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BACKGROUND: Up to 50% of those attending for low-dose computed tomography screening for lung cancer continue to smoke and co-delivery of smoking cessation services alongside screening may maximise clinical benefit. Here we present data from an opt-out co-located smoking cessation service delivered alongside the Yorkshire Lung Screening Trial (YLST). METHODS: Eligible YLST participants were offered an immediate consultation with a smoking cessation practitioner (SCP) at their screening visit with ongoing smoking cessation support over subsequent weeks. RESULTS: Of 2150 eligible participants, 1905 (89%) accepted the offer of an SCP consultation during their initial visit, with 1609 (75%) receiving ongoing smoking cessation support over subsequent weeks. Uptake of ongoing support was not associated with age, ethnicity, deprivation or educational level in multivariable analyses, although men were less likely to engage (adjusted OR (ORadj) 0.71, 95% CI 0.56-0.89). Uptake was higher in those with higher nicotine dependency, motivation to stop smoking and self-efficacy for quitting. Overall, 323 participants self-reported quitting at 4â weeks (15.0% of the eligible population); 266 were validated by exhaled carbon monoxide (12.4%). Multivariable analyses of eligible smokers suggested 4-week quitting was more likely in men (ORadj 1.43, 95% CI 1.11-1.84), those with higher motivation to quit and previous quit attempts, while those with a stronger smoking habit in terms of cigarettes per day were less likely to quit. CONCLUSIONS: There was high uptake for co-located opt-out smoking cessation support across a wide range of participant demographics. Protected funding for integrated smoking cessation services should be considered to maximise programme equity and benefit.
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Abandono do Hábito de Fumar , Tabagismo , Masculino , Humanos , Abandono do Hábito de Fumar/métodos , Serviços de Saúde Comunitária , Pulmão , TomografiaRESUMO
The advent of multi-cancer early detection (MCED) tests has the potential to revolutionise the diagnosis of cancer, improving patient outcomes through early diagnosis and increased use of curative therapies. The ongoing NHS-Galleri trial is evaluating an MCED test developed by GRAIL, and is using as its primary endpoint the absolute incidence of late-stage cancer. Proponents of this outcome argue that if the test reduces the number of patients with advanced, incurable cancer, it can be reasonably assumed to be benefitting patients by reducing cancer mortality. Here, we argue that this assumption may not always hold due to the phenomenon of micro-metastatic disease, and propose an adjustment to the trial outcome so that it may better reflect the expected effect of the test on cancer mortality.
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Segunda Neoplasia Primária , Neoplasias , Humanos , Detecção Precoce de Câncer , Neoplasias/diagnóstico , Neoplasias/terapiaRESUMO
INTRODUCTION: Although lung cancer screening is being implemented in the UK, there is uncertainty about the optimal invitation strategy. Here, we report participation in a community screening programme following a population-based invitation approach, examine factors associated with participation, and compare outcomes with hypothetical targeted invitations. METHODS: Letters were sent to all individuals (age 55-80) registered with a general practice (n=35 practices) in North and East Manchester, inviting ever-smokers to attend a Lung Health Check (LHC). Attendees at higher risk (PLCOm2012NoRace score≥1.5%) were offered two rounds of annual low-dose CT screening. Primary care recorded smoking codes (live and historical) were used to model hypothetical targeted invitation approaches for comparison. RESULTS: Letters were sent to 35 899 individuals, 71% from the most socioeconomically deprived quintile. Estimated response rate in ever-smokers was 49%; a lower response rate was associated with younger age, male sex, and primary care recorded current smoking status (adjOR 0.55 (95% CI 0.52 to 0.58), p<0.001). 83% of eligible respondents attended an LHC (n=8887/10 708). 51% were eligible for screening (n=4540/8887) of whom 98% had a baseline scan (n=4468/4540). Screening adherence was 83% (n=3488/4199) and lung cancer detection 3.2% (n=144) over 2 rounds. Modelled targeted approaches required 32%-48% fewer invitations, identified 94.6%-99.3% individuals eligible for screening, and included 97.1%-98.6% of screen-detected lung cancers. DISCUSSION: Using a population-based invitation strategy, in an area of high socioeconomic deprivation, is effective and may increase screening accessibility. Due to limitations in primary care records, targeted approaches should incorporate historical smoking codes and individuals with absent smoking records.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Fumantes , Fumar/epidemiologia , Programas de Rastreamento , Fatores SocioeconômicosRESUMO
PURPOSE: Screening with low-dose computed tomography reduces lung cancer (LC) mortality. Risk prediction models used for screening selection do not include genetic variables. Here, we investigated the performance of previously published polygenic risk scores (PRSs) for LC, considering their potential to improve screening selection. METHODS: We validated 9 PRSs in a high-risk case-control cohort, comprising genotype data from 652 surgical patients with LC and 550 cancer-free, high-risk (PLCOM2012 score ≥ 1.51%) participants of the Manchester Lung Health Check, a community-based LC screening program (n = 550). Discrimination (area under the curve [AUC]) between cases and controls was assessed for each PRS independently and alongside clinical risk factors. RESULTS: Median age was 67 years, 53% were female, 46% were current smokers, and 76% were National Lung Screening Trial eligible. Median PLCOM2012 score among controls was 3.4%, 80% of cases were early stage. All PRSs significantly improved discrimination, AUC increased between +0.002 (P = .02) and +0.015 (P < .0001), compared with clinical risk factors alone. The best-performing PRS had an independent AUC of 0.59. Two novel loci, in the DAPK1 and MAGI2 genes, were significantly associated with LC risk. CONCLUSION: PRSs may improve LC risk prediction and screening selection. Further research, particularly examining clinical utility and cost-effectiveness, is required.
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Neoplasias Pulmonares , Humanos , Feminino , Idoso , Masculino , Medição de Risco/métodos , Fatores de Risco , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Genótipo , Estudos de Casos e ControlesRESUMO
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.
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Neoplasias Hepáticas , Neoplasias do Colo do Útero , Feminino , Humanos , Detecção Precoce de Câncer , Ásia , MamaRESUMO
BACKGROUND: Screening with low-dose computed tomography (LDCT) reduces lung cancer mortality; however, the most effective strategy for optimising participation is unknown. Here we present data from the Yorkshire Lung Screening Trial, including response to invitation, screening eligibility and uptake of community-based LDCT screening. METHODS: Individuals aged 55-80â years, identified from primary care records as having ever smoked, were randomised prior to consent to invitation to telephone lung cancer risk assessment or usual care. The invitation strategy included general practitioner endorsement, pre-invitation and two reminder invitations. After telephone triage, those at higher risk were invited to a Lung Health Check (LHC) with immediate access to a mobile CT scanner. RESULTS: Of 44 943 individuals invited, 50.8% (n=22 815) responded and underwent telephone-based risk assessment (16.7% and 7.3% following first and second reminders, respectively). A lower response rate was associated with current smoking status (adjusted OR 0.44, 95% CI 0.42-0.46) and socioeconomic deprivation (adjusted OR 0.58, 95% CI 0.54-0.62 for the most versus the least deprived quintile). Of those responding, 34.4% (n=7853) were potentially eligible for screening and offered a LHC, of whom 86.8% (n=6819) attended. Lower uptake was associated with current smoking status (adjusted OR 0.73, 95% CI 0.62-0.87) and socioeconomic deprivation (adjusted OR 0.78, 95% CI 0.62-0.98). In total, 6650 individuals had a baseline LDCT scan, representing 99.7% of eligible LHC attendees. CONCLUSIONS: Telephone risk assessment followed by a community-based LHC is an effective strategy for lung cancer screening implementation. However, lower participation associated with current smoking status and socioeconomic deprivation underlines the importance of research to ensure equitable access to screening.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Programas de Rastreamento , PulmãoRESUMO
Lung cancer (LC) is the most common global cancer. An individual's risk of developing LC is mediated by an array of factors, including family history of the disease. Considerable research into genetic risk factors for LC has taken place in recent years, with both low-penetrance and high-penetrance variants implicated in increasing or decreasing a person's risk of the disease. LC is the leading cause of cancer death worldwide; poor survival is driven by late onset of non-specific symptoms, resulting in late-stage diagnoses. Evidence for the efficacy of screening in detecting cancer earlier, thereby reducing lung-cancer specific mortality, is now well established. To ensure the cost-effectiveness of a screening programme and to limit the potential harms to participants, a risk threshold for screening eligibility is required. Risk prediction models (RPMs), which provide an individual's personal risk of LC over a particular period based on a large number of risk factors, may improve the selection of high-risk individuals for LC screening when compared with generalised eligibility criteria that only consider smoking history and age. No currently used RPM integrates genetic risk factors into its calculation of risk. This review provides an overview of the evidence for LC screening, screening related harms and the use of RPMs in screening cohort selection. It gives a synopsis of the known genetic risk factors for lung cancer and discusses the evidence for including them in RPMs, focusing in particular on the use of polygenic risk scores to increase the accuracy of targeted lung cancer screening.
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Detecção Precoce de Câncer , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Pulmão/diagnóstico por imagem , Análise Custo-Benefício/economia , Feminino , Mutação em Linhagem Germinativa/genética , Humanos , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/patologia , Masculino , Programas de Rastreamento , Polimorfismo de Nucleotídeo Único/genética , Medição de Risco , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: There is limited research exploring how smoking cessation treatment should be implemented into lung cancer screening in the United Kingdom. This study aimed to understand attitudes and preferences regarding the integration of smoking cessation support within lung cancer screening from the perspective of those eligible. METHODS: Thirty-one lung cancer screening eligible individuals aged 55-80 years with current or former smoking histories were recruited using community outreach and social media. Two focus groups (three participants each) and 25 individual telephone interviews were conducted. Data were analysed using the framework approach to thematic analysis. RESULTS: Three themes were generated: (1) bringing lung cancer closer to home, where screening was viewed as providing an opportunity to motivate smoking cessation, depending on perceived personal risk and screening result; (2) a sensitive approach to cessation with the uptake of cessation support considered to be largely dependent on screening practitioners' communication style and expectations of stigma and (3) creating an equitable service that focuses on ease of access as a key determinant of uptake, where integrating cessation within the screening appointment may sustain increased quit motivation and prevent loss to follow-up. CONCLUSIONS: The integration of smoking cessation into lung cancer screening was viewed positively by those eligible to attend. Screening appointments providing personalized lung health information may increase cessation motivation. Services should proactively support participants with possible fatalistic views regarding risk and decreased cessation motivation upon receiving a good screening result. To increase engagement in cessation, services need to be person-centred. PATIENT OR PUBLIC CONTRIBUTION: This study has included patient and public involvement throughout, including input regarding study design, research materials, recruitment strategies and research summaries.
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Atitude Frente a Saúde , Detecção Precoce de Câncer , Neoplasias Pulmonares , Abandono do Hábito de Fumar , Idoso , Idoso de 80 Anos ou mais , Atitude , Detecção Precoce de Câncer/psicologia , Grupos Focais , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/psicologia , Pessoa de Meia-Idade , Motivação , Pesquisa Qualitativa , Abandono do Hábito de Fumar/psicologia , Reino UnidoRESUMO
BACKGROUND: Optimising smoking cessation services within a low radiation-dose computed tomography (LDCT) lung cancer screening programme has the potential to improve cost-effectiveness and overall efficacy of the programme. However, evidence on the optimal design and integration of cessation services is limited. We co-developed a personalised cessation and relapse prevention intervention incorporating medical imaging collected during lung cancer screening. The intervention is designed to initiate and support quit attempts among smokers attending screening as part of the Yorkshire Enhanced Stop Smoking study (YESS: ISRCTN63825779). Patients and public were involved in the development of an intervention designed to meet the needs of the target population. METHODS: An iterative co-development approach was used. Eight members of the public with a history of smoking completed an online survey to inform the visual presentation of risk information in subsequent focus groups for acceptability testing. Three focus groups (n = 13) were conducted in deprived areas of Yorkshire and South Wales with members of the public who were current smokers or recent quitters (within the last year). Exemplar images of the heart and lungs acquired by LDCT, absolute and relative lung cancer risk, and lung age were shown. Data were analysed thematically, and discussed in stakeholder workshops. Draft versions of the intervention were developed, underpinned by the Extended Parallel Processing Model to increase self-efficacy and response-efficacy. The intervention was further refined in a second stakeholder workshop with a patient panel. RESULTS: Individual LDCT scan images of the lungs and heart, in conjunction with artistic impressions to facilitate interpretation, were considered by public participants to be most impactful in prompting cessation. Public participants thought it important to have a trained practitioner guiding them through the intervention and emphasising the short-term benefits of quitting. Presentation of absolute and relative risk of lung cancer and lung age were considered highly demotivating due to reinforcement of fatalistic beliefs. CONCLUSION: An acceptable personalised intervention booklet utilising LDCT scan images has been developed for delivery by a trained smoking cessation practitioner. Our findings highlight the benefit of co-development during intervention development and the need for further evaluation of effectiveness.
Supporting patients to stop smoking when they attend lung cancer screening will improve the overall benefit and value for money of the service. This study developed a booklet containing pictures of a person's own lungs and heart taken during a lung cancer screening scan. The booklet shows areas of damage to the heart and lungs caused by smoking, delivered alongside positive messages to build confidence to stop smoking and let patients know about the benefits of stopping smoking. To develop the booklet, we worked with members of public who currently or used to smoke. Eight members of public completed a survey asking about the best ways to present information about risk. Thirteen members of the public took part in focus groups to co-develop the booklet. One workshop with academic and healthcare professionals and one workshop with a public involvement panel were held to develop and finalise the booklet. Members of the public said they wanted information about the short-term benefits of quitting smoking, and that coloured drawings next to the scan picture would help them to understand what the scan picture meant. Having someone specially trained to guide them through the booklet was considered important. Being told about their risk for lung cancer in the future was off-putting and might discourage a quit attempt. We have co-developed a booklet to support people to quit smoking when they go for lung cancer screening. The booklet is currently being tested to see whether it can support people to quit smoking.
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Neoplasias Pulmonares , Abandono do Hábito de Fumar , Humanos , Abandono do Hábito de Fumar/métodos , Detecção Precoce de Câncer , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/prevenção & controle , Fumantes , Fumar/efeitos adversos , Fumar/terapiaRESUMO
BACKGROUND: The National Health Service England (NHS) classifies individuals as eligible for lung cancer screening using two risk prediction models, PLCOm2012 and Liverpool Lung Project-v2 (LLPv2). However, no study has compared the performance of lung cancer risk models in the UK. METHODS: We analysed current and former smokers aged 40-80 years in the UK Biobank (N = 217,199), EPIC-UK (N = 30,813), and Generations Study (N = 25,777). We quantified model calibration (ratio of expected to observed cases, E/O) and discrimination (AUC). RESULTS: Risk discrimination in UK Biobank was best for the Lung Cancer Death Risk Assessment Tool (LCDRAT, AUC = 0.82, 95% CI = 0.81-0.84), followed by the LCRAT (AUC = 0.81, 95% CI = 0.79-0.82) and the Bach model (AUC = 0.80, 95% CI = 0.79-0.81). Results were similar in EPIC-UK and the Generations Study. All models overestimated risk in all cohorts, with E/O in UK Biobank ranging from 1.20 for LLPv3 (95% CI = 1.14-1.27) to 2.16 for LLPv2 (95% CI = 2.05-2.28). Overestimation increased with area-level socioeconomic status. In the combined cohorts, USPSTF 2013 criteria classified 50.7% of future cases as screening eligible. The LCDRAT and LCRAT identified 60.9%, followed by PLCOm2012 (58.3%), Bach (58.0%), LLPv3 (56.6%), and LLPv2 (53.7%). CONCLUSION: In UK cohorts, the ability of risk prediction models to classify future lung cancer cases as eligible for screening was best for LCDRAT/LCRAT, very good for PLCOm2012, and lowest for LLPv2. Our results highlight the importance of validating prediction tools in specific countries.
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Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Seleção de Pacientes , Adulto , Idoso , Calibragem , Estudos de Coortes , Detecção Precoce de Câncer/normas , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Classe Social , Medicina Estatal , Reino Unido/epidemiologiaRESUMO
INTRODUCTION: Low-dose CT (LDCT) screening of high-risk smokers reduces lung cancer (LC) specific mortality. Determining screening eligibility using individualised risk may improve screening effectiveness and reduce harm. Here, we compare the performance of two risk prediction models (PLCOM2012 and Liverpool Lung Project model (LLPv2)) and National Lung Screening Trial (NLST) eligibility criteria in a community-based screening programme. METHODS: Ever-smokers aged 55-74, from deprived areas of Manchester, were invited to a Lung Health Check (LHC). Individuals at higher risk (PLCOM2012 score ≥1.51%) were offered annual LDCT screening over two rounds. LLPv2 score was calculated but not used for screening selection; ≥2.5% and ≥5% thresholds were used for analysis. RESULTS: PLCOM2012 ≥1.51% selected 56% (n=1429) of LHC attendees for screening. LLPv2 ≥2.5% also selected 56% (n=1430) whereas NLST (47%, n=1188) and LLPv2 ≥5% (33%, n=826) selected fewer. Over two screening rounds 62 individuals were diagnosed with LC; representing 87% (n=62/71) of 6-year incidence predicted by mean PLCOM2012 score (5.0%). 26% (n=16/62) of individuals with LC were not eligible for screening using LLPv2 ≥5%, 18% (n=11/62) with NLST criteria and 7% (n=5/62) with LLPv2 ≥2.5%. NLST eligible Manchester attendees had 2.5 times the LC detection rate than NLST participants after two annual screens (≈4.3% (n=51/1188) vs 1.7% (n=438/26 309); p<0.0001). Adverse measures of health, including airflow obstruction, respiratory symptoms and cardiovascular disease, were positively correlated with LC risk. Coronary artery calcification was predictive of LC (adjOR 2.50, 95% CI 1.11 to 5.64; p=0.028). CONCLUSION: Prospective comparisons of risk prediction tools are required to optimise screening selection in different settings. The PLCOM2012 model may underestimate risk in deprived UK populations; further research focused on model calibration is required.
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Detecção Precoce de Câncer , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Seleção de Pacientes , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Fumar , Tomografia Computadorizada por Raios X , Reino UnidoRESUMO
INTRODUCTION: Targeted low-dose CT lung cancer screening reduces lung cancer mortality. England's Targeted Lung Health Check programme uses risk prediction tools to determine eligibility for biennial screening among people with a smoking history aged 55-74. Some participants initially ineligible for lung cancer screening will later become eligible with increasing age and ongoing tobacco exposure. It is, therefore, important to understand how many people could qualify for reinvitation, and after how long, to inform implementation of services. METHODS: We prospectively predicted future risk (using Prostate, Lung, Colorectal and Ovarian trial's risk model (PLCOm2012) and Liverpool Lung Project version 2 (LLPv2) risk models) and time-to-eligibility of 5345 participants to estimate how many would become eligible through the course of a Lung Health Check screening programme for 55-74 years. RESULTS: Approximately a quarter eventually become eligible, with those with the lowest baseline risks unlikely to ever become eligible. Time-to-eligibility is shorter for participants with higher baseline risk, increasing age and ongoing smoking status. At a PLCOm2012 threshold ≥1.51%, 68% of those who continue to smoke become eligible compared with 18% of those who have quit. DISCUSSION: Predicting which participants may become eligible, and when, during a screening programme can help inform reinvitation strategies and service planning. Those with risk scores closer to the eligibility threshold, particularly people who continue to smoke, will reach eligibility in subsequent rounds while those at the lowest risk may be discharged from the programme from the outset.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Pessoa de Meia-Idade , Masculino , Idoso , Detecção Precoce de Câncer/métodos , Feminino , Tomografia Computadorizada por Raios X , Estudos Prospectivos , Inglaterra/epidemiologia , Fumar/epidemiologia , Fumar/efeitos adversos , Medição de Risco , Definição da Elegibilidade , Programas de Rastreamento/métodos , Fatores de RiscoRESUMO
As a result of an increased focus on early detection including lung cancer screening, combined with more curative treatment options, the 5-year survival rates for lung cancer are improving. Welcome though this is, it brings new, hitherto unseen challenges. As more patients are cured and survive longer, they are at risk of developing second primary cancers, particularly lung cancer. In this review, we examine the challenges that surveillance, diagnosis, and management of second primary lung cancer (SPLC) bring and how these can be addressed. Recent data from prospective follow-up studies suggests that the incidence of SPLC may be higher than previously appreciated, partly due to an increase in multi-focal adenocarcinoma spectrum disease. Over 5 years, up to 1 in 6 long-term lung cancer survivors may develop a SPLC. Although not routinely used in clinical practice at present, genomic approaches for differentiating SPLC from intrapulmonary metastases of the first primary are emerging, and we highlight how this could be used to help differentiate lesions. An accurate distinction between SPLC and the recurrence of the first primary is of paramount importance due to the very different management strategies that may be required. Wrongly classifying an SPLC as a recurrence of the first primary may have significant consequences for patient management and overall survival. Updated approaches to the classification of SPLC combining clinical history, histopathological assessment, and genomic profiling are needed. Finally, we review the potential role of early detection biomarkers in the identification of SPLC, focusing in particular on blood-based biomarkers that are being examined in a multi-center prospective study recruiting lung cancer survivors.
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OBJECTIVES: To evaluate radiation doses for all low-dose CT scans performed during the first year of a lung screening trial. METHODS: For all lung screening scans that were performed using a CT protocol that delivered image quality meeting the RSNA QIBA criteria, radiation dose metrics, participant height, weight, gender, and age were recorded. Values of volume CT dose index (CTDIvol) and dose length product (DLP) were evaluated as a function of weight in order to assess the performance of the scan protocol across the participant cohort. Calculated effective doses were used to establish the additional lifetime attributable cancer risks arising from trial scans. RESULTS: Median values of CTDIvol, DLP, and effective dose (IQR) from the 3521 scans were 1.1 mGy (0.70), 42.4 mGycm (24.9), and 1.15 mSv (0.67), whilst for 60-80kg participants the values were 1.0 mGy (0.30), 35.8 mGycm (11.4), and 0.97 mSv (0.31). A statistically significant correlation between CTDIvol and weight was identified for males (r = 0.9123, P < .001) and females (r = 0.9052, P < .001), however, the effect of gender on CTDIvol was not statistically significant (P = .2328) despite notable differences existing at the extremes of the weight range. The additional lifetime attributable cancer risks from a single scan were in the range 0.001%-0.006%. CONCLUSIONS: Low radiation doses can be achieved across a typical lung screening cohort using scan protocols that have been shown to deliver high levels of image quality. The observed dose levels may be considered as typical values for lung screening scans on similar types of scanners for an equivalent participant cohort. ADVANCES IN KNOWLEDGE: Presentation of typical radiation dose levels for CT lung screening examinations in a large UK trial. Effective radiation doses can be of the order of 1 mSv for standard sized participants. Lifetime attributable cancer risks resulting from a single low-dose CT scan did not exceed 0.006%.
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Neoplasias Pulmonares , Pulmão , Feminino , Humanos , Masculino , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Doses de Radiação , Tórax , Tomografia Computadorizada por Raios X/métodos , Ensaios Clínicos como AssuntoRESUMO
INTRODUCTION: Lung cancer is the most common cause of cancer death globally. In 2022 the UK National Screening Committee recommended the implementation of a national targeted lung cancer screening programme, aiming to improve early diagnosis and survival rates. Research studies and services internationally consistently observe socioeconomic and smoking-related inequalities in screening uptake. Pathway navigation (PN) is a process through which a trained pathway navigator guides people to overcome barriers to accessing healthcare services, including screening. This nested randomised controlled trial aims to determine whether a PN intervention results in more individuals participating in lung cancer screening compared with the usual written invitation within a previous non-responder population as part of the Yorkshire Lung Screening Trial (YLST). METHODS AND ANALYSIS: A two-arm randomised controlled trial and process evaluation nested within the YLST. Participants aged 55-80 (inclusive) who have not responded to previous postal invitations to screening will be randomised by household to receive PN or usual care (a further postal invitation to contact the screening service for a lung health check) between March 2023 and October 2024. The PN intervention includes a postal appointment notification and prearranged telephone appointment, during which a pathway navigator telephones the participant, following a four-step protocol to introduce the offer and conduct an initial risk assessment. If eligible, participants are invited to book a low-dose CT (LDCT) lung cancer screening scan. All pathway navigators receive training from behavioural psychologists on motivational interviewing and communication techniques to elicit barriers to screening attendance and offer solutions. COPRIMARY OUTCOMES: The number undergoing initial telephone assessment of lung cancer risk. The number undergoing an LDCT screening scan.Secondary outcomes include demographic, clinical and risk parameters of people undergoing telephone risk assessment; the number of people eligible for screening following telephone risk assessment; the number of screen-detected cancers diagnosed; costs and a mixed-methods process evaluation.Descriptive analyses will be used to present numbers, proportions and quantitative components of the process evaluation. Primary comparisons of differences between groups will be made using logistic regression. Applied thematic analysis will be used to interpret qualitative data within a conceptual framework based on the COM-B framework. A health economic analysis of the PN intervention will also be conducted. ETHICS AND DISSEMINATION: The study is approved by the Greater Manchester West Research Ethics Committee (18-NW-0012) and the Health Research Authority following the Confidentiality Advisory Group review. Results will be shared through peer-reviewed scientific journals, conference presentations and on the YLST website. TRIAL REGISTRATION NUMBERS: ISRCTN42704678 and NCT03750110.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem , Detecção Precoce de Câncer/métodos , Idoso , Pessoa de Meia-Idade , Masculino , Feminino , Navegação de Pacientes , Idoso de 80 Anos ou mais , Ensaios Clínicos Controlados Aleatórios como Assunto , Reino Unido , Programas de Rastreamento/métodos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Acessibilidade aos Serviços de SaúdeRESUMO
OBJECTIVES: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal malignancies to community-based CT screening for lung cancer within the Yorkshire Lung Screening Trial (YLST). This study explored the acceptability of the combined screening approach to participants and healthcare professionals (HCPs) involved in the trial. METHODS: We conducted semi-structured interviews with eight HCPs and 25 participants returning for the second round of scanning within YLST, 20 who had taken up the offer of the additional abdominal CT scan and five who had declined. Transcripts were analysed using thematic analysis, guided by the Theoretical Framework of Acceptability. RESULTS: Overall, combining the offer of a non-contrast abdominal CT scan alongside the low-dose thoracic CT was considered acceptable to participants, including those who had declined the abdominal scan. The offer of the additional scan made sense and fitted well within the process, and participants could see benefits in terms of efficiency, cost and convenience both for themselves as individuals and also more widely for the NHS. Almost all participants made an instant decision at the point of initial invitation based more on trust and emotions than the information provided. Despite this, there was a clear desire for more time to decide whether to accept the scan or not. HCPs also raised concerns about the burden on the study team and wider healthcare system arising from additional workload both within the screening process and downstream following findings on the abdominal CT scan. CONCLUSIONS: Adding a non-contrast abdominal CT scan to community-based CT screening for lung cancer is acceptable to both participants and healthcare professionals. Giving potential participants prior notice and having clear pathways for downstream management of findings will be important if it is to be offered more widely.
Assuntos
Detecção Precoce de Câncer , Neoplasias Renais , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Detecção Precoce de Câncer/métodos , Idoso , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico , Pesquisa Qualitativa , Aceitação pelo Paciente de Cuidados de Saúde , Programas de Rastreamento/métodosRESUMO
Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor. Whole-exome sequencing enabled comparison of tumors and PDX models and we provide an adapted mouse reference genome for improved removal of NOD scid gamma (NSG) mouse-derived reads from sequencing data. PDX model establishment caused a genomic bottleneck, with models often representing a single tumor subclone. While distinct tumor subclones were represented in independent models from the same tumor, individual PDX models did not fully recapitulate intratumor heterogeneity. On-going genomic evolution in mice contributed modestly to the genomic distance between tumors and PDX models. Our study highlights the importance of considering primary tumor heterogeneity when using PDX models and emphasizes the benefit of comprehensive tumor sampling.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Heterogeneidade Genética , Neoplasias Pulmonares , Camundongos Endogâmicos NOD , Camundongos SCID , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Animais , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Feminino , Sequenciamento do Exoma , Genômica/métodos , Masculino , Ensaios Antitumorais Modelo de Xenoenxerto , Xenoenxertos , Modelos Animais de Doenças , Idoso , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Patients with non-small cell lung cancer and nodal disease are a heterogeneous group with varied patterns of disease. The aim of this study was to assess long-term outcomes of patients with skip N2 disease in comparison to those with N1 or non-skip N2 disease. MATERIALS AND METHODS: A retrospective review of 445 patients undergoing anatomical lung resection for primary lung cancer between 2012 and 2019 with post-operative histological confirmation of nodal disease was undertaken. Log rank analysis was used to assess differences in estimated median overall survival according to nodal status. Multivariable Cox regression analysis was performed to determine whether skip N2 disease was independently associated with overall survival. RESULTS: Mean patient age was 67.0 years (standard deviation ± 9.2 years) and 48.1% (n = 214) were male. In total, 20.7% (n = 92) of patients had N1 disease, 32.1% (n = 143) had skip N2 disease and 47.2% (n = 210) had non-skip N2 disease. Post-operative upstaging took place in 33.0% (n = 147) of patients. Median follow-up time was 35 months (interquartile range 14-68 months). Skip N2 patients had significantly longer estimated median overall survival in comparison to their non-skip N2 counterparts (47 months vs 28 months, log rank analysis p = 0.029) and non-skip N2 disease remained independently associated with reduced overall survival after multivariable analysis (hazard ratio 1.421, 95% confidence interval 1.060-1.907, p = 0.019). CONCLUSION: Skip N2 disease is a positive prognostic factor for patients with N2 lung cancer, suggesting that lung cancer staging guidelines should consider separating N2 disease into additional subgroups in order to improve prognostic accuracy.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Masculino , Idoso , Feminino , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Metástase Linfática/patologia , Mediastino/patologia , Prognóstico , Linfonodos/cirurgia , Linfonodos/patologia , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
OBJECTIVE: As lung cancer screening is rolled-out, there is a need to develop an effective quality assurance (QA) framework around radiology reporting to ensure optimal implementation. Here, we report a structured QA process for low-dose CT (LDCT) scans performed in the Yorkshire Lung Screening Trial. METHODS: Negative LDCT scans were single read after using computer-aided detection software. The radiology QA process included reviewing 5% of negative scans selected at random, and all cases with a subsequent diagnosis of extrapulmonary cancer or interval lung cancer not detected on the baseline scan. Radiologists were not informed of the reason for review and original radiology reports were scored as either "satisfactory", "satisfactory with learning points", or "unsatisfactory". RESULTS: From 6650 participants undergoing LDCT screening, 208 negative scans were reviewed alongside 11 cases with subsequent extrapulmonary cancer and 10 cases with interval lung cancer. Overall, only three reports were ultimately judged "unsatisfactory", 1% of randomly selected negative scans (n = 2/208) and one interval lung cancer scan (n = 1/10). Four out of a total of five cases judged "satisfactory with learning points" were related to oesophageal abnormalities where the participant was subsequently diagnosed with oesophageal cancer. CONCLUSION: The described process attempts to minimise bias in retrospective review of screening scans, and may represent a framework for future QA of national screening programmes. ADVANCES IN KNOWLEDGE: This study describes a structured QA process for a lung cancer screening programme, involving blinded second-read of LDCT screening scans to ensure fair, constructive audit of clinical performance.