Impact of Silicone Stent Placement in Symptomatic Airway Obstruction due to Non-Small Cell Lung Cancer - A French Multicenter Randomized Controlled Study: The SPOC Trial.

BACKGROUND: Therapeutic bronchoscopy (TB) is an accepted strategy for the symptomatic management of central airway malignant obstruction. Stent insertion is recommended in case of extrinsic compression, but its value in preventing airway re-obstruction after endobronchial treatment without extrinsic compression is unknown. OBJECTIVE: Silicone stent Placement in symptomatic airway Obstruction due to non-small cell lung Cancer (SPOC) is the first randomized controlled trial investigating the potential benefit of silicone stent insertion after successful TB in symptomatic malignant airway obstruction without extrinsic compression. METHOD: We planned an inclusion of 170 patients in each group (stent or no stent) over a period of 3 years with 1-year follow-up. The 1-year survival rate without symptomatic local recurrence was the main endpoint. Recurrence rate, survival, quality of life, and stent tolerance were secondary endpoints. During 1-year follow-up, clinical events were monitored by flexible bronchoscopies and were evaluated by an independent expert committee. RESULTS: Seventy-eight patients (mean age 65 years) were randomized into 2 arms: stents (n = 40) or no stents (n = 38) after IB. Consequently, our main endpoint could not be statistically answered. Improvement of dyspnea symptoms is noticeable in each group but lasts longer in the stent group. Stents do not change the survival curve but reduce unattended bronchoscopies. In the no stent group, 19 new TB were performed with 16 stents inserted contrasting with 10 rigid bronchoscopies and 3 stents placed in the stent group. In a subgroup analysis according to the oncologic management protocol following TB (first-line treatment and other lines or palliation), the beneficial effect of stenting on obstruction recurrence was highly significant (p < 0.002), but was not observed in the naïve group, free from first-line chemotherapy. CONCLUSION: Silicone stent placement maintains the benefit of TB after 1 year on dyspnea score, obstruction's recurrence, and the need for new TB. Stenting does not affect the quality of life and is suggested for patients after failure of first-line chemotherapy. It is not suggested in patients without previous oncologic treatment.

Current Practice of Airway Stenting in the Adult Population in Europe: A Survey of the European Association of Bronchology and Interventional Pulmonology (EABIP).

BACKGROUND: Airway stenting (AS) commenced in Europe circa 1987 with the first placement of a dedicated silicone airway stent. Subsequently, over the last 3 decades, AS was spread throughout Europe, using different insertion techniques and different types of stents. OBJECTIVES: This study is an international survey conducted by the European Association of Bronchology and Interventional Pulmonology (EABIP) focusing on AS practice within 26 European countries. METHODS: A questionnaire was sent to all EABIP National Delegates in February 2015. National delegates were responsible for obtaining precise and objective data regarding the current AS practice in their country. The deadline for data collection was February 2016. RESULTS: France, Germany, and the UK are the 3 leading countries in terms of number of centres performing AS. These 3 nations represent the highest ranked nations within Europe in terms of gross national income. Overall, pulmonologists perform AS exclusively in 5 countries and predominately in 12. AS is performed almost exclusively in public hospitals. AS performed under general anaesthesia is the rule for the majority of institutions, and local anaesthesia is an alternative in 9 countries. Rigid bronchoscopy techniques are predominant in 20 countries. Amongst commercially available stents, both Dumon and Ultraflex are by far the most commonly deployed. Finally, 11 countries reported that AS is an economically viable activity, while 10 claimed that it is not. CONCLUSION: This EABIP survey demonstrates that there is significant heterogeneity in AS practice within Europe. Therapeutic bronchoscopy training and economic issues/reimbursement for procedures are likely to be the primary reasons explaining these findings.

High alveolar concentration of nitric oxide is associated with alveolitis in scleroderma.

Alveolar concentration of nitric oxide (C(A)NO) is a non invasive prognostic marker of systemic sclerosis (SSc) lung disease. There is, however, as yet no direct evidence showing concomitant increase of C(A)NO and the presence of inflammatory cells in alveoli. We have therefore measured C(A)NO and performed broncho-alveolar lavage (BAL) in SSc patients. Exhaled NO was measured, by the means of two different models, the two-compartment model (2CM) and the trumpet model with axial diffusion (TMAD), in 22 SSc patients and compared with 15 healthy controls. BAL was performed in all SSc patients. Alveolitis was defined as lymphocytes >14%, polymorphonuclears >4%, or eosinophils >3% on cell count in BAL fluid. Comparisons of C(A)NO levels were made between SSc patients with, and without, alveolitis. Levels of C(A)NO were significantly higher in SSc patients as compared with controls (p<0.001). Median C(A)NO was significantly higher in SSc patients with alveolitis as compared with SSc patients without alveolitis (8.4ppb; 1st and 3rd interquartile range: 6.0-10.5 vs 3.3ppb; 2.2-3.5; p=0.004 for 2CM and 5.4ppb; 3.2-9.2 vs 3.2ppb; 1.4-3.3, p=0.02 for TMAD), while bronchial airway output of NO (J'awNO, p=0.19), and fractional exhaled NO (F(E)NO, p=0.12) were comparable. C(A)NO was consistently high in SSc patients with alveolitis irrespective of the methods chosen (TMAD or 2CM). Our findings showed that increased C(A)NO was associated with alveolitis in patients with SSc. We submit that C(A)NO could be used as a reliable non-invasive surrogate biomarker of alveolitis in scleroderma lung disease.

Optimization of small-cell lung cancer chemotherapy with heparin: a comprehensive retrospective study of 239 patients treated in a single specialized center.

PURPOSE: In first-line management for small-cell lung cancer (SCLC), the combination of a platinum salt and etoposide is recommended, with thoracic radiotherapy and prophylactic cranial irradiation in selected patients. Anticoagulants, including heparin, are rarely used. We analyzed the results of these different treatments in a comprehensive population of patients with SCLC. PATIENTS AND METHODS: We retrospectively analyzed clinical and therapeutic characteristics of SCLC patients managed in our center during the period 1990-2002. RESULTS: First-, second- and third-line chemotherapy was received by 98.3, 47.3 and 11.7%, respectively; 55% received curative heparin. The 2-year survival rates were 31 and 7% among patients with localized and metastatic disease, 33 and 15% among patients treated with the PCDE (cisplatin-cyclophosphamide-doxorubicin-etoposide) regimen with and without heparin, and 27 and 12% among patients treated with the PE (cisplatin or carboplatin-etoposide) regimen with and without heparin, respectively. The 2-year survival rate among the 27 patients who received an optimal combination of PCDE, heparin, thoracic radiotherapy and prophylactic cranial irradiation was 44.2%. In multivariate analysis, localized disease, younger age, use of heparin and inclusion in a clinical trial were independently associated with a better outcome. CONCLUSION: Despite the bias inherent in a retrospective, single-center study, these results support chemotherapy optimization for SCLC patients and confirm the value of heparin in this setting.

Clinical efficacy and cost-effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration for preoperative staging of non-small-cell lung cancer: Results of a French prospective multicenter trial (EVIEPEB).

This two-step study evaluated the cost-effectiveness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for presurgery staging of non-small cell lung cancer (NSCLC) in France (EVIEPEB; ClinicalTrial.gov identifier NCT00960271). Step 1 consisted of a high-benchmark EBUS-TBNA-training program in participating hospital centers. Step 2 was a prospective, national, multicenter study on patients with confirmed or suspected NSCLC and an indication for mediastinal staging with at least one lymph node > 1 cm in diameter. Patients with negative or uninformative EBUS-TBNA and positron-emission tomography-positive or -negative nodes, respectively, underwent either mediastinoscopy or surgery. Direct costs related to final diagnosis of node status were prospectively recorded. Sixteen of 22 participating centers were certified by the EBUS-TBNA-training program and enrolled 163 patients in Step 2. EBUS-TBNA was informative for 149 (91%) patients (75 malignant, 74 non-malignant) and uninformative for 14 (9%). Mediastinoscopy was avoided for 80% of the patients. With a 52% malignant-node rate, EBUS-TBNA positive- and negative-predictive values, respectively, were 100% and 90%. EBUS-TBNA was cost-effective, with expected savings of €1,450 per patient, and would have remained cost-effective even if all EBUS-TBNAs had been performed under general anesthesia or the cost of the procedure had been 30% higher (expected cost-saving of €994 and €1,427 per patient, respectively). After EBUS-TBNA training and certification of participating centers, the results of this prospective multicenter study confirmed EBUS-TBNA cost-effectiveness for NSCLC staging.

Chylous reflux into localized pulmonary lymphangiectasis.

Spontaneous chylothorax is uncommon and may originate from different etiologies either pleural, pulmonary, or mediastinal. Chyloptysis is a still rarer clinical problem and always of pulmonary origin. We report 2 cases: the first, a 63-year-old woman presenting with a chylothorax, and the second, a 28-year-old man with chyloptysis. Both were successfully treated with a medium chain triglyceride diet. Lymphangiograms demonstrated an identical origin for the 2 cases: reflux from the thoracic duct into right lower lobe lung lymphangiectasis. In our experience, chylous reflux into pulmonary lymphangiectasis is not as rare as believed and many cases probably remain undiagnosed.

Oral second- and third-line lomustine-etoposide-cyclophosphamide chemotherapy for small cell lung cancer.

PURPOSE: There is no standard therapy for progressive or recurrent small cell lung cancer (SCLC). Lomustine, etoposide and cyclophosphamide oral chemotherapy were evaluated in a feasibility study of efficacy survival and toxicity. PATIENTS AND METHODS: 71 patients were included in this study, 36 in second-line and 35 in third-line chemotherapy. They received lomustine (CCNU) 80 or 120mg on D1 only, etoposide 100mg from D1 until D6 up to D14 and cyclophosphamide 100mg from D1 until D6 up to D14 every 4 weeks. The dosages of CCNU and duration of administration of the other two drugs were adapted to an original therapeutic risk level table on D1 and throughout treatment. Evaluation based on clinical status, response and weekly blood counts was performed before each cycle until progression. RESULTS: 70 patients were evaluable. They received between 1 and 20 cycles of treatment (mean=3.7 for second-line and 3.0 for third-line treatment). Complete responses were observed for 3 patients in each line, and partial responses were noted in 13 patients in second-line and 8 patients in third-line, resulting in a total response rate of 27/70=38%. Median-survival time estimated from the start of second- or third-line treatment was the same in the two subgroups: 4.4 months, but the patients in two subgroups presented different clinical characteristics. Haematological toxicity was severe with three toxic deaths as frequently observed in this setting, but hospitalisations were uncommon during this fully oral treatment that provided a very good quality of life for these out-patients. Consumption of health care resources for this low-cost and ambulatory treatment was limited. CONCLUSION: The similar efficacy with acceptable safety, the ease of administration in out-patients and the economical advantages justify comparison of this oral chemotherapy with conventional intravenous chemotherapy. A randomised phase II trial is on-going in France for second-line SCLC patients on this theme.