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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.)

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).)

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).)

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.)

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.)

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.)

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).)

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.)

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.)

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.)

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: Programmed death-ligand 1 (PD-L1) expression on cancer cells is a clinically important biomarker to select patients with non-small cell lung cancer (NSCLC) for treatment with programmed death-1/PD-L1 inhibitors. Clinical trials of immunotherapy in patients with NSCLC have required histologic evidence for PD-L1 testing; in clinical practice, cytologic samples commonly are acquired in patients with advanced disease., Research Question: This study aims to investigate whether endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples are adequate for PD-L1 testing in NSCLC., Study Design and Methods: This study investigates the sampling adequacy of EBUS-TBNA for PD-L1 testing when compared with other methods. Furthermore, the relationship between clinicopathologic characteristics and PD-L1 expression in the study population have been examined. Five hundred seventy-seven NSCLC specimens were analyzed from consecutive patients with NSCLC across six centers in the United Kingdom and one center in the United States between January 2015 and December 2016., Results: In the EBUS-TBNA group (189 specimens), the overall percentage of patients with successful PD-L1 testing was 94.7%. There was no significant difference in sampling adequacy with other methods of tissue acquisition. Older patients had higher failure rates of PD-L1 testing (OR, 1.06; P = .008). In multivariate analysis, advanced N-stage (P = .048) and presence of brain metastasis (P < .001) were associated with high PD-L1 expression., Interpretation: This large multicenter study shows that EBUS-TBNA provides samples adequate for PD-L1 testing and that advanced N stage and the presence of brain metastasis are associated with high PD-L1 expression., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

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.)

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.)

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.)

Background: The presence of comorbidity affects the care of cancer patients, many of whom are living with multiple comorbidities. The prevalence of cancer comorbidity, beyond summary metrics, is not well known. This study aims to estimate the prevalence of comorbid conditions among cancer patients in England, and describe the association between cancer comorbidity and socio-economic position, using population-based electronic health records., Methods: We linked England cancer registry records of patients diagnosed with cancer of the colon, rectum, lung or Hodgkin lymphoma between 2009 and 2013, with hospital admissions records. A comorbidity was any one of fourteen specific conditions, diagnosed during hospital admission up to 6 years prior to cancer diagnosis. We calculated the crude and age-sex adjusted prevalence of each condition, the frequency of multiple comorbidity combinations, and used logistic regression and multinomial logistic regression to estimate the adjusted odds of having each condition and the probability of having each condition as a single or one of multiple comorbidities, respectively, by cancer type., Results: Comorbidity was most prevalent in patients with lung cancer and least prevalent in Hodgkin lymphoma patients. Up to two-thirds of patients within each of the four cancer patient cohorts we studied had at least one comorbidity, and around half of the comorbid patients had multiple comorbidities. Our study highlighted common comorbid conditions among the cancer patient cohorts. In all four cohorts, the odds of having a comorbidity and the probability of multiple comorbidity were consistently highest in the most deprived cancer patients., Conclusions: Cancer healthcare guidelines may need to consider prominent comorbid conditions, particularly to benefit the prognosis of the most deprived patients who carry the greater burden of comorbidity. Insight into patterns of cancer comorbidity may inform further research into the influence of specific comorbidities on socio-economic inequalities in receipt of cancer treatment and in short-term mortality.

Introduction: Lung cancer screening (LCS) by low-dose computed tomography (LDCT) offers an opportunity to impact both lung cancer and coronary heart disease mortality through detection of coronary artery calcification (CAC). Here, we explore the value of CAC and cardiovascular disease (CVD) risk assessment in LCS participants in the Lung Screen Uptake Trial (LSUT)., Methods: In this cross-sectional study, current and ex-smokers aged 60-75 were invited to a 'lung health check'. Data collection included a CVD risk assessment enabling estimation of 10 year CVD risk using the QRISK2 score. Participants meeting the required lung cancer risk underwent an ungated, non-contrast LDCT. Descriptive data, bivariate associations and a multivariate analysis of predictors of statin use are presented., Results: Of 1005 individuals enrolled, 680 were included in the final analysis. 421 (61.9%) had CAC present and in 49 (7.2%), this was heavy. 668 (98%) of participants had a QRISK2≥10% and QRISK2 was positively associated with increasing CAC grade (OR 4.29 (CI 0.93 to 19.88) for QRISK2=10%-20% and 12.29 (CI 2.68 to 56.1) for QRISK2≥20% respectively). Of those who qualified for statin primary prevention (QRISK2≥10%), 56.8% did not report a history of statin use. In the multivariate analysis statin use was associated with age, body mass index and history of hypertension and diabetes., Conclusions: LCS offers an important opportunity for instituting CVD risk assessment in all LCS participants irrespective of the presence of LDCT-detected CAC. Further studies are needed to determine whether CAC could enhance uptake and adherence to primary preventative strategies., Competing Interests: Competing interests: SMJ, MR, JLD and CH are supported by funding for a large trial of low dose CT screening, called the ‘SUMMIT Study’ by GRAIL Inc. SQ collaborates on the SUMMIT study. SMJ has received honoraria from Astra Zeneca, BARD1 Bioscience and Achilles Therapeutics for being an Advisory Board Expert and travel to a US conference. SMJ receives grant funding from Owlstone for a separate research study and has a family member with a financial association with Astra Zeneca. MR has received travel funding for a conference from Takeda and an honorarium for speaking at educational meeting from Astra Zeneca. AN is a member of the Advisory Board for Aidence Artificial Intelligence. RS has received honoraria, consulting and speaker fees from Amgen, Sanofi and Bayer. SMJ, MR, JLD, CH, SQ, AN and RS perceive that these disclosures pose no academic conflict for this study. All other authors have no other competing interests to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: Whole-body magnetic resonance imaging is advocated as an alternative to standard pathways for staging cancer., Objectives: The objectives were to compare diagnostic accuracy, efficiency, patient acceptability, observer variability and cost-effectiveness of whole-body magnetic resonance imaging and standard pathways in staging newly diagnosed non-small-cell lung cancer (Streamline L) and colorectal cancer (Streamline C)., Design: The design was a prospective multicentre cohort study., Setting: The setting was 16 NHS hospitals., Participants: Consecutive patients aged ≥ 18 years with histologically proven or suspected colorectal (Streamline C) or non-small-cell lung cancer (Streamline L)., Interventions: Whole-body magnetic resonance imaging. Standard staging investigations (e.g. computed tomography and positron emission tomography-computed tomography)., Reference Standard: Consensus panel decision using 12-month follow-up data., Main Outcome Measures: The primary outcome was per-patient sensitivity difference between whole-body magnetic resonance imaging and standard staging pathways for metastasis. Secondary outcomes included differences in specificity, the nature of the first major treatment decision, time and number of tests to complete staging, patient experience and cost-effectiveness., Results: Streamline C - 299 participants were included. Per-patient sensitivity for metastatic disease was 67% (95% confidence interval 56% to 78%) and 63% (95% confidence interval 51% to 74%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -5% to 13%; p  = 0.51). Specificity was 95% (95% confidence interval 92% to 97%) and 93% (95% confidence interval 90% to 96%) respectively, a difference of 2% (95% confidence interval -2% to 6%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 96% and 95% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 8 days (95% confidence interval 6 to 9 days) and 13 days (95% confidence interval 11 to 15 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 5 days (95% confidence interval 3 to 7 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £216 (95% confidence interval £211 to £221) versus £285 (95% confidence interval £260 to £310). Streamline L - 187 participants were included. Per-patient sensitivity for metastatic disease was 50% (95% confidence interval 37% to 63%) and 54% (95% confidence interval 41% to 67%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -7% to 15%; p  = 0.73). Specificity was 93% (95% confidence interval 88% to 96%) and 95% (95% confidence interval 91% to 98%), respectively, a difference of 2% (95% confidence interval -2% to 7%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 98% and 99% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 13 days (95% confidence interval 12 to 14 days) and 19 days (95% confidence interval 17 to 21 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 6 days (95% confidence interval 4 to 8 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £317 (95% confidence interval £273 to £361) versus £620 (95% confidence interval £574 to £666). Participants generally found whole-body magnetic resonance imaging more burdensome than standard imaging but most participants preferred the whole-body magnetic resonance imaging staging pathway if it reduced time to staging and/or number of tests., Limitations: Whole-body magnetic resonance imaging was interpreted by practitioners blinded to other clinical data, which may not fully reflect how it is used in clinical practice., Conclusions: In colorectal and non-small-cell lung cancer, the whole-body magnetic resonance imaging staging pathway has similar accuracy to standard staging pathways, is generally preferred by patients, improves staging efficiency and has lower staging costs. Future work should address the utility of whole-body magnetic resonance imaging for treatment response assessment., Trial Registration: Current Controlled Trials ISRCTN43958015 and ISRCTN50436483., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 66. See the NIHR Journals Library website for further project information., Competing Interests: Stuart A Taylor reports personal fees from Robarts Clinical Trials Inc. (London, ON, Canada) outside the submitted work. Andrea Rockall reports personal fees from Guerbet (Paris, France) outside the submitted work. Vicky Goh and Anwar Padhani report grants from Siemens AG (Erlangen, Germany) outside the submitted work. Steve Halligan reports non-financial support from iCad Inc. (Nashua, NH, USA) outside the submitted work and was a member of the Health Technology Assessment (HTA) commissioning board (2008–14). Stephen Morris declares past membership of the National Institute for Health Research (NIHR) HTA Clinical Evaluation and Trials Board (2007–9), HTA Commissioning Board (2009–13), Public Health Research Board (2011–17), Health Services and Delivery Research (HSDR) Commissioning Board (2014–16) and HSDR Board (2014–18), and current membership of the NIHR Programme Grants for Applied Research expert subpanel (2015–present) and HSDR Evidence Synthesis Sub Board (2016–present).

Aims: We present the first analysis of the management and outcomes of stage III non-small cell lung cancer (NSCLC) conducted in England using National Lung Cancer Audit data., Materials and Methods: Patients diagnosed with stage III NSCLC in 2016 were identified. Linked datasets (including Hospital Episode Statistics, the National Radiotherapy Dataset, the Systemic Anti-Cancer Dataset, pathology reports and death certificate data) were used to categorise the treatment received. Kaplan-Meier survival curves were obtained, with survival defined from the date of diagnosis to the date of death., Results: In total, 6276 cases of stage III NSCLC were analysed: 3827 stage IIIA and 2449 stage IIIB; 1047 (17%) patients were treated with radical radiotherapy with 676 (11%) of these also receiving chemotherapy. Twenty per cent of patients with stage IIIA disease underwent surgery, with half of these also receiving chemotherapy, predominantly delivered in the adjuvant setting. Of note, 2148 (34%) patients received palliative-intent treatment and 2265 (36%) received no active anti-cancer treatment. The 1-year survival was 32.9% (37.4% for stage IIIA), with the highest survival seen for those patients receiving chemotherapy and surgery., Conclusions: We highlight important gaps in the optimal care of patients with stage III NSCLC in England. Multimodality treatment with either surgery or radical radiotherapy combined with chemotherapy was delivered to less than one-fifth of patients, even though these regimens are considered optimal. Timely access to specialist resources and staff, the practice of effective shared decision making and challenging preconceptions have the potential to optimise management., (Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Conflicts of Interest: The author has no conflicts of interest to declare.

Objectives: To determine the importance placed by patients on attributes associated with whole-body MRI (WB-MRI) and standard cancer staging pathways and ascertain drivers of preference., Methods: Patients recruited to two multi-centre diagnostic accuracy trials comparing WB-MRI with standard staging pathways in lung and colorectal cancer were invited to complete a discrete choice experiment (DCE), choosing between a series of alternate pathways in which 6 attributes (accuracy, time to diagnosis, scan duration, whole-body enclosure, radiation exposure, total scan number) were varied systematically. Data were analysed using a conditional logit regression model and marginal rates of substitution computed. The relative importance of each attribute and probabilities of choosing WB-MRI-based pathways were estimated., Results: A total of 138 patients (mean age 65, 61% male, lung n = 72, colorectal n = 66) participated (May 2015 to September 2016). Lung cancer patients valued time to diagnosis most highly, followed by accuracy, radiation exposure, number of scans, and time in the scanner. Colorectal cancer patients valued accuracy most highly, followed by time to diagnosis, radiation exposure, and number of scans. Patients were willing to wait 0.29 (lung) and 0.45 (colorectal) weeks for a 1% increase in pathway accuracy. Patients preferred WB-MRI-based pathways (probability 0.64 [lung], 0.66 [colorectal]) if they were equivalent in accuracy, total scan number, and time to diagnosis compared with a standard staging pathway., Conclusions: Staging pathways based on first-line WB-MRI are preferred by the majority of patients if they at least match standard pathways for diagnostic accuracy, time to diagnosis, and total scan number., Key Points: • WB-MRI staging pathways are preferred to standard pathways by the majority of patients provided they at least match standard staging pathways for accuracy, total scan number, and time to diagnosis. • For patients with lung cancer, time to diagnosis was the attribute valued most highly, followed by accuracy, radiation dose, number of additional scans, and time in a scanner. Preference for patients with colorectal cancer was similar. • Most (63%) patients were willing to trade attributes, such as faster diagnosis, for improvements in pathway accuracy and reduced radiation exposure.

Background: Whole-body MRI (WB-MRI) could be an alternative to multimodality staging of colorectal cancer, but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in colorectal cancer., Methods: The Streamline C trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed colorectal cancer. Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or polyp cancer. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs), and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN43958015, and is complete., Findings: Between March 26, 2013, and Aug 19, 2016, 1020 patients were screened for eligibility. 370 patients were recruited, 299 of whom completed the trial; 68 (23%) had metastasis at baseline. Pathway sensitivity was 67% (95% CI 56 to 78) for WB-MRI and 63% (51 to 74) for standard pathways, a difference in sensitivity of 4% (-5 to 13, p=0·51). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (95% [95% CI 92-97]) and standard pathways (93% [90-96], p=0·48). Agreement with the multidisciplinary team's final treatment decision was 96% for WB-MRI and 95% for the standard pathway. Time to complete staging was shorter for WB-MRI (median, 8 days [IQR 6-9]) than for the standard pathway (13 days [11-15]); a 5-day (3-7) difference. WB-MRI required fewer tests (median, one [95% CI 1 to 1]) than did standard pathways (two [2 to 2]), a difference of one (1 to 1). Mean per-patient staging costs were £216 (95% CI 211-221) for WB-MRI and £285 (260-310) for standard pathways., Interpretation: WB-MRI staging pathways have similar accuracy to standard pathways and reduce the number of tests needed, staging time, and cost., Funding: UK National Institute for Health Research., (Copyright © 2019 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.)

Introduction: Data from the National Lung Cancer Audit (NLCA) often show variation in outcomes between lung cancer units which are not entirely explained by case mix. We explore the association between the organisation of services and patient outcome., Methods: Details of service provision were collected via an electronic survey in June 2017. An overall organisational score derived from eleven key service factors from national lung cancer commissioning guidance was calculated for each organisation. The results for each hospital were linked to their patient outcome results from the 2015 NLCA cases. Multivariate logistic regression analysis was used to link the organisational score to patient outcomes., Results: Lung cancer unit organisational audit scores varied from 0 to 11. Thirty-eight (29%) units had a score of 0-4, 64 (50%) had a score of 5-7 and 27 (21%) had a score of 8-11. Multivariate regression analysis revealed that, compared with an organisational score of 0-4, patients seen at units with a score of 8-11 had higher 1-year survival (adjusted OR (95% CI)=2.30 (1.04 to 5.08), p<0.001), higher curative-intent treatment rate (adjusted OR (95% CI)=1.62 (1.26 to 2.09), p<0.001) and greater likelihood of receiving treatment within 62 days (adjusted OR (95% CI)=1.49 (1.20 to 1.86), p<0.001)., Conclusion: National variation in the provision of services and workforce remain. We provide evidence that adherence to the national lung commissioning guidance has the potential to improve patient outcomes within the current service structure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Lung cancer screening has the potential to save lives, but it also carries a risk of potential harms. Explaining the benefits and harms of screening in a way that is balanced and comprehensible to individuals with various levels of education is essential. Although a shared decision-making approach is mandated by the Centers for Medicare & Medicaid Services, there have been no randomized studies to evaluate the impact of different forms of lung screening information. Objectives: To evaluate the impact of a novel information film on informed decision-making in individuals considering participating in lung cancer screening. Methods: A subset of participants from LSUT (Lung Screen Uptake Trial) were randomly allocated either to view the information film and receive a written information booklet or to receive the booklet alone. The primary outcome was the objective knowledge score after intervention. Secondary outcomes included subjective knowledge, decisional conflict, final screening participation, and acceptability of the materials. Univariate and multivariate analyses were performed to determine differences in pre- and postintervention knowledge scores in both groups and between groups for the primary and secondary outcomes. Results: In the final analysis of 229 participants, both groups showed significantly improved subjective and objective knowledge scores after intervention. This improvement was greatest in the film + booklet group, where mean objective knowledge improved by 2.16 points (standard deviation [SD] 1.8) compared with 1.84 points (SD 1.9) in the booklet-alone group (β coefficient 0.62; confidence interval, 0.17-1.08; P = 0.007 in the multivariable analysis). Mean subjective knowledge increased by 0.92 points (SD 1.0) in the film + booklet group and 0.55 points (SD 1.1) in the booklet-alone group (β coefficient 0.32; CI, 0.05-0.58; P = 0.02 in the multivariable analysis). Decisional certainty was higher in the film + booklet (mean 8.5/9 points [SD 1.3], group than in the booklet-alone group (mean 8.2/9 points [SD 1.5]). Both information materials were well accepted, and there were no differences in final screening participation rates between groups. Conclusions: The information film improved knowledge and reduced decisional conflict without affecting lung-screening uptake. Clinical trial registered with clinicaltrials.gov (NCT02558101).

Background: Whole-body magnetic resonance imaging (WB-MRI) could be an alternative to multi-modality staging of non-small-cell lung cancer (NSCLC), but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in NSCLC., Methods: The Streamline L trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed NSCLC that was potentially radically treatable on diagnostic chest CT (defined as stage IIIb or less). Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or histologies other than NSCLC. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs) and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN50436483, and is complete., Findings: Between Feb 26, 2013, and Sept 5, 2016, 976 patients were screened for eligibility. 353 patients were recruited, 187 of whom completed the trial; 52 (28%) had metastasis at baseline. Pathway sensitivity was 50% (95% CI 37-63) for WB-MRI and 54% (41-67) for standard pathways, a difference of 4% (-7 to 15, p=0·73). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (93% [88-96]) and standard pathways (95% [91-98], p=0·45). Agreement with the multidisciplinary team's final treatment decision was 98% for WB-MRI and 99% for the standard pathway. Time to complete staging was shorter for WB-MRI (13 days [12-14]) than for the standard pathway (19 days [17-21]); a 6-day (4-8) difference. The number of tests required was similar WB-MRI (one [1-1]) and standard pathways (one [1-2]). Mean per-patient costs were £317 (273-361) for WBI-MRI and £620 (574-666) for standard pathways., Interpretation: WB-MRI staging pathways have similar accuracy to standard pathways, and reduce the staging time and costs., Funding: UK National Institute for Health Research., (Copyright © 2019 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.)

The therapeutic scenario for elderly patients with advanced NSCLC has been limited to radiotherapy and chemotherapy. Recently, a novel therapeutic approach based on targeting the immune-checkpoints has showed noteworthy results in advanced NSCLC. PD1/PD-L1 pathway is co-opted by tumor cells through the expression of PD-L1 on the tumor cell surface and on cells within the microenvironment, leading to suppression of anti-tumor cytolytic T-cell activity by the tumor. The success of immune-checkpoints inhibitors in clinical trials led to rapid approval by the FDA and EMA. Currently, data regarding efficacy and safety of ICIs in older subjects is limited by the poor number of elderly recruited in clinical trials. Careful assessment and management of comorbidities is essential to achieve better outcomes and limit the immune related adverse events in elderly NSCLC patients.

Competing Interests: Competing interests: NN and GM were members of the NICE Guideline Committee. The committee’s declarations of interest are available on the NICE website (https://www.nice.org.uk/guidance/NG122/history). RM and TM are NICE staff and have no relevant interests to declare.

Background: Clinical staging of non-small cell lung cancer (NSCLC) helps determine the prognosis and treatment of patients; few data exist on the accuracy of clinical staging and the impact on treatment and survival of patients. We assessed whether participant or trial characteristics were associated with clinical staging accuracy as well as impact on survival., Methods: We used individual participant data from randomized controlled trials (RCTs), supplied for a meta-analysis of preoperative chemotherapy (± radiotherapy) vs surgery alone (± radiotherapy) in NSCLC. We assessed agreement between clinical TNM (cTNM) stage at randomization and pathologic TNM (pTNM) stage, for participants in the control group., Results: Results are based on 698 patients who received surgery alone (± radiotherapy) with data for cTNM and pTNM stage. Forty-six percent of cases were cTNM stage I, 23% were cTNM stage II, and 31% were cTNM stage IIIa. cTNM stage disagreed with pTNM stage in 48% of cases, with 34% clinically understaged and 14% clinically overstaged. Agreement was not associated with age (P = .12), sex (P = .62), histology (P = .82), staging method (P = .32), or year of randomization (P = .98). Poorer survival in understaged patients was explained by the underlying pTNM stage. Clinical staging failed to detect T4 disease in 10% of cases and misclassified nodal disease in 38%., Conclusions: This study demonstrates suboptimal agreement between clinical and pathologic staging. Discrepancies between clinical and pathologic T and N staging could have led to different treatment decisions in 10% and 38% of cases, respectively. There is therefore a need for further research into improving staging accuracy for patients with stage I-IIIa NSCLC., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing or remaining static. The cellular basis of this clinical observation is unknown. Here, we profile the genomic, transcriptomic, and epigenomic landscape of CIS in a unique patient cohort with longitudinally monitored pre-invasive disease. Predictive modeling identifies which lesions will progress with remarkable accuracy. We identify progression-specific methylation changes on a background of widespread heterogeneity, alongside a strong chromosomal instability signature. We observed mutations and copy number changes characteristic of cancer and chart their emergence, offering a window into early carcinogenesis. We anticipate that this new understanding of cancer precursor biology will improve early detection, reduce overtreatment, and foster preventative therapies targeting early clonal events in lung cancer.

Introduction: We investigated socioeconomic disparities and the role of the main prognostic factors in receiving major surgical treatment in patients with lung cancer in England., Methods: Our study comprised 31 351 patients diagnosed with non-small cell lung cancer in England in 2012. Data from the national population-based cancer registry were linked to Hospital Episode Statistics and National Lung Cancer Audit data to obtain information on stage, performance status and comorbidities, and to identify patients receiving major surgical treatment. To describe the association between prognostic factors and surgery, we performed two different analyses: one using multivariable logistic regression and one estimating cause-specific hazards for death and surgery. In both analyses, we used multiple imputation to deal with missing data., Results: We showed strong evidence that the comorbidities 'congestive heart failure', 'cerebrovascular disease' and 'chronic obstructive pulmonary disease' reduced the receipt of surgery in early stage patients. We also observed gender differences and substantial age differences in the receipt of surgery. Despite accounting for sex, age at diagnosis, comorbidities, stage at diagnosis, performance status and indication of having had a PET-CT scan, the socioeconomic differences persisted in both analyses: more deprived people had lower odds and lower rates of receiving surgery in early stage lung cancer., Discussion: Comorbidities play an important role in whether patients undergo surgery, but do not completely explain the socioeconomic difference observed in early stage patients. Future work investigating access to and distance from specialist hospitals, as well as patient perceptions and patient choice in receiving surgery, could help disentangle these persistent socioeconomic inequalities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)