Long-Term Consequences of Spirometry During Military Routine Medical Examinations on Smoking Cessation Compared to Minimal Advice.

BACKGROUND: Smoking kills 8 million people a year worldwide. It is the most prevalent cause of death in France by cancer, cardiovascular, or respiratory diseases. Minimal advice consists in asking patients who smoke if they are interested in quitting. It is effective in reducing smoking. The French High Health Authority recommends its systematic use with patients, whatever their reason for seeking treatment. The beneficial effect of spirometry on smoking cessation is controversial. The objective of our study was to measure the consequences of spirometry associated with minimal advice, compared with only minimal advice in soldiers seen during a routine medical examination. METHODS: Our prospective, longitudinal, open, multicenter, controlled, randomized study was conducted among French military smokers presenting for an occupational medicine visit. Each participant received, depending on their group (intervention or control), either minimal advice associated with an evaluation of lung function by mini-spirometer, or only minimal advice. Follow-up visits were performed at 6 and 12 months. The primary objective was self-reported tobacco use cessation at 6 months. RESULTS: A total of 267 participants (126 in the intervention group and 141 for the control arm) were included in 10 centers between June 2019 and June 2020. The response rate was 75.6% at 6 months. The cessation rates were 17% and 18% in the intervention and control groups, respectively, with no significant difference between the two groups (P = 0.9). The cessation rate in the general population was 13% at 6 months. CONCLUSIONS: Spirometry does not seem to influence smoke cessation on a military population at 6 months. The overall cessation rate in our study was well in excess of the 3-6% expected from only providing minimal which is underused in general practice and should be encouraged.

Improvement in severe asthma patients receiving biologics and factors associated with persistent insufficient control: a real-life national study.

BACKGROUND: Biological therapies have revolutionized the treatment of severe asthma with type 2 inflammation. Although such treatments are very effective in reducing exacerbation and the dose of oral steroids, little is known about the persistence of symptoms in severe asthma patients treated with biologics. PURPOSE: We aim to describe asthma control and healthcare consumption of severe asthma patients treated with biologics. DESIGN: The Second Souffle study is a real-life prospective observational study endorsed by the Clinical Research Initiative in Severe Asthma: a Lever for Innovation & Science Network. METHODS: Adults with a confirmed diagnosis of severe asthma for at least 12 months' duration were enrolled in the study. A self-administered questionnaire including the Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ) and a compliance evaluation test was given to the patients. Healthcare consumption within 12 months prior to enrolment was documented. In patients receiving biologics, doctors indicated whether the patients were biologic responders or non-responders. RESULTS: The characteristics of 431 patients with severe asthma were analysed. Among them, 409 patients (94.9%) presented asthma with type 2 inflammation (T2 high) profile, and 297 (72.6%) patients with a T2 high phenotype were treated with a biologic. Physicians estimated that 88.2% of patients receiving biologics were responders. However, asthma control was only achieved in 25.3% of those patients (ACQ > 0.75). A high proportion of patients (77.8%) identified as responders to biologics were not controlled according to the ACQ score. About 50% of patients continue to use oral corticosteroids either daily (25.2%) or more than three times a year for at least three consecutive days (25.6%). Gastro-oesophageal Reflux Disease (GERD) and Obstructive Sleep Apnoea syndrome (OSA) were identified as independent factors associated with uncontrolled asthma. CONCLUSION: Although a high proportion of severe asthma patients respond to biologics, only 25.3% have controlled asthma. GERD and OSA are independent factors of uncontrolled asthma.

Pulmonary embolism diagnostic strategies in patients with COPD exacerbation: Post-hoc analysis of the PEP trial.

BACKGROUND: The prevalence of pulmonary embolism (PE) is approximately 11-17 % in patients with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). The optimal diagnostic strategy for PE in these patients remains undetermined. AIMS: To evaluate the safety and efficacy of standard (revised Geneva and Wells PE scores combined with fixed D-dimer cut-off) and computed tomography pulmonary angiogram (CTPA)-sparing diagnostic strategies (ADJUST-PE, YEARS, PEGeD, 4PEPS) in patients with AE-COPD. METHOD: Post-hoc analyses of data from the multicenter prospective PEP study were performed. The primary outcome was the diagnostic failure rate of venous thromboembolism (VTE) during the entire study period. Secondary outcomes included diagnostic failure rate of PE and deep venous thrombosis (DVT), respectively, during the entire study period and the number of CTPA needed per diagnostic strategy. RESULTS: 740 patients were included. The revised Geneva and Wells PE scores combined with fixed D-dimer cut-off had a diagnostic failure rate of VTE of 0.7 % (95%CI 0.3 %-1.7 %), but >70.0 % of the patients needed imaging. All CTPA-sparing diagnostic algorithms reduced the need for CTPAs (-10.1 % to -32.4 %, depending on the algorithm), at the cost of an increased VTE diagnosis failure rate of up to 2.1 % (95%CI 1.2 %-3.4 %). CONCLUSION: Revised Geneva and Wells PE scores combined with fixed D-dimer cut-off were safe, but a high number of CTPA remained needed. CTPA-sparing algorithms would reduce imaging, at the cost of an increased VTE diagnosis failure rate that exceeds the safety threshold. Further studies are needed to improve diagnostic management in this population.

Randomized controlled trial of home-based vs. hospital-based pulmonary rehabilitation in post COVID-19 patients.

BACKGROUND: Between 30% and 60% of people who have been infected with COVID-19 still had symptoms 3 months after the start of the disease. Prescribing a pulmonary rehabilitation program in rehabilitation facilities for post COVID-19 patients could help alleviate the symptoms. However, rehabilitation facilities known to provide good quality care to COVID-19 patients and all other patients, could become saturated by the rise in cases. Home-based rehabilitation is a potential solution that could be sustainable in the long term to avoid this saturation and/or a very long waiting list for patients. AIM: The aim of this study was to investigate whether home-based rehabilitation would have similar effects compared to inpatient rehabilitation on physical and respiratory variables in post COVID-19 patients. DESIGN: This is a randomized controlled trial. SETTING: Pulmonary rehabilitation facility. POPULATION: Seventeen post COVID-19 patients were randomized into two groups: inpatient pulmonary rehabilitation (IPR) or home-based pulmonary rehabilitation (HPR). METHODS: The comparison of the two rehabilitation methods relied on questionnaires, physical tests and the evaluation of several respiratory parameters. A 2-way Analysis of Variance (ANOVA) with repeated measures was performed to assess the effects of time (pre- vs. post-rehabilitation), group (IPR vs. HPR) and their interaction for all parameters. RESULTS: The main result of this study is that distance covered in the 6MWT (6MWD) shows significant improvements, between pre- and postrehabilitation program in both groups (+95 m in IPR group vs.+72 m in HPR group, P<0.001) with no significant interaction between time and group (P=0.420). CONCLUSIONS: These results suggest that home-based pulmonary rehabilitation would be as efficient as IPR to decrease physical sequelae in post COVID-19 patients. CLINICAL REHABILITATION IMPACT: It is possible to suggest both methods (home-based rehabilitation or inpatient pulmonary rehabilitation) according to the specificities of each patient and depending on hospital saturation. The choice of one or the other method should not be made to the detriment of the patient.

Enoxaparin versus Placebo to Prevent Symptomatic Venous Thromboembolism in Hospitalized Older Adult Medical Patients.

BACKGROUND: Admission to the hospital is a major risk factor for the development of venous thromboembolism (VTE). Whether thromboprophylaxis with low-molecular-weight heparin prevents symptomatic VTE in medically ill, hospitalized older adults remains debated. METHODS: In a prospective, randomized, placebo-controlled, double-blind, multicenter trial, older adults (>70 years of age) hospitalized for acute medical conditions were randomly assigned to receive 40 mg a day of low-molecular-weight heparin (enoxaparin) or placebo for 6 to 14 days. The primary efficacy outcome was the cumulative incidence of symptomatic VTE (distal or proximal deep vein thrombosis, fatal or nonfatal pulmonary embolism) at 30 days. The primary safety outcome was major bleeding. Secondary outcomes included efficacy and safety outcomes at 90 days. RESULTS: The trial was prematurely discontinued in September 2020, 5 years after enrollment began, because of drug supply issues. By the time of trial discontinuation, 2559 patients had been randomly assigned at 47 centers. Median age was 82 years and 60% of patients were female. In the intention-to-treat population, the primary efficacy outcome occurred in 22 out of 1278 (cumulative incidence, 1.8%) patients in the enoxaparin group and in 27 out of 1263 (cumulative incidence, 2.2%) patients in the placebo group (cumulative incidence difference, −0.4 percentage points; 95% confidence interval, −1.5 to 0.7), with no significant difference in time to VTE (P=0.46). The incidence of major bleeding was 0.9% in the enoxaparin group and 1.0% in the placebo group. At 90 days there were 14 symptomatic pulmonary emboli in the enoxaparin group and 25 in the placebo group; all 39 pulmonary embolism events resulted in hospital readmission and/or death, with 5 deaths from pulmonary embolism in the enoxaparin group and 11 deaths in the placebo group. CONCLUSIONS: This trial of thromboprophylaxis in medically ill, hospitalized older adults did not demonstrate that enoxaparin reduced the risk of symptomatic VTE after 1 month. Because the trial was prematurely discontinued, larger trials are needed to definitively address this question. (Funded by the French Ministry of Health Programme Hospitalier de Recherche Clinique, grant number PHRC-N-13-0283; ClinicalTrials.gov number, NCT02379806.)

Management of patients with synchronous head-and-neck and lung cancers: SYNCHRON GFPC 15-01 study.

Purpose: Few data have been published on the management of patients with synchronous head-and-neck cancer (HNC) and lung cancer (LC). This observational study was undertaken to describe the management of these patients in multiple centers. Materials and Methods: All patients consecutively diagnosed with synchronous HNC and LC in 26 French centers were included. Information was collected on patients' clinical characteristics, management, and outcomes. Those characteristics and treatments were analyzed descriptively. Kaplan-Meier progression-free and overall survival probabilities were estimated. Results: The study included 132 patients: 83% male; median age: 63.7 (range: 62.1-65.4) years; all current or former smokers; Eastern Cooperative Oncology Group performance status: 0 or 1 for 21.9% or 65.9% of the patients, respectively; cardiovascular comorbidities: 63%; chronic obstructive pulmonary disease: 33%; and previous cancer: 11%. HNC histology was 98% squamous: 23.5% oral cavity, 26.5% oropharyngeal, 22.0% hypopharyngeal, and 28.0% laryngeal. LCs were mainly localized (47.7% Stage I and 9.9% Stage II): 38% squamous, 49% adenocarcinomas, and 13% others. LC diagnosis impacted HNC management for 38% of the patients, with a median time from HNC diagnosis to first HNC treatment of 40 days. HNC impacted LC management for 48% of the patients, with a median time from LC diagnosis-to-LC treatment interval of 41 days. Conclusions: Synchronous LC at HNC diagnosis impacted management and outcomes of both cancers. Specific recommendations should be elaborated to improve the management of these patients.

Alleged Allergy to Penicillin and Isolation Issues: Toward New Practices for French Navy?

INTRODUCTION: According to the literature, 8% of the population claim to have an allergy to penicillin. Allergy tests show that 90% of these patients tolerate this molecule. Physicians working in the French Navy are faced with situations of real isolation and only have a limited number of antibiotics on board, the majority of which are penicillins. They must anticipate the risks linked to the prescription of antibiotics before the mission. However, there is no French recommendation, either military or civilian, intended for general practitioners clarifying the management and allergy assessments of patients alleging a history of allergy to penicillin. This study is the first to evaluate the professional practices of French military practitioners taking care of these patients. The main objective was to evaluate the proportion of sailors who reported an allergy to penicillin and who have never been referred for a consultation with an allergist, by studying the medical files of all the submariners working on the submersible ballistic nuclear submarines squadron in Brest. The secondary objective was to compare these data with the practices of Navy doctors by means of questionnaires. MATERIAL AND METHODS: Our work is composed of two parts: monocentric study of the digital and paper medical files of Brest submariners (n = 814) looking for allergist consultation reports in cases alleging an allergy to penicillin, then comparison with a multicentric collection of all Navy doctors' practices collected by an anonymized questionnaire (n = 37 out of 53 practicing at the time of the study). RESULTS: Forty-seven subjects out of 814 alleged an allergy to penicillin (5.8%). Among them, only 12 (25.5%) had undergone allergy tests, of which 3 (6.4%) were confirmed to be allergic, with no cross-reaction between ß-lactam antibiotics. Yet, according to the questionnaire, 25 doctors (67%) report referring their patients to an allergist and 16 (43%) report having had difficulties at sea in connection with the prescription of antibiotics for these patients. CONCLUSIONS: A study of medical records shows that the allergic risk is not anticipated for 74.5% of patients labeled allergic, despite the difficulties encountered at sea. Standardization of practices within the French Navy is necessary to avoid the prescription of second-line antibiotics, less effective and sometimes unavailable on board, and to improve patient safety in isolation situations. In agreement with French military allergists, we propose, in this article, guidelines for a systematic exploration of allegations of allergy to penicillin in the French Navy.

Prevalence of Pulmonary Embolism Among Patients With COPD Hospitalized With Acutely Worsening Respiratory Symptoms.

IMPORTANCE: The prevalence of pulmonary embolism in patients with chronic obstructive pulmonary disease (COPD) and acutely worsening respiratory symptoms remains uncertain. OBJECTIVE: To determine the prevalence of pulmonary embolism in patients with COPD admitted to the hospital for acutely worsening respiratory symptoms. DESIGN, SETTING, AND PARTICIPANTS: Multicenter cross-sectional study with prospective follow-up conducted in 7 French hospitals. A predefined pulmonary embolism diagnostic algorithm based on Geneva score, D-dimer levels, and spiral computed tomographic pulmonary angiography plus leg compression ultrasound was applied within 48 hours of admission; all patients had 3-month follow-up. Patients were recruited from January 2014 to May 2017 and the final date of follow-up was August 22, 2017. EXPOSURES: Acutely worsening respiratory symptoms in patients with COPD. MAIN OUTCOMES AND MEASURES: The primary outcome was pulmonary embolism diagnosed within 48 hours of admission. Key secondary outcome was pulmonary embolism during a 3-month follow-up among patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulant treatment. Other outcomes were venous thromboembolism (pulmonary embolism and/or deep vein thrombosis) at admission and during follow-up, and 3-month mortality, whether venous thromboembolism was clinically suspected or not. RESULTS: Among 740 included patients (mean age, 68.2 years [SD, 10.9 years]; 274 women [37.0%]), pulmonary embolism was confirmed within 48 hours of admission in 44 patients (5.9%; 95% CI, 4.5%-7.9%). Among the 670 patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulation, pulmonary embolism occurred in 5 patients (0.7%; 95% CI, 0.3%-1.7%) during follow-up, including 3 deaths related to pulmonary embolism. The overall 3-month mortality rate was 6.8% (50 of 740; 95% CI, 5.2%-8.8%). The proportion of patients who died during follow-up was higher among those with venous thromboembolism at admission than the proportion of those without it at admission (14 [25.9%] of 54 patients vs 36 [5.2%] of 686; risk difference, 20.7%, 95% CI, 10.7%-33.8%; P < .001). The prevalence of venous thromboembolism was 11.7% (95% CI, 8.6%-15.9%) among patients in whom pulmonary embolism was suspected (n = 299) and was 4.3% (95% CI, 2.8%-6.6%) among those in whom pulmonary embolism was not suspected (n = 441). CONCLUSIONS AND RELEVANCE: Among patients with chronic obstructive pulmonary disease admitted to the hospital with an acute worsening of respiratory symptoms, pulmonary embolism was detected in 5.9% of patients using a predefined diagnostic algorithm. Further research is needed to understand the possible role of systematic screening for pulmonary embolism in this patient population.

Impact of Tobacco Smoking on the Risk of COVID-19: A Large Scale Retrospective Cohort Study.

INTRODUCTION: Preliminary reports indicated that smokers could be less susceptible to coronavirus SARS-CoV-2, which causes Covid-19. However, once infected an increased risk of severe disease is reported. We investigated the association between smoking and COVID-19 during an outbreak of the disease on a naval vessel. METHODS: We conducted a cross-sectional, observational study on the 1769 sailors of the same navy aircraft carrier at sea exposed at the same time to SARS-CoV2 to investigate the link between tobacco consumption and Covid-19. RESULTS: Among the 1688 crewmembers (87% men; median age = 28 [interquartile range 23-35]) included, 1279 (76%) developed Covid-19 (1038 [62%] reverse-transcriptase- polymerase chain reaction testing-positive and 241 [14%] with only clinical signs). One hundred and seven patients were hospitalized. The univariable analysis odds ratio (OR) for Covid-19 infection was 0.59 (95% confidence interval [CI], 0.45-0.78; p < .001) for current smokers versus former and nonsmokers; sex, body mass index or blood group had no significant impact. Crewmembers >50 years old had an increased risk of contracting Covid-19 (OR, 2.84 [95% CI, 1.30-7.5]; p = .01). Multivariable analysis retained the lower risk of current smokers becoming infected (OR, 0.64 [0.49-0.84]; p < .001) and age >50 years was significatively associated with Covid-19 (OR, 2.6 [1.17-6.9]; p = .03). CONCLUSIONS: Current smoking status was associated with a lower risk of developing Covid-19 but cannot be considered as efficient protection against infection. The mechanism of the lower susceptibility of smokers to SARS-CoV-2 requires further research. TRIAL REGISTRATION: IRB no.: 0011873-2020-09. IMPLICATIONS: (1) Recent epidemiologic data suggest a paradoxical link between smoking and COVID-19. (2) Among the 1688 crewmembers (with an attack rate of 76% and exposed at the same time in the same place to SARS-CoV2), we found a significantly lower risk for developing COVID-19 in current smokers (71%) versus former and nonsmokers (80%). This finding strongly supports the need for further research on nicotine physiological pathway and its impact on COVID-19 infection whilst emphasizing that tobacco smoking should not be considered as efficient protection against COVID-19.

Targeting the MET-Signaling Pathway in Non-Small-Cell Lung Cancer: Evidence to Date.

The c-MET proto-oncogene (MET) plays an important role in lung oncogenesis, affecting cancer-cell survival, growth and invasiveness. The MET receptor in non-small-cell lung cancer (NSCLC) is a potential therapeutic target. The development of high-output next-generation sequencing techniques has enabled better identification of anomalies in the MET pathway, like the MET exon-14 (METex14) mutation. Moreover, analyses of epidermal growth factor-receptor (EGFR) and mechanisms of resistance to tyrosine-kinase inhibitors (TKIs) demonstrated the importance of MET amplification as an escape mechanism in patients with TKI-treated EGFR-mutated NSCLCs. This review summarizes the laboratory findings on MET and its anomalies, trial results on METex14 alterations and MET amplification in non-EGFR mutated NSCLCs, and acquired resistance to TKI in EGFR-mutated NSCLCs. The outcomes of the first trials with anti-MET agents on non-selected NSCLC patients or those selected for MET overexpression were disappointing. Two situations seem the most promising today for the use of anti-MET agents to treat these patients: tumors harboring METex14 and those EGFR-sensitive mutation mutated under TKI-EGFR with a MET-amplification mechanism of resistance or EGFR-resistance mutation.

Assessment of preoperative noninvasive ventilation before lung cancer surgery: The preOVNI randomized controlled study.

OBJECTIVES: The preOVNI study was a randomized, controlled, open-label study that investigated whether preoperative noninvasive ventilation (NIV) could reduce postoperative complications after lung cancer surgery. METHODS: Adult patients with planned lung cancer resection and with at least 1 cardiac or respiratory comorbidity were included and randomly assigned to preoperative NIV (at least 7 days and 4 h/day) or no NIV. The primary endpoint was the rate of postoperative protocol-defined complications. RESULTS: Three hundred patients were included. In the NIV group, the median NIV duration was 8 days. No difference of postoperative complication rates was evidenced: 42.6% in NIV group and 44.8% in no-NIV group (P = .75). The rate of pneumonia was greater in no-NIV group compared with the NIV group, but statistical significance was not achieved (28.0 vs 37.7%, respectively; P = .08). The type of surgery (open or minimally invasive) did not impact these results after multivariable analysis. CONCLUSIONS: No benefit was evidenced for preoperative NIV before lung cancer surgery. Further studies should determine the optimal perioperative management to decrease the rate of postoperative complications.

Effect of Early Initiation of Varenicline on Smoking Cessation in COPD Patients Admitted for Exacerbation: The Save Randomized Clinical Trial.

Our main objective was to demonstrate that, in smoker patients hospitalised for Chronic Obstructive Pulmonary Disease (COPD) exacerbation, early initiation of varenicline during 12 weeks, combined with an intensive counselling, is associated with a higher continuous abstainers rate (CAR) at one year as compared to intensive counselling alone. In this multicenter, prospective, double-blind, randomised study, 81 smoking COPD patients hospitalised for an acute exacerbation for at least 24 h were allocated to receive either varenicline (n = 42) or placebo (n = 39) for 12 weeks, in association with an intensive counselling in the 2 groups, and followed up for 40 weeks. The primary outcome was CAR at week 52. Secondary outcomes included CAR at week 12 and 26, partial abstinence rate (PAR) at week 12, 26 and 52, nicotinic substitute consumption and adverse events. At week 52, CAR was not different in placebo and varenicline groups (25.6%). At week 12, CAR was significantly higher in the varenicline group (50%) as compared to placebo group (27%) (p = 0.041). Nicotine consumption was significantly higher at week 52 in the placebo group (55.3%) as compared to the varenicline group (24.4%) (p = 0.005). There was no significant difference in PAR at week 12, 26 and 52; the frequency of adverse events was similar between the two groups. Among active smoker COPD patients with exacerbation, 12-week varenicline associated with intensive counselling for smoking cessation increased the rate of continuous abstainers as compared to placebo. However, benefit was not maintained after varenicline discontinuation.Clinical Trials Registration: URL: http://www.controlled-trials.com. Unique identifier: NCT01694732.

Management and outcomes of non-small cell lung cancer patients with rapid progression under second-or-more-line immune checkpoint inhibitors: ERORECI study (GFPC 2016-04).

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been approved as second-line therapy for advanced non-small cell lung cancers (NSCLCs) progressing after platinum-based chemotherapy. However, some patients' disease progressed rapidly and sometimes exhibited explosive tumor progression. This descriptive, prospective study aimed to assess the characteristics of nonresponders with rapid progression (RP), defined as progression-free survival (PFS) ≤2 or 2-4 months under ICIs. METHODS: This analysis included all consecutive ICI-treated (second-or-more line) patients with RP ≤4 months from 1 September 2016 to 31 August 2017 and compared the clinical characteristics, treatments, and outcomes (overall survival [OS]; responses; PFS, according to treatment line) of NSCLCs that progressed after ≤2 vs 2-4 months on ICIs. RESULTS: Comparisons of the 224 (70.2%) patients with ≤2-month and 95 (29.8%) with 2- to 4-month RP revealed the former had less frequent nonsmokers and ECOG PS = 0, more frequent stage IV disease and higher neutrophil/lymphocyte ratio. Their respective ICI PFS rates were: 1.6 [95% CI: 0.1-2] and 2.7 [2.0-4.2] months, with 16.5% and 11.6% having partial responses to first- and second-line therapies post-ICI chemotherapy. Their respective median OS rates were 6.0 and 9.0 months (P ≤ .009). Multivariate analysis retained only PFS of the first-line therapy pre-ICI and neutrophil/lymphocyte ratio at ICI onset as being significantly associated with ≤2-month RP. CONCLUSION: In the real-life setting, NSCLC RP on ICI remains a challenge. New descriptive and analytic studies are needed to identify factors predictive of RP.

Patent Foramen Ovale and Ischemic Stroke in Patients With Pulmonary Embolism: A Prospective Cohort Study.

Background: Pulmonary embolism (PE) is associated with increased risk for ischemic stroke, but the underlying mechanism remains unclear. The authors hypothesized that paradoxical embolism through patent foramen ovale (PFO) should be the main mechanism. Objective: To determine the frequency of recent ischemic stroke in patients with symptomatic PE according to whether PFO was detected. Design: Prospective cohort study with masked assessment of stroke outcomes. (ClinicalTrials.gov: NCT01216423). Setting: 4 French hospital centers. Participants: 361 consecutive patients with symptomatic acute PE from 13 November 2009 through 21 December 2015. Intervention: Systematic contrast transthoracic echocardiography (TTE) and cerebral magnetic resonance imaging (MRI) within 7 days after enrollment. Measurements: Recent symptomatic or silent ischemic stroke was diagnosed on the basis of clinical examination and cerebral MRI showing a hypersignal on the trace diffusion-weighted image with reduction or pseudonormalization of apparent diffusion coefficient. Results: Contrast TTE was conclusive in 324 of 361 patients and showed PFO in 43 patients (13%). The median age was 66 years (interquartile range, 54 to 77 years). In total, 51% of patients (145/284) had associated deep venous thrombosis, 91% (279/306) had cardiovascular risk factors, and 10% (16/151) presented with arrhythmia (no difference between PFO and non-PFO groups). Cerebral MRI was conclusive in 315 patients. Recent ischemic stroke was more frequent in the PFO group than in the non-PFO group (9 of 42 patients [21.4%] vs. 15 of 273 patients [5.5%]; difference in proportions, 15.9 percentage points [95% CI, 4.7 to 30.7 percentage points]). Limitation: Because of inconclusive contrast TTE or MRI, 46 patients were excluded from analysis. Conclusion: Frequency of recent ischemic stroke in patients with symptomatic PE was higher in patients with PFO than in those without PFO. This finding supports the hypothesis that paradoxical embolism is an important mechanism of ischemic stroke in patients with PFO. Primary Funding Source: French Ministry of Health.

First-Line Treatment of Non-Small-Cell Lung Cancer (NSCLC) with Immune Checkpoint Inhibitors.

Treatment of advanced-stage or metastatic non-small-cell lung cancers (NSCLCs) without EGFR mutations or ALK rearrangements, which can now be treated with molecularly targeted therapies, had been based on cytotoxic chemotherapy for a long time. Immune checkpoint inhibitors (ICIs), notably antibodies directed against programmed cell-death protein-1 (PD-1) and its ligand (PD-L1) have transformed therapeutic standards in thoracic oncology. These ICIs are now the reference second-line treatment and numerous phase III trials have examined their efficacy in treatment-naïve patients. First-line pembrolizumab monotherapy was validated for patients with ≥ 50% of tumor cells expressing PD-L1; pembrolizumab, atezolizumab, and nivolumab have obtained good outcomes in combination with chemotherapy or another immunotherapy. However, in this context, other phase III trials yielded negative findings for nivolumab alone (CheckMate-026) or in combination (MYSTIC trial). Biomarkers, such as PD-L1 and the tumor mutation burden (TMB), enable better selection of patients who should benefit the most from first-line ICI use.

Potential Antiangiogenic Treatment Eligibility of Patients with Squamous Non-Small-Cell Lung Cancer: EPISQUAMAB Study (GFPC 2015-01).

BACKGROUND: Antiangiogenic agents have improved the prognosis of non-squamous non-small-cell lung cancers (NSCLCs), even though all the patients are not eligible to receive them because of counterindications linked to the tumor's characteristics or comorbidities. Much less information is available about the eligibility of patients with squamous non-small-cell lung cancers (SQ-NSCLCs) to receive antivascular endothelial growth-factor (VEGF) treatments, even though such molecules are being developed for this histology. This study was undertaken to determine the percentage of advanced SQ-NSCLC patients who would be eligible to receive an antiVEGF agent as second-line systemic therapy. METHODS: This observational, multicenter, prospective study evaluated advanced SQ-NSCLC patients' criteria for ineligibility to receive an antiVEGF during a multidisciplinary meeting to choose their standard second-line systemic therapy. RESULTS: Among the 317 patients included, 53.6% had at least one ineligibility criterion, and ~20% had at least two, with disease extension to large vessels (39.8%), tumor cavitation (20.5%), cardiovascular disease (11%) and/or hemoptysis (7.2%) being the most frequent. Patients with an ECOG performance score of 1/2 had more cardiovascular contraindications that those with scores of 0. CONCLUSION: Almost half of the SQ-NSCLC patients included in this study would have been eligible to receive an antiVEGF agent. The development of these molecules for these indications should be encouraged.

New PDL1 inhibitors for non-small cell lung cancer: focus on pembrolizumab.

The advent of immune-checkpoint inhibitors during the past decade represents a major advancement in the treatment of non-small cell lung cancer (NSCLC) with personalized treatment. Platinum-based chemotherapy has reached its efficacy threshold, with its use remaining limited by its toxicity. For NSCLC, inhibitors of the PD1 protein and its ligand PDL1 show promising clinical activity and induce durable responses in patients with advanced disease. The US Food and Drug Administration has approved pembrolizumab for treatment-naïve metastatic NSCLC with ≥50% of tumor cells expressing PDL1 and for metastatic NSCLC with ≥1% PDL1 expression after progression following first-line platinum-based doublet chemotherapy. In 2017, it also authorized the first-line combination of pembrolizumab and carboplatin-pemetrexed chemotherapy without selection based on PDL1 expression, but European health authorities are still waiting for the results of a Phase III trial. In this review, the clinical results of published and ongoing studies evaluating pembrolizumab for advanced NSCLC are analyzed and the potential role of PDL1 as a factor predictive of overall responses addressed.