Pulmonary fibrosis and lung cancer: an analysis of the Clinical Practice Research Datalink linked to the National Cancer Registration Dataset.

We quantified the proportion of diagnoses of pulmonary fibrosis (PF) among 25 136 people with lung cancer and 250 583 matched controls and compared the natural history of lung cancer in people with and without PF. Diagnoses of PF were more common in people with lung cancer than those without (1.5% vs 0.8%, OR 1.97; 95% CI 1.77 to 2.21). Within people with PF, squamous cell carcinoma was more (22.9% vs 19.1%), and adenocarcinoma was less common (18.0% vs 21.3%). People with PF were less likely to have stage 4 disease at diagnosis (OR 0.43, 95% CI 0.28 to 0.65) but their survival was worse.

The incidence of lung cancer amongst primary care chest radiograph referrals; an evaluation of national and local datasets within the UK.

OBJECTIVES: To determine the incidence of lung cancer amongst primary care referrals for investigation with a chest radiograph (CXR). METHOD: Retrospective evaluation of datasets from the national Clinical Practice Research Datalink (CPRD) and from a single large regional centre. Data was extracted for cohorts of consecutive adults aged over 40-yrs for whom a CXR had been performed between 2016 and 2018. Using cancer registry data, the incidence of lung cancer within a two-years of the CXR referral and the variations with age, gender and smoking status were evaluated. RESULTS: A total of 291 294 CXR events were evaluated from the combined datasets. The incidence of lung cancer amongst GP CXR referrals was 1.4% in CPRD with a consistent correlation with increasing age and smoking status. The incidence of lung cancer within two-years of the CXR varied between 0.03% (95%CI 0.0-0.1) amongst never smokers aged 40-45 years to 4.8% (95%CI 4.2-5.5) amongst current-smokers aged 70-75 years. The findings were similar for the single large centre data, although cancer incidence was higher. CONCLUSIONS: A simple estimation and stratification of the risk of lung cancer amongst primary care referrals for investigation with a CXR is possible using age and smoking status. ADVANCES IN KNOWLEDGE: This is the first estimate of the incidence of lung cancer amongst primary care CXR referrals and a demonstration of how the demographic information contained within a request could be used to optimise investigations and interpret test results.

Determining the impact of an artificial intelligence tool on the management of pulmonary nodules detected incidentally on CT (DOLCE) study protocol: a prospective, non-interventional multicentre UK study.

INTRODUCTION: In a small percentage of patients, pulmonary nodules found on CT scans are early lung cancers. Lung cancer detected at an early stage has a much better prognosis. The British Thoracic Society guideline on managing pulmonary nodules recommends using multivariable malignancy risk prediction models to assist in management. While these guidelines seem to be effective in clinical practice, recent data suggest that artificial intelligence (AI)-based malignant-nodule prediction solutions might outperform existing models. METHODS AND ANALYSIS: This study is a prospective, observational multicentre study to assess the clinical utility of an AI-assisted CT-based lung cancer prediction tool (LCP) for managing incidental solid and part solid pulmonary nodule patients vs standard care. Two thousand patients will be recruited from 12 different UK hospitals. The primary outcome is the difference between standard care and LCP-guided care in terms of the rate of benign nodules and patients with cancer discharged straight after the assessment of the baseline CT scan. Secondary outcomes investigate adherence to clinical guidelines, other measures of changes to clinical management, patient outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: This study has been reviewed and given a favourable opinion by the South Central-Oxford C Research Ethics Committee in UK (REC reference number: 22/SC/0142).Study results will be available publicly following peer-reviewed publication in open-access journals. A patient and public involvement group workshop is planned before the study results are available to discuss best methods to disseminate the results. Study results will also be fed back to participating organisations to inform training and procurement activities. TRIAL REGISTRATION NUMBER: NCT05389774.

Risk of COVID-19 death for people with a pre-existing cancer diagnosis prior to COVID-19-vaccination: A systematic review and meta-analysis.

While previous reviews found a positive association between pre-existing cancer diagnosis and COVID-19-related death, most early studies did not distinguish long-term cancer survivors from those recently diagnosed/treated, nor adjust for important confounders including age. We aimed to consolidate higher-quality evidence on risk of COVID-19-related death for people with recent/active cancer (compared to people without) in the pre-COVID-19-vaccination period. We searched the WHO COVID-19 Global Research Database (20 December 2021), and Medline and Embase (10 May 2023). We included studies adjusting for age and sex, and providing details of cancer status. Risk-of-bias assessment was based on the Newcastle-Ottawa Scale. Pooled adjusted odds or risk ratios (aORs, aRRs) or hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated using generic inverse-variance random-effects models. Random-effects meta-regressions were used to assess associations between effect estimates and time since cancer diagnosis/treatment. Of 23 773 unique title/abstract records, 39 studies were eligible for inclusion (2 low, 17 moderate, 20 high risk of bias). Risk of COVID-19-related death was higher for people with active or recently diagnosed/treated cancer (general population: aOR = 1.48, 95% CI: 1.36-1.61, I2 = 0; people with COVID-19: aOR = 1.58, 95% CI: 1.41-1.77, I2 = 0.58; inpatients with COVID-19: aOR = 1.66, 95% CI: 1.34-2.06, I2 = 0.98). Risks were more elevated for lung (general population: aOR = 3.4, 95% CI: 2.4-4.7) and hematological cancers (general population: aOR = 2.13, 95% CI: 1.68-2.68, I2 = 0.43), and for metastatic cancers. Meta-regression suggested risk of COVID-19-related death decreased with time since diagnosis/treatment, for example, for any/solid cancers, fitted aOR = 1.55 (95% CI: 1.37-1.75) at 1 year and aOR = 0.98 (95% CI: 0.80-1.20) at 5 years post-cancer diagnosis/treatment. In conclusion, before COVID-19-vaccination, risk of COVID-19-related death was higher for people with recent cancer, with risk depending on cancer type and time since diagnosis/treatment.

Impact of the SARS-CoV-2 pandemic on lung cancer survival in England: an analysis of the rapid cancer registration dataset.

Early changes in lung cancer care can affect survival. Given the decrease in diagnosis during lockdowns, we calculated their impact on survival using National Lung Cancer Audit data. Percentage survival and HRs for death were compared between 2019 and lockdown periods of 2020. Decreased survival was observed from the first national lockdown onwards and within 90 days of diagnosis. HRs were highest for people diagnosed at the end of 2020 at 1.26 (95% CI 1.20 to 1.32) for death within 90 days and 1.51 (95% CI 1.42 to 1.60) for death between 91 and 270 days. Further work is needed on measures to mitigate this impact.

ERS/ESTS/ESTRO/ESR/ESTI/EFOMP statement on management of incidental findings from low dose CT screening for lung cancer.

BACKGROUND: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. METHODS: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. RESULTS: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. CONCLUSIONS: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible.

ERS/ESTS/ESTRO/ESR/ESTI/EFOMP statement on management of incidental findings from low dose CT screening for lung cancer.

BACKGROUND: Screening for lung cancer with low radiation dose computed tomography has a strong evidence base, is being introduced in several European countries and is recommended as a new targeted cancer screening programme. The imperative now is to ensure that implementation follows an evidence-based process that will ensure clinical and cost effectiveness. This European Respiratory Society (ERS) task force was formed to provide an expert consensus for the management of incidental findings which can be adapted and followed during implementation. METHODS: A multi-European society collaborative group was convened. 23 topics were identified, primarily from an ERS statement on lung cancer screening, and a systematic review of the literature was conducted according to ERS standards. Initial review of abstracts was completed and full text was provided to members of the group for each topic. Sections were edited and the final document approved by all members and the ERS Science Council. RESULTS: Nine topics considered most important and frequent were reviewed as standalone topics (interstitial lung abnormalities, emphysema, bronchiectasis, consolidation, coronary calcification, aortic valve disease, mediastinal mass, mediastinal lymph nodes and thyroid abnormalities). Other topics considered of lower importance or infrequent were grouped into generic categories, suitable for general statements. CONCLUSIONS: This European collaborative group has produced an incidental findings statement that can be followed during lung cancer screening. It will ensure that an evidence-based approach is used for reporting and managing incidental findings, which will mean that harms are minimised and any programme is as cost-effective as possible.

Clinical trials in cancer screening, prevention and early diagnosis (SPED): a systematic mapping review.

BACKGROUND: Global annual cancer incidence is forecast to rise to 27.5 M by 2040, a 62% increase from 2018. For most cancers, prevention and early detection are the most effective ways of reducing mortality. This study maps trials in cancer screening, prevention, and early diagnosis (SPED) to identify areas of unmet need and highlight research priorities. METHODS: A systematic mapping review was conducted to evaluate all clinical trials focused on cancer SPED, irrespective of tumour type. The National Cancer Research Institute (NCRI) portfolio, EMBASE, PubMed and Medline were searched for relevant papers published between 01/01/2007 and 01/04/2020. References were exported into Covidence software and double-screened. Data were extracted and mapped according to tumour site, geographical location, and intervention type. RESULTS: One hundred seventeen thousand seven hundred one abstracts were screened, 5157 full texts reviewed, and 2888 studies included. 1184 (52%) trials focussed on screening, 554 (24%) prevention, 442 (20%) early diagnosis, and 85 (4%) a combination. Colorectal, breast, and cervical cancer comprised 61% of all studies compared with 6.4% in lung and 1.8% in liver cancer. The latter two are responsible for 26.3% of global cancer deaths compared with 19.3% for the former three. Number of studies varied markedly according to geographical location; 88% were based in North America, Europe, or Asia. CONCLUSIONS: This study shows clear disparities in the volume of research conducted across different tumour types and according to geographical location. These findings will help drive future research effort so that resources can be directed towards major challenges in cancer SPED.

Defining the road map to a UK national lung cancer screening programme.

Lung cancer screening with low-dose CT was recommended by the UK National Screening Committee (UKNSC) in September, 2022, on the basis of data from trials showing a reduction in lung cancer mortality. These trials provide sufficient evidence to show clinical efficacy, but further work is needed to prove deliverability in preparation for a national roll-out of the first major targeted screening programme. The UK has been world leading in addressing logistical issues with lung cancer screening through clinical trials, implementation pilots, and the National Health Service (NHS) England Targeted Lung Health Check Programme. In this Policy Review, we describe the consensus reached by a multiprofessional group of experts in lung cancer screening on the key requirements and priorities for effective implementation of a programme. We summarise the output from a round-table meeting of clinicians, behavioural scientists, stakeholder organisations, and representatives from NHS England, the UKNSC, and the four UK nations. This Policy Review will be an important tool in the ongoing expansion and evolution of an already successful programme, and provides a summary of UK expert opinion for consideration by those organising and delivering lung cancer screenings in other countries.

Developing a Pan-European Technical Standard for a Comprehensive High-quality Lung Cancer CT Screening Program. An ERS Technical Standard.

Screening for lung cancer with low radiation dose computed tomography (LDCT) has a strong evidence base. The European Council adopted a recommendation in November 2022 that lung cancer screening be implemented using a stepwise approach. The imperative now is to ensure that implementation follows an evidence-based process that delivers clinical and cost effectiveness. This ERS Taskforce was formed to provide a technical standard for a high-quality lung cancer screening program. METHOD: A collaborative group was convened to include members of multiple European societies (see below). Topics were identified during a scoping review and a systematic review of the literature was conducted. Full text was provided to members of the group for each topic. The final document was approved by all members and the ERS Scientific Advisory Committee. RESULTS: Ten topics were identified representing key components of a screening program. The action on findings from the LDCT were not included as they are addressed by separate international guidelines (nodule management and clinical management of lung cancer) and by a linked taskforce (incidental findings). Other than smoking cessation, other interventions that are not part of the core screening process were not included (e.g. pulmonary function measurement). Fifty-three statements were produced and areas for further research identified. CONCLUSION: This European collaborative group has produced a technical standard that is a timely contribution to implementation of LCS. It will serve as a standard that can be used, as recommended by the European Council, to ensure a high quality and effective program.

Brain imaging in lung cancer staging: A real-world, multi-centre study of prevalence of brain metastases, impact on treatment and re-modelling of the NICE health economic analysis.

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.

The Impact of COVID-19 on Lung Cancer Incidence in England: Analysis of the National Lung Cancer Audit 2019 and 2020 Rapid Cancer Registration Datasets.

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

Lung nodules: sorting the wheat from the chaff.

Pulmonary nodules are a common finding on CT scans of the chest. In the United Kingdom, management should follow British Thoracic Society Guidelines, which were published in 2015. This review covers key aspects of nodule management also looks at new and emerging evidence since then.

Lung Cancer Screening: New Perspective and Challenges in Europe.

Randomized-controlled trials have shown clear evidence that lung cancer screening with low-dose CT in a high-risk population of current or former smokers can significantly reduce lung-cancer-specific mortality by an inversion of stage distribution at diagnosis. This paper will review areas in which there is good or emerging evidence and areas which still require investment, research or represent implementation challenges. The implementation of population-based lung cancer screening in Europe is variable and fragmented. A number of European countries seem be on the verge of implementing lung cancer screening, mainly through the implementation of studies or trials. The cost and capacity of CT scanners and radiologists are considered to be the main hurdles for future implementation. Actions by the European Commission, related to its published Europe's Beating Cancer Plan and the proposal to update recommendations on cancer screening, could be an incentive to help speed up its implementation.

Ninety-day mortality following lung cancer surgery: outcomes from the English national clinical outcomes audit.

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.

The Future of Lung Cancer Screening: Current Challenges and Research Priorities.

Lung cancer is the leading cause of cancer-related deaths worldwide, primarily because most people present when the stage is too advanced to offer any reasonable chance of cure. Over the last two decades, evidence has accumulated to show that early detection of lung cancer, using low-radiation dose computed tomography, in people at higher risk of the condition reduces their mortality. Many countries are now making progress with implementing programmes, although some have concerns about cost-effectiveness. Lung cancer screening is complex, and many factors influence clinical and cost-effectiveness. It is important to develop strategies to optimise each element of the intervention from selection and participation through optimal scanning, management of findings and treatment. The overall aim is to maximise benefits and minimise harms. Additional integrated interventions must include at least smoking cessation. In this review, we summarize the evidence that has accumulated to guide optimisation of lung cancer screening, discuss the remaining open questions about the best approach and identify potential barriers to successful implementation.

Selection of eligible participants for screening for lung cancer using primary care data.

Lung cancer screening is effective if offered to people at increased risk of the disease. Currently, direct contact with potential participants is required for evaluating risk. A way to reduce the number of ineligible people contacted might be to apply risk-prediction models directly to digital primary care data, but model performance in this setting is unknown. METHOD: The Clinical Practice Research Datalink, a computerised, longitudinal primary care database, was used to evaluate the Liverpool Lung Project V.2 (LLPv2) and Prostate Lung Colorectal and Ovarian (modified 2012) (PLCOm2012) models. Lung cancer occurrence over 5-6 years was measured in ever-smokers aged 50-80 years and compared with 5-year (LLPv2) and 6-year (PLCOm2012) predicted risk. RESULTS: Over 5 and 6 years, 7123 and 7876 lung cancers occurred, respectively, from a cohort of 842 109 ever-smokers. After recalibration, LLPV2 produced a c-statistic of 0.700 (0.694-0.710), but mean predicted risk was over-estimated (predicted: 4.61%, actual: 0.9%). PLCOm2012 showed similar performance (c-statistic: 0.679 (0.673-0.685), predicted risk: 3.76%. Applying risk-thresholds of 1% (LLPv2) and 0.15% (PLCOm2012), would avoid contacting 42.7% and 27.4% of ever-smokers who did not develop lung cancer for screening eligibility assessment, at the cost of missing 15.6% and 11.4% of lung cancers. CONCLUSION: Risk-prediction models showed only moderate discrimination when applied to routinely collected primary care data, which may be explained by quality and completeness of data. However, they may substantially reduce the number of people for initial evaluation of screening eligibility, at the cost of missing some lung cancers. Further work is needed to establish whether newer models have improved performance in primary care data.

Lung cancer for the non-respiratory physician.

Lung cancer continues to be the leading cause of cancer death globally. Delayed diagnosis is a major contributing factor to poor outcomes and remains a key challenge to overcome. While debate around the implementation of lung cancer screening for asymptomatic high-risk individuals continues, rapid access to relevant diagnostic tests is essential. The new National Optimal Lung Cancer Pathway describes 'diagnostic standards of care' in an effort to implement best practice, reduce variation and improve delays in diagnosis, staging and treatment of lung cancer. Lung cancer treatment continues to develop with new surgical techniques, radiotherapy options and more drugs being licensed as part of standard treatment. We provide an overview of the core lung cancer diagnostic steps, recognition and management of acute presentations as well as the latest treatment options.

Analysis of the baseline performance of five UK lung cancer screening programmes.

INTRODUCTION: Low-dose CT (LDCT) screening reduces lung cancer specific mortality. Several countries, including the UK, are evaluating the clinical impact and cost-effectiveness of LDCT screening using the latest evidence. In this paper we report baseline screening performance from five UK-based lung cancer screening programmes. METHODS: Data was collected at baseline from each screening programme. Measures of performance included prevalence of screen detected lung cancer, rate of surveillance imaging for indeterminate findings and surgical resection rates. Screening related harms were assessed by measuring false positive rates, number of invasive tests with associated complications in individuals without lung cancer and benign surgical resection rates. RESULTS: A total of 11,148 individuals had a baseline LDCT scan during the period of analysis (2011 to 2020). Overall, 84.7% (n = 9,440) of baseline LDCT scans were categorised as negative, 11.1% (n = 1,239) as indeterminate and 4.2% (n = 469) as positive. The prevalence of screen detected lung cancer was 2.2%, ranging between 1.8% and 4.4% for individual programmes. The surgical resection rate was 66% (range 46% to 83%) and post-surgical 90-day mortality for those with lung cancer 1.2% (n = 2/165). The false positive rate was 2% (n = 219/10,898) and of those with a positive result, one in two had lung cancer diagnosed (53.3%). An invasive test was required in 0.6% (n = 61/10,898) of screening attendees without lung cancer; there were no associated major complications or deaths. The benign surgical resection rate was 4.6% (n = 8/173), equating to 0.07% of the screened population. DISCUSSION: The performance of UK-based lung cancer screening programmes, delivered within or aligned to the National Health Service, compares favourably to published clinical trial data. Reported harms, including false positive and benign surgical resection rates are low. Ongoing monitoring of screening performance is vital to ensure standards are maintained and harms minimised.