Yorkshire Enhanced Stop Smoking (YESS) study: a protocol for a randomised controlled trial to evaluate the effect of adding a personalised smoking cessation intervention to a lung cancer screening programme

Introduction: Integration of smoking cessation (SC) into lung cancer screening is essential to optimise clinical and cost effectiveness. The most effective way to use this ‘teachable moment’ is unclear. The Yorkshire Enhanced Stop Smoking study will measure the effectiveness of an SC service integrated within the Yorkshire Lung Screening Trial (YLST) and will test the efficacy of a personalised SC intervention, incorporating incidental findings detected on the low-dose CT scan performed as part of YLST. / Methods and analysis: Unless explicitly declined, all smokers enrolled in YLST will see an SC practitioner at baseline and receive SC support over 4 weeks comprising behavioural support, pharmacotherapy and/or a commercially available e-cigarette. Eligible smokers will be randomised (1:1 in permuted blocks of random size up to size 6) to receive either an enhanced, personalised SC support package, including CT scan images, or continued standard best practice. Anticipated recruitment is 1040 smokers (January 2019–December 2020). The primary objective is to measure 7-day point prevalent carbon monoxide (CO) validated SC after 3 months. Secondary outcomes include CO validated cessation at 4 weeks and 12 months, self-reported continuous cessation at 4 weeks, 3 months and 12 months, attempts to quit smoking and changes in psychological variables, including perceived risk of lung cancer, motivation to quit smoking tobacco, confidence and efficacy beliefs (self and response) at all follow-up points. A process evaluation will explore under which circumstances and on which groups the intervention works best, test intervention fidelity and theory test the mechanisms of intervention impact. / Ethics and dissemination: This study has been approved by the East Midlands-Derby Research Ethics Committee (18/EM/0199) and the Health Research Authority/Health and Care Research Wales. Results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and via the YLST website. / Trial registration numbers: ISRCTN63825779, NCT03750110

Yorkshire Lung Screening Trial (YLST): protocol for a randomised controlled trial to evaluate invitation to community-based low-dose CT screening for lung cancer versus usual care in a targeted population at risk

Introduction: Lung cancer is the world’s leading cause of cancer death. Low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in the US National Lung Screening Trial. Here, we present the Yorkshire Lung Screening Trial (YLST), which will address key questions of relevance for screening implementation. / Methods and analysis: Using a single-consent Zelen’s design, ever-smokers aged 55–80 years registered with a general practice in Leeds will be randomised (1:1) to invitation to a telephone-based risk-assessment for a Lung Health Check or to usual care. The anticipated number randomised by household is 62 980 individuals. Responders at high risk will be invited for LDCT scanning for lung cancer on a mobile van in the community. There will be two rounds of screening at an interval of 2 years. Primary objectives are (1) measure participation rates, (2) compare the performance of PLCOM2012 (threshold ≥1.51%), Liverpool Lung Project (V.2) (threshold ≥5%) and US Preventive Services Task Force eligibility criteria for screening population selection and (3) assess lung cancer outcomes in the intervention and usual care arms. Secondary evaluations include health economics, quality of life, smoking rates according to intervention arm, screening programme performance with ancillary biomarker and smoking cessation studies. / Ethics and dissemination: The study has been approved by the Greater Manchester West research ethics committee (18-NW-0012) and the Health Research Authority following review by the Confidentiality Advisory Group. The results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and on the YLST website. / Trial registration numbers: ISRCTN42704678 and NCT03750110

Uptake and 4-week quit rates from an opt-out co-located smoking cessation service delivered alongside community-based low-dose computed tomography screening within the Yorkshire Lung Screening Trial.

BACKGROUND: Up to 50% of those attending for low-dose computed tomography screening for lung cancer continue to smoke and co-delivery of smoking cessation services alongside screening may maximise clinical benefit. Here we present data from an opt-out co-located smoking cessation service delivered alongside the Yorkshire Lung Screening Trial (YLST). METHODS: Eligible YLST participants were offered an immediate consultation with a smoking cessation practitioner (SCP) at their screening visit with ongoing smoking cessation support over subsequent weeks. RESULTS: Of 2150 eligible participants, 1905 (89%) accepted the offer of an SCP consultation during their initial visit, with 1609 (75%) receiving ongoing smoking cessation support over subsequent weeks. Uptake of ongoing support was not associated with age, ethnicity, deprivation or educational level in multivariable analyses, although men were less likely to engage (adjusted OR (ORadj) 0.71, 95% CI 0.56-0.89). Uptake was higher in those with higher nicotine dependency, motivation to stop smoking and self-efficacy for quitting. Overall, 323 participants self-reported quitting at 4 weeks (15.0% of the eligible population); 266 were validated by exhaled carbon monoxide (12.4%). Multivariable analyses of eligible smokers suggested 4-week quitting was more likely in men (ORadj 1.43, 95% CI 1.11-1.84), those with higher motivation to quit and previous quit attempts, while those with a stronger smoking habit in terms of cigarettes per day were less likely to quit. CONCLUSIONS: There was high uptake for co-located opt-out smoking cessation support across a wide range of participant demographics. Protected funding for integrated smoking cessation services should be considered to maximise programme equity and benefit

Prognostic and predictive biomarkers in early stage NSCLC: CTCs and serum/plasma markers

Resection of early stage non-small cell lung cancer (NSCLC) offers patients the best hope of cure, however recurrence rates post-resection remain high suggesting the presence of micro-metastatic disease at the time of surgery undetected by standard staging methods. A critical step in the metastatic cascade is the entry of tumor cells into the circulation enabling their distribution to and seeding of distant organs. This review explores the evidence for predictive and prognostic circulating biomarkers in the early stage NSCLC population. We summarize studies that have explored a variety of targets including circulating proteins, nucleic acids and more recently circulating tumor cells (CTCs) as potentially clinically relevant biomarkers in the early stage setting. Circulating biomarkers may add clinically relevant information about the biological behavior of tumors over and above that provided by pathological staging. Improvement in the stratification of patients according to the likelihood of metastatic relapse after radical treatments such as surgical resection could allow more effective targeting of systemic therapies such as adjuvant chemotherapy

Co-development of an evidence-based personalised smoking cessation intervention for use in a lung cancer screening context.

BACKGROUND: Optimising smoking cessation services within a low radiation-dose computed tomography (LDCT) lung cancer screening programme has the potential to improve cost-effectiveness and overall efficacy of the programme. However, evidence on the optimal design and integration of cessation services is limited. We co-developed a personalised cessation and relapse prevention intervention incorporating medical imaging collected during lung cancer screening. The intervention is designed to initiate and support quit attempts among smokers attending screening as part of the Yorkshire Enhanced Stop Smoking study (YESS: ISRCTN63825779). Patients and public were involved in the development of an intervention designed to meet the needs of the target population. METHODS: An iterative co-development approach was used. Eight members of the public with a history of smoking completed an online survey to inform the visual presentation of risk information in subsequent focus groups for acceptability testing. Three focus groups (n = 13) were conducted in deprived areas of Yorkshire and South Wales with members of the public who were current smokers or recent quitters (within the last year). Exemplar images of the heart and lungs acquired by LDCT, absolute and relative lung cancer risk, and lung age were shown. Data were analysed thematically, and discussed in stakeholder workshops. Draft versions of the intervention were developed, underpinned by the Extended Parallel Processing Model to increase self-efficacy and response-efficacy. The intervention was further refined in a second stakeholder workshop with a patient panel. RESULTS: Individual LDCT scan images of the lungs and heart, in conjunction with artistic impressions to facilitate interpretation, were considered by public participants to be most impactful in prompting cessation. Public participants thought it important to have a trained practitioner guiding them through the intervention and emphasising the short-term benefits of quitting. Presentation of absolute and relative risk of lung cancer and lung age were considered highly demotivating due to reinforcement of fatalistic beliefs. CONCLUSION: An acceptable personalised intervention booklet utilising LDCT scan images has been developed for delivery by a trained smoking cessation practitioner. Our findings highlight the benefit of co-development during intervention development and the need for further evaluation of effectiveness