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Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data.

Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare the efficacy of six versus fewer planned cycles of platinum-based chemotherapy.

METHODS: All randomised trials comparing six versus fewer planned cycles of first-line platinum-based chemotherapy for patients with advanced non-small-cell lung cancer were eligible for inclusion in this systematic review and meta-analysis. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportion of patients with an objective response, and toxicity. Statistical analyses were by intention-to-treat, stratified by trial. Overall survival and progression-free survival were compared by log-rank test. The proportion of patients with an objective response was compared with a Mantel-Haenszel test. Prespecified analyses explored effect variations by trial and patient characteristics.

FINDINGS: Five eligible trials were identified; individual patient data could be collected from four of these trials, which included 1139 patients-568 of whom were assigned to six cycles, and 571 to three cycles (two trials) or four cycles (two trials). Patients received cisplatin (two trials) or carboplatin (two trials). No evidence indicated a benefit of six cycles of chemotherapy on overall survival (median 9·54 months [95% CI 8·98-10·69] in patients assigned to six cycles vs 8·68 months [8·03-9·54] in those assigned to fewer cycles; hazard ratio [HR] 0·94 [95% CI 0·83-1·07], p=0·33) with slight heterogeneity between trials (p=0·076; I(2)=56%). We recorded no evidence of a treatment interaction with histology, sex, performance status, or age. Median progression-free survival was 6·09 months (95% CI 5·82-6·87) in patients assigned to six cycles and 5·33 months (4·90-5·62) in those assigned to fewer cycles (HR 0·79, 95% CI 0·68-0·90; p=0·0007), and 173 (41·3%) of 419 patients assigned to six cycles and 152 (36·5%) of 416 patients assigned to three or four cycles had an objective response (p=0·16), without heterogeneity between the four trials. Anaemia at grade 3 or higher was slightly more frequent with a longer duration of treatment: 12 (2·9%) of 416 patients assigned to three-to-four cycles and 32 (7·8%) of 411 patients assigned to six cycles had severe anaemia.

INTERPRETATION: Six cycles of first-line platinum-based chemotherapy did not improve overall survival compared with three or four courses in patients with advanced non-small-cell lung cancer. Our findings suggest that fewer than six planned cycles of chemotherapy is a valid treatment option for these patients.

FUNDING: None.

Long-term survival outcomes of video-assisted thoracic surgery for patients with non-small cell lung cancer.

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Video-assisted thoracic surgery (VATS) has been shown to be a safe alternative to conventional thoracotomy for patients with non-small cell lung cancer (NSCLC). However, popularization of this relatively novel technique has been slow, partly due to concerns about its long-term outcomes. The present study aimed to evaluate the long-term survival outcomes of patients with NSCLC after VATS, and to determine the significant prognostic factors on overall survival.

METHODS: Consecutive patients diagnosed with NSCLC referred to one institution for VATS were identified from a central database. Patients were treated by either complete-VATS or assisted-VATS, as described in previous studies. A number of baseline patient characteristics, clinicopathologic data and treatment-related factors were analyzed as potential prognostic factors on overall survival.

RESULTS: Between January 2000 and December 2007, 1,139 patients with NSCLC who underwent VATS and fulfilled a set of predetermined inclusion criteria were included for analysis. The median age of the entire group was 60 years, with 791 male patients (69%). The median 5-year overall survival for Stage I, II, III and IV disease according to the recently updated TNM classification system were 72.2%, 47.5%, 29.8% and 28.6%, respectively. Female gender, TNM stage, pT status, and type of resection were found to be significant prognostic factors on multivariate analysis.

CONCLUSIONS: VATS offers a viable alternative to conventional open thoracotomy for selected patients with clinically resectable NSCLC.

Safety and feasibility of video-assisted thoracoscopic surgery for stage IIIA lung cancer.

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OBJECTIVE: The current study was prospectively designed to explore the application of video-assisted thoracoscopic surgery (VATS) radical treatment for patients with stage IIIA lung cancer, with the primary endpoints being the safety and feasibility of this operation and the second endpoints being the survival and complications after the surgery.

METHODS: A total of 51 patients with radiologically or mediastinoscopically confirmed stage IIIA lung cancer underwent VATS radical treatment, during which the standard pulmonary lobectomy and mediastinal lymph node dissection were performed after pre-operative assessment. The operative time, intraoperative blood loss/complications, postoperative recovery, postoperative complications, and lymph node dissection were recorded and analyzed. This study was regarded as successful if the surgical success rate reached 90% or higher.

RESULTS: A total of 51 patients with non-small cell lung cancer (NSCLC) were enrolled in this study from March 2009 to February 2010. The median post-operative follow-up duration was 50.5 months. Of these 51 patients, 41 (80.4%) had N2 lymph node metastases. All patients underwent the thoracoscopic surgeries, among whom 50 (98%) received pulmonary lobectomy and mediastinal lymph node dissection completely under the thoracoscope, 6 had their incisions extended to about 6 cm due to larger tumor sizes, and 1 had his surgery performed using a 12 cm small incision for handling the adhesions between lymph nodes and blood vessels. No patient was converted to conventional open thoracotomy. No perioperative death was noted. One patient received a second surgery on the second post-operative day due to large drainage (>1,000 mL), and the postoperative recovery was satisfactory. Up to 45 patients (88.2%) did not suffer from any perioperative complication, and 6 (11.8%) experienced one or more complications.

CONCLUSIONS: VATS radical treatment is a safe and feasible treatment for stage IIIA lung cancer.

Non specific pattern of lung function in a respiratory physiology unit: causes and prevalence: results of an observational cross-sectional and longitudinal study.

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ATS/ERS Task Force has highlighted that special attention must be paid when FEV1 and FVC are concomitantly decreased (<5th percentile) and the FEV1/FVC ratio is normal (>5th percentile) because a possible cause of this non specific pattern (NSP) is collapse of small airways with normal TLC measured by body plethysmography (>5th percentile). Our objectives were to determine the main lung diseases associated with this pattern recorded prospectively in a lung function testing (LFT) unit, the prevalence of this pattern in our LFT and among the diseases identified, and its development.

METHODS: Observational study of routinely collected data selected from our Clinical Database Warehouse.

RESULTS: The prevalence of NSP was 841/12 775 tests (6.6%, 95% CI: 6.2 to 7.0%). NSP was mainly associated with seven lung diseases: asthma (prevalence of NSP among asthmatics: 12.6%), COPD/emphysema (prevalence 8.6%), bronchiectasis (12.8%), sarcoidosis (10.7%), interstitial pneumonia (4.0%), pulmonary hypertension (8.9%) and bilateral lung transplantation for cystic fibrosis (36.0%). LFT measurements were described in 185 patients with NSP and indisputable nonoverlapping causes. A moderate defect (FEV1: 66 +/- 9% predicted) with mild lung hyperinflation (FRC: 111 +/- 27%, RV: 131 +/- 33% predicted: suggesting distal airway obstruction) was evidenced whatever the underlying cause. A long term stability of NSP was evidenced in 130 / 185 patients (70% 95% CI: 64 to 77%).

CONCLUSIONS: NSP is observed in asthma, COPD/emphysema, bronchiectasis, sarcoidosis, pulmonary hypertension, interstitial pneumonia and after bilateral lung transplantation and remains stable in the majority of patients.

Asthma and obesity in children: current evidence and potential systems biology approaches.

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Both obesity and asthma are highly prevalent, complex diseases modified by multiple factors. Genetic, developmental, lung mechanical, immunological and behavioural factors have all been suggested as playing a causal role between the two entities, however their complex mechanistic interactions are still poorly understood and evidence of causality in children remains scant. Equally lacking is evidence of effective treatment strategies, despite the fact that imbalances at vulnerable phases in childhood can impact long-term health.

This review is targeted at both clinicians frequently faced with the dilemma of how to investigate and treat the obese asthmatic child and researchers interested in the topic. Highlighting the breadth of the spectrum of factors involved, this review collates evidence regarding the investigation and treatment of asthma in obese children, particularly in comparison to current approaches in 'difficult-to-treat' childhood asthma.

Finally, the authors propose hypotheses for future research from a systems-based perspective. This article is protected by copyright. All rights reserved.

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