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Objectives We conducted a systematic review and meta-analysis of survival following treatment recommended by the European Society of Medical Oncology for SCLC in order to determine a benchmark for novel therapies to be compared with. Materials and methods Randomized controlled trials and observational studies reporting overall survival following chemotherapy for SCLC were included. We calculated survival at 30 and 90-days along with 1-year, 2-year and median. Results We identified 160 for inclusion. There were minimal 30-day deaths. Survival was 99 % (95 %CI 98.0–99.0 %, I233.9 %, n = 77) and 90 % (95 %CI 89.0–92.0 %, I279.5 %, n = 73) at 90 days for limited (LD-SCLC) and extensive stage (ED-SCLC) respectively. The median survival for LD-SCLC was 18.1 months (95 %CI 17.0–19.1 %, I277.3 %, n = 110) and early thoracic radiotherapy (thoracic radiotherapy 18.4 months (95 %CI 17.3–19.5, I278.4 %, n = 100)) vs no radiotherapy 11.7 months (95 %CI 9.1–14.3, n = 10), prophylactic cranial irradiation (PCI 19.7 months vs No PCI 13.0 months (95 %CI 18.5–21.0, I275.7 %, n = 78 and 95 %CI 10.5–16.6, I281.1 %, n = 15 respectively)) and better performance status (PS0–1 22.5 months vs PS0–4 15.3 months (95 %CI 18.7–26.1, I272.4 %, n = 11 and 95 %CI 11.5–19.1 I277.9 %, n = 13)) augmented this. For ED-SCLC the median survival was 9.6 months (95 %CI 8.9–10.3 %, I295.2 %, n = 103) and this improved when irinotecan + cisplatin was used, however studies that used this combination were mostly conducted in Asian populations where survival was better. Survival was not improved with the addition of thoracic radiotherapy or PCI. Survival for both stages of cancer was better in modern studies and Asian cohorts. It was poorer for studies administering carboplatin + etoposide but this regimen was used in studies that had fewer patient selection criteria. Conclusion Early thoracic radiotherapy and PCI should be offered to people with LD-SCLC in accordance with guideline recommendations. The benefit of the aforementioned therapies to treat ED-SCLC and the use of chemotherapy in people with poor PS is less clear.

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was demonstrated in the National Lung Screening Trial (NLST) to reduce mortality from the disease. European mortality data has recently become available from the Nelson randomised controlled trial, which confirmed lung cancer mortality reductions by 26% in men and 39–61% in women. Recent studies in Europe and the USA also showed positive results in screening workers exposed to asbestos. All European experts attending the “Initiative for European Lung Screening (IELS)”—a large international group of physicians and other experts concerned with lung cancer—agreed that LDCT-LCS should be implemented in Europe. However, the economic impact of LDCT-LCS and guidelines for its effective and safe implementation still need to be formulated. To this purpose, the IELS was asked to prepare recommendations to implement LCS and examine outstanding issues. A subgroup carried out a comprehensive literature review on LDCT-LCS and presented findings at a meeting held in Milan in November 2018. The present recommendations reflect that consensus was reached.

Rapid and continuing advances in biomarker testing are not being matched by take-up in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. This paper sets out the potential of biomarker testing, the unfolding precision and range of possible diagnosis and prediction, and the many obstacles to adoption. It offers case studies of biomarker testing in breast, ovarian, prostate, lung, thyroid and colon cancers, and derives specific lessons as to the potential and actual use of each of them. It also draws lessons about how to improve access and alignment, and to remedy the data deficiencies that impede development. And it suggests solutions to outstanding issues - notably including funding and the tangled web of obtaining reimbursement or equivalent coverage that Europe's fragmented health system implies. It urges a European evolution towards an initial minimum testing scenario, which would guarantee universal access to a suite of biomarker tests for the currently most common conditions, and, further into the future, to an optimum testing scenario in which a much wider range of biomarker tests would be introduced and become part of a more sophisticated health system articulated around personalised medicine. For exploiting genomics to the full, it argues the need for a new policy framework for Europe. Biomarker testing is not an issue that can be treated in isolation, since the purpose of testing is to improve health. Its use is therefore always closely linked to specific health challenges and needs to be viewed in the broader policy context in the EU and more widely. The paper is the result of extensive engagement with experts and decision makers to develop the framework, and consequently represents a wide consensus of views on how healthcare systems should respond from push and pull factors at local, national and cross-border and EU level. It contains strong views and clear recommendations springing from the convictions of patients, clinicians, academics, medicines authorities, HTA bodies, payers, the diagnostic, pharmaceutical and ICT industries, and national policy makers. ispartof: Biomed Hub vol:5 issue:3 pages:182-223 ispartof: location:Switzerland status: Published online

IntroductionLung cancer is a common cancer, with over 1.3 million cases worldwide each year. Early diagnosis using computed tomography (CT) screening has been shown to reduce mortality but also detect non-malignant nodules that require follow-up scanning or alternative methods of investigation. Practical and accurate tools that can predict the probability that a lung nodule is benign or malignant will help reduce costs and the risk of morbidity and mortality associated with lung cancer. MethodsRetrospectively collected data from 1500 patients with pulmonary nodule(s) of up to 15 mm detected on routinely performed CT chest scans aged 18 years old or older from three academic centres in the UK will be used to to develop risk stratification models. Radiological, clinical and patient characteristics will be combined in multivariable logistic regression models to predict nodule malignancy. Data from over 1000 participants recruited in a prospective phase of the study will be used to evaluate model performance. Discrimination, calibration and clinical utility measures will be presented.

Background Thirty-day mortality after treatment for lung cancer is a measure of unsuccessful outcome and where treatment should have been avoided. Guidelines recommend offering chemotherapy to individuals with small-cell lung cancer (SCLC) who have poorer performance status (PS) because of its high initial response rate. However, this comes with an increased risk of toxicity and early death. We quantified real-world 30-day mortality in SCLC after chemotherapy, established the factors associated with this and compared these with the factors that influence receipt of chemotherapy. Methods We used linked national English data sets to define the factors associated with both receiving chemotherapy and 30-day mortality after chemotherapy. Results We identified 3715 people diagnosed with SCLC, of which 2235 (60.2%) received chemotherapy. There were 174 (7.8%) deaths within 30 days of chemotherapy. The adjusted odds of receiving chemotherapy decreased with older age, worsening PS and increasing comorbidities. Thirty-day mortality was independently associated with poor PS [PS 2 vs PS 0, adjusted odds ratio (OR) 3.75, 95% confidence interval (CI) 1.71–8.25] and stage (extensive vs limited adjusted OR 1.68, 95% CI 1.03–2.74) but in contrast was not associated with increasing age. Both chemotherapy administration and 30-day mortality varied by hospital network. Conclusions To reduce variation in chemotherapy administration, predictors of 30-day mortality could be used as an adjunct to improve suboptimal patient selection. We have quantified 30-day mortality risk by the two independently associated factors, PS and stage, so that patients and clinicians can make better informed decisions about the potential risk of early death after chemotherapy.

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

Key messages #### What is the key question? #### What is the bottom line? #### Why read on? Pulmonary nodules are common, with a prevalence of 14%–36%,1–5 usually less in case series of nodules that are incidentally detected on thoracic CT scans performed for a variety of clinical indications. Clinical management of CT-detected pulmonary nodules was based initially on a statement made by the Fleischner Society in 2005.6 Three further guidelines and one statement have been published since 2013 incorporating emerging evidence. The Fleischner Society provided specific recommendations for subsolid nodule management in 2013.7 In the same year, the American College of Chest Physicians (ACCP) issued nodule guidance as part of its recommendations for the diagnosis and management of lung cancer.8 In 2015, the British Thoracic Society (BTS) published guidelines for nodule management, accompanied by a comprehensive evidence review.9 Most recently, the Fleischner Society updated their guidance for management and measurement of nodules, replacing both their 2005 and 2013 guidance.10 11 Clinician awareness of, and adherence to, such guidance has historically been poor, and remains so.12–16 Guidelines that differ in their recommendations are a potential source of confusion and thus risk increasing variation in clinical practice rather than achieving one of …

Historically, the prognosis for individuals diagnosed with lung cancer has been bleak. However, the past 10 years have seen important advances in treatment and diagnosis which have translated into the first improvements seen in lung cancer survival. This review highlights the major advances in treatments with curative intent, systemic targeted therapies, palliative care and early diagnosis in lung cancer. We discuss the pivotal research that underpins these new technologies/strategies and their current position in clinical practice.

Lung cancer screening with low-dose CT can save lives. This European Union (EU) position statement presents the available evidence and the major issues that need to be addressed to ensure the successful implementation of low-dose CT lung cancer screening in Europe. This statement identified specific actions required by the European lung cancer screening community to adopt before the implementation of low-dose CT lung cancer screening. This position statement recommends the following actions: a risk stratification approach should be used for future lung cancer low-dose CT programmes; that individuals who enter screening programmes should be provided with information on the benefits and harms of screening, and smoking cessation should be offered to all current smokers; that management of detected solid nodules should use semi-automatically measured volume and volume-doubling time; that national quality assurance boards should be set up to oversee technical standards; that a lung nodule management pathway should be established and incorporated into clinical practice with a tailored screening approach; that non-calcified baseline lung nodules greater than 300 mm(3), and new lung nodules greater than 200 mm(3), should be managed in multidisciplinary teams according to this EU position statement recommendations to ensure that patients receive the most appropriate treatment; and planning for implementation of low-dose CT screening should start throughout Europe as soon as possible. European countries need to set a timeline for implementing lung cancer screening.

BackgroundThe NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial.MethodsFrom October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care). Eligible participants (aged 50-75) had a risk score (LLPv2) ≥ 4.5% of developing lung cancer over five years. Data were collected on lung cancer cases to 31 December 2019 and deaths to 29 February 2020 through linkage to national registries. The primary outcome was mortality due to lung cancer. We included our results in a random-effects meta-analysis to provide a synthesis of the latest randomised trial evidence.Findings1 987 participants in the intervention and 1 981 in the usual care arms were followed for a median of 7.3 years (IQR 7.1-7.6), 86 cancers were diagnosed in the LDCT arm and 75 in the control arm. 30 lung cancer deaths were reported in the screening arm, 46 in the control arm, (relative rate 0.65 [95% CI 0.41-1.02]; p=0.062). The meta-analysis indicated a significant reduction in lung cancer mortality with a pooled overall relative rate of 0.84 (95% CI 0.76-0.92) from nine eligible trials.InterpretationThe UKLS trial of single LDCT indicates a reduction of lung cancer death of similar magnitude to the NELSON and NLST trials and was included in a meta-analysis of nine randomised trials which provides unequivocal support for lung cancer screening in identified risk groups.FundingNIHR Health Technology Assessment programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation.

IntroductionOptimal 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 analysisPatient 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 disseminationEthical approval has been obtained. Results will be disseminated via publications, national bodies and networks, and patient and public involvement groups.Trial registrationNCT04540757

BackgroundLung cancer is the leading cause of cancer deaths. Around 70% of patients first presenting to specialist care have advanced disease, at which point current treatments have little effect on survival. The issue for primary care is how to recognise patients earlier and investigate appropriately. This requires an assessment of the risk of lung cancer.AimThe aim of this study was to systematically review the existing risk prediction tools for patients presenting in primary care with symptoms that may indicate lung cancerDesign and settingSystematic review of primary care data.MethodMedline, PreMedline, Embase, the Cochrane Library, Web of Science, and ISI Proceedings (1980 to March 2016) were searched. The final list of included studies was agreed between two of the authors, who also appraised and summarised them.ResultsSeven studies with between 1482 and 2 406 127 patients were included. The tools were all based on UK primary care data, but differed in complexity of development, number/type of variables examined/included, and outcome time frame. There were four multivariable tools with internal validation area under the curves between 0.88 and 0.92. The tools all had a number of limitations, and none have been externally validated, or had their clinical and cost impact examined.ConclusionThere is insufficient evidence for the recommendation of any one of the available risk prediction tools. However, some multivariable tools showed promising discrimination. What is needed to guide clinical practice is both external validation of the existing tools and a comparative study, so that the best tools can be incorporated into clinical decision tools used in primary care.

Introduction The NLST and NELSON studies demonstrated lung cancer mortality reduction from low-dose CT (LDCT) lung cancer screening. Local implementation pilots of ‘Lung Health Checks’ indicate feasibility in the NHS. NHS England will now fund 10 aligned projects for a national Lung Health Check pilot as a major centre-piece of the early diagnosis agenda of the NHS Long Term Plan. We report on methodological approaches to deliver this project and progress towards deployment. Methods Sites selected from Clinical Commissioning Groups in 10 Cancer Alliances had highest incidence and mortality from lung cancer, excluding those where screening pilots or research projects were already underway. Approximately 600,000 individuals will be invited with an expected 200,000 scans over the next four years, including baseline and 24 month incident round scanning. To support quality and governance, NHS England published a National Protocol (January 2019), are developing a Quality Assurance Framework, minimum dataset, Incidental Findings Protocol and Research Standard (assisted by CRUK). NHSE are supported by the CT Screening Advisory Committee, a sub-group of the Clinical Expert Group for Lung Cancer, NHSE. Cancer Alliances are being assisted in developing detailed delivery plans by the National Cancer Programme team. Results Detailed delivery plans have been provided by all regions. 47 radiologists will attend a national education program with clearly defined metrics for a national quality assurance training standard including volumetry and computer-aided detection. Standard participant materials are in production and QA evaluator appointed. Data on infrastructure readiness, progress against delivery milestones and final supporting documents relating to quality and governance will be presented. Conclusions The Lung Health Check program will be a major national flagship for respiratory medicine and a key component of the Long Term Plan aspirations to achieve early stage diagnosis in 75% of cancer cases. The program will inform the international literature on implementation of potentially revolutionary lung cancer screening but careful adherence to QA and demonstration of efficacy through appropriate evaluation is critical. Potential barriers include participant uptake; workforce capacity and data flow/information governance. The Standard Protocol is already being used by several European countries as a template for local protocol development. On behalf of the CT Screening Advisory Group, Clinical Expert Group for Lung Cancer and NHS England National Cancer Team.

BackgroundEstimation of the clinical probability of malignancy in patients with pulmonary nodules will facilitate early diagnosis, determine optimum patient management strategies and reduce overall costs.MethodsData from the UK Lung Cancer Screening trial were analysed. Multivariable logistic regression models were used to identify independent predictors and to develop a parsimonious model to estimate the probability of lung cancer in lung nodules detected at baseline and at 3-month and 12-month repeat screening.ResultsOf 1994 participants who underwent CT scan, 1013 participants had a total of 5063 lung nodules and 52 (2.6%) of the participants developed lung cancer during a median follow-up of 4 years. Covariates that predict lung cancer in our model included female gender, asthma, bronchitis, asbestos exposure, history of cancer, early and late onset of family history of lung cancer, smoking duration, FVC, nodule type (pure ground-glass and part-solid) and volume as measured by semiautomated volumetry. The final model incorporating all predictors had excellent discrimination: area under the receiver operating characteristic curve (AUC 0.885, 95% CI 0.880 to 0.889). Internal validation suggested that the model will discriminate well when applied to new data (optimism-corrected AUC 0.882, 95% CI 0.848 to 0.907). The risk model had a good calibration (goodness-of-fit χ[8] 8.13, p=0.42).ConclusionsOur model may be used in estimating the probability of lung cancer in nodules detected at baseline and at 3 months and 12 months from baseline, allowing more efficient stratification of follow-up in population-based lung cancer screening programmes.Trial registration number78513845.

IntroductionLung cancer screening (LCS) by low-dose CT has been shown to improve mortality, but individuals must consider the potential benefits and harms before making an informed decision about taking part. Shared decision-making is required for LCS in USA, though screening-eligible individuals’ specific views of these harms, and their preferences for accessing this information, are not well described.MethodsIn this qualitative study, we aimed to explore knowledge and perceptions around lung cancer and LCS with a focus on harms. We carried out seven focus groups with screening-eligible individuals, which were divided into current versus former smokers and lower versus higher educational backgrounds; and 16 interviews with health professionals including general practitioners, respiratory physicians, lung cancer nurse specialists and public health consultants. Interviews and focus groups were audio-recorded and transcribed. Data were coded inductively and analysed using the framework method.ResultsFatalistic views about lung cancer as an incurable disease dominated, particularly among current smokers, and participants were often unaware of curative treatment options. Despite this, beliefs that screening is sensible and worthwhile were expressed. Generally participants felt they had the ‘right’ to an informed decision, though some cautioned against information overload. The potential harms of LCS were poorly understood, particularly overdiagnosis and radiation exposure, but participants were unlikely to be deterred by them. Strong concerns about false-negative results were expressed, while false-positive results and indeterminate nodules were also reported as concerning.ConclusionsThese findings demonstrate the need for LCS information materials to highlight information on the benefits of early detection and options for curative treatment, while accurately presenting the possible harms. Information needs are likely to vary between individuals and we recommend simple information materials to be made available to all individuals considering participating in LCS, with signposting to more detailed information for those who require it.

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).

Purpose Appropriate lung nodule management is essential to minimizing unnecessary patient recall in lung cancer screening. Two European guidelines provide differing recommendations in that participants with nodules ≥100 mm3 or ≥80 mm3 respectively should be recalled, at baseline. Nodule size estimation is known to vary between volumetry software packages (VSPs). The aim of this study was to examine the impact of choice of VSP on participant recall rates, when applying different European nodule management guidelines. An additional aim was to compare recall rates between 7 VSPs and manual diameter measurements. Methods 156 small-sized lung nodules (50–150 mm3) from the UK Lung Screening trial were measured using 7 different VSPs (VSP1-7) and also using manual diameter. The type of VSP used in the NELSON study (VSP1), on which European nodule management guidelines are based, provided the reference standard. Nodule size was compared using Bland Altman, and recall rates by Mcnemar’s test. Results Compared to the reference standard, a 100 mm3 threshold for recall, resulted in no difference in recall rates only for VSP 5 & 7. Using an 80mm3 threshold resulted in no difference in recall rates for VSP2 & 6. Recall rates were significantly higher for VSP 4 regardless of threshold and when using manual diameter measurements. Conclusions Appropriate nodule size thresholds for recall in screening depend on the type of volumetry software used. The results highlight the importance of benchmarking of volumetry packages.

Screening for lung cancer with low radiation dose CT has been shown to be effective in reducing lung cancer mortality by two major randomised controlled trials. Lung cancer screening is set to become the largest targeted cancer screening programme globally, but the effectiveness of the programme is dependent on many different factors. This article describes the key evidence for lung cancer screening, the key factors important for optimisation and the progress towards implementation.

In lung cancer, outcome measurement has been mostly limited to survival. Proper assessment of the value of lung cancer treatments, and the performance of institutions delivering care, requires more comprehensive measurement of standardised outcomes. The International Consortium for Health Outcomes Measurement convened an international, multidisciplinary working group of patient representatives, medical oncologists, surgeons, radiation oncologists, pulmonologists, palliative care specialists, registry experts and specialist nurses to review existing data and practices. Using a modified Delphi method, the group developed a consensus recommendation (“the set”) on the outcomes most essential to track for patients with lung cancer, along with baseline demographic, clinical and tumour characteristics (case-mix variables) for risk adjustment. The set applies to patients diagnosed with nonsmall cell lung cancer and small cell lung cancer. Our working group recommends the collection of the following outcomes: survival, complications during or within 6 months of treatment and patient-reported domains of health-related quality of life including pain, fatigue, cough and dyspnoea. Case-mix variables were defined to improve interpretation of comparisons. We defined an international consensus recommendation of the most important outcomes for lung cancer patients, along with relevant case-mix variables, and are working to support adoption and reporting of these measures globally., ICHOM Lung Cancer Standard Set of patient-centred outcomes: aligning global efforts to improve lung cancer care http://ow.ly/bFDR300EhY7

The British Thoracic Society guideline on the investigation and management of pulmonary nodules is based on a comprehensive and systematic review of the literature on pulmonary nodules. Recent evidence has suggested that significant changes to existing guidelines are necessary. The use of 2 malignancy prediction calculators to better characterize the risk of malignancy was firmly supported by evidence, as were the recommendations for a higher nodule size threshold for follow‑up (≥5 mm or ≥80 mm3) and a reduction of the follow‑up period to 1 year for solid pulmonary nodules. Although caution is required where there is a history of cancer, both of these recommendations will reduce the number of follow‑up computed tomographies, thereby improving cost‑effectiveness and pressure on imaging services. Recent evidence has also confirmed the superiority of volumetry as the preferred measurement method and clarified the management of nodules with extended volume‑doubling times. Acknowledging the good prognosis of subsolid nodules, there are recommendations for less aggressive options in their management. The guidelines recommend ordinal scale reporting for positron emission tomography-computed tomography to facilitate incorporation into risk models. There are recommendations on when biopsy is most helpful, the threshold for treatment without histological confirmation, and surgical and nonsurgical treatment. The guideline also provides evidence‑based recommendations about the information that people need and that should be provided for them. The complexity of managing pulmonary nodules is made more accessible by 4 management algorithms. In the real world, it is surprising how easy these are to follow and how they seem to follow an intuitive approach.

In the modern lung cancer service, the first visit to hospital is where the initial investigation pathway is formulated to ensure that as much diagnostic and staging information is obtained with least risk and discomfort for the patient. It is of over-riding importance to ensure that this is in line with the patient’s wishes and appropriate to the fitness of the individual as well as the potential treatment. To do this a contrast-enhanced computed tomogram (CT) of the lower neck, chest and upper abdomen should be available at the time of the first clinical assessment. At this time, performance status is recorded, and blood tests and spirometry obtained. The most effective next test (usually a biopsy) can then be selected. Clear information should be given to the patient, who must have access to support from a lung cancer nurse specialist. Clinical assessment and spirometry will identify the need for further tests to assess fitness. The exact sequence of investigations will vary according to the clinical and CT findings, but to ensure the most accurate stage and therefore most effective treatment, pathological confirmation of findings on imaging is usually sought, with samples provided that are adequate for sub-classification of tumours.

The prevailing questions at this time in both the public mind and the clinical establishment is, do we have sufficient evidence to implement lung cancer Computed Tomography (CT) screening in Europe? If not, what is outstanding? This review addresses the twelve major areas, which are critical to any decision to implement CT screening and where we need to assess whether we have sufficient evidence to proceed to a recommendation for implementation in Europe. The readiness level of these twelve categories in 2015 have been with colour coded, where green indicates we have sufficient evidence, amber is borderline evidence and red requires further evidence. Recruitment from the 'Hard to Reach' community still remains at red, while mortality data, cost effectiveness and screening interval are all categorised as amber. The integration of smoking cessation into CT screening programmes is still considered to be category amber. The US Preventive Services Task Force have recommended that CT screening is implemented in the USA utilising the NLST criteria, apart from continuing screening to 80 years of age. The cost effectiveness of the NLST was calculated to be $81,000/QALY, however, its well recognised that the costs of medical care in the USA, is far higher than that of Europe. Medicare have agreed to cover the cost of screening but have stipulated a number of stringent requirements for inclusion. To date we do not have good CT screening mortality data available in Europe and eagerly await the publication of the NELSON trial data in 2016 and then the pooled UKLS and NELSON data thereafter. However in the meantime we should start planning for implementation in Europe, especially in the areas of the radiological service provision and accreditation, as well as identifying novel mechanisms to recruit from the hardest to reach communities.

BACKGROUND: Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial.METHODS: The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction.RESULTS: 247 354 individuals aged 50-75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm(3) or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm(3) at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569).CONCLUSIONS: The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective-this needs to be confirmed using data on observed lung cancer mortality reduction.TRIAL REGISTRATION: ISRCTN 78513845.

Objectives: The use of cross-sectional imaging in clinical medicine has been a major step forward in the management of many conditions but with that comes the increasing demand on resources and the detection of other potentially significant findings. This, in the context of a shortage of skilled radiologists, means that new ways of working are important. In thoracic CT, pulmonary nodules are a significant challenge because they are so common. Poor and inconsistent management can both cause harm to patients and waste resources so it is important that the latest guidelines are followed. The latter mandate the use of semi-automated volumetry that allows more precise management but is time-consuming. Methods: Reporting radiographers were iteratively trained in the use of semi-automated volumetry for pulmonary nodules by experienced thoracic radiologists. Once trained in this specific aspect, radiographers completed reporting of pulmonary nodules, checked by radiologists. Results: Radiographer reporting reduced radiologist time in reporting nodules and measuring their volume. Most of the volumetry was completed prior to the multidisciplinary meeting. This facilitated an increase in the number of patients discussed in 60 min from 15 to 22. Radiographers failed to detect few nodules, although a second read by radiologists is required in any case for other aspects of the reporting. Conclusion: Reporting radiographers, working with radiologists in a supportive setting, can deliver the radiology in a lung nodule pathway, reducing the time commitment from radiologists and the pulmonary nodule multidisciplinary team members, whilst using this as an opportunity to conduct research.

Lung cancer is the most common cause of cancer death in the UK, and survival from the disease is persistently poor. Efforts to improve outcomes for patients have focused on ways of reducing late diagnosis of the disease, and access to optimal treatment. Research on lung cancer screening has so far provided some evidence of an impact on lung cancer mortality, but there is some debate about whether implementation of a national screening programme should await further trial data, principally that from the NELSON trial. The ongoing poor outcomes and the belief amongst some clinicians that there is sufficient evidence has prompted several local projects testing out lung screening in their communities, sometimes referred to as lung health checks or proactive approaches to high-risk individuals. Funding from NHS England has been forthcoming to support this. Acknowledging roll-out of such activities, which effectively constitute local lung screening in the absence of a NSC recommendation, it was timely to bring key national stakeholders together with academic and clinical experts, to agree a way forward. Cancer Research UK therefore convened a closed workshop in March 2018, involving national and international expertise. This paper outlines the proceedings, key discussion points, highlighted research gaps, and areas of consensus and next steps.

IntroductionLung cancer outcomes in England are inferior to comparable countries. Patient or disease characteristics, healthcare-seeking behaviour, diagnostic pathways, and oncology service provision may contribute. We aimed to quantify associations between geographic variations in treatment and survival of patients in England.MethodsWe retrieved detailed cancer registration data to analyse the variation in survival of 176,225 lung cancer patients, diagnosed 2010-2014. We used Kaplan-Meier analysis and Cox proportional hazards regression to investigate survival in the two-year period following diagnosis.ResultsSurvival improved over the period studied. The use of active treatment varied between geographical areas, with inter-quintile ranges of 9%–17% for surgical resection, 4%–13% for radical radiotherapy, and 22%–35% for chemotherapy. At 2 years, there were 188 potentially avoidable deaths annually for surgical resection, and 373 for radical radiotherapy, if all treated proportions were the same as in the highest quintiles. At the 6 month time-point, 318 deaths per year could be postponed if chemotherapy use for all patients was as in the highest quintile. The results were robust to statistical adjustments for age, sex, socio-economic status, performance status and co-morbidity.ConclusionThe extent of use of different treatment modalities varies between geographical areas in England. These variations are not attributable to measurable patient and tumour characteristics, and more likely reflect differences in clinical management between local multi-disciplinary teams. The data suggest improvement over time, but there is potential for further survival gains if the use of active treatments in all areas could be increased towards the highest current regional rates.

Successful implementation of low dose CT (LDCT) lung cancer screening, depends on a number of well-researched factors that improve the balance between benefits and harms. One of the most important is the identification of individuals at high risk of developing and dying from lung cancer. There is debate about the threshold that defines high enough risk and the method for estimating risk, with several multivariable risk models available. The findings from the PanCan study shed further light on this topic.

Publisher’s Note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations., Background: A minority of European countries have participated in international comparisons with high level data on lung cancer. However, the nature and extent of data collection across the continent is simply unknown, and without accurate data collection it is not possible to compare practice and set benchmarks to which lung cancer services can aspire. Methods: Using an established network of lung cancer specialists in 37 European countries, a survey was distributed in December 2014. The results relate to current practice in each country at the time, early 2015. The results were compiled and then verified with co-authors over the following months. Results: Thirty-five completed surveys were received which describe a range of current practice for lung cancer data collection. Thirty countries have data collection at the national level, but this is not so in Albania, BosniaHerzegovina, Italy, Spain and Switzerland. Data collection varied from paper records with no survival analysis, to well-established electronic databases with links to census data and survival analyses. Conclusion: Using a network of committed clinicians, we have gathered validated comparative data reporting an observed difference in data collection mechanisms across Europe. We have identified the need to develop a welldesigned dataset, whilst acknowledging what is feasible within each country, and aspiring to collect high quality data for clinical research., No research funding was received.

The European Position Statement (EUPS) expert group comprised of individuals who have been actively involved in the planning and execution of all the low dose CT (LDCT) randomised controlled European screening trials. They have argued that as lung cancer screening with LDCT saves lives, planning for implementation needs to be started by the national health organisations throughout Europe. The EUPS examined the current evidence which supports the planning for the implementation of lung cancer screening, as well as areas which require further work. One of the major areas the EUPS focused on was the management of prevalent lung nodules in CT-screening programmes, lung nodules at incident screening (newly detected) and CT-detected lung nodules in clinical practice should be managed with different protocols, due to different pre-test lung cancer probability. The EUPS provides nine recommendations and a "Call to Action" for implementation, which is naturally dependent on the outcome of the NELSON trial. Clearly, the issue is how Europe can take this forward as part of the political agenda of individual countries, as well as that of the EU Commission. An EU policy document has been developed, which focuses on the key steps in the implementation of cost effective lung cancer screening in Europe.

Lung cancer screening is receiving increasing attention worldwide, both in the medical community and the general public. Multiple randomised trials — including the US National Lung Screening Trial (NLST), the Multicentric Italian Lung Detection trial, and preliminary results from the Dutch-Belgian NELSON trial — have provided definitive evidence that low-dose CT screening can reduce lung cancer mortality. However, any screening programme is associated with both benefits and harms, and accurately communicating these to patients and the general public is a complex challenge. Given the complexity of the debate, it is difficult for primary care providers to understand and explain the benefits and harms of screening to their patients. Multiple graphical tools have been developed and published to aid this conversation, each based on the NLST, and other bespoke graphics have been used in pilot studies. However, some of the published graphics can be misleading, and all represent outcomes based on the NLST protocol, which is now nearly 20 years old. We engaged an international group of lung screening experts with the goal of assembling and providing accurate and balanced information on the benefits and harms of NLST-like low-dose CT screening. We compiled these results into an infographic, along with a full-page version with explanatory text. Our new infographic represents a contemporary interpretation of the findings of NLST using a modern protocol.

Background Mortality in early stage, resectable lung cancer is sufficiently high to warrant consideration of post-surgical treatment. Novel markers to stratify resectable lung cancer patients may help with the selection of treatment to improve outcome. Methods Primary tumour tissue from 485 patients, surgically treated for stage I–II lung adenocarcinoma, was analysed for the RNA expression of 31 cell cycle progression (CCP) genes by quantitative polymerase chain reaction (PCR). The expression average, the CCP score, was combined with pathological stage into a prognostic score (PS). Cox proportional hazards regression assessed prediction of 5-year lung cancer mortality above clinical variables. The PS threshold was tested for risk discrimination by the Mantel–Cox log-rank test. Results The CCP score added significant information above clinical markers (all patients, P = 0.0029; stage I patients, P = 0.013). The prognostic score was a superior predictor of outcome compared to pathological stage alone (PS, P = 0.00084; stage, P = 0.24). Five-year lung cancer mortality was significantly different between the low-risk (90%, 95% confidence interval (CI) 81–95%), and high-risk groups (65%, 95% CI 57–72%), P = 4.2 × 10–6). Conclusions The CCP score is an independent prognostic marker in early stage lung adenocarcinoma. The prognostic score provides superior risk estimates than stage alone. The threefold higher risk in the high-risk group defines a subset of patients that should consider therapeutic choices to improve outcome.

This guideline is based on a comprehensive review of the literature on pulmonary nodules and expert opinion. Although the management pathway for the majority of nodules detected is straightforward it is sometimes more complex and this is helped by the inclusion of detailed and specific recommendations and the 4 management algorithms below. The Guideline Development Group (GDG) wanted to highlight the new research evidence which has led to significant changes in management recommendations from previously published guidelines. These include the use of two malignancy prediction calculators (section ‘Initial assessment of the probability of malignancy in pulmonary nodules’, algorithm 1) to better characterise risk of malignancy. There are recommendations for a higher nodule size threshold for follow-up (≥5 mm or ≥80 mm3) and a reduction of the follow-up period to 1 year for solid pulmonary nodules; both of these will reduce the number of follow-up CT scans (sections ‘Initial assessment of the probability of malignancy in pulmonary nodules’ and ‘Imaging follow-up’, algorithms 1 and 2). Volumetry is recommended as the preferred measurement method and there are recommendations for the management of nodules with extended volume doubling times (section ‘Imaging follow-up’, algorithm 2). Acknowledging the good prognosis of sub-solid nodules (SSNs), there are recommendations for less aggressive options for their management (section ‘Management of SSNs’, algorithm 3). The guidelines provide more clarity in the use of further imaging, with ordinal scale reporting for PET-CT recommended to facilitate incorporation into risk models (section ‘Further imaging in management of pulmonary nodules’) and more clarity about the place of biopsy (section ‘Non-imaging tests and non-surgical biopsy’, algorithm 4). There are recommendations for the threshold for treatment without histological confirmation (sections ‘Surgical excision biopsy’ and ‘Non-surgical treatment without pathological confirmation of malignancy’, algorithm 4). Finally, and possibly most importantly, there are evidence-based recommendations about the information that people …

Guidelines encourage the utilization of best practice based on the latest evidence or expert consensus opinion. If used correctly they can drive changes to service provision that are important for patients and offer a confident, defensible foundation for the clinical health-care professional. Producing good, evidence-based clinical guidelines is an expensive process even when accounting for the fact that the clinical health-care professionals on the development groups do much of the work in their spare time. If a guideline is not subsequently used widely and correctly, the value of the whole exercise has to be questioned. If the uptake of recommendations is slow, they may be out of date by the time they are being used and even inhibit the adoption of more contemporary guidelines; it appears that this may apply to guidelines on the management of pulmonary nodules. A previous evaluation of the use of current pulmonary nodule guidelines found that 44.7% received care inconsistent with recommendations, and the strongest independent predictor of this was inappropriate advice given by the radiologist.1 Other studies have consistently shown poor adherence to pulmonary nodule guidelines.2-4

Patients with stage I non-small cell lung cancer (NSCLC) are potentially cured by surgical resection. Over the last 10 years stereotactic ablative radiotherapy (SABR) has also become widely available as a treatment for some of these patients. The obvious benefits of SABR over surgery are the lack of immediate operative morality risk and post-operative complications, but the concern is that this early advantage may be off-set by tumour recurrence and reduced longer term survival. A prospective evaluation of SABR given between 2004 and 2006 to 59 medically inoperable patients with tumours less than 5cm diameter, showed that primary tumour control was excellent at 97%. Unfortunately a substantial number of cases (22% at 3 years) developed disseminated recurrence; 3.5% had hilar or mediastinal recurrence and the majority developed more distant metastases soon after SABR, suggesting occult disease at the time of treatment (1). A retrospective propensity matched analysis of video-assisted thoracoscopic surgery (VATS) lobectomy vs. SABR in early stage NSCLC (64 patients in each group) supported this finding: loco-regional control was superior in the SABR group although overall survival was not significantly different (2).