P. Barber

Smoking is associated with a decrease of O6-alkylguanine-DNA alkyltransferase activity in bronchial epithelial cells

O6‐alkylguanine‐DNA alkyltransferase (MGMT) represents the first line of defense against the toxic, mutagenic and carcinogenic effects of O6‐alkylguanine adducts in DNA. These adducts mediate the biological activity from a series of alkylating agents, such as the tobacco‐specific nitrosamines, believed to contribute to the carcinogenicity of tobacco smoke. There have been conflicting reports on the effects of smoking on MGMT activity in lung and other tissues. Here, we investigate MGMT activity in peripheral blood mononuclear cells (PBMC) and lung bronchial epithelial cells (BEC), extracted by lung brushings, from smokers and nonsmokers attending a bronchoscopy clinic. MGMT activity was significantly lower in BECs (geometric mean; 95% confidence interval 1.02; 0.86–1.20 fmol/μg DNA) than in PBMCs (7.86; 6.70–9.59 fmol/μg DNA; p < 0.001), suggesting that bronchial epithelia may be particularly sensitive to alkylation damage. More importantly our results indicate that activity in BECs is significantly decreased in samples from current smokers (0.71; 0.54–0.93 fmol/μg DNA) compared to nonsmokers (1.25; 1.03–1.51 fmol/μg DNA; p = 0.002). This could represent an important contribution to the carcinogenicity of tobacco smoke.

Implementing lung cancer screening: baseline results from a community-based ‘Lung Health Check’ pilot in deprived areas of Manchester

We report baseline results of a community-based, targeted, low-dose CT (LDCT) lung cancer screening pilot in deprived areas of Manchester. Ever smokers, aged 55–74 years, were invited to ‘lung health checks’ (LHCs) next to local shopping centres, with immediate access to LDCT for those at high risk (6-year risk ≥1.51%, PLCOM2012 calculator). 75% of attendees (n=1893/2541) were ranked in the lowest deprivation quintile; 56% were high risk and of 1384 individuals screened, 3% (95% CI 2.3% to 4.1%) had lung cancer (80% early stage) of whom 65% had surgical resection. Taking lung cancer screening into communities, with an LHC approach, is effective and engages populations in deprived areas.

The mediation of social influences on smoking cessation and awareness of the early signs of lung cancer

BackgroundWhilst there has been no clear consensus on the potential for earlier diagnosis of lung cancer, recent research has suggested that the time between symptom onset and consultation can be long enough to plausibly affect prognosis. In this article, we present findings from a qualitative study involving in-depth interviews with patients who had been diagnosed with lung cancer (n = 11), and people who were at heightened risk of developing the disease (n = 14).MethodsA grounded theory methodology was drawn upon to conduct thematic and narrative based approaches to analysis.ResultsThe paper focuses on three main themes which emerged from the study: i) fatalism and resignation in pathways to help-seeking and the process of diagnosis; ii) Awareness of smoking risk and response to cessation information and advice. iii) The role of social and other networks on help-seeking. Key findings included: poor awareness among participants of the symptoms of lung cancer; ambivalence about the dangers of smoking; the perception of lung cancer as part of a homogenisation of multiple illnesses; close social networks as a key trigger in help-seeking.ConclusionsWe suggest that future smoking cessation and lung cancer awareness campaigns could usefully capitalise on the influence of close social networks, and would benefit from taking a ‘softer’ approach.

Targeted lung cancer screening selects individuals at high risk of cardiovascular disease

BACKGROUND Cardiovascular disease (CVD) is a major cause of morbidity and mortality in populations eligible for lung cancer screening. The aim of this study was to determine whether a brief CV risk assessment, delivered as part of a targeted community-based lung cancer screening programme, was effective in identifying individuals at high risk who might benefit from primary prevention. METHODS The Manchester Lung Screening Pilot consisted of annual low dose CT (LDCT) over 2 screening rounds, targeted at individuals in deprived areas at high risk of lung cancer (age 55-74 and 6-year risk ≥1.51%, using PLCOM2012 risk model). All participants of the second screening round were eligible to take part in the study. Ten-year CV risk was estimated using QRISK2 in participants without CVD and compared to age (±5 years) and sex matched Health Survey for England (HSE) controls; high risk was defined as QRISK2 score ≥10%. Coronary artery calcification (CAC) was assessed on LDCT scans and compared to QRISK2 score. RESULTS Seventy-seven percent (n=920/1,194) of screening attendees were included in the analysis; mean age 65.6 ± 5.4 and 50.4% female. QRISK2 and lung cancer risk (PLCOM2012) scores were correlated (r = 0.26, p < 0.001). Median QRISK2 score was 21.1% (IQR 14.9-29.6) in those without established CVD (77.6%, n = 714/920), double that of HSE controls (10.3%, IQR 6.6-16.2; n = 714) (p < 0.001). QRISK2 score was significantly higher in those with CAC (p < 0.001). Screening attendees were 10-fold more likely to be classified high risk (OR 10.2 [95% CI 7.3-14.0]). One third (33.7%, n = 310/920) of all study participants were high risk but not receiving statin therapy for primary CVD prevention. DISCUSSION Opportunistic CVD risk assessment within a targeted lung cancer screening programme is feasible and is likely to identify a very large number of individuals suitable for primary prevention.

“To know or not to know…?” Push and pull in ever smokers lung screening uptake decision-making intentions

In the United States, lung cancer screening aims to detect cancer early in nonsymptomatic current and former smokers. A lung screening pilot service in an area of high lung cancer incidence in the United Kingdom has been designed based on United States trial evidence. However, our understanding of acceptability and reasons for lung screening uptake or decline in a United Kingdom nontrial context are currently limited.

S13 Manchester lung screening, targeting high-risk individuals in deprived areas of the community

Background Lung cancer (LC) is the commonest cause of cancer-related death in the world. Screening with low-dose computer tomography (LDCT) had been shown to reduce LC specific and all-cause mortality. Benefit is greatest in those at highest risk, such as current smokers from areas of high socio-economic deprivation, yet participation in these ‘hard-to-reach’ populations remains a challenge. The aim of this NHS implementation project was to assess LC screening within the community in deprived areas. Abstract S13 Figure 1 Comparison of median Index of Multiple Deprivation (IMD) of Manchester and United Kingdom Lung Cancer Screening (UKLS) populations. Methods Ever smokers, aged 55–74, registered at 14 participating general practitioner (GP) practices in deprived areas of Manchester were invited to attend and have a free ‘Lung Health Check’ (LHC) in a mobile unit located at their local shopping centres. Lung cancer risk score (PLCOM2012), respiratory symptoms and spirometry were assessed as part of the LHC. Those at high risk of LC, i.e., 6 year lung cancer risk ≥1.51%, were offered immediate LDCT in a co-located mobile CT scanner. All active smokers were provided with smoking cessation advice. Results The maximum available capacity of the service was filled within days of going live. A total of 2541 individuals attended for a LHC and consented to data analysis. The mean age was 64.1±5.5 and 51.0% (n=1,296) were female. 74.5% (n=1,893) of participants were ranked in the lowest quintile of deprivation in England. The majority of individuals had left school by the age of 16 (n=2,078; 81.8%), most without gaining any ‘O’ levels (n=1,567; 61.7%). A significant number of participants reported a history of previous respiratory disease (n=566; 22.3%), pervious cancer (n=291; 11.5%), family history of LC (n=553; 21.8%) or asbestos exposure (n=612; 24.1%). 56.2% (n=1,429) qualified for LDCT screening of which 52.8% were active smokers. 46 lung cancers were detected in 42 individuals, a prevalence of 3.0%, of which 80.4% were early stage (I+II). A treatment with curative intent was offered to 89.1% of screen detected cancers. Conclusion Taking lung cancer screening into the community can identify and affect those at most risk, the so-called ‘hard-to-reach’ populations. This Results in a significant stage shift in screen detected lung cancers in deprived populations.

S33 Performance of EBUS-TBNA in the pathological subtyping and molecular testing of non-small cell lung cancer (NSCLC) in a UK thoracic oncology centre

Introduction The categorisation of NSCLC into squamous and non-squamous subtypes is an important requirement for the optimisation of patient care as this may modify chemotherapy regimens and direct molecular testing. The lung cancer national audit highlights the need to minimise the rate of NSCLC not otherwise specified (NSCLC-NOS).1 The aim of our study was to determine whether samples obtained by endobronchial ultrasound guided-transbronchial needle aspiration (EBUS-TBNA) could be used to pathologically subtype NSCLC and provide sufficient material for molecular testing. Methods A prospectively maintained database of consecutive patients with suspected lung cancer referred to our unit, a UK regional thoracic oncology centre, was analysed. All patients diagnosed with NSCLC by EBUS-TBNA cytology at our centre between Sept 2013 and Sept 2014 were included in the study. Results A total of 89 patients were diagnosed with NSCLC using EBUS-TBNA. The pathological subtypes were: n = 46 (51.7%) squamous cell carcinoma, n = 41 (46%) adenocarcinoma and n = 2 (2.2%) NSCLC-NOS. All samples with a new diagnosis of non-squamous subtype were sent for EGFR mutation analysis, with sufficient material in 97% (n = 35/36) and one activating mutation was identified. ALK analysis was successfully performed in all 5 samples in which this was requested. Additional molecular testing was requested in 9 samples with sufficient material in 89% (n = 8/9). Conclusions EBUS-TBNA cytology can be used to successfully subtype NSCLC and provide adequate material for molecular testing in the majority of cases. The rate of NSCLC-NOS in our study (2.2%) compares favourably with local cancer network (13.5%) and national (12.9%) figures. Reference 1 National lung cancer audit report 2014 doi http://www.hscic.gov.uk/catalogue/PUB16019/clin-audi-supp-prog-lung-nlca-2014-rep.pdf

Endobronchial ultrasound images: bronchial artery and pulmonary emboli

Received for publication April 15, 2014; accepted December 9, 2014. From the *North West Lung Centre, University Hospital of South Manchester, Wythenshawe; and wThe Institute of Inflammation and Repair, The University of Manchester, Manchester, UK. Disclosure: R.B. has received grant funding from AstraZeneca and Lilly Oncology and honoraria from Eli-Lilly, AstraZeneca, Chiesi, and Almirall. M.E. fellowship post is half funded by Lilly Oncology. The other authors have no conflict of interest or other disclosures. Reprints: Matthew Evison, MRCP, MBChB, North West Lung Centre, University Hospital of South Manchester, Southmoor Road, Wythenshawe M23 9LT, UK (e-mails: matthewevison@hotmail.co.uk; matthew.evison@uhsm.nhs.uk). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved. IMAGES IN INTERVENTIONAL PULMONOLOGY

The mediation of social influences on smoking cessation and awareness of the early signs of lung cancer. BMC Public Health. In Press

BackgroundWhilst there has been no clear consensus on the potential for earlier diagnosis of lung cancer, recent research has suggested that the time between symptom onset and consultation can be long enough to plausibly affect prognosis. In this article, we present findings from a qualitative study involving in-depth interviews with patients who had been diagnosed with lung cancer (n = 11), and people who were at heightened risk of developing the disease (n = 14).MethodsA grounded theory methodology was drawn upon to conduct thematic and narrative based approaches to analysis.ResultsThe paper focuses on three main themes which emerged from the study: i) fatalism and resignation in pathways to help-seeking and the process of diagnosis; ii) Awareness of smoking risk and response to cessation information and advice. iii) The role of social and other networks on help-seeking. Key findings included: poor awareness among participants of the symptoms of lung cancer; ambivalence about the dangers of smoking; the perception of lung cancer as part of a homogenisation of multiple illnesses; close social networks as a key trigger in help-seeking.ConclusionsWe suggest that future smoking cessation and lung cancer awareness campaigns could usefully capitalise on the influence of close social networks, and would benefit from taking a ‘softer’ approach.

51 Bronchoscopy with endobronchial ultrasound in patients with suspected lung cancer recurrence or progression following treatment

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