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Purpose: Recent clinical trials and meta-analyses have shown that both CHART (continuous hyperfractionated accelerated radiation therapy) and induction chemotherapy offer a survival advantage over conventional radical radiotherapy for patients with inoperable non-small cell-lung cancer (NSCLC). This multicenter randomized controlled trial (INCH) was set up to assess the value of giving induction chemotherapy before CHART.Methods and Materials: Patients with histologically confirmed, inoperable, Stage I-III NSCLC were randomized to induction chemotherapy (ICT) (three cycles of cisplatin-based chemotherapy followed by CHART) or CHART alone.Results: Forty-six patients were randomized (23 in each treatment arm) from 9 UK centers. As a result of poor accrual, the trial was closed in December 2007. Twenty-eight patients were male, 28 had squamous cell histology, 34 were Stage IIIA or IIIB, and all baseline characteristics were well balanced between the two treatment arms. Seventeen (74%) of the 23 ICT patients completed the three cycles of chemotherapy. All 42 (22 CHART + 20 ICT) patients who received CHART completed the prescribed treatment. Median survival was 17 months in the CHART arm and 25 months in the ICT arm (hazard ratio of 0.60 [95% CI 0.31-1.16], p = 0.127). Grade 3 or 4 adverse events (mainly fatigue, dysphagia, breathlessness, and anorexia) were reported for 13 (57%) CHART and 13 (65%) ICT patients.Conclusions: This small randomized trial indicates that ICT followed by CHART is feasible and well tolerated. Despite closing early because of poor accrual, and so failing to show clear evidence of a survival benefit for the additional chemotherapy, the results suggest that CHART, and ICT before CHART, remain important options for the treatment of inoperable NSCLC and deserve further study. [ABSTRACT FROM AUTHOR]

Lung cancer screening (LCS) reduces lung cancer-related mortality; however, uptake remains low compared with other cancer screening programmes. In this observational study, we report the impact of timed appointments and reminders on participation in our regional LCS programme.Initial uptake of timed appointments was 53.0% (n=17 274/32 593), higher than previously reported in the UK, while initial uptake of open invitations was 29.8% (n=10 246/34 371). Among initial non-responders, 17.5% (n=4263/24 400) completed triage following a reminder. The increased participation following reminders only partially offset the significant difference in initial uptake between the two appointment types.Timed appointments and reminders are strongly advocated to increase participation in national LCS programmes., Competing Interests: Competing interests: SMJ has received fees for advisory board membership in the last three years from Bard1 Lifescience. He has received grant income from GRAIL Inc. He is an unpaid member of a GRAIL advisory board. He has received lecture fees for academic meetings from Cheisi and AstraZeneca. His wife works for AstraZeneca. AN has received a consultation fee from MSD and honoraria speaking engagements from Mevis Medical Solutions. He is an Honorary Executive Committee member for the British Society of Thoracic Imaging, Co-chair of the British Thoracic Society Pulmonary Nodule Guideline Development Group, Lung Taskforce member for the British Lung Foundation and clinical lead for the NHS England Targeted Lung Health Checks Programme. NN reports honoraria for non-promotional educational talks or advisory boards, or support for attending meetings from Amgen, AstraZeneca, AXANA, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, EQRx, Fujifilm, Guardant Health, Intuitive, Janssen, Lilly, Merck Sharp & Dohme, Olympus and Roche. He is a member of British Thoracic Oncology Group steering committee, director of UK Lung Cancer Coalition and Clinical Director of National Lung Cancer Audit., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Competing Interests: Competing interests: None declared.

Introduction: Lung cancer screening (LCS) enables the delivery of smoking cessation interventions to a population experiencing long-term tobacco dependence, but the optimal delivery method remains unclear. Here, we report uptake and short-term outcomes of an 'opt-out' smoking cessation referral strategy in an LCS cohort., Methods: Individuals currently smoking tobacco who attended a face-to-face lung health check in the SUMMIT study (NCT03934866) were offered very brief advice on smoking cessation and where possible, an 'opt-out' referral to their local stop smoking service (SSS). Aggregate data on referral outcomes were obtained from each SSS individually., Results: 33.7% (n=2090/6203) of individuals currently smoking tobacco consented to a practitioner-made 'opt-out' smoking cessation referral. 42.7% (n=893/2090) of these individuals resided in boroughs where SSS were not present or required self-referral. Males (adjusted OR (aOR) 1.16), younger individuals (55-59: aOR 1.70, 60-64: aOR 1.71 and 65-69: aOR 1.78) and those of ethnic minority backgrounds (Asian: aOR 1.31, Black: aOR 1.71 and Mixed: aOR 1.72) were more likely to consent, while individuals from the most deprived socioeconomic quintile were less likely to do so (aOR 0.65).High level of motivation to quit within a defined time frame (aOR 1.92), previous quit attempts in the past 12 months (1-4: aOR 1.65 and ≥5: aOR 1.54) and time to first cigarette of ≤60 min (<5: aOR 2.07, 6-30: aOR 1.55 and 31-60: aOR 1.56) were measures of tobacco dependence associated with a higher likelihood of providing consent.Outcomes were available for 742 referrals. An appointment with the service was accepted by 47.3% (n=351/742) of individuals, following which 65.5% (n=230/351) set a quit date. The 4-week quit rate among those setting a quit date and all individuals referred was 57.4% (n=132/230) and 17.8% (n=132/742), respectively., Conclusion: A proactive, 'opt-out' smoking cessation referral strategy for individuals currently smoking tobacco who interact with an LCS programme may be beneficial., Competing Interests: Competing interests: AB, PV, AC, RP, CRK, JLD, CH, ST, HH and JM were or are employed by University College London (UCL) through SUMMIT Study funding provided by GRAIL, Inc. SLQ collaborates on the SUMMIT study and has received honorarium from Elsevier for writing a book chapter and payment for a presentation/website context piece from Global Lung Cancer Coalition. SMJ has received fees for advisory board membership in the last three years from Bard1 Lifescience. He has received grant income from GRAIL, Inc. He is an unpaid member of a GRAIL advisory board. He has received lecture fees for academic meetings from Cheisi and AstraZeneca. His wife works for AstraZeneca. AH has received support for travel for an advisory board meeting for Roche. He is on an academic scientific advisory board for each of Adela Bio, Roche and Luventix who are developing multicancer blood or urine tests, but receives no payments/ honoraria for this from any of these companies. NN reports honoraria for non-promotional educational talks or advisory boards from Amgen, AstraZeneca, AXANA, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, EQRx, Fujifilm, Guardant Health, Intuitive, Janssen, Lilly, Merck Sharp & Dohme, Olympus, and Roche. He has received support for attending meetings and/or travel from Astra Zeneca, Fujifilm, Intuitive, Merck Sharp & Dohme and Olympus. He is a member of British Thoracic Oncology Group steering committee, director of UK Lung Cancer Coalition and Clinical Director of National Lung Cancer Audit. All authors perceive that these disclosures pose no academic conflict for this study and declare no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

A previously healthy woman in her 40s presented with a 6-month history of increasing cough and breathlessness following COVID-19 infection. She experienced vocal hoarseness and recurrent respiratory infections during this time, requiring several antibiotic courses. She was treated for gastro-oesophageal reflux and trialled on inhaled corticosteroids, without improvement. Further work up included CT scan, demonstrating tracheal thickening, endobronchial narrowing and mucosal abnormalities. Bronchoscopy with biopsies demonstrated amyloidosis. She was referred to a specialist centre with further work up including serum amyloid P component (SAP) scan, echo and bloodwork. She was diagnosed with localised tracheobronchial amyloidosis and referred to interventional respiratory for treatment. Bronchoscopy demonstrated severe narrowing in left main, left upper and lower lobes and to a lesser extent, the right main bronchus. Endobronchial treatment included diode laser therapy, electrocautery and cryorecanalisation. Significant improvement was seen on 3 months post surveillance bronchoscopy. Following this treatment, the patient experienced sustained improvement in breathlessness and cough., Competing Interests: Competing interests: MM and RD have no disclosures. RT received honoraria for (1) non-promotional educational talks and travel from Fujifilm, Medflix, MIMS and Olympus and (2) advisory board from Intuitive Surgical. NN reports honoraria for non-promotional educational talks or advisory boards from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, EQRx, Fujifilm, Guardant Health, Intuitive, Janssen, Lilly, Merck Sharp & Dohme, Sanofi, Olympus and Roche. NN is supported by a Medical Research Council Clinical Academic Research Partnership (MR/T02481X/1)., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background and Objective: Approximately 16,000 new cases of lung cancer are diagnosed each year in Australia and Aotearoa New Zealand, and it is the leading cause of cancer death in the region. Unwarranted variation in lung cancer care and outcomes has been described for many years, although clinical quality indicators to facilitate benchmarking across Australasia have not been established. The purpose of this study was to establish clinical quality indicators applicable to lung and other thoracic cancers across Australia and Aotearoa New Zealand., Methods: Following a literature review, a modified three round eDelphi consensus process was completed between October 2022 and June 2023. Participants included clinicians from all relevant disciplines, patient advocates, researchers and other stakeholders, with representatives from all Australian states and territories and Aotearoa New Zealand. Consensus was set at a threshold of 70%, with the first two rounds conducted as online surveys, and the final round held as a hybrid in person and virtual consensus meeting., Results: The literature review identified 422 international thoracic oncology indicators, and a total of 71 indicators were evaluated over the course of the Delphi consensus. Ultimately, 27 clinical quality indicators reached consensus, covering the continuum of thoracic oncologic care from diagnosis to first line treatment. Indicators benchmarking supportive care were poorly represented. Attendant numeric quality standards were developed to facilitate benchmarking., Conclusion: Twenty-seven clinical quality indicators relevant to thoracic oncology care in Australasia were developed. Real world implementation will now be explored utilizing a prospective dataset collected across Australia., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Background: Lung cancer screening with low-dose computed tomography has been started in some high-income countries and is being considered in others. In many settings uptake remains low. Optimal strategies to increase uptake, including for high-risk subgroups, have not been elucidated. This study used a system dynamics approach based on expert consensus to identify (I) the likely determinants of screening uptake and (II) interactions between these determinants that may affect screening uptake., Methods: Consensus data on key factors influencing screening uptake were developed from existing literature and through two stakeholder workshops involving clinical and consumer experts. These factors were used to develop a causal loop diagram (CLD) of lung cancer screening uptake., Results: The CLD comprised three main perspectives of importance for a lung cancer screening program: participant, primary care, and health system. Eight key drivers in the system were identified within these perspectives that will likely influence screening uptake: (I) patient stigma; (II) patient fear of having lung cancer; (III) patient health literacy; (IV) patient waiting time for a scan appointment; (V) general practitioner (GP) capacity; (VI) GP clarity on next steps after an abnormal computed tomography (CT); (VII) specialist capacity to accept referrals and undertake evaluation; and (VIII) healthcare capacity for scanning and reporting. Five key system leverage points to optimise screening uptake were also identified: (I) patient stigma influencing willingness to receive a scan; (II) GP capacity for referral to scans; (III) GP capacity to increase patients' health literacy; (IV) specialist capacity to connect patients with timely treatment; and (V) healthcare capacity to reduce scanning waiting times., Conclusions: This novel approach to investigation of lung cancer screening implementation, based on Australian expert stakeholder consensus, provides a system-wide view of critical factors that may either limit or promote screening uptake., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-425/coif). E.S. received speaker honoraria from Astra Zeneca, Merck Sharp & Dohme and the Limbic; support for attending meetings and travel from Astra Zeneca LOBES 2022; received ad hoc advisory board payment from Bristol Myers Squibb 2022. E.S. is the Deputy Board Chair Thoracic Oncology Group of Australasia (unpaid) and also the Editor-in-chief for the JTO CRR. F.B. reports honoraria for educational talks to primary care and secondary care specialists from Boehringer Ingelheim and Astra Zeneca. N.N. reports research funding from a Medical Research Council Clinical Academic Research Partnership, CRUK, NIHR, Horizon Europe and UKRI (Grant number MR/T02481X/1); reports honoraria for non-promotional educational talks or advisory boards from Astra Zeneca, Bristol Myers Squibb, Fujifilm, Intuitive, Janssen, Lilly, Merck Sharp & Dohme, Olympus, Sanofi and Roche; he also received support for attending meetings from Astra Zeneca, Fujifilm, Intuitive, Merck Sharp & Dohme and Olympus. He also reports consulting fees from Amgen, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, EQRx, Fujifilm, Guardant Health, Intuitive, Janssen, Lilly, Merck Sharp & Dohme, Olympus, and Roche and has leadership roles for the British Thoracic Oncology Group, UK Lung Cancer Coalition and National Lung Cancer Audit. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Synthetic data promise privacy-preserving data sharing for healthcare research and development. Compared with other privacy-enhancing approaches-such as federated learning-analyses performed on synthetic data can be applied downstream without modification, such that synthetic data can act in place of real data for a wide range of use cases. However, the role that synthetic data might play in all aspects of clinical model development remains unknown. In this work, we used state-of-the-art generators explicitly designed for privacy preservation to create a synthetic version of ever-smokers in the UK Biobank before building prognostic models for lung cancer under several data release assumptions. We demonstrate that synthetic data can be effectively used throughout the medical prognostic modeling pipeline even without eventual access to the real data. Furthermore, we show the implications of different data release approaches on how synthetic biobank data could be deployed within the healthcare system., (© 2024. The Author(s).)

Background: Advanced diagnostic bronchoscopy targeting the lung periphery has developed at an accelerated pace over the last two decades, whereas evidence to support introduction of innovative technologies has been variable and deficient. A major gap relates to variable reporting of diagnostic yield, in addition to limited comparative studies. Objectives: To develop a research framework to standardize the evaluation of advanced diagnostic bronchoscopy techniques for peripheral lung lesions. Specifically, we aimed for consensus on a robust definition of diagnostic yield, and we propose potential study designs at various stages of technology development. Methods: Panel members were selected for their diverse expertise. Workgroup meetings were conducted in virtual or hybrid format. The cochairs subsequently developed summary statements, with voting proceeding according to a modified Delphi process. The statement was cosponsored by the American Thoracic Society and the American College of Chest Physicians. Results: Consensus was reached on 15 statements on the definition of diagnostic outcomes and study designs. A strict definition of diagnostic yield should be used, and studies should be reported according to the STARD (Standards for Reporting Diagnostic Accuracy Studies) guidelines. Clinical or radiographic follow-up may be incorporated into the reference standard definition but should not be used to calculate diagnostic yield from the procedural encounter. Methodologically robust comparative studies, with incorporation of patient-reported outcomes, are needed to adequately assess and validate minimally invasive diagnostic technologies targeting the lung periphery. Conclusions: This American Thoracic Society/American College of Chest Physicians statement aims to provide a research framework that allows greater standardization of device validation efforts through clearly defined diagnostic outcomes and robust study designs. High-quality studies, both industry and publicly funded, can support subsequent health economic analyses and guide implementation decisions in various healthcare settings.

Machine learning (ML)-based risk prediction models hold the potential to support the health-care setting in several ways; however, use of such models is scarce. We aimed to review health-care professional (HCP) and patient perceptions of ML risk prediction models in published literature, to inform future risk prediction model development. Following database and citation searches, we identified 41 articles suitable for inclusion. Article quality varied with qualitative studies performing strongest. Overall, perceptions of ML risk prediction models were positive. HCPs and patients considered that models have the potential to add benefit in the health-care setting. However, reservations remain; for example, concerns regarding data quality for model development and fears of unintended consequences following ML model use. We identified that public views regarding these models might be more negative than HCPs and that concerns (eg, extra demands on workload) were not always borne out in practice. Conclusions are tempered by the low number of patient and public studies, the absence of participant ethnic diversity, and variation in article quality. We identified gaps in knowledge (particularly views from under-represented groups) and optimum methods for model explanation and alerts, which require future research., Competing Interests: Declaration of interests RG is funded by the National Institute for Health and Care Research (NIHR) for this study (NIHR302604). TC is a co-founder of and owns stock in Mortimer Health and is supported by the Wellcome Trust via a Wellcome Clinical PhD Training Fellowship (REF 22890/Z/21/Z). SMJ is supported by Cancer Research UK (CRUK; EDDCPGM\100002) and Medical Research Council (MRC; MR/W025051/1) programme grants; received fees for advisory board membership in the last three years from Bard1 Lifescience; received grant income from Owlstone and GRAIL; is an unpaid member of a GRAIL advisory board; has received lecture fees for academic meetings from Cheisi and AstraZeneca; and receives support from the CRUK Lung Cancer Centre and the CRUK City of London Centre, the Rosetrees Trust, the Roy Castle Lung Cancer foundation, the Longfonds BREATH Consortia, MRC UKRMP2 Consortia, the Garfield Weston Trust, and University College London (UCL) Hospitals Charitable Foundation where this work was partly undertaken and who also received a proportion of funding from the Department of Health's NIHR Biomedical Research Centre's funding scheme. SMJ's wife works for AstraZeneca. MvdS is a Director at the Cambridge Centre for AI in Medicine, which receives funding from AstraZeneca and GSK. JS is funded by NIHR Applied Research Collaboration North Thames, NIHR (policy research programme, programme grant, health service and delivery grant, and capacity building funding), and the UK Prevention Research Partnership. NN is supported by an MRC Clinical Academic Research Partnership (MR/T02481X/1); received a grant from the CRUK early diagnosis grant for the Real-time cancer analytics (REACT) study (EICEDAAP\100012); reports honoraria for non-promotional educational talks or advisory boards from Amgen, AstraZeneca, Boehringer ingelheim, Bristol Myers Squibb, EQRx, Fujifilm, Guardant Health, Intuitive, Janssen, Lilly, MSD, Olympus, OncLive, PeerVoice, Pfizer, Roche, and Takeda outside of the current work; holds positions as the Director of UK Lung cancer coalition, member of the Steering Committee of British Thoracic Oncology Group, and Clinical Director of National Lung Cancer Audit; and reports stock and stock options in OneWelbeck, The Physicians’ Clinic (HCA), and Pharmacierge. AJ declares no competing interests. The views expressed in this publication are those of the authors and not necessarily those of the NIHR, National Health Service, or the UK Department of Health and Social Care., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Early changes in lung cancer care can affect survival. Given the decrease in diagnosis during lockdowns, we calculated their impact on survival using National Lung Cancer Audit data. Percentage survival and HRs for death were compared between 2019 and lockdown periods of 2020. Decreased survival was observed from the first national lockdown onwards and within 90 days of diagnosis. HRs were highest for people diagnosed at the end of 2020 at 1.26 (95% CI 1.20 to 1.32) for death within 90 days and 1.51 (95% CI 1.42 to 1.60) for death between 91 and 270 days. Further work is needed on measures to mitigate this impact., Competing Interests: Competing interests: DB reports grants from Cancer Research UK, personal fees from Roche, personal fees from Astra Zeneca, personal fees from MSD, personal fees from BMS, outside the submitted work. RH reports personal fees from Galapagos, outside the submitted work. NN is supported by an MRC Clinical Academic Research Partnership (MR/T02481X/1). NN has received fees or non-financial support from Amgen, Astra Zeneca, Bristol-Meyers Squibb, Lilly & Co, Merck Sharp and Dohme, Olympus, Oncimmune, OncLive, PeerVoice, Pfizer and Takeda, outside of the submitted work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Different treatment options are now possible both for surgical candidates and for those NSCLC patients deemed not suitable for surgery. Despite the treatments available, only a limited number of less advanced stages are potentially curable, with many patients suffering local recurrence or distant metastases. FDG-PET/CT is commonly used in many centers for post-treatment evaluation, follow-up, or surveillance; Nonetheless, there is no clear consensus regarding the indications in these cases. Based upon the results of a literature review and local expertise from a large lung cancer unit, we built clinical evidence-based recommendations for the use of FDG-PET/CT in response assessment. We found that in general this is not recommended earlier than 3 months from treatment; however, as described in detail the correct timing will also depend upon the type of treatment used. We also present a structured approach to assessing treatment changes when reporting FDG-PET/CT, using visual or quantitative approaches., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Risk-based screening for lung cancer is currently being considered in several countries; however, the optimal approach to determine eligibility remains unclear. Ensemble machine learning could support the development of highly parsimonious prediction models that maintain the performance of more complex models while maximising simplicity and generalisability, supporting the widespread adoption of personalised screening. In this work, we aimed to develop and validate ensemble machine learning models to determine eligibility for risk-based lung cancer screening., Methods and Findings: For model development, we used data from 216,714 ever-smokers recruited between 2006 and 2010 to the UK Biobank prospective cohort and 26,616 high-risk ever-smokers recruited between 2002 and 2004 to the control arm of the US National Lung Screening (NLST) randomised controlled trial. The NLST trial randomised high-risk smokers from 33 US centres with at least a 30 pack-year smoking history and fewer than 15 quit-years to annual CT or chest radiography screening for lung cancer. We externally validated our models among 49,593 participants in the chest radiography arm and all 80,659 ever-smoking participants in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial. The PLCO trial, recruiting from 1993 to 2001, analysed the impact of chest radiography or no chest radiography for lung cancer screening. We primarily validated in the PLCO chest radiography arm such that we could benchmark against comparator models developed within the PLCO control arm. Models were developed to predict the risk of 2 outcomes within 5 years from baseline: diagnosis of lung cancer and death from lung cancer. We assessed model discrimination (area under the receiver operating curve, AUC), calibration (calibration curves and expected/observed ratio), overall performance (Brier scores), and net benefit with decision curve analysis. Models predicting lung cancer death (UCL-D) and incidence (UCL-I) using 3 variables-age, smoking duration, and pack-years-achieved or exceeded parity in discrimination, overall performance, and net benefit with comparators currently in use, despite requiring only one-quarter of the predictors. In external validation in the PLCO trial, UCL-D had an AUC of 0.803 (95% CI: 0.783, 0.824) and was well calibrated with an expected/observed (E/O) ratio of 1.05 (95% CI: 0.95, 1.19). UCL-I had an AUC of 0.787 (95% CI: 0.771, 0.802), an E/O ratio of 1.0 (95% CI: 0.92, 1.07). The sensitivity of UCL-D was 85.5% and UCL-I was 83.9%, at 5-year risk thresholds of 0.68% and 1.17%, respectively, 7.9% and 6.2% higher than the USPSTF-2021 criteria at the same specificity. The main limitation of this study is that the models have not been validated outside of UK and US cohorts., Conclusions: We present parsimonious ensemble machine learning models to predict the risk of lung cancer in ever-smokers, demonstrating a novel approach that could simplify the implementation of risk-based lung cancer screening in multiple settings., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: NN reports honoraria for non-promotional educational talks, conference support or advisory boards from Amgen, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Guardant Health, Janssen, Lilly, Merck Sharp & Dohme, Olympus, OncLive, PeerVoice, Pfizer, and Takeda. SMJ has received fees for advisory board membership in the last three years from Astra-Zeneca, Bard1 Lifescience, and Johnson and Johnson. He has received grant income from Owlstone and GRAIL Inc. He has received assistance with travel to an academic meeting from Cheisi. TC and SMJ are founders of, and own stock in, Mortimer Health., (Copyright: © 2023 Callender et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The COVID-19 pandemic has caused significant disruption to health-care services and delivery worldwide. The impact of the pandemic and associated national lockdowns on lung cancer incidence in England have yet to be assessed., Research Question: What was the impact of the first year of the COVID-19 pandemic on the incidence and presentation of lung cancer in England?, Study Design and Methods: In this retrospective observational study, incidence rates for lung cancer were calculated from The National Lung Cancer Audit Rapid Cancer Registration Datasets for 2019 and 2020, using midyear population estimates from the Office of National Statistics as the denominators. Rates were compared using Poisson regression according to time points related to national lockdowns in 2020., Results: Sixty-four thousand four hundred fifty-seven patients received a diagnosis of lung cancer across 2019 (n = 33,088) and 2020 (n = 31,369). During the first national lockdown, a 26% reduction in lung cancer incidence was observed compared with the equivalent calendar period of 2019 (adjusted incidence rate ratio [IRR], 0.74; 95% CI, 0.71-0.78). This included a 23% reduction in non-small cell lung cancer (adjusted IRR, 0.77; 95% CI, 0.74-0.81) and a 45% reduction in small cell lung cancer (adjusted IRR, 0.55; 95% CI, 0.46-0.65) incidence. Thereafter, incidence rates almost recovered to baseline, without overcompensation (adjusted IRR, 0.96; 95% CI, 0.94-0.98)., Interpretation: The incidence rates of lung cancer in England fell significantly by 26% during the first national lockdown in 2020 and did not compensate later in the year., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: There is a critical need to understand the optimal treatment regimen in patients with potentially resectable stage III-N2 nonsmall cell lung cancer (NSCLC)., Methods: A systematic review of randomised controlled trials was carried out using a literature search including the CDSR, CENTRAL, DARE, HTA, EMBASE and MEDLINE bibliographic databases. Selected trials were used to perform a Bayesian fixed-effects network meta-analysis and economic modelling of treatment regimens relevant to current-day treatment options: chemotherapy plus surgery (CS), chemotherapy plus radiotherapy (CR) and chemoradiotherapy followed by surgery (CRS)., Findings: Six trials were prioritised for evidence synthesis. The fixed-effects network meta-analyses demonstrated an improvement in disease-free survival (DFS) for CRS versus CS and CRS versus CR of 0.34   years (95% CI 0.02-0.65) and 0.32   years (95% CI 0.05-0.58) respectively, over a 5-year period. No evidence of effect was observed in overall survival although point estimates favoured CRS. The probabilities that CRS had a greater mean survival time and greater probability of being alive than the reference treatment of CR at 5   years were 89% and 86% respectively. Survival outcomes for CR and CS were essentially equivalent. The economic model calculated that CRS and CS had incremental cost-effectiveness ratios of £19 000/quality-adjusted life-year (QALY) and £78 000/QALY compared to CR. The probability that CRS generated more QALYs than CR and CS was 94%., Interpretation: CRS provides an extended time in a disease-free state leading to improved cost-effectiveness over CR and CS in potentially resectable stage III-N2 NSCLC., Competing Interests: Conflicts of interest: R. Maconachie currently works as Associate Director, Value, Access and Devolved Nations, Merck, Sharp and Dohme (UK) Ltd (MSD). During the time of this work, his role was Technical Adviser, Centre for Guidelines, National Institute for Health and Care Excellence (NICE). MSD market treatments for lung cancer but this work was completed entirely while in employment with NICE and there are no obvious conflicts of interest related to MSD's activities. NICE funds the technical support unit at the University of Bristol which supported C.H. Daly and N.J Welton for the work on this manuscript. N. Navani is supported by a Medical Research Council Academic Research Partnership (MR/T02481X/1). This work was partly undertaken at The University College London Hospitals/University College London that received a proportion of funding from the Department of Health's National Institute for Health Research (NIHR) Biomedical Research Centre's funding scheme. N. Navani reports honoraria for non-promotional educational talks or advisory boards from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Guardant, Janssen, Lilly, Merck Sharp & Dohme, OIympus, OncLive, PeerVoice, Pfizer and Takeda. M. Evison reports honoraria for non-promotional educational talks or advisory boards from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Merck Sharp & Dohme and Pfizer. N.J Welton has received honoraria for delivering masterclasses/workshops/courses on behalf of Association of the British Pharmaceutical Industry (ABPI), Takeda, Cochrane Ireland, NICE International and NICE Scientific Advice, and Centre for Global Development, all outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Introduction: In 2019, the National Institute for Health and Care Excellence (NICE) updated their recommendations with respect to brain imaging in the staging of non-small cell lung cancer (NSCLC) based on an analytic cost-effectiveness model using published data and modelling assumptions from committee experts. In this study, we aimed to re-run this model using real-world multi-centre UK data., Materials and Methods: Retrospective data was collected on consecutive patients with radically treatable clinical stage II and III lung cancer from eleven acute NHS Trusts during the calendar year 01/01/2018 to 31/12/2018. Following a written application to the NICE lung cancer guideline committee, we were granted access to the NG122 brain imaging economic model for the purpose of updating the input parameters in line with the real-world findings from this study., Results: A total of 444 patients had data for analysis. The combined prevalence of occult brain metastases was 6.2% (10/165) in stage II and 6% (17/283) in stage III, compared to 9.5% and 9.3% used in the NICE economic model. 30% of patients with clinical stage III NSCLC and occult BMs on pre-treatment imaging went onto complete the planned curative intent treatment of extracranial disease, 60% completed SRS to the brain and 30% completed WBRT. This compares to 0%, 10% and 0% in the NICE assumptions. The health economic analysis concluded that brain imaging was no longer cost-effective in stage II disease (ICERs £50,023-£115,785) whilst brain imaging remained cost-effective for stage III patients (ICERs 17,000-£22,173), with MRI being the most cost-effective strategy., Conclusion: This re-running of the NICE health economic model with real-world data strongly supports the NICE guideline recommendation for brain imaging prior to curative-intent treatment in stage III lung cancer but questions the cost-effectiveness of CT brain imaging prior to curative-intent treatment in stage II lung cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RM currently works as Associate Director, Value Access and Devolved Nations, Merck, Sharp and Dohme (UK) Ltd. During the time of this work his role was Technical Adviser, Centre for Guidelines, National Institute for Health and Care Excellence. MSD market treatments for lung cancer but this work was completed entirely while in employment with NICE and there are no obvious COI related to MSD’s activities. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Lung cancer is the leading cause of cancer-associated mortality worldwide 1 . Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource., (© 2023. The Author(s).)

Metastatic disease is responsible for the majority of cancer-related deaths 1 . We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse., (© 2023. The Author(s).)

Background: Lung cancer screening with low-dose CT reduces lung cancer mortality, but screening requires equitable uptake from candidates at high risk of lung cancer across ethnic and socioeconomic groups that are under-represented in clinical studies. We aimed to assess the uptake of invitations to a lung health check offering low-dose CT lung cancer screening in an ethnically and socioeconomically diverse cohort at high risk of lung cancer., Methods: In this multicentre, prospective, longitudinal cohort study (SUMMIT), individuals aged 55-77 years with a history of smoking in the past 20 years were identified via National Health Service England primary care records at practices in northeast and north-central London, UK, using electronic searches. Eligible individuals were invited by letter to a lung health check offering lung cancer screening at one of four hospital sites, with non-responders re-invited after 4 months. Individuals were excluded if they had dementia or metastatic cancer, were receiving palliative care or were housebound, or declined research participation. The proportion of individuals invited who responded to the lung health check invitation by telephone was used to measure uptake. We used univariable and multivariable logistic regression analyses to estimate associations between uptake of a lung health check invitation and re-invitation of non-responders, adjusted for sex, age, ethnicity, smoking, and deprivation score. This study was registered prospectively with ClinicalTrials.gov, NCT03934866., Findings: Between March 20 and Dec 12, 2019, the records of 2 333 488 individuals from 251 primary care practices across northeast and north-central London were screened for eligibility; 1 974 919 (84·6%) individuals were outside the eligible age range, 7578 (2·1%) had pre-existing medical conditions, and 11 962 (3·3%) had opted out of particpation in research and thus were not invited. 95 297 individuals were eligible for invitation, of whom 29 545 (31·0%) responded. Due to the COVID-19 pandemic, re-invitation letters were sent to only a subsample of 4594 non-responders, of whom 642 (14·0%) responded. Overall, uptake was lower among men than among women (odds ratio [OR] 0·91 [95% CI 0·88-0·94]; p<0·0001), and higher among older age groups (1·48 [1·42-1·54] among those aged 65-69 years vs those aged 55-59 years; p<0·0001), groups with less deprivation (1·89 [1·76-2·04] for the most vs the least deprived areas; p<0·0001), individuals of Asian ethnicity (1·14 [1·09-1·20] vs White ethnicity; p<0·0001), and individuals who were former smokers (1·89 [1·83-1·95] vs current smokers; p<0·0001). When ethnicity was subdivided into 16 groups, uptake was lower among individuals of other White ethnicity than among those with White British ethnicity (0·86 [0·83-0·90]), whereas uptake was higher among Chinese, Indian, and other Asian ethnicities than among those with White British ethnicity (1·33 [1·13-1·56] for Chinese ethnicity; 1·29 [1·19-1·40] for Indian ethnicity; and 1·19 [1·08-1·31] for other Asian ethnicity)., Interpretation: Inviting eligible adults for lung health checks in areas of socioeconomic and ethnic diversity should achieve favourable participation in lung cancer screening overall, but inequalities by smoking, deprivation, and ethnicity persist. Reminder and re-invitation strategies should be used to increase uptake and the equity of response., Funding: GRAIL., Competing Interests: Declaration of interests JLD, CH, ST, HH, and PV were employed by University College London (UCL) as clinical research fellows through SUMMIT Study funding provided by GRAIL. SMJ has received travel expenses from AstraZeneca, BARD1 Bioscience, Optellum, Jansen, Takeda, Evidera, and Achilles Therapeutics for participation on advisory boards; has received honoraria for lectures from Chiesi; and has received travel expenses from AstraZeneca for a US conference. AH has received one honorarium for an advisory board meeting for GRAIL; has received consulting fees from Evidera (for a GRAIL-initiated project); and has previously owned shares in Illumina. NN has received honoraria for advisory, education, and consultancy work from Amgen, AstraZeneca, Bristol-Meyers Squibb, Guardant Health, Janssen, Lilly & Co, Merck Sharp & Dohme, Olympus, Oncimmune, OncLive, PeerVoice, Pfizer, and Takeda, all outside of the submitted work. AN has received consulting fees from Aidence BV, Faculty Science Limited, and MSD; and has received expenses for travelling to a conference from Takeda. A-MM, JT, LF, VB, KG, FB, CL, TA, JM, AD, and SLQ declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Epidermal growth factor receptor (EGFR) mutations (EGFRm) are common oncogene drivers in non-small cell lung cancer (NSCLC). This real-world study explored treatment patterns and time to receive EGFRm test results in patients with advanced EGFRm NSCLC., Methods: A cross-sectional medical chart review was completed May-August 2020 in Australia, Canada, Germany, Italy, South Korea, Taiwan, UK, and USA. Eligible patients had advanced NSCLC and a positive EGFRm test result January-December 2017. Data were abstracted from NSCLC diagnosis to end of follow-up (31 March 2020) or patient's death whichever occurred earlier. The index date was the date of EGFRm confirmation., Results: 223 physicians provided data for 1,793 patients. Patients' mean age was 64.7 years, 54 % were male, 30.7 % had no history of smoking. Overall, 78 % of EGFRm test results were received ≤ 2 weeks after request (range of median 7-14 days across countries). Median time from advanced NSCLC diagnosis to EGFRm test result was 18 days (median range 10-22 days across countries). Over a third (37 %) of patients received a systemic treatment prior to EGFRm result; chemotherapy (25 %) and EGFR-TKI (15 %) were most commonly prescribed; post-EGFR test-result was EGFR-TKI (68 %); 80 % of patients initiated EGFR-TKI at any time point post-NSCLC diagnosis. Of those receiving a first-line EGFR-TKI post-EGFRm testing, 84 % received a TKI alone, 12 % in combination with chemotherapy, and 3 % with other treatments. Median time from first-line EGFR-TKI initiation post-EGFRm testing to first subsequent treatment was 19.8 months., Conclusion: Over one-fifth of patients wait >14 days for their EGFRm test results, affecting their likelihood of receiving first-line EGFR-TKI with 20 % of patients never receiving EGFR TKI treatment. There was significant inter-country variability in the proportion of patients receiving EGFR TKIs. Our study highlights the need to improve EGFRm testing turnaround times and treatment initiation across countries., Competing Interests: Declaration of Competing Interest Janakiraman Subramanian: Advisory board member for AstraZeneca, Boehringer Ingelheim, Daichi-Sankyo, Eli Lilly, G1 therapeutics, Jazz Pharma, Janssen, Novartis, Pfizer; Takeda; Speaker honorarium from AstraZeneca, G1 therapeutics, Janssen, Jazz Pharma & Boehringer Ingelheim. Natasha Leighl: Honoraria received for CME lectures from Amgen, BMS, GlaxoSmithKline, MSD, Novartis, Puma Biotechnology, Sanofi Genzyme and Takeda; Institutional research funding received from Amgen, Array, AstraZeneca, Bayer, BMS, Eli Lilly, EMD Serono, Guardant Health, Inivata, MSD, Novartis, Pfizer, Roche and Takeda. Yoon-La Choi: No disclosures or potential conflicts of interest. Teh-Ying Chou: No disclosures or potential conflicts of interest. Jeffrey Gregg is an employee of Harbinger Oncology, Cambridge, MA, USA. Rina Hui: Advisory board member for AstraZeneca, BMS, Eisai, Eli Lilly, Merck, MSD, Novartis, OncoSec, Pfizer, Roche, Seagen; Speaker honorarium from AstraZeneca, Eli Lilly, MSD, Novartis. Antonio Marchetti: No disclosures or potential conflicts of interest. Neal Navani is supported by an MRC Clinical Academic Research Partnership (MR/T02481X/1), and has received honoraria or non-financial support for advisory boards or speaker bureau from Amgen, AstraZeneca, Bristol-Meyers Squibb, Guardant, Janssen, Lilly & Co, Merck Sharp and Dohme, Olympus, Oncimmune, OncLive, PeerVoice, Pfizer and Takeda, outside of the submitted work. Maiyan Chau and Aliki Taylor are employees of AstraZeneca, Cambridge, UK; Maiyan Chau owns stock and stock options in AstraZeneca. Doreen A Kahangire is a Consultant of AZ Cambridge, UK and does not own or hold stock options. Tom Bailey, Mark Silvey, Rebecca Makin, and Liane Gillespie‑Akar are employees of Adelphi Real World, Bollington, Cheshire, UK., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Large lung nodules (≥15 mm) have the highest risk of malignancy, and may exhibit important differences in phenotypic or clinical characteristics to their smaller counterparts. Existing risk models do not stratify large nodules well. We aimed to develop and validate an integrated segmentation and classification pipeline, incorporating deep-learning and traditional radiomics, to classify large lung nodules according to cancer risk., Methods: 502 patients from five U.K. centres were recruited to the large-nodule arm of the retrospective LIBRA study between July 2020 and April 2022. 838 CT scans were used for model development, split into training and test sets (70% and 30% respectively). An nnUNet model was trained to automate lung nodule segmentation. A radiomics signature was developed to classify nodules according to malignancy risk. Performance of the radiomics model, termed the large-nodule radiomics predictive vector (LN-RPV), was compared to three radiologists and the Brock and Herder scores., Findings: 499 patients had technically evaluable scans (mean age 69 ± 11, 257 men, 242 women). In the test set of 252 scans, the nnUNet achieved a DICE score of 0.86, and the LN-RPV achieved an AUC of 0.83 (95% CI 0.77-0.88) for malignancy classification. Performance was higher than the median radiologist (AUC 0.75 [95% CI 0.70-0.81], DeLong p = 0.03). LN-RPV was robust to auto-segmentation (ICC 0.94). For baseline solid nodules in the test set (117 patients), LN-RPV had an AUC of 0.87 (95% CI 0.80-0.93) compared to 0.67 (95% CI 0.55-0.76, DeLong p = 0.002) for the Brock score and 0.83 (95% CI 0.75-0.90, DeLong p = 0.4) for the Herder score. In the international external test set (n = 151), LN-RPV maintained an AUC of 0.75 (95% CI 0.63-0.85). 18 out of 22 (82%) malignant nodules in the Herder 10-70% category in the test set were identified as high risk by the decision-support tool, and may have been referred for earlier intervention., Interpretation: The model accurately segments and classifies large lung nodules, and may improve upon existing clinical models., Funding: This project represents independent research funded by: 1) Royal Marsden Partners Cancer Alliance, 2) the Royal Marsden Cancer Charity, 3) the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, 4) the National Institute for Health Research (NIHR) Biomedical Research Centre at Imperial College London, 5) Cancer Research UK (C309/A31316)., Competing Interests: Declaration of interests Dr Navani is supported by a Medical Research Council Clinical Academic Research Partnership (MR/T02481X/1). This work was partly undertaken at the University College London Hospitals/University College London that received a proportion of funding from the Department of Health’s National Institute for Health Research (NIHR) Biomedical Research Centre’s funding scheme (NN). Dr Navani reports honoraria for educational talks or advisory boards from Amgen, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Guardant Health, Janssen, Lilly, Merck Sharp & Dohme, Olympus, OncLive, PeerVoice, Pfizer, and Takeda. Dr Nair receives research grants from the Department of Health’s NIHR Biomedical Research Centre and GRAIL. He has received consulting fees from Aidence BV, Faculty Science Limited and MSD. He has received a travel bursary from Takeda. He participates on advisory boards for Aidence BV and Faculty Science Limited. He has leadership roles within the British Society of Thoracic Imaging, the British Lung Foundation and the NHS England Targeted Lung Health Checks Programme. Dr Lee is funded by the Royal Marsden NIHR BRC, and Royal Marsden Cancer charity. RL's institution receives compensation for time spent in a secondment role for the lung health check program and as a National Specialty Lead for the National Institute of Health and Care Research. He has received research funding from CRUK, Innovate UK (co-funded by GE Healthcare, Roche and Optellum), SBRI (co-applicant in grants with QURE.AI), RM Partners Cancer Alliance and NIHR (co-applicant in grants with Optellum). He has received honoraria from CRUK. Professor Devaraj is employed by and has stocks in Brainomix. He receives consulting fees from Roche and Boehringer Ingelheim. The other authors report no potential conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Since 2014, the National Lung Cancer Audit (NLCA) has been evaluating the performance of the UK NHS lung cancer services against established standards of care. Prior to the onset of the COVID-19 pandemic, the NLCA's annual reports revealed a steady stream of improvements in early diagnosis, access to surgery, treatment with anti-cancer therapies, input from specialist nursing and survival for patients with lung cancer in the NHS. In January 2022, the NLCA reported on the negative impact COVID-19 has had on all aspects of the lung cancer diagnosis and treatment pathway within the NHS. This article details the fundamental changes made to the NLCA data collection and analysis process during the COVID-19 pandemic and details the negative impact COVID-19 had on NHS lung cancer patient outcomes during 2020., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Lung cancer screening (LCS) eligibility is largely determined by tobacco consumption. Primary care smoking data could guide LCS invitation and eligibility assessment. We present observational data from the SUMMIT Study, where individual self-reported smoking status was concordant with primary care records in 75.3%. However, 10.3% demonstrated inconsistencies between historic and most recent smoking status documentation. Quantified tobacco consumption was frequently missing, precluding direct LCS eligibility assessment. Primary care recorded "ever-smoker" status, encompassing both recent and historic documentation, can be used to target LCS invitation. Identifying those with missing or erroneous "never-smoker" smoking status is crucial for equitable invitation to LCS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Targeted therapy against actionable variants has revolutionised the treatment landscape for non-small cell lung cancer (NSCLC). Approximately half of NSCLC adenocarcinomas have an actionable variant, making molecular testing a critical component of the diagnostic process to personalise therapeutic options, optimise clinical outcomes and minimise toxicity. Recently, genomic testing in England has undergone major changes with the introduction of Genomic Laboratory Hubs, designed to consolidate and enhance existing laboratory provision and deliver genomic testing as outlined in the National Genomic Test Directory. Similar changes are ongoing in Scotland, Wales and Northern Ireland. However, multiple challenges exist with current tissue acquisition procedures and the molecular testing pathway in the UK, including quantity and quality of available tissue, adequacy rates, test availability among genomic laboratories, turnaround times, multidisciplinary team communication, and limited guidance and standardisation. The COVID-19 pandemic has added an extra layer of complexity. Herein, we summarise best practice recommendations, based on expert opinion, to overcome existing challenges in the UK. The least invasive biopsy technique should be undertaken with the aim of acquiring the greatest quality and quantity of tissue. Use of sedation should be considered to improve patient experience. Rapid on-site evaluation may also be useful to help guide adequate sampling, and liquid biopsy may be beneficial in some instances. Sample processing should be appropriate to facilitate biomarker testing, in particular, next-generation sequencing for comprehensive genomic information. Steps to optimise tissue utilisation and turnaround times, such as planning of tissue usage, limiting immunohistochemistry, tumour enrichment, and reflex testing at diagnosis, should be implemented. Guidelines for tissue acquisition and sample processing may help to improve sample adequacy to perform downstream testing. Communication among genomic laboratories will help to standardise test availability across England and local auditing could identify further areas for optimisation, including ways to improve turnaround times and adequacy rates., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Eligibility for lung cancer screening (LCS) requires assessment of lung cancer risk, based on smoking history alongside demographic and medical factors. Reliance on individual face-to-face eligibility assessment risks inefficiency and costliness. The SUMMIT Study introduced a telephone-based lung cancer risk assessment to guide invitation to face-to-face LCS eligibility assessment, which significantly increased the proportion of face-to-face attendees eligible for LCS. However, levels of agreement between phone screener and in-person responses were lower in younger individuals and minority ethnic groups. Telephone-based risk assessment is an efficient way to optimise selection for LCS appointments but requires further iteration to ensure an equitable approach., Competing Interests: Competing interests: JLD, CH, ST, HH, PV, JM, AH and SMJ are investigators for the SUMMIT Study within which the present study cohort is embedded. SUMMIT is sponsored and conducted by University College London and funded by GRAIL LLC. through a research grant awarded to SMJ as principal investigator. SLQ collaborates on the SUMMIT study and has received honorarium from Elsevier for writing a book chapter. AN is a member of the advisory board for Aidence BV. AH has received an honorarium for an advisory board meeting for GRAIL, a consultation fee for Evidera Inc for a GRAIL initiated project, and previously owned shares in Illumina. SMJ has received honoraria from Astra Zeneca, BARD1 Bioscience and Jansen for being an Advisory Board Expert and travel to a US conference. SMJ received grant funding from Owlstone for a separate research study and has a family member who is an employee of Astra Zeneca. SMJ has received travel funding for a conference from Takeda and an honorarium for planning and speaking at educational meetings from Astra Zeneca. All authors perceive that these disclosures pose no academic conflict for this study and declare no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Successful lung cancer screening delivery requires sensitive, timely reporting of low-dose computed tomography (LDCT) scans, placing a demand on radiology resources. Trained non-radiologist readers and computer-assisted detection (CADe) software may offer strategies to optimise the use of radiology resources without loss of sensitivity. This report examines the accuracy of trained reporting radiographers using CADe support to report LDCT scans performed as part of the Lung Screen Uptake Trial (LSUT)., Methods: In this observational cohort study, two radiographers independently read all LDCT performed within LSUT and reported on the presence of clinically significant nodules and common incidental findings (IFs), including recommendations for management. Reports were compared against a 'reference standard' (RS) derived from nodules identified by study radiologists without CADe, plus consensus radiologist review of any additional nodules identified by the radiographers., Results: A total of 716 scans were included, 158 of which had one or more clinically significant pulmonary nodules as per our RS. Radiographer sensitivity against the RS was 68-73.7%, with specificity of 92.1-92.7%. Sensitivity for detection of proven cancers diagnosed from the baseline scan was 83.3-100%. The spectrum of IFs exceeded what could reasonably be covered in radiographer training., Conclusion: Our findings highlight the complexity of LDCT reporting requirements, including the limitations of CADe and the breadth of IFs. We are unable to recommend CADe-supported radiographers as a sole reader of LDCT scans, but propose potential avenues for further research including initial triage of abnormal LDCT or reporting of follow-up surveillance scans., Key Points: • Successful roll-out of mass screening programmes for lung cancer depends on timely, accurate CT scan reporting, placing a demand on existing radiology resources. • This observational cohort study examines the accuracy of trained radiographers using computer-assisted detection (CADe) software to report lung cancer screening CT scans, as a potential means of supporting reporting workflows in LCS programmes. • CADe-supported radiographers were less sensitive than radiologists at identifying clinically significant pulmonary nodules, but had a low false-positive rate and good sensitivity for detection of confirmed cancers., (© 2022. The Author(s).)

Background: Previous studies regarding the prevalence of frailty in patients with lung cancer and mortality in frail patients with lung cancer are inconsistent and require clarification., Research Question: What is the prevalence and impact of frailty in patients with lung cancer?, Study Design and Methods: This systematic review and meta-analysis used a combination of free-text terms and medical subject headings terms, according to the database requirements in MEDLINE/PubMed, Scopus, and Cochrane Library from inception until November 15, 2020., Results: A total of 2,571 articles were identified, and 16 articles involving 4,183 patients were included for study. The prevalence of frailty in lung cancer was 45% (95% CI, 28-61; I 2  = 99.5%; P < .0001). In patients with lung cancer, frailty was associated with an increased hazard ratio for mortality (hazard ratio, 3.01; 95% CI, 1.77-5.10; P < .001)., Interpretation: The prevalence of frailty in lung cancer is 45%, which has a significant negative impact on survival of patients with lung cancer. These results highlight the importance of measuring frailty, which provides important prognostic information, and may provide opportunities for interventions to improve outcomes in patients with lung cancer., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: National targets for timely diagnosis and management of a potential cancer are driven in part by the perceived risk of disease progression during avoidable delays. However, it is unclear to what extent time-to-treatment impacts prognosis for patients with non-small cell lung cancer, with previous reviews reporting mixed or apparently paradoxical associations. This systematic review focuses on potential confounders in order to identify particular patient groups which may benefit most from timely delivery of care., Methods: Medline, EMBASE and Cochrane databases were searched for publications between January 2012 and October 2020, correlating timeliness in secondary care pathways to patient outcomes. The protocol is registered with PROSPERO (the International Prospective Register of Systematic Reviews; ID 99239). Prespecified factors (demographics, performance status, histology, stage and treatment) are examined through narrative synthesis., Results: Thirty-seven articles were included. All but two were observational. Timely care was generally associated with a worse prognosis in those with advanced stage disease (6/8 studies) but with better outcomes for patients with early-stage disease treated surgically (9/12 studies). In one study, patients with squamous cell carcinoma referred for stereotactic ablative radiotherapy benefited more from timely care, compared with patients with adenocarcinoma. One randomised controlled trial supported timeliness as being advantageous in those with stage I-IIIA disease., Conclusion: There are limitations to the available evidence, but observed trends suggest timeliness to be of particular importance in surgical candidates. In more advanced disease, survival trends are likely outweighed by symptom burden, performance status or clinical urgency dictating timeliness of treatment., Competing Interests: Competing interests: This project has received funding from a CRUK Early Diagnosis Advisory Group (EDAG) project award, C11558/A25623. SG is supported by funding from CRUK project award C11558/A25623. TR is funded by a National Institute for Health Research (NIHR) Doctoral Research Fellowship (ref: DRF-2016-09-054), and was previously supported by a Royal Marsden Partners (RMP) Research Fellowship. NN is supported by an MRC Clinical Academic Research Partnership (MR/T02481X/1). SMJ and HH are supported by a grant from GRAIL Inc for work on the SUMMIT study. SMJ has received funding from Jansen and fees from Bard1, Takeda and Astra Zeneca, outside of the submitted work. MDP has received lecture fees for Astra Zeneca, outside of the submitted work. NN has received fees or non-financial support from Amgen, Astra Zeneca, Bristol-Meyers Squibb, Lilly & Co, Merck Sharp and Dohme, Olympus, Oncimmune, OncLive, PeerVoice, Pfizer and Takeda, outside of the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Accurately explaining perioperative mortality and risk to patients is an essential part of shared decision making. In the case of lung cancer surgery, the currently available multivariable mortality prediction tools perform poorly, and could mislead patients. Using data from 2004 to 2012, this group has previously produced data tables for 90-day postoperative mortality, to be used as a communication aid in the consenting process. Using National Lung Cancer Clinical Outcomes audit data from 2017 to 2018, we have produced updated early mortality tables, to reflect current thoracic surgery practice., Competing Interests: Competing interests: HM has nothing to disclose. DRB reports grants from Cancer Research UK, personal fees from Roche, personal fees from Astra Zeneca, personal fees from MSD, personal fees from BMS, outside the submitted work. RH reports personal fees from Galapagos, outside the submitted work. NN is supported by an MRC Clinical Academic Research Partnership (MR/T02481X/1). NN has received fees or non-financial support fromAmgen, Astra Zeneca, Bristol-Meyers Squibb, Lilly & Co, Merck Sharp and Dohme, Olympus,Oncimmune, OncLive, PeerVoice, Pfizer and Takeda, outside of the submitted work. DWreports grants from Medtronic, personal fees from Astra Zeneca UK, and is a salariedemployee of the NHS England Improvement GIRFT programme. ELO'D has nothing to disclose., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Delivering lung cancer care during the COVID-19 pandemic has posed significant and ongoing challenges. There is a lack of published COVID-19 and lung cancer evidence-based reviews, including for the whole patient pathway. We searched for COVID-19 and lung cancer publications and brought together a multidisciplinary group of stakeholders to review and comment on the evidence and challenges. A rapid review of the literature was undertaken up to 28 October 2020, producing 144 papers, with 113 full texts screened. We focused on new primary data collection (qualitative or quantitative evidence) and excluded case reports, editorials and commentaries. Following exclusions, 15 published papers were included in the review and are summarised. They included one qualitative paper and 14 quantitative studies (surveys or cohort studies), with a total of 2295 lung cancer patients data included (mean study size 153 patients; range 7-803). Review of current evidence and commentary included awareness and help-seeking; lung cancer screening; primary care assessment and referral; diagnosis and treatment in secondary care, including oncology and surgery; patient experience and palliative care. Cross-cutting themes and challenges were identified using qualitative methods for patients, healthcare professionals and service delivery, with a clear need for continued studies to guide evidence-based decision-making., (© 2021. The Author(s), under exclusive licence to Cancer Research UK.)

Introduction: Optimal treatment for 'potentially resectable' stage III-N2 non-small cell lung cancer (NSCLC) requires multimodality treatment: local treatment (surgery or radiotherapy) and systemic anticancer therapy. There is no clear evidence of superiority for survival between the two approaches and little research has explored quality of life (QOL). This study will inform the design of a phase III randomised trial of surgery versus no surgery as part of multimodality treatment for stage III-N2 NSCLC with QOL as a primary outcome., Methods and Analysis: Patient participants will be randomised to receive multimodality treatment (1) with surgery OR (2) without surgery. The Quintet Recruitment Intervention will be used to maximise recruitment. Eligible patients will have 'potentially resectable' N2 NSCLC and have received a multidisciplinary team recommendation for multimodality treatment. Sixty-six patients and their carers will be recruited from 8 UK centres. Patient/carer QOL questionnaires will be administered at baseline, weeks 6, 9, 12 and month 6. Semistructured interviews will be conducted. Quantitative data will be analysed descriptively and qualitative data will be analysed using framework analysis., Ethics and Dissemination: Ethical approval has been obtained. Results will be disseminated via publications, national bodies and networks, and patient and public involvement groups., Trial Registration: NCT04540757., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Optimal management of people with advanced NSCLC depends on accurate identification of predictive markers. Yet, real-world data in this setting are limited. We describe the impact, timeliness, and outcomes of molecular testing for patients with advanced NSCLC and good performance status in England., Methods: In collaboration with Public Health England, patients with stages IIIB to IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 0 to 2, in England, between June 2017 and December 2017, were identified. All English hospitals were invited to record information., Results: A total of 60 of 142 invited hospitals in England participated in this study and submitted data on 1157 patients. During the study period, 83% of patients with advanced adenocarcinoma underwent molecular testing for three recommended predictive biomarkers (EGFR, ALK, and programmed death-ligand 1). A total of 80% of patients with nonsquamous carcinomas on whom biomarker testing was performed had adequate tissue for analysis on initial sampling. First-line treatment with a tyrosine kinase inhibitor was received by 71% of patients with adenocarcinoma and a sensitizing EGFR mutation and by 59% of those with an ALK translocation. Of patients with no driver mutation and a programmed death-ligand 1 expression of greater than or equal to 50%, 47% received immunotherapy., Conclusions: We present a comprehensive data set for molecular testing in England. Although molecular testing is well established in England, timeliness and uptake of targeted therapies should be improved., (© 2021 The Authors.)

Non-small cell lung cancer (NSCLC) accounts for approximately one in five cancer-related deaths, and management requires increasingly complex decision making by health care professionals. Many centers have therefore adopted a multidisciplinary approach to patient care, using the expertise of various specialists to provide the best evidence-based, personalized treatment. However, increasingly complex disease staging, as well as expanded biomarker testing and multimodality management algorithms with novel therapeutics, have driven the need for multifaceted, collaborative decision making to optimally guide the overall treatment process. To keep up with the rapidly evolving treatment landscape, national-level guidelines have been introduced to standardize patient pathways and ensure prompt diagnosis and treatment. Such strategies depend on efficient and effective communication between relevant multidisciplinary team members and have both improved adherence to treatment guidelines and extended patient survival. This article highlights the value of a multidisciplinary approach to diagnosis and staging, treatment decision making, and adverse event management in NSCLC. IMPLICATIONS FOR PRACTICE: This review highlights the value of a multidisciplinary approach to the diagnosis and staging of non-small cell lung cancer (NSCLC) and makes practical suggestions as to how multidisciplinary teams (MDTs) can be best deployed at individual stages of the disease to improve patient outcomes and effectively manage common adverse events. The authors discuss how a collaborative approach, appropriately leveraging the diverse expertise of NSCLC MDT members (including specialist radiation and medical oncologists, chest physicians, pathologists, pulmonologists, surgeons, and nursing staff) can continue to ensure optimal per-patient decision making as treatment options become ever more specialized in the era of biomarker-driven therapeutic strategies., (© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

The Lung Screen Uptake Trial tested a novel invitation strategy to improve uptake and reduce socioeconomic and smoking-related inequalities in lung cancer screening (LCS) participation. It provides one of the first UK-based 'real-world' LCS cohorts. Of 2012 invited, 1058 (52.6%) attended a 'lung health check'. 768/996 (77.1%) in the present analysis underwent a low-dose CT scan. 92 (11.9%) and 33 (4.3%) participants had indeterminate pulmonary nodules requiring 3-month and 12-month surveillance, respectively; 36 lung cancers (4.7%) were diagnosed (median follow-up: 1044 days). 72.2% of lung cancers were stage I/II and 79.4% of non-small cell lung cancer had curative-intent treatment., Competing Interests: Competing interests: SMJ, MR, JLD, CH, ST and HH are supported by funding for a large trial of low dose CT screening, called the ‘SUMMIT Study’ by GRAIL Inc. SLQ and NN collaborate on the SUMMIT Study. SMJ has received honoraria from AstraZeneca, BARD1 Bioscience and Janssen for being an Advisory Board Expert and travel to a US conference. SMJ received grant funding from Owlstone for a separate research study and has a family member who has a financial association with AstraZeneca. MR has received travel funding for a conference from Takeda and an honorarium for planning and speaking at educational meetings from AstraZeneca., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: During the COVID-19 lockdown, referrals via the 2-week-wait urgent pathway for suspected cancer in England, UK, are reported to have decreased by up to 84%. We aimed to examine the impact of different scenarios of lockdown-accumulated backlog in cancer referrals on cancer survival, and the impact on survival per referred patient due to delayed referral versus risk of death from nosocomial infection with severe acute respiratory syndrome coronavirus 2., Methods: In this modelling study, we used age-stratified and stage-stratified 10-year cancer survival estimates for patients in England, UK, for 20 common tumour types diagnosed in 2008-17 at age 30 years and older from Public Health England. We also used data for cancer diagnoses made via the 2-week-wait referral pathway in 2013-16 from the Cancer Waiting Times system from NHS Digital. We applied per-day hazard ratios (HRs) for cancer progression that we generated from observational studies of delay to treatment. We quantified the annual numbers of cancers at stage I-III diagnosed via the 2-week-wait pathway using 2-week-wait age-specific and stage-specific breakdowns. From these numbers, we estimated the aggregate number of lives and life-years lost in England for per-patient delays of 1-6 months in presentation, diagnosis, or cancer treatment, or a combination of these. We assessed three scenarios of a 3-month period of lockdown during which 25%, 50%, and 75% of the normal monthly volumes of symptomatic patients delayed their presentation until after lockdown. Using referral-to-diagnosis conversion rates and COVID-19 case-fatality rates, we also estimated the survival increment per patient referred., Findings: Across England in 2013-16, an average of 6281 patients with stage I-III cancer were diagnosed via the 2-week-wait pathway per month, of whom 1691 (27%) would be predicted to die within 10 years from their disease. Delays in presentation via the 2-week-wait pathway over a 3-month lockdown period (with an average presentational delay of 2 months per patient) would result in 181 additional lives and 3316 life-years lost as a result of a backlog of referrals of 25%, 361 additional lives and 6632 life-years lost for a 50% backlog of referrals, and 542 additional lives and 9948 life-years lost for a 75% backlog in referrals. Compared with all diagnostics for the backlog being done in month 1 after lockdown, additional capacity across months 1-3 would result in 90 additional lives and 1662 live-years lost due to diagnostic delays for the 25% backlog scenario, 183 additional lives and 3362 life-years lost under the 50% backlog scenario, and 276 additional lives and 5075 life-years lost under the 75% backlog scenario. However, a delay in additional diagnostic capacity with provision spread across months 3-8 after lockdown would result in 401 additional lives and 7332 life-years lost due to diagnostic delays under the 25% backlog scenario, 811 additional lives and 14 873 life-years lost under the 50% backlog scenario, and 1231 additional lives and 22 635 life-years lost under the 75% backlog scenario. A 2-month delay in 2-week-wait investigatory referrals results in an estimated loss of between 0·0 and 0·7 life-years per referred patient, depending on age and tumour type., Interpretation: Prompt provision of additional capacity to address the backlog of diagnostics will minimise deaths as a result of diagnostic delays that could add to those predicted due to expected presentational delays. Prioritisation of patient groups for whom delay would result in most life-years lost warrants consideration as an option for mitigating the aggregate burden of mortality in patients with cancer., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Whole body magnetic resonance imaging (WB-MRI) may be more efficient in staging cancers, but can be harder for patients to tolerate. We examined predictors of patient preference for WB-MRI vs. CT/ PET-CT for staging colorectal or lung cancer., Methods: Patients recruited prospectively to two multicentre trials comparing diagnostic accuracy of WB-MRI with standard staging scans were sent two questionnaires: the first, administered at trial registration, captured demographics, educational level and comorbidities; the second, administered after staging completion, measured emotional distress (GHQ-12), positive mood (PANAS), perceived scan burden, patients' beliefs about WB-MRI, and preference for either WB-MRI or CT (colorectal trial), WB-MRI or PET-CT (lung trial). Preference for WB-MRI or CT/ PET-CT was analysed using logistic regression., Results: Baseline and post-staging questionnaires were completed by 97 and 107 patients, respectively. Overall, 56/107 (52%) preferred WB-MRI over standard scans and were more likely to have no additional comorbidities, higher positive mood, greater awareness of potential benefits of WB-MRI and lower levels of perceived WB-MRI scan burden. In adjusted analyses, only awareness of potential WB-MRI benefits remained a significant predictor (OR: 1.516, 95% CIs 1.006-2.284, P = 0.047). Knowledge that WB-MRI does not use radiation predicted preference (adjusted OR: 3.018, 95% CIs 1.099-8.288, P = 0.032), although only 45/107 (42%) patients were aware of this attribute., Conclusions: A small majority of patients undergoing staging of colorectal or lung cancer prefer WB-MRI to CT/ PET-CT. Raising awareness of the potential benefits of WB-MRI, notably lack of ionizing radiation, could influence preference., (© 2020 The Authors. Journal of Medical Imaging and Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Radiologists.)

Interventional pulmonology is a dynamic and evolving field in respiratory medicine. Advances have improved the ability to diagnose and manage diseases of the airways. A shift toward early detection of malignant disease has generated a focus on innovative diagnostic techniques. With patient populations living longer with malignant and benign diseases, the role for interventional bronchoscopy has grown. In cancer groups, novel immunotherapies have improved the prospects of clinical outcomes and reignited a focus on optimizing patient performance status to enable access to anticancer therapy. This review discusses current and emerging diagnostic modalities and therapeutic approaches available to manage airway diseases., Competing Interests: Disclosure Dr S. Shaefi is supported by a Grant for Early Medical/Surgical Specialists’ Transition to Aging Research (GEMSSTAR) award (R03AG060179) from the National Institute on Aging and a Mentored Clinical Scientist Research Career Development Award from the National Institute of General Medical Sciences (K08GM134220). This work was undertaken partly at UCLH/UCL, which received a proportion of funding from the Department of Health NIHR Biomedical Research Centre funding stream. Dr N. Navani is supported by a Medical Research Council fellowship (MR/T02481X/1)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Rationale: Individuals eligible for lung cancer screening (LCS) by low-dose computed tomography (LDCT) are also at risk of chronic obstructive pulmonary disease (COPD) due to age and smoking exposure. Whether the LCS episode is useful for early detection of COPD is not well established. Objectives: To explore associations between symptoms, comorbidities, spirometry, and emphysema in participants enrolled in the Lung Screen Uptake Trial. Methods: This cross-sectional study was a prespecified analysis nested within Lung Screen Uptake Trial, which was a randomized study testing the impact of differing invitation materials on attendance of 60- to 75-year-old smokers and ex-smokers to a "lung health check" between November 2015 and July 2017. Participants with a smoking history ≥30 pack-years and who quit ≤15 years ago, or meeting a lung cancer risk of ≥1.51% via the Prostate Lung Colorectal Ovarian model or ≥2.5% via the Liverpool Lung Project model, were offered LDCT. COPD was defined and classified according to the GOLD (Global Initiative for Obstructive Lung Disease) criteria using prebronchodilator spirometry. Analyses included the use of descriptive statistics, chi-square tests to examine group differences, and univariable and multivariable logistic regression to explore associations between symptom prevalence, airflow limitation, and visually graded emphysema. Results: A total of 560 of 986 individuals included in the analysis (57%) had prebronchodilator spirometry consistent with COPD; 67% did not have a prior history of COPD and were termed "undiagnosed." Emphysema prevalence in those with known and "undiagnosed" COPD was 73% and 68%, respectively. A total of 32% of those with "undiagnosed COPD" had no emphysema on LDCT. Inhaler use and symptoms were more common in the "known" than the "undiagnosed" COPD group (63% vs. 33% with persistent cough [ P  < 0.001]; 73% vs. 33% with dyspnea [ P  < 0.001]). Comorbidities were common in all groups. Adjusted odds ratio (aOR) of respiratory symptoms were more significant for airflow obstruction (aOR GOLD 1 and 2, 1.57; confidence interval [CI], 1.14-2.17; aOR GOLD 3 and 4, 4.6; CI, 2.17-9.77) than emphysema (aOR mild, 1.12; CI, 0.81-1.55; aOR moderate, 1.33; CI, 0.85-2.09; aOR severe, 4.00; CI, 1.57-10.2). Conclusions: There is high burden of "undiagnosed COPD" and emphysema in LCS participants. Adding spirometry findings to the LDCT enhances identification of individuals with COPD.Clinical trial registered with www.clinicaltrials.gov (NCT02558101).

Rationale: Low uptake of low-dose computed tomography (LDCT) lung cancer screening, particularly by current smokers of a low socioeconomic position, compromises effectiveness and equity. Objectives: To compare the effect of a targeted, low-burden, and stepped invitation strategy versus control on uptake of hospital-based Lung Health Check appointments offering LDCT screening. Methods: In a two-arm, blinded, between-subjects, randomized controlled trial, 2,012 participants were selected from 16 primary care practices using these criteria: 1 ) aged 60 to 75 years, 2 ) recorded as a current smoker within the last 7 years, and 3 ) no prespecified exclusion criteria contraindicating LDCT screening. Both groups received a stepped sequence of preinvitation, invitation, and reminder letters from their primary care practitioner offering prescheduled appointments. The key manipulation was the accompanying leaflet. The intervention group's leaflet targeted psychological barriers and provided low-burden information, mimicking the concept of the U.K. Ministry of Transport's annual vehicle test ("M.O.T. For Your Lungs"). Measurements and Main Results: Uptake was 52.6%, with no difference between intervention (52.3%) and control (52.9%) groups in unadjusted (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.82-1.16) or adjusted (OR, 0.98; 95% CI, 0.82-1.17) analyses. Current smokers were less likely to attend (adjusted OR, 0.70; 95% CI, 0.56-0.86) than former smokers. Socioeconomic deprivation was significantly associated with lower uptake for the control group only ( P  < 0.01). Conclusions: The intervention did not improve uptake. Regardless of trial arm, uptake was considerably higher than previous clinical and real-world studies, particularly given that the samples were predominantly lower socioeconomic position smokers. Strategies common to both groups, including a Lung Health Check approach, could represent a minimum standard.Clinical trial registered with www.clinicaltrials.gov (NCT02558101) and registered prospectively with the International Standard Registered Clinical/Social Study (N21774741).

Background: Approximately 15%-20% of all non-small cell lung cancer (NSCLC) cases present with stage I disease. Surgical resection traditionally offers the best chance of a cure but some patients will not have this treatment due to older age, comorbidities or personal choice. Stereotactic ablative radiotherapy (SABR) has become an established curative intent treatment option for patients who are not selected for or do not choose surgery. The aim of this study is to compare survival at 90 days, 6 months, 1 year and 2 years for patients who received either lobectomy or SABR., Methods: We used data from the 2015 National Lung Cancer Audit database and linked with Hospital Episode Statistics and the radiotherapy dataset to identify patients with NSCLC stage IA-IB and performance status (PS) 0-2 who underwent surgery or SABR treatment. We assessed the likelihood of death at 90 days, 6 months, 1 year and 2 year after diagnosis and procedure date to observe survival between two patient groups., Results: We identified 2373 patients in our cohort, 476 of whom had SABR. The median difference between date of diagnosis and date of treatment for surgery patients was 17 days while for SABR patients it was 73 days. Increasing age and worsening PS were associated with having SABR rather than surgery. Survival between the two treatment modalities was similar early on but by 1-year people who had surgery did better than those who had SABR (adjusted ORs 2.12, 95% CI 1.35 to 2.31). This difference persisted at 2 years and when the analysis was restricted to patients aged <80 years and with PS 0 or 1 and stage IA only., Conclusion: Our analysis suggests that patients who have lobectomy have a better survival compared with SABR patients; however, we found considerable delays in patients receiving SABR which may contribute to poorer long-term outcomes with this treatment option. Reducing these delays should be a key focus in development and reorganisation of services., Competing Interests: Competing interests: AK has conducted the statistical analysis for the National Lung Cancer Audit annual reports for the past 4 years, which were funded by Royal College of Physicians. None of the authors have received any personal earnings from any funding body for this work. RH has a grant provided by the British Lung Foundation chair of respiratory epidemiology., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)