a computer-generated sequence using the minimisation method. Procedures were repeated every 6 months for the first 2 years and yearly until 5 years. The primary endpoint was overall survival analysed in the intention-to-treat population. Secondary endpoints, also analysed in the intention-to-treat population, included disease-free survival. This trial is registered with ClinicalTrials.gov, NCT00198341, and is active, but not enrolling.Between Jan 3, 2005, and Nov 30, 2012, 1775 patients were enrolled and randomly assigned to a follow-up group (888 patients to the minimal follow-up group; 887 patients to the CT-based follow-up group). Median overall survival was not significantly different between follow-up groups (8·5 years [95% CI 7·4-9·6] in the minimal follow-up group vs 10·3 years [8·1-not reached] in the CT-based follow-up group; adjusted hazard ratio [HR] 0·95, 95% CI 0·83-1·10; log-rank p=0·49). Disease-free survival was not significantly different between follow-up groups (median not reached [95% CI not estimable-not estimable] in the minimal follow-up group vs 4·9 [4·3-not reached] in the CT-based follow-up group; adjusted HR 1·14, 95% CI 0·99-1·30; log-rank p=0·063). Recurrence was detected in 246 (27·7%) of 888 patients in the minimal follow-up group and in 289 (32·6%) patients of 887 in the CT-based follow-up group. Second primary lung cancer was diagnosed in 27 (3·0%) patients in the minimal follow-up group and 40 patients (4·5%) in the CT-based follow-up group. No serious adverse events related to the trial procedures were reported.The addition of thoracic CT scans during follow-up, which included clinic visits and chest x-rays after surgery, did not result in longer survival among patients with NSCLC. However, it did enable the detection of more cases of early recurrence and second primary lung cancer, which are more amenable to curative-intent treatment, supporting the use of CT-based follow-up, especially in countries where lung cancer screening is already implemented, alongside with other supportive measures.French Health Ministry, French National Cancer Institute, Weisbrem-Benenson Foundation, La Ligue Nationale Contre Le Cancer, and Lilly Oncology.For the French translation of the abstract see Supplementary Materials section.

Cooperative groups' involvement is increasing in academic oncological research. We aimed to assess the impact of sponsoring by cooperative groups in France on the availability of results of academic randomized trials in oncology.We performed a systematic search using ClinicalTrials.gov and the European Clinical Trials Register. We searched for all academic randomized trials in oncology conducted in France between January 1, 2005 and January 1, 2015. The inclusion criteria were: completed or terminated, phase 2 or 3 randomized trials with an academic (non-industry) sponsor. The main outcome was the publication of the results of trial (either as a journal article or as posting results in a registry) across each type of sponsor.We included 211 randomized trials, mainly phase 3 (n = 135, 64%) and evaluating pharmacological treatments (n = 149, 71%). French cooperative groups were involved in 69 trials (33%), as part of a collaboration in one third (n = 23) of instances. Seventy-one (34%) trials were run by oncologic hospitals, 50 (23%) by university hospitals, and 21 (10%) by European organizations. Seventy-seven randomized trials (36%) had available results (published n = 73, posted n = 6). Cooperative groups were involved in half of those that have been published (37/73). The cumulative probability of results availability was 57% for cooperative groups, 41% for European organizations, 32% for oncologic hospitals, and 17% for university hospital at 10 years from the beginning of trials (p = 0.0006). In the case of collaboration with cooperative groups, the cumulative probability of results availability achieved 59% for university hospitals and 74% for oncologic hospitals.The availability of results of randomized trials in oncology remains limited and almost exclusively through publications, but is higher when cooperative groups are involved.Sponsoring by a cooperative group should become the rule in academic trials to increase availability of trial results.

MicroAbstract Lung cancer screening by LD CT scan demonstrated in prior studies a decrease in lung cancer mortality, as well as in overall mortality. The aim of our prospective multicentric study was to assess the implementation of three annual lung cancer screenings in a real-life setting in France. The results of the second round of our study showed the feasibility of this screening program in the general population and revealed that it would indeed be necessary to further optimise screening participation during the subsequent rounds by improving communication with the target population and the respective healthcare professionals. Summary Introduction: Over the last few years, lung cancer screening by low-dose CT scan has demonstrated a decrease in lung cancer mortality. While this method has been in use since 2013 in the United States of America, no European country has yet implemented a systematic screening program. We hereby report the results from the second round of screening from a French cohort study. Patients and Methods: DEP KP80 is a prospective study evaluating lung cancer screening by means of three low-dose computer tomography (CT) scans at 1-yr intervals in 1,307 participants, aged 55 to 74 years old, all smokers or former smokers, having quit within the last 15 years, with over 30 pack years. The results of the first round demonstrated it was possible to conduct effective screening in real-life situations. Results: Participation was lower in this second round than in the first (35.3% vs. 73.1%, p Conclusion: As with the first round, the results of this second round confirm the feasibility and efficacy of lung cancer screening. The lower participation rate for this second round is proof of the need to improve awareness among participants and healthcare professionals of the relevance of committing to an annual screening program.

Lung cancers screening, what methods what results? Because lung cancers are the leading cause of death from cancer, because there is effective treatment for the early stages and because it is possible to target smokers, lung cancers screening is essential. Neither chest x-ray, sputum cytology, nor blood markers are useful for this screening. Only the low-dose chest scanner had demonstrated in two randomized studies with large numbers of heavy smokers or former smokers that it significantly reduces the specific mortality from lung cancers.Comment dépister les cancers du poumon, et avec quels résultats ? Parce que les cancers du poumon représentent la première cause de mortalité par cancer, parce qu’on dispose d’un traitement efficace pour les stades précoces et parce qu’il est possible de cibler les fumeurs, le dépistage de ces cancers s’impose. Ni la radiographie pulmonaire, ni l’examen cytologique des expectorations, ni les marqueurs sanguins ne sont utiles à ce dépistage. Seul le scanner thoracique faiblement dosé a démontré dans deux études randomisées comportant d’importants effectifs de grands fumeurs ou anciens fumeurs qu’il réduisait significativement la mortalité spécifique des cancers du poumon.

Resume Etat des connaissances Programmed cell death-ligand 1 (PD-L1) est une proteine membranaire facilitant l’echappement tumoral vis-a-vis de l’immunite. Le durvalumab est un anticorps monoclonal bloquant l’interaction PD-L1/PD-1 entre lymphocytes T et cellules tumorales, ayant montre des reponses durables et une toxicite acceptable en phase I/II dans les cancers bronchiques non a petites cellules (CBNPC) metastatiques. Methodes Dans cette etude de phase II, 3 perfusions de durvalumab (10 mg/kg a j1, j15, j29) sont administrees en neo-adjuvant a des patients ≥ 18 ans, indice de performance (PS) 0–1, ayant un CBNPC de stade clinique IB (> 4 cm) ou II. La chimiotherapie et la radiotherapie preoperatoire ne sont pas permises. L’objectif principal est la faisabilite d’une resection chirurgicale complete. Un taux de resection complete Resultats attendus L’immunotherapie neo-adjuvante est faisable et pourrait ameliorer la survie des CBNPC de stade precoce.

Resume La chirurgie est le traitement de reference des CNPC de stades I, II et IIIA. Plusieurs essais randomises de phase III de chimiotherapie adjuvante ou neoadjuvante avec une chimiotherapie a base de platine ont ete menes dans les cancers de stades I, II et IIIA. Ces essais ont demontre un gain de survie significatif de la chimiotherapie adjuvante ou neoadjuvante evalue a 5 % a 5 ans dans les stades II et IIIA. Ce benefice a ete confirme par deux meta-analyses sur donnees individuelles. En revanche pour les stades I, le benefice de la chimiotherapie n’est que suggere dans les stades IB > 4 cm. La place de la radiotherapie adjuvante dans les tumeurs N2, sera precisee par l’essai Lung-ART/IFCT-0503. L’impact des traitements cibles peri-operatoires des patients ayant des alterations moleculaires est actuellement suggere par une etude chez des mutes EGFR. Enfin, la place des inhibiteurs de points de controle de l’immunite est actuellement etudiee dans des essais neoadjuvants et adjuvants de phase III. Des resultats preliminaires d’essais neoadjuvants sont encourageants. © 2020 SPLF. Publie par Elsevier Masson SAS. Tous droits reserves.

Resume Introduction Le Plan Cancer 2014–2019 insiste sur l’importance de la collaboration entre tous les acteurs de la recherche clinique dans la lutte contre le cancer, dont les intergroupes et groupes cooperateurs. Cette enquete avait pour objectif de definir le profil des investigateurs du reseau des Groupes cooperateurs en oncologie et d’identifier certains facteurs qui pouvaient faciliter ou freiner leur activite de recherche clinique. Methodes Un questionnaire a ete envoye a tous les investigateurs ayant participe en 2014 a une etude promue par l’un des 10 membres du reseau des Groupes cooperateurs en oncologie. Il portait sur leur profil, et leur activite de recherche ainsi que sur la structuration de la recherche clinique au sein de leur etablissement. Resultats D’apres les resultats des 366 medecins repondants, les etudes des Groupes cooperateurs en oncologie ont represente une part importante de l’activite de recherche clinique des investigateurs en France en 2014. Ces groupes participent a l’ouverture de centres dans toutes les regions francaises. Une forte activite de recherche clinique des medecins (inclusions de patients > 10) est fortement associee au nombre d’attaches de recherche clinique ou de techniciens d’etudes cliniques (plus de 2 equivalents temps plein (ETP), OR = 11,16 [3,82–32,6] compare a 0 ETP) ainsi qu’a l’exercice de cette activite dans un centre hospitalier universitaire par rapport a un centre hospitalier (OR = 2,15 [1,20–3,83]). Conclusion Cette enquete a permis d’identifier des elements susceptibles de renforcer l’activite de recherche clinique des investigateurs afin de permettre ainsi a un nombre croissant de patients de beneficier de l’innovation therapeutique.

Background Adjuvant treatment in resected stage I non-small-cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/β. We explored the feasibility and efficacy of adjuvant pazopanib in this population. Patients and methods In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/day (P800) for 6 months with a two-step Fleming design. The primary endpoint was compliance (percentage of patients receiving ≥3 months pazopanib). From the interim analysis after 64 patients were included, the IDMC recommended reducing to pazopanib 400 mg/day (P400) due to insufficient compliance, with a one-step Fleming. Although unplanned, survival data were analyzed. Results A total of 71 patients were enrolled in each arm; 61% were male, 91% were smokers, median age was 60 years, 80% had pathological stage IA, and 16% had squamous cell carcinoma. Pazopanib compliance was 38% [95% confidence interval (CI) 23–55] with P800, increasing to 69% (95% CI 50–84; P = 0.027) with P400. Two patients had grade 4 toxicities with P800. The most common grade 3 toxicities were increased transaminases (16%), hypertension (13%), and diarrhea (9%) with P800, and gastrointestinal disorders (16%; 6% diarrhea) and hypertension (6%) with P400. Median follow-up was 47 months. Three-year recurrence-free survival was 76% (95% CI 65%–86%) with pazopanib and 83% (95% CI 74%–92%) with placebo [hazard ratio = 1.3 (95% CI 0.6–2.7), P = 0.53]. Five-year overall survival was 83% (95% CI 72–94) with pazopanib and 94% [95% CI 88–100] with placebo [hazard ratio = 1.8 (95% CI 0.6–5.5), P = 0.26]. Conclusions In resected stage I NSCLC patients adjuvant 400 mg/day pazopanib but not 800 mg/day was feasible, although possibly infra-therapeutic and failed to improve relapse-free survival.

Resume L’etude NLST a demontre chez plus de 53 000 grands fumeurs ou anciens grands fumeurs que le depistage annuel par scanner faiblement dose diminue de 20 % la mortalite specifique par cancer bronchopulmonaire et de 6,7 % la mortalite globale. Neanmoins, plusieurs inconvenients potentiels de ce depistage par scanner ont ete regulierement mis en avant, tels que le risque de surdiagnostic, l’irradiation liee aux scanners, et surtout le nombre eleve de faux positifs pouvant generer des examens invasifs et potentiellement dangereux, alterer la qualite de vie et l’anxiete et majorer les couts. Tous ces obstacles theoriques a l’implantation du depistage ont ete abordes dans de nombreuses publications recentes qui concluent pour la plupart a un rapport benefice/risque favorable au scanner. La plupart des societes savantes americaines recommandent de fait ce depistage. En France, un groupe d’experts s’est egalement prononce favorablement en recommandant ce depistage aux fumeurs ou anciens fumeurs de 55 a 75 ans ayant fume au minimum 30 paquets/annees. Ce groupe suggerait egalement la realisation d’etudes cliniques pour preciser et adapter la mise en œuvre de ce depistage aux contraintes et particularites francaises. La Haute Autorite de sante a toutefois juge que la mise en place de ce depistage en France etait prematuree.

International audience; Objectives: In most lung screening programmes, only subjects ≥ 55 years old and smoking ≥ 30 pack-years are eligible to undergo chest low-dose computed tomography. Whether the same criteria should apply to people living with HIV (PLHIV) is uncertain, given the increased lung cancer risks associated with immunodeficiency and high rates of smoking. We assessed different outcomes obtained from simulating one round of lung cancer screening in PLHIV using different age and smoking thresholds for eligibility.Methods: Data from the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS)-CO4 French Hospital Database on HIV (FHDH) cohort of PLHIV and a national representative survey of PLHIV in care in 2011 (the ANRS-VESPA2 [enquête sur les personnes atteintes] study) were used to estimate the maximum proportion of incident lung cancers occurring between 2012 and 2016 that would have potentially been detected by screening in 2011. Secondary outcomes were numbers of eligible subjects in the cohort and numbers of subjects needed to screen (NNS) to detect one lung cancer.Results: Among 77819 PLHIV in 2011 (median age 46 years; 66% men), 285 subjects subsequently developed lung cancer. Adoption of the US Preventive Services Task Force (USPSTF) recommendations (55-80 years; ≥ 30 pack-years) would have detected 31% of lung cancers at most. Lowering the minimum age to 50 and 45 years would have detected 49% and 60% of cancers, respectively, but would have greatly increased the number of eligible subjects and the NNS to detect one case of lung cancer.Conclusions: Use of the USPSTF criteria would have detected only a minority of lung cancers in a large French cohort of PLHIV in 2011. Screening PLHIV at younger ages (45 or 50 years) and/or the use of lower smoking thresholds (20 pack-years) may be beneficial, despite the consequently higher numbers of eligible subjects and NNS to detect one case of lung cancer, and should be evaluated in future studies.

Background Lung cancer mortality has been found to decrease significantly with low-dose (LD) computed tomographic (CT) screening among current or former smokers. However, such a screening program is not implemented in France. This study assessed the feasibility of a lung cancer screening program using LD CT scan in a French administrative territory. We report here the results of the first screening round. Patients and Methods DEP KP80 was a single-arm prospective study initiated in May 2016. Participants aged 55 to 74 years, current or former smokers of ≥ 30 pack-years, were recruited. An annual LD CT scan was scheduled. Our algorithms considered nodules 10 mm as positive; for intermediate nodules between 5 and 10 mm, 3-month CT scan with doubling time measurement was recommended. All general practitioners, pulmonologists, and radiologists from the Somme department were solicited to participate. Subjects were selected by general practitioners or pulmonologists who checked the inclusion criteria and prescribed the CT scan. Results Over a 2.5-year period, 1307 subjects were recruited. Screening was negative in 733 cases (77.2%), positive in 54 (5.7%), and indeterminate in 162 (17.1%). After the 3-month scans, 57 subjects screened positive: 26 patients exhibited 31 lung cancers (67.7% of stage 0 to I), of whom 76.9% underwent surgical resection, and 29 had no cancer (false-positive rate = 3.1%). The prevalence of lung cancer was 2.7%. Conclusion This study demonstrated the feasibility of organized lung cancer screening using LD CT scan within a real-life context in the general population.

International audience; A shift in mortality and morbidity has been observed in people living with human immunodeficiency virus (PLWHIV) from acquired immunodeficiency syndrome (AIDS) to non-AIDS diseases. Lung cancer has the highest incidence rates among all the non-AIDS-defining malignancies and is associated with mortality rates that exceed those of other cancers. Strategies to increase lung cancer survival in PLWHIV are needed. Lung cancer screening with chest LDCT has been shown to be efficient in the general population at risk. The objective of this review is to discuss lung cancer screening with chest computed tomography in PLWHIV. Lung cancer screening in PLWHIV is feasible. Whether PLWHIV could benefit from an age threshold for screening that is earlier than the minimum age of 55 years usually required in the general population still needs further investigation. Studies evaluating smoking cessation programs and how they could be articulated with lung cancer screening programs are also needed in PLWHIV.

Resume Introduction Le depistage du cancer bronchique par scanner thoracique faible dose annuel permet une reduction de mortalite. Une enquete menee en Rhone-Alpes pointait le besoin de formation des medecins sur le depistage. Les tests de concordance de script (TCS) sont une modalite d’evaluation du raisonnement clinique en situation d’incertitude, mais n’ont jamais ete utilises en France pour l’evaluation de connaissance en formation continue. Methode Un questionnaire comprenant 5 questions a choix multiples (QCM) et deux scenarios de TCS a ete envoye par courriel a tous les medecins et internes inscrits sur les listes de diffusion de la Societe de pneumologie de langue francaise (SPLF) et de l’association des jeunes pneumologues (AJPO2). Resultats Au total, 190 reponses ont ete analysees. Soixante-dix pour cent consideraient que reduire la mortalite etait le meilleur critere d’efficacite et 75 % que le scanner sans injection etait le meilleur examen de depistage. Quarante-cinq pour cent connaissaient les criteres d’eligibilite recommandes et 62 % la frequence de realisation des scanners. La participation a des reunions de concertation pluridisciplinaires, le fait d’avoir une qualification en oncologie thoracique etaient des variables significativement associees a un meilleur score aux QCM et aux TCS. Les scores obtenus aux QCM et aux TCS etaient correles (Rho de Spearman 0,339 ; p Conclusion Les TCS sont realisables a grande echelle par voie electronique et semblent pertinents. Les connaissances des pneumologues sur le depistage et sa pratique restent imparfaites.

Background: The molecular profiling of patients with advanced non-small-cell lung cancer (NSCLC) for known oncogenic drivers is recommended during routine care. Nationally, however, the feasibility and effects on outcomes of this policy are unknown. We aimed to assess the characteristics, molecular profiles, and clinical outcomes of patients who were screened during a 1-year period by a nationwide programme funded by the French National Cancer Institute. Methods This study included patients with advanced NSCLC, who were routinely screened for EGFR mutations, ALK rearrangements, as well as HER2 (ERBB2), KRAS, BRAF, and PIK3CA mutations by 28 certified regional genetics centres in France. Patients were assessed consecutively during a 1-year period from April, 2012, to April, 2013. We measured the frequency of molecular alterations in the six routinely screened genes, the turnaround time in obtaining molecular results, and patients' clinical outcomes. This study is registered with ClinicalTrials.gov, number NCT01700582. Findings 18 679 molecular analyses of 17 664 patients with NSCLC were done (of patients with known data, median age was 64·5 years [range 18–98], 65% were men, 81% were smokers or former smokers, and 76% had adenocarcinoma). The median interval between the initiation of analysis and provision of the written report was 11 days (IQR 7–16). A genetic alteration was recorded in about 50% of the analyses; EGFR mutations were reported in 1947 (11%) of 17 706 analyses for which data were available, HER2 mutations in 98 (1%) of 11 723, KRAS mutations in 4894 (29%) of 17 001, BRAF mutations in 262 (2%) of 13 906, and PIK3CA mutations in 252 (2%) of 10 678; ALK rearrangements were reported in 388 (5%) of 8134 analyses. The median duration of follow-up at the time of analysis was 24·9 months (95% CI 24·8–25·0). The presence of a genetic alteration affected first-line treatment for 4176 (51%) of 8147 patients and was associated with a significant improvement in the proportion of patients achieving an overall response in first-line treatment (37% [95% CI 34·7–38·2] for presence of a genetic alteration vs 33% [29·5–35·6] for absence of a genetic alteration; p=0·03) and in second-line treatment (17% [15·0–18·8] vs 9% [6·7–11·9]; p

Summary Background Malignant pleural mesothelioma is an aggressive cancer with poor prognosis, linked to occupational asbestos exposure. Vascular endothelial growth factor is a key mitogen for malignant pleural mesothelioma cells, therefore targeting of vascular endothelial growth factor might prove effective. We aimed to assess the effect on survival of bevacizumab when added to the present standard of care, cisplatin plus pemetrexed, as first-line treatment of advanced malignant pleural mesothelioma. Methods In this randomised, controlled, open-label, phase 3 trial, we recruited patients aged 18–75 years with unresectable malignant pleural mesothelioma who had not received previous chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0–2, had no substantial cardiovascular comorbidity, were not amenable to curative surgery, had at least one evaluable (pleural effusion) or measurable (pleural tumour solid thickening) lesion with CT, and a life expectancy of >12 weeks from 73 hospitals in France. Exclusion criteria were presence of central nervous system metastases, use of antiaggregant treatments (aspirin ≥325 mg per day, clopidogrel, ticlopidine, or dipyridamole), anti-vitamin K drugs at a curative dose, treatment with low-molecular-weight heparin at a curative dose, and treatment with non-steroidal anti-inflammatory drugs. We randomly allocated patients (1:1; minimisation method used [random factor of 0·8]; patients stratified by histology [epithelioid vs sarcomatoid or mixed histology subtypes], performance status score [0–1 vs 2], study centre, or smoking status [never smokers vs smokers]) to receive intravenously 500 mg/m 2 pemetrexed plus 75 mg/m 2 cisplatin with (PCB) or without (PC) 15 mg/kg bevacizumab in 21 day cycles for up to six cycles, until progression or toxic effects. The primary outcome was overall survival (OS) in the intention-to treat population. Treatment was open label. This IFCT-GFPC-0701 trial is registered with ClinicalTrials.gov, number NCT00651456. Findings From Feb 13, 2008, to Jan 5, 2014, we randomly assigned 448 patients to treatment (223 [50%] to PCB and 225 [50%] to PC). OS was significantly longer with PCB (median 18·8 months [95% CI 15·9–22·6]) than with PC (16·1 months [14·0–17·9]; hazard ratio 0·77 [0·62–0·95]; p=0·0167). Overall, 158 (71%) of 222 patients given PCB and 139 (62%) of 224 patients given PC had grade 3–4 adverse events. We noted more grade 3 or higher hypertension (51 [23%] of 222 vs 0) and thrombotic events (13 [6%] of 222 vs 2 [1%] of 224) with PCB than with PC. Interpretation Addition of bevacizumab to pemetrexed plus cisplatin significantly improved OS in malignant pleural mesothelioma at the cost of expected manageable toxic effects, therefore it should be considered as a suitable treatment for the disease. Funding Intergroupe Francophone de Cancerologie Thoracique (IFCT).

In 2011, the investigators of the National Lung Cancer Screening Trial reported significant decreases in lung cancer mortality (20 %) and overall mortality (6.7 %) in a selected high-risk population screened by annual low-dose computed tomography. In so doing, they relaunched the debate on lung cancer screening. In this review, we report on what has changed in this field since the publication of the NLST. We analyze results from ongoing or recent randomized trials, present data on screening optimization (such as population selection or nodule management), and discuss the practical aspects of screening, including economics considerations.

Introduction Le traitement pre-operatoire par inhibiteurs des points de controle immunitaire peut etre benefique pour les CBNPC de stade precoce. IFCT-1601 IONESCO est un essai multicentrique evaluant la faisabilite du durvalumab neoadjuvant. Methodes Les patients ayant un CBNPC resecable de stade IB > 4cm-IIIA non N2 (TNM 8e edition) recevaient 3 cures de durvalumab 750 mg (J1, 15, 29) avant la chirurgie. Le critere principal etait le % de resection chirurgicale complete (R0); les criteres d’evaluation secondaires etaient la tolerance, la survie globale (SG), la survie sans recidive (SSR), le temps entre la premiere perfusion et l’intervention chirurgicale, le taux de reponse (RECIST 1.1), le taux de reponse pathologique majeure (MPR). Resultats 50 pts ont ete inclus (04/2017 - 08/2019). 46 patients sont eligibles. 70 % hommes, âge median, 61 ans; tous ECOG PS 0-1; 94 % (ex-)fumeurs; 25 adenocarcinomes, 21 epidermoides; stades IB/IIA/IIB/IIIA n = 5/14/29/2. Parmi les 46 pts eligibles, 9 ont eu une pneumonectomie, 31 une lobectomie, 3 une bilobectomie et 3 une thoracotomie exploratrice (2 carcinoses pleurales; 1 envahissement de l’œsophage). L’etude a ete interrompue en raison d’un exces de mortalite postoperatoire a 90 jours (4 deces, 9 % avec 1 deces brutal a domicile; 1 fistule tracheale, 1 complication chirurgicale et une detresse respiratoire aigue). 3 des 4 pts decedes presentaient des comorbidites cardiovasculaires (3 hypertensions arterielles; 1 maladie arterielle peripherique; 1 cardiopathie ischemique), ou autres (1 BPCO grave; 1 diabete). 41 pts etaient R0 (90 %). Il n’y a pas eu d’EI de grade 3-5 lies au durvalumab. 4/46 pts presentaient une PR, 36 SD et 6 PD. Le temps median entre la premiere perfusion et l’intervention chirurgicale etait de 37 jours (29–46). %SG a 12 m [IC a 95 %]: 89,1 % [75,8–95,3]; %SSR a 12 m [IC a 95 %]: 78,2 % [63,3–87,6]. Le taux de MPR etait de 18,6 % avec 3 pts en reponse pathologique complete. Il existait une correlation significative entre les taux de MPR et la reponse radiologique (p = 0,028). Les pts avec MPR avaient une SSR significativement plus longue (SSR de 12 m: % [IC 95 %] 100 % contre 77,1 % [59,5–87,9], p = 0,045). Conclusion L’essai a ete arrete en raison d’une mortalite postoperatoire excessive a 90 jours. Les deces etaient dus a des complications postoperatoires probablement liees a des comorbidites et non a une toxicite directe du durvalumab. Les taux de MPR etaient significativement correles a la reponse radiologique et a la SSR.

Resume Apres chirurgie d’un carcinome bronchique non a petites cellules (CBNPC), la plupart des recommandations internationales proposent une surveillance clinique et par scanner thoracique. L’essai IFCT-0302 est la seule etude de phase III a evaluer l’impact de la surveillance tomodensitometrique sur la survie. Elle a compare deux types de surveillance : une surveillance par examen clinique et radiographie thoracique et une surveillance par examen clinique, radiographie thoracique, scanner thoraco-abdominal et fibroscopie bronchique. La surveillance etait semestrielle pendant deux ans puis annuelle jusqu’a la cinquieme annee. Parmi les 1 775 patients inclus, 82 % ont ete operes d’un CBNPC de stade I-II. Il n’existait pas de difference de survie globale, avec un taux de survie a 5 ans de 66,7 % dans le groupe surveillance clinico-radiologique et de 65,8 % dans le groupe surveille par scanner (HR = 0,95 ; IC 95% = 0,82-1,09 ; p = 0,37). Les analyses exploratoires suggerent toutefois qu’au-dela de 2 ans, le scanner pourrait avoir un interet, probablement plus en detectant precocement des seconds cancers broncho-pulmonaires que des recidives. La surveillance des formes localement avancees, traitees par chimio-radiotherapie, repose sur peu de donnees et est plutot basee sur des consensus d’experts, de meme que la surveillance des CBNPC traites par radiotherapie stereotaxique. Au-dela du versant carcinologique, la surveillance apres traitement local ou loco-regional, s’inscrit dans une evaluation globale des patients, integrant l’aide au sevrage tabagique et la prise en charge des comorbidites. © 2020 SPLF. Publie par Elsevier Masson SAS. Tous droits reserves.

Resume Les essais de phase III de chimiotherapie adjuvante et neoadjuvante ont montre un benefice de survie de l’ordre de 5 % mais la recherche clinique dans ce domaine est difficile car la duree de ces essais, qui prennent comme objectif principal la survie globale, est voisine de 10 ans. Pour raccourcir ces delais, l’utilisation de criteres de substitution comme la survie sans maladie ou la survie sans recidive est possible, mais ne permet pas de diminuer de facon importante la duree des etudes. Plusieurs travaux dans et en dehors du cancer du poumon ont montre que la reponse complete histologique ou meme le pourcentage de cellules tumorales viables apres chimiotherapie pouvaient etre correles a la survie et devenir ainsi un critere de substitution interessant. Si ceci est verifie, les etudes cliniques de chimiotherapie preoperatoire devraient pouvoir etre raccourcies, ce qui permettrait aux patients d’acceder plus rapidement a des traitements innovants en situation perioperatoire.

Resume Un depistage annuel par scanner faiblement dose diminue de 20 % la mortalite specifique par cancer bronchopulmonaire et de 6,7 % la mortalite globale par rapport a une radiographie thoracique. Plusieurs inconvenients potentiels du depistage du cancer bronchopulmonaire par scanner sont toutefois regulierement discutes, tels que le surdiagnostic, l'irradiation liee aux scanners, un effet possiblement negatif sur le tabagisme, le nombre eleve de faux positifs, la qualite de vie, l'anxiete et le cout. Tous ces obstacles theoriques a l'implantation du depistage ont ete abordes dans de nombreuses publications recentes qui concluent pour la plupart a un rapport benefices/risques favorable au scanner. D'ailleurs, la plupart des societes savantes americaines recommandent maintenant le depistage scanographique en considerant que le benefice est superieur aux inconvenients. En France, on ne dispose pas encore de recommandations officielles mais un groupe d'experts s'est prononce favorablement en recommandant que ce depistage soit reserve aux fumeurs ou anciens fumeurs de 55 a 74 ans ayant fume au minimum 30 paquets/annee et soit mis en place dans un cadre strictement organise, prenant en charge le sevrage tabagique, avec des regles precises de realisation des scanners et de gestion des positifs. Des etudes complementaires demandees a l'horizon du plan cancer 2014-2019 sont egalement attendues.

Objectives We evaluated the impact of age in a randomized phase II trial that compared three first-line drugs in elderly patients with advanced non-small cell lung cancer (NSCLC) and a poor performance status (PS). Materials and Methods Patients with advanced NSCLC with a PS of 2 or 3 were enrolled into a multicenter randomized trial: arm A, gefitinib; arm B, gemcitabine; and arm C, docetaxel. We performed subgroup analyses according to age. Results Between December 2004 and June 2007, 127 patients were enrolled. Analyses were performed between the two subgroups aged n =56) and ≥70years (older, n =71). Patients mainly had adenocarcinoma (46% young vs. 51%: elderly), of which 62% vs. 75% had a PS of 2, respectively. Significantly more elderly patients were women and non-smokers, and there was a non-significant trend towards more PS-2 among the elderly. Progression-free survival (PFS) was 1.4months (95% CI: 1.1–1.9) for younger compared to 2.3months (95% CI: 2.1–2.9) for elderly patients. Overall survival (OS) was 2.0months (95% CI: 1.5–2.4) and 3.7months (95% CI: 2.4–4.8), respectively. Toxicity did not differ between younger and older patients. NSCLC was better controlled in elderly patients after three cycles of monotherapy compared to younger patients ( p =0.034). When adjusted for stratification criteria, age was the main prognostic factor for PFS. Adjusted HRs for PFS was 0.57 (95% CI: 0.38–0.85) for the elderly compared to patients aged p =0.004). Conclusions Older patients had a decreased risk of progression/death compared to younger patients. Single-agent chemotherapy can be considered for patients aged ≥70years with a PS of 2.

The French Cancer Plan 2014-2019 stresses the importance of strengthening collaboration between all stakeholders involved in the fight against cancer, including cancer cooperative groups and intergroups. This survey aimed to describe the basics characteristics and clinical research activity among the Cancer Cooperative Groups (Groupes coopérateurs en oncologie). The second objective was to identify facilitators and barriers to their research activity.A questionnaire was sent to all the clinicians involved in 2014 as investigators in a clinical trial sponsored by one of the ten members of the Cancer Cooperative Groups network. The questions were related to their profile, research activity and the infrastructure existing within their healthcare center to support clinical research and related compliance activities.In total, 366 investigators responded to our survey. The academic clinical trials sponsored by the Cancer Cooperative Groups represented an important part of the research activity of the investigators in France in 2014. These academic groups contributed to the opening of many research sites throughout all regions in France. Factors associated with a higher participation of investigators (more than 10 patients enrolled in a trial over a year) include the existing support of healthcare professionals (more than 2 clinical research associate (CRA) OR=11.16 [3.82-32.6] compared to none) and the practice of their research activity in a University Hospital Center (CHU) rather than a Hospital Center (CH) (OR=2.15 [1.20-3.83]).This study highlighted factors that can strengthen investigator clinical research activities and subsequently improve patient access to evidence-based new cancer therapies in France.

Resume Les cancers bronchopulmonaires non a petites cellules sont diagnostiques au stade polymetastatique dans la moitie des cas. Leur pronostic, malgre les progres recents, reste dans l’ensemble tres mauvais, avec une mediane de survie avoisinant douze mois. Les formes oligometastatiques ne comportant que de une a cinq metastases meritent d’etre individualisees. Elles peuvent etre synchrones ou metachrones. Les principaux sites metastatiques concernes sont les surrenales, le cerveau et le poumon pour lesquels, a une chirurgie bifocale ou une radiotherapie stereotaxique, est generalement associe un traitement systemique. De longues survies sont parfois possibles, surtout lorsqu’il n’y a pas d’envahissement ganglionnaire mediastinal. Encore plus rarement ont ete decrits des cas de cancers oligometastatiques impliquant d’autres tissus tels l’os, la peau, le foie, le rein ou la rate… quelquefois egalement accessibles a la realisation de plusieurs traitements a visee radicale. Dans ces cas aussi, l’extension ganglionnaire mediastinale est le principal facteur pronostique. La place du traitement systemique n’est de loin pas definie de par le fait que les cas decrits sont isoles. Il est probable que ces cancers oligometastatiques qui n’evoluent pas vers un cancer multimetastatique ont un profil biologique different, comme quelques etudes - notamment sur les microARN - tendent a le montrer.

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.

There is no dedicated study on second-line treatment for elderly patients with advanced nonsmall cell lung cancer (NSCLC). We report the results on second-line erlotinib therapy from our previously published phase III study comparing single-agent therapy with platinum-based doublet (carboplatin plus paclitaxel) therapy in 451elderly patients. Erlotinib was given to patients exhibiting disease progression or experiencing excessive toxicity during first-line therapy, until further progression or unacceptable toxicity. In total, 292 (64.7%) patients received erlotinib as second-line therapy. Initial performance status 0–1, stage IV NSCLC and an Activities of Daily Living score of 6 were independent factors for receiving erlotinib. Median (95% CI) overall survival was 4 (3.2–6.7) versus 6.8 (5.0–8.3) months in the single-agent and doublet arms, respectively (p=0.089). Performance status 0–1, never having smoked, adenocarcinoma and weight loss ≤5% were favourable independent prognostic factors of survival, whereas the randomisation arm had no significant impact. Among the 292 patients who received erlotinib, 60 (20.5%) experienced grade 3–4 toxic effects, the most frequent being rash. Erlotinib as second-line therapy is feasible, leading to efficacy results similar to those obtained in a previous randomised study that was not dedicated to elderly patients, with acceptable toxicity. Erlotinib is a feasible second-line therapy in elderly patients with advanced nonsmall cell carcinoma

Most of the cases of non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage and are treated with platinum-doublet chemotherapy. However, some patients are refractory to this treatment. The aim of this study was to identify the clinical and molecular characteristics of patients with refractory disease. All consecutive patients between 2003 and 2006, who received a platinum-doublet chemotherapy as first-line treatment for stage IIIb-IV NSCLC, were included. Refractory patients were defined as early progressive disease (PD) at the first evaluation of chemotherapy according to WHO criteria. The clinical, histo-pathological, and molecular characteristics (EGFR: exon 19, 20, 21 and KRAS: exon 2 by PCR sequencing; ALK by immunohistochemistry) and survival of refractory patients with initial PD (r-patients) and controlled disease (c-patients) were compared by univariate analyses. Factors that differed between the two groups (p-value0.25 in univariate analyses) were entered into multivariate analysis. In this study, 178 patients were included. The first tumor assessment was carried out after a median of three cycles (range 1-4). Forty-six (25.8%) patients were refractory. Clinical presentation was similar between r- and c-patients. The sarcomatoid histological subtype was more common in r-patients than c-patients (10.9% vs. 1.5%, respectively; p=0.057). The proportion of EGFR (5.2% vs. 9.6%, p=0.224) and KRAS mutations (11.1% vs. 5.7%, p=0.357), and the expression of ALK (6.3% vs. 2.5%, p=0.327) did not differ significantly between the two groups. In multivariate analysis, sarcomatoid histological subtype was the only factor associated with early PD (OR=7.50; 95%CI: 1.02-55.45; p=0.048). r-Patients had significantly shorter survival than c-patients (median 5 months (IQR 3.2-9.9) vs. 15.4 months (IQR 9.9-22.5), respectively; p0.0001). In conclusion, patients with early PD under platinum-doublet chemotherapy had shorter survival than c-patients. Sarcomatoid histological subtype was the only independent factor associated with early PD.

Lung cancer is a common and serious disease, only early stage are curable. It is a logical candidate for a screening policy, especially as current and former smokers are easy to identify. The inefficiency of the chest radiograph is now proven, while the low-dose CT has shown promising data following a recent randomized study in North America. Yet, this is not specific and find a great number of benign anomalies. These limitations must be well known to physicians, radiologists and chest physicians if they use the individual screening.

Purpose This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non–small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy. Patients and Methods Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m2 days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m2 once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS). Results PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P < .001) and erlotinib (median, 2.9 v 1.9 months; HR, 0.69; 95% CI, 0.54 to 0.88; log-rank P = .003) versus observation; this benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events. Conclusion Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.

An estimated 10–25% of lung cancers worldwide occur in never smokers, i.e. individuals having smoked less than 100 cigarettes in their lifetime. Lung cancer in never smokers (LCINS) is more frequent in women, although large geographic variations are found. Histologically, adenocarcinomas predominate. The mere existence of LCINS suggests that risk factors other than smoking must be present. Exposure to environmental tobacco smoke (particularly in women) and exposure to workplace carcinogens (particularly in men) are the two most important alternative risk factors. However, a history of either is absent in more than a third of LCINS. The large proportion of women in LCINS suggest a hormonal element that may interact with other identified factors such as hereditary risks, a history of respiratory infections or disease, exposure to air pollution, cooking and heating fumes, or exposure to ionising radiation. The study of genomic polymorphisms finds constitutive DNA variations across subjects according to their smoking status, particularly in genes coding for enzymes that participate in the metabolism of certain carcinogens, in those coding for DNA repair enzymes, or in genes associated with tobacco addiction, or inflammatory processes. The type of molecular mutation in p53 or KRAS varies with smoking status. EGFR mutations are more frequent in never smokers, as are EML4-ALK fusions. The mutually exclusive nature of certain mutations is a strong argument in favour of separate genetic paths to cancer for ever smokers and never smokers. In the present paper we review current clinical and molecular aspects of LCINS.

Evaluation of: Jalal SI, Riggs HD, Melnyk A et al. Updated survival and outcomes for older adults with inoperable stage III non-small-cell lung cancer treated with cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel: analysis of a Phase III trial from the Hoosier Oncology Group (HOG) and US Oncology. Ann. Oncol. doi:10.1093/annonc/mdr565 (2011) (Epub ahead of print). The paper by Jalal et al. reports updated survival of a Phase III trial of concurrent chemoradiation with or without consolidation docetaxel for locally advanced non-small-cell lung cancer, and efficacy and tolerability data in patients ≥70 years. Of the 243 enrolled patients, 166 were randomized and 64 were aged ≥70 years (26%). There was no benefit of consolidation docetaxel. Median and 3-year survival was 17.1 months and 21.8% in patients ≥70 years, and 22.8 months and 34% in patients

Background and objective: Only a small proportion of patients with advanced non-small cell lung cancer (NSCLC) have a life expectancy greater than 2 years. The aim of this study was to identify the factors associated with long-term survival of patients with advanced NSCLC. Methods: Patients who had received chemotherapy for stage IIIb or IV NSCLC that was not amenable to radiotherapy were studied retrospectively. Data were gathered prospectively from a comprehensive database. Long-term survivors (>2 years) were compared with the other patients, with respect to clinical, biological and tumour–node–metastasis criteria. Results: Data for 245 consecutive patients were collected. Thirty nine patients (15.9%) survived for more than 2 years. Long-term survivors were more likely to have had metastases at fewer sites (P = 0.008), an absence of bone metastases (P = 0.01), a performance status (PS) of 0–1 at first progression of the tumour (P = 0.002), a tumour that was controlled with first (P 3 months (P 110 g/L at first progression of the tumour (P = 0.02). In multivariate analysis, surgery, maintenance treatment, time to first progression of the tumour of >3 months, a PS of 0–1 at first progression, the number of chemotherapy agents received, and LDH levels, were significant predictors of long-term survival. Conclusions: Assessment of these factors, and the use of maintenance therapy, when possible, may identify a population of patients with NSCLC that is likely to have a prolonged life expectancy.

Introduction: Pemetrexed is approved to treat non-small cell lung cancer and has an overall favorable toxicity profile. A case of pemetrexed-induced cutaneous adverse events (CAE), i.e., periorbital edema with conjunctivitis and edema of the limbs, leading to severe fluid retention, was diagnosed in our unit. The aim of this study was to evaluate the incidence and risk factors for CAEs. Methods: Patients treated with pemetrexed were identified from a prospective cohort. To detect pemetrexed-associated CAEs, questionnaires were answered by patients and the referring oncologist. Results: Included were 107 patients treated with four cycles or more of pemetrexed. Pemetrexed-induced CAEs were observed in 37 of 107 (35%) total patients (TPs) and 25 of 47 (53%) alive patients (APs). Conjunctivitis was the most frequent CAE: 27 of 107 (25%) in TPs and 21 of 47 (44%) in APs. Periorbital edema occurred in 16 of 107 (15%) TPs and 14 of 47 (30%) APs. Limb edema was present in 14 of 107 (13%) TPs and 12 of 47 (25%) APs. Only two cases of CAE influenced pemetrexed treatment. No significant differences in age, body surface area, smoking status, and performance status were detected. Patients with CAE had more cycles of pemetrexed (7 versus 5.5; p = 0.028). In univariate and multivariate analyses, gender ratio was statistically different ( p = 0.031): 48% (12/25) of women in the CAE group versus only 18% (4/18) in the control group. Conclusion: Pemetrexed induces frequent conjunctivitis, peripheral edema, and edema of the limbs. Female gender seems to be an independent risk for CAE. CAEs are frequently disabling and symptomatic treatment should be proposed.

Resume Justification La chimiotherapie a base de platine associee a une irradiation concomitante est le traitement conventionnel propose aux patients atteints d’un cancer bronchique non a petites cellules (CBNPC) localement avance, inoperable. De nouvelles associations therapeutiques, faisant notamment appel aux therapies biologiques ciblees, sont necessaires. Methodes Les patients eligibles, ayant un CBNPC non prealablement traite, non epidermoide, recevront une irradiation thoracique (66 Gy) concomitante a une chimiotherapie par cisplatine (75 mg/m2) et pemetrexed (500 mg/m2) administres au jour 1 d’un cycle de 21 jours pour un maximum de quatre cycles ; une perfusion hebdomadaire de cetuximab sera associee des le debut du traitement. L’objectif principal de cette etude de phase II (IFCT 0803) est d’apprecier le taux de controle de la maladie a la 16e semaine, un mois apres la fin du traitement. En se basant sur la procedure de Simon, en deux etapes, un total de 106 patients est necessaire avec une analyse intermediaire apres inclusion des 34 premiers malades. Resultats attendus Cet essai fournira des informations sur la faisabilite, l’efficacite et la tolerance de cette nouvelle association therapeutique. Un essai de phase III, testant l’apport propre du cetuximab pourra etre envisage si l’etude atteint son objectif principal.

Resume L’etude NLST a montre que le depistage du cancer du poumon par scanner low dose entraine une diminution significative de la mortalite specifique et de la mortalite globale. Ces donnees ont permis l’elaboration de recommandations des societes savantes nordamericaines et a un « avis d’experts » francais.

International audience; BACKGROUND: To compare 3 treatment strategies in chemotherapy naive patients with advanced NSCLC and a PS 2-3. PATIENTS AND METHODS: Patients were assigned to gefitinib 250mg daily (n=43) or to gemcitabine (1250mg/m(2) d 1, 8 q 21d) (n=42) or docetaxel (75mg/m(2) d 1 q 21d) (n=42). Treatments were taken until progression or toxicity. The primary endpoint was progression-free survival. Secondary end points were response and overall survival. RESULTS: Disease control rates were 20.9%, 33.4% and 38.1%, respectively. Median PFS was 1.9 months in the gefitinib arm, 2.0 months in the gemcitabine arm and 2.0 months in the docetaxel arm (HR gemcitabine versus gefitinib: 0.74, 95%CI: [0.48; 1.16], HR docetaxel versus gefitinib: 0.67, 95%CI: [0.43; 1.05]). Median survival times were 2.2, 2.4 and 3.5 months, respectively (HR gemcitabine versus gefitinib: 0.76, 95%CI: [0.48; 1.20], HR docetaxel versus gefitinib: 0.69, 95%CI: [0.44; 1.09]). There were more grade 3-4 adverse events in the docetaxel arm when compared with either the gefitinib arm or the gemcitabine arm. CONCLUSION: In unselected NSCLC patients with PS 2-3, gefitinib, gemcitabine and docetaxel achieved similar results. Docetaxel was associated with higher rates of adverse events.

Resume Nous rapportons l’observation d’une femme senegalaise hospitalisee a Paris pour une dyspnee d’effort revelant une fibrose et une hypertension arterielle pulmonaires. En l’absence d’etiologie evidente de cette fibrose, une biopsie pulmonaire chirurgicale etait realisee et revelait une granulomatose bilharzienne. Le diagnostic de poumon bilharzien chronique etait pose. Les manifestations de la bilharziose pulmonaire chronique associent hypertension arterielle pulmonaire et miliaire. Certaines formes peuvent evoluer vers la fibrose comme l’illustre notre observation et posent alors des problemes diagnostiques en dehors des zones d’endemie parasitaire. A cote des atteintes bilharziennes aigues observees chez le touriste, la possibilite de formes chroniques chez le migrant originaire de zone d’endemie doit etre connue dans les pays industrialises.

Resume Parce que c’est une maladie frequente et grave, dont le diagnostic est souvent porte avec retard et dont les populations a risque sont bien definies, le cancer broncho-pulmonaire (CBP) est un candidat logique a une politique de depistage. La preuve de l’impact du depistage par radiographie standard sur la survie n’a jusqu’a ce jour pas ete apportee. Recemment le scanner faiblement dose s’est impose comme une technique beaucoup plus sensible que la radiographie, capable de detecter des tumeurs de petits stades. Neanmoins, c’est aussi un examen tres peu specifique decelant un nombre eleve d’anomalies benignes et pouvant conduire de ce fait a des examens inutiles. Ainsi la demonstration de l’impact du scanner sur la mortalite par CBP passe par la mise en œuvre d’etudes randomisees.