David R Baldwin

Guidelines on the radical management of patients with lung cancer.

A joint initiative by the British Thoracic Society and the Society for Cardiothoracic Surgery in Great Britain and Ireland was undertaken to update the 2001 guidelines for the selection and assessment of patients with lung cancer who can potentially be managed by radical treatment.

UK Lung Screen (UKLS) nodule management protocol: modelling of a single screen randomised controlled trial of low-dose CT screening for lung cancer

The UK Lung Screen (UKLS) is a randomised controlled trial of the use of low-dose multidetector CT for lung cancer screening. It completed the Health Technology Appraisal (HTA)-funded feasibility stage in October 2009 and the pilot UKLS will be initiated in early 2011. The pilot will randomise 4000 subjects to either low-dose CT screening or no screening. The full study, due to start in September 2012, if progression criteria are met, will randomise a further 28 000 subjects from seven centres in the UK. Subjects will be selected if they have sufficient risk of developing lung cancer according to the Liverpool Lung Project risk model. The UKLS employs the ‘Wald Single Screen Design’, which was modelled in the UKLS feasibility study. This paper describes the modelling of nodule management in UKLS by using volumetric analysis with a single initial screen design and follow-up period of 10 years. This modelling has resulted in the development and adoption of the UKLS care pathway, which will be implemented in the planned CT screening trial in the UK.

Pulmonary disposition of antimicrobial agents: methodological considerations.

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British Thoracic Society guidelines for the investigation and management of pulmonary nodules.

The British Thoracic Society guideline for the investigation and management of pulmonary nodules is published as a supplement to this edition of the journal. It provides recommendations for the management of an individual with single or multiple pulmonary nodules and is a comprehensive reference text.

British Thoracic Society guidelines for the investigation and management of pulmonary nodules: accredited by NICE

This guideline is based on a comprehensive review of the literature on pulmonary nodules and expert opinion. Although the management pathway for the majority of nodules detected is straightforward it is sometimes more complex and this is helped by the inclusion of detailed and specific recommendations and the 4 management algorithms below. The Guideline Development Group (GDG) wanted to highlight the new research evidence which has led to significant changes in management recommendations from previously published guidelines. These include the use of two malignancy prediction calculators (section ‘Initial assessment of the probability of malignancy in pulmonary nodules’, algorithm 1) to better characterise risk of malignancy. There are recommendations for a higher nodule size threshold for follow-up (≥5 mm or ≥80 mm3) and a reduction of the follow-up period to 1 year for solid pulmonary nodules; both of these will reduce the number of follow-up CT scans (sections ‘Initial assessment of the probability of malignancy in pulmonary nodules’ and ‘Imaging follow-up’, algorithms 1 and 2). Volumetry is recommended as the preferred measurement method and there are recommendations for the management of nodules with extended volume doubling times (section ‘Imaging follow-up’, algorithm 2). Acknowledging the good prognosis of sub-solid nodules (SSNs), there are recommendations for less aggressive options for their management (section ‘Management of SSNs’, algorithm 3). The guidelines provide more clarity in the use of further imaging, with ordinal scale reporting for PET-CT recommended to facilitate incorporation into risk models (section ‘Further imaging in management of pulmonary nodules’) and more clarity about the place of biopsy (section ‘Non-imaging tests and non-surgical biopsy’, algorithm 4). There are recommendations for the threshold for treatment without histological confirmation (sections ‘Surgical excision biopsy’ and ‘Non-surgical treatment without pathological confirmation of malignancy’, algorithm 4). Finally, and possibly most importantly, there are evidence-based recommendations about the information that people …

Pulmonary disposition of antimicrobial agents: in vivo observations and clinical relevance.

The rationale for measuring the concentrations of antimicrobial agents at potential sites of infection other than serum is that pathogens may be confined to sites which are separated from the blood by significant barriers to antimicrobial agent movement. Thus, the concentrations within these sites may differ markedly from those observed in serum, and clinical efficacy may be more directly related to the concentrations of drugs local to the pathogen. In the lung, the relationship between concentrations of drug at the site of infection and clinical efficacy is not clear because of difficulties with studies designed to measure efficacy. First, there

UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening

Background Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial. Methods The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction. Results 247 354 individuals aged 50–75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm3 or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm3 at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569). Conclusions The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective—this needs to be confirmed using data on observed lung cancer mortality reduction. Trial registration ISRCTN 78513845.

Early mortality after surgical resection for lung cancer: an analysis of the English National Lung cancer audit

Introduction For appropriately staged non-small cell lung cancer (NSCLC) surgical resection can dramatically improve survival, but some may not be offered this treatment because of concerns about perioperative mortality. Methods We used data from the National Lung Cancer Audit (NLCA) to determine the proportions of English patients who died within 30 and 90 days after surgery for NSCLC. We quantified the predictors of early postoperative death and using these results devised a score to predict risk of death within 90 days of surgery. Results We analysed data on 10 991 patients operated on between 2004 and 2010. Three per cent (334) of patients died within 30 days of their procedure and 5.9% (647) within 90 days. Age was strongly associated with early postoperative death (adjusted OR within 90 days for 80–84 years vs 70–74 years: 1.46, 95% CI 1.07 to 1.98); significant associations were also observed with performance status (PS) (adjusted OR within 90 days for PS 2 vs PS 0: 2.40, 95% CI 1.68 to 3.41), as well as lung function, stage and procedure type. Conclusions Our results show that age is the most important predictor of death within both of these early postoperative periods. We used the data in the NLCA to develop a predictive score, based on an English population and specific to lung cancer surgery, which estimates risk of death within 90 days; this score should be tested in future cohorts.

Effect of addition of exercise to chest physiotherapy on sputum expectoration and lung function in adults with cystic fibrosis

Promotion of sputum expectoration by chest physiotherapy is an essential part of cystic fibrosis management. The role of exercise in improving sputum expectoration and lung function in these patients is more contentious. We therefore investigated the effect of adding an exercise programme to conventional chest physiotherapy in eight adult subjects (four male) with cystic fibrosis. Subjects were treated on two non-consecutive days of the second week of a course of in-patient antibiotic therapy in a cross-over fashion. On the exercise and physiotherapy day, subjects exercised 60 min before physiotherapy. On the physiotherapy alone day, subjects rested for 60 min instead of exercising. Physiotherapy was administered on both study days (postural drainage, percussion, deep breathing, vibrations, forced expiratory technique and coughing). Lung function tests were performed at baseline, after exercise or rest and again immediately and 30 min after physiotherapy. Sputum weights were measured in the 60 min of exercise or rest (period A) and for the 60 min physiotherapy period and 30 min after physiotherapy (period B). Mean total sputum expectoration (period A and B) was 14 g on physiotherapy alone and 21.5 g (4.8) on exercise and physiotherapy (mean difference 7.5 g, 95% CI 1.4-13.6 g, P = 0.02). Mean sputum weights during period A (i.e. rest vs. exercise) on physiotherapy alone and exercise and physiotherapy were 2.6 and 7 g respectively (mean difference 4.4 g, 95% CI-0.07-8.8 g, P = 0.053).(ABSTRACT TRUNCATED AT 250 WORDS)

Lung cancer diagnosis and staging with endobronchial ultrasound-guided transbronchial needle aspiration compared with conventional approaches: an open-label, pragmatic, randomised controlled trial

Summary Background The diagnosis and staging of lung cancer is an important process that identifies treatment options and guides disease prognosis. We aimed to assess endobronchial ultrasound-guided transbronchial needle aspiration as an initial investigation technique for patients with suspected lung cancer. Methods In this open-label, multicentre, pragmatic, randomised controlled trial, we recruited patients who had undergone a CT scan and had suspected stage I to IIIA lung cancer, from six UK centres and randomly assigned them to either endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) or conventional diagnosis and staging (CDS), for further investigation and staging. If a target node could not be accessed by EBUS-TBNA, then endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was allowed as an alternative procedure. Randomisation was stratified according to the presence of mediastinal lymph nodes measuring 1 cm or more in the short axis and by recruiting centre. We used a telephone randomisation method with permuted blocks of four generated by a computer. Because of the nature of the intervention, masking of participants and consenting investigators was not possible. The primary endpoint was the time-to-treatment decision after completion of the diagnostic and staging investigations and analysis was by intention-to-diagnose. This trial is registered with ClinicalTrials.gov, number NCT00652769. Findings Between June 10, 2008, and July 4, 2011, we randomly allocated 133 patients to treatment: 66 to EBUS-TBNA and 67 to CDS (one later withdrew consent). Two patients from the EBUS-TBNA group underwent EUS-FNA. The median time to treatment decision was shorter with EBUS-TBNA (14 days; 95% CI 14–15) than with CDS (29 days; 23–35) resulting in a hazard ratio of 1·98, (1·39–2·82, p<0·0001). One patient in each group had a pneumothorax from a CT-guided biopsy sample; the patient from the CDS group needed intercostal drainage and was admitted to hospital. Interpretation Transbronchial needle aspiration guided by endobronchial ultrasound should be considered as the initial investigation for patients with suspected lung cancer, because it reduces the time to treatment decision compared with conventional diagnosis and staging techniques. Funding UK Medical Research Council.