Etiological Work-Up for Adults with Bronchiectasis: A Predictive Diagnostic Score for Primary Ciliary Dyskinesia and Cystic Fibrosis.

BACKGROUND: etiological investigations are not done for all adult patients with bronchiectasis because of the availability and interpretation of tests. The aim of the study was to elaborate a score to identify patients at high risk of having cystic fibrosis or primary ciliary dyskinesia (CF/PCD), which require appropriate management. METHODS: diagnostic work-ups were carried out on a French monocenter cohort, and results were subjected to logistic-regression analyses to identify the independent factors associated with CF/PCD diagnosis and, thereby, elaborate a score to validate in a second cohort. RESULTS: among 188 patients, 158 had no obvious diagnosis and were enrolled in the algorithm-construction group. In multivariate analyses, age at symptom onset (8.69 (2.10-35.99); p = 0.003), chronic ENT symptoms or diagnosed sinusitis (10.53 (1.26-87.57); p = 0.03), digestive symptoms or situs inversus (5.10 (1.23-21.14); p = 0.025), and Pseudomonas. aeruginosa and/or Staphylococcus aureus isolated from sputum (11.13 (1.34-92.21); p = 0.02) are associated with CF or PCD. Receiver operating characteristics curve analysis, using a validation group of 167 patients with bronchiectasis, confirmed the score's performance with AUC 0.92 (95% CI: 0.84-0.98). CONCLUSIONS: a clinical score may help identify adult patients with bronchiectasis at higher risk of having CF or PCD.

Anti-tumour effect of low molecular weight heparin in localised lung cancer: a phase III clinical trial.

The anti-tumour and anti-metastatic properties of heparins have not been tested in patients with early stage cancer. Whether adjuvant low molecular weight heparin (LMWH) tinzaparin impacts the survival of patients with resected non-small cell lung cancer (NSCLC) was investigated.Patients with completely resected stage I, II or IIIA NSCLC were randomly allocated to receive subcutaneous tinzaparin 100 IU·kg-1 once a day for 12 weeks or no treatment in addition to standard of care. The trial was open-label with blinded central adjudication of study outcomes. The primary outcome was overall survival.In 549 patients randomised to tinzaparin (n=269) or control (n=280), mean±sd age was 61.6±8.9 years, 190 (34.6%) patients had stage II-III disease, and 220 (40.1%) patients received adjuvant chemotherapy. Median follow-up was 5.7 years. There was no significant difference in overall survival between groups (hazard ratio (HR) 1.24, 95% CI 0.92-1.68; p=0.17). There was no difference in the cumulative incidence of recurrence between groups (subdistribution HR 0.94, 95% CI 0.68-1.30; p=0.70).Adjuvant tinzaparin had no detectable impact on overall and recurrence-free survival of patients with completely resected stage I-IIIA NSCLC. These results do not support further clinical evaluation of LMWHs as anti-tumour agents.

Intracerebral efficacy and tolerance of nivolumab in non-small-cell lung cancer patients with brain metastases.

OBJECTIVES: Although nivolumab has shown efficacy against non-small-cell lung cancers (NSCLCs), patients with active brain metastases (BMs) were excluded from pivotal clinical trials. Hence, data regarding nivolumab intracerebral activity and safety in NSCLC patients with BMs are scarce. MATERIALS AND METHODS: We conducted a retrospective multicenter study on NSCLC patients with BMs treated with nivolumab. The primary endpoint was intracerebral objective response rate (IORR), according to RECIST criteria. Secondary endpoints included intracerebral control rate, intracerebral and general progression-free survival (PFS), overall survival (OS) and tolerance. RESULTS AND CONCLUSION: Forty-three patients were included. BMs were locally pretreated in 34 (79%) patients and active in 16 (37%) patients. Median follow-up was 5.7 (95% CI: 2.7-8.4) months. IORR and extracerebral response rate were, respectively, 9% (95% CI: 3-23%) and 11% (95% CI: 4-26%). Intracerebral control rate was 51% (95% CI: 37-66%). Median intracerebral and general PFS lasted 3.9 (95% CI: 2.8-11.1) and 2.8 (95% CI: 1.8-4.6) months, respectively. Median OS was 7.5 (95% CI: 5.6-not reached) months. Five neurological adverse events occurred, including 1 grade-4 transient ischemic attack of uncertain imputability and 1 grade-3 neurological deficit; neither required nivolumab discontinuation. Nivolumab intracerebral activity was similar to its reported extracerebral efficacy, with an acceptable safety profile. Prospective and controlled data are needed to determine nivolumab's place in treatment of NSCLC patients with BMs.

Delays for diagnosis and treatment of lung cancers: a systematic review.

BACKGROUND AND AIMS: The impact of diagnosis and treatment delays for non-small cell lung cancer management is poorly understood, even if the literature on the subject is currently increasing in importance. We have few indicators that can serve as reference for quality assurance actions. The objective of this review was to review the literature on the subject. METHODS: A literature search, using the words 'human lung cancer delay' and 'human lung cancer waiting time', was undertaken in Medline database. RESULTS: Several studies analyzed these delays mostly in a monocentric setting. There is an important variability in the definition of these delays, in the collection methods and in the results obtained. However, it seems distinctly clear that long delays are frequently observed in less symptomatic patients and, therefore, are accompanied by better prognosis. CONCLUSION: More standardized definitions and procedures to calculate time intervals between cancer diagnosis and treatment should be implemented to better understand the delays of lung cancer management.

Crizotinib Associated with Ground-Glass Opacity Predominant Pattern Interstitial Lung Disease: A Retrospective Observational Cohort Study with a Systematic Literature Review.

BACKGROUND: Crizotinib, an oral tyrosine kinase inhibitor that targets anaplastic lymphoma kinase, has proven to offer sustained progression-free survival in anaplastic lymphoma kinase-rearranged non-small-cell lung cancers. Occurrence of severe interstitial lung disease (ILD) was one of the crucial adverse events reported in randomized clinical trials and case reports. METHODS: In September 2011, we observed a crizotinib-associated ILD case. Following this index case, we reviewed the clinical and computed tomographic scan features of all patients treated with crizotinib in our department, between October 2010 and July 2013, comparing patients with and without ILD. A systematic literature review was performed. RESULTS: During this period, 29 patients were treated with crizotinib, five of whom developed ILD, in addition to the index case. Two types of adverse lung reactions may be observed in patients undergoing crizotinib therapy. The first is a severe, usually fatal, ILD that occurs during the first month of treatment (n = 1). The second is a less severe ILD, occurring later in time (n = 5). It occurs gradually with only few clinical symptoms, but predominant ground-glass opacities on computed tomography, along with an intensive lymphocytic alveolitis in bronchoalveolar lavage fluid. These cases had a longer response with a median progression-free survival duration at 19.9 months (17.9-23.5) compared with 6.2 months (1.2-13.6) for controls (p = 0.04). CONCLUSION: Forty-nine cases of crizotinib-associated ILD have been identified by the systematic review of the literature, including our six cases. Two types of adverse lung reactions may be observed with different presentation, prognosis, and treatment. Their potential mechanisms should be clarified. Nine patients with the less severe form of ILD were safely retreated.