A randomised controlled trial testing acceptance of practitioner-referral versus self-referral to stop smoking services within the Lung Screen Uptake Trial.

BACKGROUND AND AIMS: Optimising smoking cessation (SC) referral strategies within lung cancer screening (LCS) could significantly reduce lung cancer mortality. This study aimed to measure acceptance of referral to SC support by either practitioner-referral or self-referral among participants attending a hospital-based lung health check appointment for LCS as part of the Lung Screen Uptake Trial. DESIGN: Single-blinded two-arm randomised controlled trial. SETTING: England. PARTICIPANTS: Six hundred forty-two individuals ages 60 to 75 years, who self-reported currently smoking or had a carbon monoxide reading over 10 ppm during the lung health check appointment. INTERVENTION AND COMPARATOR: Participants were randomised (1:1) to receive either a contact information card for self-referral to a local stop smoking service (SSS) (self-referral, n = 360) or a SSS referral made on their behalf by the nurse or trial practitioner (practitioner-referral, n = 329). MEASUREMENTS: The primary outcome was acceptance of the practitioner-referral (defined as participants giving permission for their details to be shared with the local SSS) compared with acceptance of the self-referral (defined as participants taking the physical SSS contact information card to refer themselves to the local SSS). FINDINGS: Half (49.8%) accepted the practitioner-made referral to a local SSS, whereas most (88.5%) accepted the self-referral. The odds of accepting the practitioner-referral were statistically significantly lower (adjusted odds ratio = 0.10; 95% confidence interval = 0.06-0.17) than the self- referral. In analyses stratified by group, greater quit confidence, quit attempts and Black ethnicity were associated with increased acceptance within the practitioner-referral group. There were no statistically significant interactions between acceptance by referral group and any of the participants' demographic or smoking characteristics. CONCLUSIONS: Among participants in hospital-based lung cancer screening in England who self-reported smoking or met a carbon monoxide cut-off, both practitioner-referral and self-referral smoking cessation strategies were highly accepted. Although self-referral was more frequently accepted, prior evidence suggests practitioner-referrals increase quit attempts, suggesting practitioner-referrals should be the first-line strategy within lung cancer screening, with self-referral offered as an alternative.

Preferences for Decision Control among a High-Risk Cohort Offered Lung Cancer Screening: A Brief Report of Secondary Analyses from the Lung Screen Uptake Trial (LSUT).

Background. Personal autonomy in lung cancer screening is advocated internationally, but health systems diverge in their approach, mandating either shared decision making (with a health care professional) or individual decision making. Studies of other cancer screening programs have found that individual preferences for the level of involvement in screening decisions vary across different sociodemographic groups and that aligning approaches with individual preferences has the potential to improve uptake. Method. For the first time, we examined preferences for decision control among a cohort of UK-based high-risk lung cancer screening candidates (N = 727). We used descriptive statistics to report the distribution of preferences and chi-square tests to examine associations between decision preferences and sociodemographic variables. Results. Most (69.7%) preferred to be involved in the decision with varying degrees of input from a health care professional. Few (10.2%) wanted to make the decision alone. Preferences were also associated with educational attainment. Conclusion. These findings suggest one-size-fits-all approaches may be inadequate in meeting diverse preferences, particularly those placing sole onus on the individual. Highlights: Preferences for involvement in decision making about lung cancer screening are heterogeneous among high-risk individuals in the United Kingdom and vary by educational attainment.Further work is needed to understand how policy makers might implement hybrid approaches to accommodate individual preferences and optimize lung cancer screening program outcomes.

Acceptability of a standalone written leaflet for the National Health Service for England Targeted Lung Health Check Programme: A concurrent, think-aloud study.

BACKGROUND: Many countries are introducing low-dose computed tomography screening programmes for people at high risk of lung cancer. Effective communication strategies that convey risks and benefits, including unfamiliar concepts and outcome probabilities based on population risk, are critical to achieving informed choice and mitigating inequalities in uptake. METHODS: This study investigated the acceptability of an aspect of NHS England's communication strategy in the form of a leaflet that was used to invite and inform eligible adults about the Targeted Lung Health Check (TLHC) programme. Acceptability was assessed in terms of how individuals engaged with, comprehended and responded to the leaflet. Semi-structured, 'think aloud' interviews were conducted remotely with 40 UK screening-naïve current and former smokers (aged 55-73). The verbatim transcripts were analysed thematically using a coding framework based on the Dual Process Theory of cognition. RESULTS: The leaflet helped participants understand the principles and procedures of screening and fostered cautiously favourable intentions. Three themes captured the main results of the data analysis: (1) Response-participants experienced anxiety about screening results and further investigations, but the involvement of specialist healthcare professionals was reassuring; (2) Engagement-participants were rapidly drawn to information about lung cancer prevalence, and benefits of screening, but deliberated slowly about early diagnosis, risks of screening and less familiar symptoms of lung cancer; (3) Comprehension-participants understood the main principles of the TLHC programme, but some were confused by its rationale and eligibility criteria. Radiation risks, abnormal screening results and numerical probabilities of screening outcomes were hard to understand. CONCLUSION: The TLHC information leaflet appeared to be acceptable to the target population. There is scope to improve aspects of comprehension and engagement in ways that would support informed choice as a distributed process in lung cancer screening. PATIENT OR PUBLIC CONTRIBUTION: The insight and perspectives of patient representatives directly informed and improved the design and conduct of this study.

Development and psychometric testing of the self-regulatory questionnaire for lung cancer screening (SRQ-LCS).

BACKGROUND: Research implicates psychological factors in low uptake of lung cancer screening. We developed and psychometrically tested a standardised measure of these psychological determinants in preparation for a prospective, longitudinal cohort study of screening uptake. METHODS: Leventhal's Common-Sense Model of Self-Regulation of Health and Illness provided the theoretical framework to generate the initial item pool. Items were refined during expert review and cognitive interviews which tested for face validity, redundancy, acceptability and comprehensibility. An online survey piloted the refined pool with 1500 current and former (quit ≤ 15 years) smokers aged 55-80. The response distributions, internal reliability and factor structure determined the final retained constructs. Regression analyses examined these constructs' associations with screening intention, smoking status and demographics. RESULTS: The final measure included seven factor-derived subscales (consequences, personal control, treatment control, illness coherence, emotional representation, behavioural response and appraisal, risk perception) with Cronbach's alphas ranging from 0.59 to 0.91 and four single-item questions (response efficacy for smoking cessation, treatment intention, perceived stigma and lung cancer survival). Most constructs were associated with smoking status and screening intention (p's < .05). CONCLUSIONS: The Self-Regulatory Questionnaire for Lung Cancer Screening (SRQ-LCS) is an acceptable, reliable and valid measure for investigating the psychological determinants of screening uptake.

USPSTF2013 versus PLCOm2012 lung cancer screening eligibility criteria (International Lung Screening Trial): interim analysis of a prospective cohort study.

BACKGROUND: Lung cancer is a major health problem. CT lung screening can reduce lung cancer mortality through early diagnosis by at least 20%. Screening high-risk individuals is most effective. Retrospective analyses suggest that identifying individuals for screening by accurate prediction models is more efficient than using categorical age-smoking criteria, such as the US Preventive Services Task Force (USPSTF) criteria. This study prospectively compared the effectiveness of the USPSTF2013 and PLCOm2012 model eligibility criteria. METHODS: In this prospective cohort study, participants from the International Lung Screening Trial (ILST), aged 55-80 years, who were current or former smokers (ie, had ≥30 pack-years smoking history or ≤15 quit-years since last permanently quitting), and who met USPSTF2013 criteria or a PLCOm2012 risk threshold of at least 1·51% within 6 years of screening, were recruited from nine screening sites in Canada, Australia, Hong Kong, and the UK. After enrolment, patients were assessed with the USPSTF2013 criteria and the PLCOm2012 risk model with a threshold of at least 1·70% at 6 years. Data were collected locally and centralised. Main outcomes were the comparison of lung cancer detection rates and cumulative life expectancies in patients with lung cancer between USPSTF2013 criteria and the PLCOm2012 model. In this Article, we present data from an interim analysis. To estimate the incidence of lung cancers in individuals who were USPSTF2013-negative and had PLCOm2012 of less than 1·51% at 6 years, ever-smokers in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) who met these criteria and their lung cancer incidence were applied to the ILST sample size for the mean follow-up occurring in the ILST. This trial is registered at ClinicalTrials.gov, NCT02871856. Study enrolment is almost complete. FINDINGS: Between June 17, 2015, and Dec 29, 2020, 5819 participants from the International Lung Screening Trial (ILST) were enrolled on the basis of meeting USPSTF2013 criteria or the PLCOm2012 risk threshold of at least 1·51% at 6 years. The same number of individuals was selected for the PLCOm2012 model as for the USPSTF2013 criteria (4540 [78%] of 5819). After a mean follow-up of 2·3 years (SD 1·0), 135 lung cancers occurred in 4540 USPSTF2013-positive participants and 162 in 4540 participants included in the PLCOm2012 of at least 1·70% at 6 years group (cancer sensitivity difference 15·8%, 95% CI 10·7-22·1%; absolute odds ratio 4·00, 95% CI 1·89-9·44; p<0·0001). Compared to USPSTF2013-positive individuals, PLCOm2012-selected participants were older (mean age 65·7 years [SD 5·9] vs 63·3 years [5·7]; p<0·0001), had more comorbidities (median 2 [IQR 1-3] vs 1 [1-2]; p<0·0001), and shorter life expectancy (13·9 years [95% CI 12·8-14·9] vs 14·8 [13·6-16·0] years). Model-based difference in cumulative life expectancies for those diagnosed with lung cancer were higher in those who had PLCOm2012 risk of at least 1·70% at 6 years than individuals who were USPSTF2013-positive (2248·6 years [95% CI 2089·6-2425·9] vs 2000·7 years [1841·2-2160·3]; difference 247·9 years, p=0·015). INTERPRETATION: PLCOm2012 appears to be more efficient than the USPSTF2013 criteria for selecting individuals to enrol into lung cancer screening programmes and should be used for identifying high-risk individuals who benefit from the inclusion in these programmes. FUNDING: Terry Fox Research Institute, The UBC-VGH Hospital Foundation and the BC Cancer Foundation, the Alberta Cancer Foundation, the Australian National Health and Medical Research Council, Cancer Research UK and a consortium of funders, and the Roy Castle Lung Cancer Foundation for the UK Lung Screen Uptake Trial.

Decision Support Tools for Low-Dose CT Lung Cancer Screening: A Scoping Review of Information Content, Format, and Presentation Methods.

Several countries mandate informed or shared decision-making for low-dose CT (LDCT) lung cancer screening, but knowledge is limited about the type of information and presentation techniques used to support decision-making in practice. This review aimed to characterize the content, format, mode, and presentation methods of decision support tools (DSTs) for LDCT lung cancer screening. DSTs reported within peer-reviewed articles (January 2000-April 2021) were identified systematically from PubMed, PsycInfo, EMBASE, and CINAHL Plus. Inclusion criteria revolved around the development or evaluation of a resource or tool intended to support individual or shared decision-making for LDCT lung cancer screening. The data-charting and extraction framework was based on the International Patient Decision Aids Standards instrument and Template for Intervention Description and Reporting. Extracted data were organized within two categories: (1) study characteristics and context, format, and mode of DST use and (2) DST content and presentation methods. This review identified 22 DSTs in paper, video, or electronic formats across 26 articles. Most DSTs (n = 13) focused on knowledge exchange, whereas seven used interactive techniques to support values clarification (eg, Likert scales) and nine DSTs guided deliberation (eg, suggested discussion topics). The DSTs addressed similar topics, but the detail, quantification of probability, and presentation methods varied considerably. None described all the potential screening harms and results. The heterogeneity in DST design may affect the quality of decision-making, particularly for participants with lower literacy and numeracy. Evidence-based consensus guidelines for DST content and presentation methods should be developed collaboratively with screening-eligible adults.

Psychological Targets for Lung Cancer Screening Uptake: A Prospective Longitudinal Cohort Study.

INTRODUCTION: Low uptake of low-dose computed tomography lung cancer screening by high-risk groups compromises its effectiveness and equity as a population-level early detection strategy. Numerous psychological factors are implicated qualitatively or retrospectively, but prospective data are needed to validate their associations with uptake behavior and specify psychological targets for intervention. METHODS: This is a prospective, longitudinal cohort study evaluating psychological correlates of lung cancer screening uptake. Ever-smokers (aged 55-77 y) were invited to a lung health check, at which low-dose computed tomography screening was offered through the SUMMIT Study-a multicenter screening implementation trial. One week after their screening invitation, 44,000 invitees were mailed the self-regulatory questionnaire for lung cancer screening. Regression analyses evaluated the constructs' associations with uptake (telephoning for an appointment) and sociodemographic characteristics. RESULTS: Higher odds of uptake were associated with both positive and negative perceptions. Positive perceptions included lung cancer controllability, benefits of early diagnosis, improved survival when lung cancer is detected early, willingness to be treated, and believing smoking cessation is effective in reducing risk. Negative perceptions included a higher lung cancer risk perception, negative beliefs about the consequences of lung cancer, perceiving lung cancer as stigmatized, and a negative emotional response. Although current smokers held the highest risk perceptions, they also reported negative perceptions that could undermine how they behave in response to their risk. CONCLUSIONS: Interventions to improve uptake should focus on changing perceptions that affect how an individual reacts when they believe their risk of lung cancer is high.

The person behind the nodule: a narrative review of the psychological impact of lung cancer screening.

Lung cancer is the leading cause of cancer mortality globally, responsible for an estimated 1.76 million deaths worldwide in 2018 alone. Screening adults at high risk of lung cancer using low-dose computed tomography (LDCT) significantly reduces lung cancer mortality by finding the disease at an early, treatable stage. Many countries are actively considering whether to implement screening for their high-risk populations in light of the recently published Dutch-Belgian trial 'NELSON'. In deciding whether to implement a national screening programme, policymakers must weigh up the evidence for the relative risks posed to the entire screened population, including the potential psychological burden. This narrative review aimed to critically summarise the evidence for both negative and positive psychological responses experienced throughout the LDCT screening pathway, to describe their magnitude, duration and clinical relevance, and to draw out different aspects of measurement design crucial to their interpretation. A further aim was to discuss the available evidence for individual differences in psychological response, as well as interventions designed to promote psychological well-being. In summary, there was no evidence that the LDCT screening process caused adverse psychological outcomes overall, although those receiving indeterminate and suspicious LDCT results did report clinically raised anxiety and lung cancer-specific distress in the short-term. There was early evidence that demographic factors, smoking status and screening-ineligibility could be associated with individual differences in propensity to experience distress. Qualitative data suggested health beliefs could be modifiable mediators of these individual differences, but their aetiology requires quantitative and prospective research. There was also some evidence of positive psychological responses that could be capitalised on, and of the potential for person-centred communication interventions to achieve this. Further research needs to be embedded in real-world LDCT lung cancer screening services and use condition-specific measures to monitor outcomes and test evidence-based communication interventions in promoting psychological well-being.

Psychological outcomes of low-dose CT lung cancer screening in a multisite demonstration screening pilot: the Lung Screen Uptake Trial (LSUT).

BACKGROUND: Previous studies of psychological burden in low-dose CT (LDCT) lung cancer screening trials may lack generalisability due to participation bias and control arms having elevated distress. METHODS: Current and former smokers (n=787, aged 60-75) within a real-world screening demonstration pilot completed measures of lung cancer worry at three time points (T0: appointment, T1: next day, T2: 3 months) and anxiety and depression at two time points (T0 and T2). A 'screening unaware' community sample (n=383) with the same age and smoking characteristics completed these measures once (T0). Mean scores were compared by sample type and LDCT result. RESULTS: Compared with the community sample (T0), mean scores were higher in the screening sample, and statistically significantly increased in adjusted analyses, for lung cancer worry at T0 and T2 (mean (M): 9.32; 95% CI 8.96 to 9.69 vs M: 11.34; 11.09 to 11.59 and M: 11.88; 11.49 to 12.27), for anxiety at T0 and T2 (M: 3.32; 2.94 to 3.70 vs M: 4.73; 4.42 to 5.04 and M: 5.78; 5.33 to 6.23) and depression at T2 (M: 3.85; 3.44 to 4.27 vs M: 4.15; 3.76 to 4.55). Scores were highest for those with indeterminate (eg, T2 anxiety M: 6.93; 5.65 to 8.21) and incidental findings (primary care follow-up M: 5.34; 4.67 to 6.02) and those ineligible for screening (M: 6.51; 5.25 to 7.77). Being female, younger, not in paid employment, not married/cohabiting with a partner and lower education predicted poorer psychological outcomes at T0, but not T2 after adjusting for baseline scores. Mean scores remained within 'normal' clinical ranges. CONCLUSION: Psychological distress was raised among high-risk individuals undergoing LDCT screening in a real-world setting, but overall differences were unlikely to be clinically meaningful. It will be critical to monitor the psychological impact of services longitudinally across diverse settings, including subgroups vulnerable to clinically elevated distress. TRIAL REGISTRATION: The Lung Screen Uptake Trial was registered prospectively with the International Standard Registered Clinical/soCial sTudy (ISRCTN) (Number: ISRCTN21774741) on 23 September 2015 and the National Institutes of Health ClinicalTrials.gov database (NCT02558101) on 22 September 2015.

Management of Lung Nodules and Lung Cancer Screening During the COVID-19 Pandemic: CHEST Expert Panel Report.

BACKGROUND: The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic. METHODS: An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed. The panel was provided with an overview of current evidence, summarized by recent guidelines related to lung cancer screening and lung nodule evaluation. The panel was convened by video teleconference to discuss and then vote on statements related to 12 common clinical scenarios. A predefined threshold of 70% of panel members voting agree or strongly agree was used to determine if there was a consensus for each statement. Items that may influence decisions were listed as notes to be considered for each scenario. RESULTS: Twelve statements related to baseline and annual lung cancer screening (n = 2), surveillance of a previously detected lung nodule (n = 5), evaluation of intermediate and high-risk lung nodules (n = 4), and management of clinical stage I non-small-cell lung cancer (n = 1) were developed and modified. All 12 statements were confirmed as consensus statements according to the voting results. The consensus statements provide guidance about situations in which it was believed to be appropriate to delay screening, defer surveillance imaging of lung nodules, and minimize nonurgent interventions during the evaluation of lung nodules and stage I non-small-cell lung cancer. CONCLUSIONS: There was consensus that during the COVID-19 pandemic, it is appropriate to defer enrollment in lung cancer screening and modify the evaluation of lung nodules due to the added risks from potential exposure and the need for resource reallocation. There are multiple local, regional, and patient-related factors that should be considered when applying these statements to individual patient care.

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for PD-L1 Testing in Non-small Cell Lung Cancer.

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

Sestrins induce natural killer function in senescent-like CD8+ T cells.

Aging is associated with remodeling of the immune system to enable the maintenance of life-long immunity. In the CD8+ T cell compartment, aging results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27-CD28-CD8+ T cells lost the signaling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic natural killer (NK) receptor NKG2D and the NK adaptor molecule DAP12, which promoted cytotoxicity against cells that expressed NKG2D ligands. Immunoprecipitation and imaging cytometry indicated that the NKG2D-DAP12 complex was associated with sestrin 2. The genetic inhibition of sestrin 2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27-CD28-CD8+ T cells. Therefore, during aging, sestrins induce the reprogramming of non-proliferative senescent-like CD27-CD28-CD8+ T cells to acquire a broad-spectrum, innate-like killing activity.

Management of Lung Nodules and Lung Cancer Screening During the COVID-19 Pandemic: CHEST Expert Panel Report.

BACKGROUND: The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic. METHODS: An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed. The panel was provided with an overview of current evidence, summarized by recent guidelines related to lung cancer screening and lung nodule evaluation. The panel was convened by video teleconference to discuss and then vote on statements related to 12 common clinical scenarios. A predefined threshold of 70% of panel members voting agree or strongly agree was used to determine if there was a consensus for each statement. Items that may influence decisions were listed as notes to be considered for each scenario. RESULTS: Twelve statements related to baseline and annual lung cancer screening (n = 2), surveillance of a previously detected lung nodule (n = 5), evaluation of intermediate and high-risk lung nodules (n = 4), and management of clinical stage I non-small cell lung cancer (n = 1) were developed and modified. All 12 statements were confirmed as consensus statements according to the voting results. The consensus statements provide guidance about situations in which it was believed to be appropriate to delay screening, defer surveillance imaging of lung nodules, and minimize nonurgent interventions during the evaluation of lung nodules and stage I non-small cell lung cancer. CONCLUSIONS: There was consensus that during the COVID-19 pandemic, it is appropriate to defer enrollment in lung cancer screening and modify the evaluation of lung nodules due to the added risks from potential exposure and the need for resource reallocation. There are multiple local, regional, and patient-related factors that should be considered when applying these statements to individual patient care.

Mapping the spectrum of psychological and behavioural responses to low-dose CT lung cancer screening offered within a Lung Health Check.

BACKGROUND: Research on the psychological impact of low-dose computed tomography (LDCT) lung cancer screening has typically been narrow in scope and restricted to the trial setting. OBJECTIVE: To explore the range of psychological and behavioural responses to LDCT screening offered as part of a Lung Heath Check (LHC), including lung cancer risk assessment, spirometry testing, a carbon monoxide reading and smoking cessation advice. METHODS: Semi-structured interviews were carried out with 28 current and former smokers (aged 60-75), who had undergone LDCT screening as part of a LHC appointment and mostly received an incidental or indeterminate result (n = 23). Framework analysis was used to map the spectrum of responses participants had across the LHC appointment and screening pathway, to their LDCT results and to surveillance. RESULTS: Interviewees reported a diverse range of both positive and negative psychological responses, beginning at invitation and spanning the entire LHC appointment (including spirometry) and LDCT screening pathway. Similarly, positive behavioural responses extended beyond smoking cessation to include anticipated implications for other cancer prevention and early detection behaviours, such as symptom presentation. Individual differences in responses appeared to be influenced by smoking status and LDCT result, as well as modifiable factors including perceived risk and health status, social support, competing priorities, fatalism and perceived stigma. CONCLUSIONS: The diverse ways in which participants responded to screening, both psychologically and behaviourally, should direct a broader research agenda to ensure all stages of screening delivery and communication are designed to promote well-being, motivate positive behaviour change and maximize patient benefit.

Management of Lung Nodules and Lung Cancer Screening During the COVID-19 Pandemic: CHEST Expert Panel Report.

Background: The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic. Materials and Methods: An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed. The panel was provided with an overview of current evidence, summarized by recent guidelines related to lung cancer screening and lung nodule evaluation. The panel was convened by video teleconference to discuss and then vote on statements related to 12 common clinical scenarios. A predefined threshold of 70% of panel members voting agree or strongly agree was used to determine if there was a consensus for each statement. Items that may influence decisions were listed as notes to be considered for each scenario. Results: Twelve statements related to baseline and annual lung cancer screening (n = 2), surveillance of a previously detected lung nodule (n = 5), evaluation of intermediate and high-risk lung nodules (n = 4), and management of clinical stage I non-small cell lung cancer (n = 1) were developed and modified. All 12 statements were confirmed as consensus statements according to the voting results. The consensus statements provide guidance about situations in which it was believed to be appropriate to delay screening, defer surveillance imaging of lung nodules, and minimize nonurgent interventions during the evaluation of lung nodules and stage I non-small cell lung cancer. Conclusion: There was consensus that during the COVID-19 pandemic, it is appropriate to defer enrollment in lung cancer screening and modify the evaluation of lung nodules due to the added risks from potential exposure and the need for resource reallocation. There are multiple local, regional, and patient-related factors that should be considered when applying these statements to individual patient care.© 2020 RSNA; The American College of Chest Physicians, published by Elsevier Inc; and The American College of Radiology, published by Elsevier Inc.

Lung Screen Uptake Trial (LSUT): Randomized Controlled Clinical Trial Testing Targeted Invitation Materials.

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

Smokers' interest in a lung cancer screening programme: a national survey in England.

BACKGROUND: Following the recommendation of lung cancer screening in the US, screening committees in several European countries are reviewing the evidence for implementing national programmes. However, inadequate participation from high-risk groups poses a potential barrier to its effectiveness. The present study examined interest in a national lung cancer screening programme and modifiable attitudinal factors that may affect participation by smokers. METHODS: A population-based survey of English adults (n = 1464; aged 50-70 years) investigated screening intentions in different invitation scenarios, beliefs about lung cancer, early detection and treatment, worry about lung cancer risk, and stigma. Data on smoking status and perceived chances of quitting were also collected, but eligibility for lung screening in the event of a national programme was unknown. RESULTS: Intentions to be screened were high in all three invitation scenarios for both current (≥ 89%) and former (≥ 94%) smokers. However, smokers were less likely to agree that early-stage survival is good (43% vs. 53%; OR: 0.64, 0.46-0.88) or be willing to have surgery for an early stage, screen-detected cancer (84% vs. 94%; OR: 0.38, 0.21-0.68), compared with former smokers. Willingness to have surgery was positively associated with screening intentions; with absolute differences of 25% and 29%. Worry about lung cancer risk was also most common among smokers (48%), and one fifth of respondents thought screening smokers was a waste of NHS money. CONCLUSIONS: A national lung cancer screening programme would be well-received in principle. To improve smokers' participation, care should be taken to communicate the survival benefits of early-stage diagnosis, address concerns about surgery, and minimise anxiety and stigma related to lung cancer risk.

The Care and Outcomes of Older Persons with Lung Cancer in England and the United States, 2008-2012.

INTRODUCTION: Although prior research has demonstrated lower lung cancer survival in England than in the United States, more detailed comparisons are needed. We conducted a population-based analysis to compare diagnostic, treatment, and survival patterns. METHODS: Data from cancer registries and administrative databases were linked for older patients with a diagnosis of NSCLC in England and the United States (2008-2012). We compared patient and clinical characteristics, as well as the distribution of age-standardized receipt of treatment by stage. We compared relative survival overall by stage and treatment. Finally, we assessed the degree to which stage distribution and stage-specific survival contributed to survival differences. RESULTS: Among patients age 66 years or older with a diagnosis of NSCLC in England (n = 86,978) and the United States (n = 84,415), the rate of pathological confirmation was 63% in England compared with 85% in the United States (a 22.2% difference [99% confidence interval: 22.8%-21.7%]). The rate of receipt of active treatment was lower in England than in the United States (46% versus 60%, for a difference of 14.0% [99% confidence interval: 13.3%-14.7%]). In England, we identified 98 excess deaths per 1000 patients with pathologically confirmed NSCLC; these additional deaths could be partially mitigated by adjusting stage at diagnosis (reduction to 54 excess deaths) or stage-specific survival (reduction to 36 excess deaths). CONCLUSIONS: Compared with patients with NSCLC in the United States, patients with NSCLC in England are less likely to present with early-stage disease and receive treatment and are more likely to die. Future work should explore whether the intensity of resources directed to diagnostic and therapeutic activity may help mitigate disparities in outcomes.

Loss of functional BAP1 augments sensitivity to TRAIL in cancer cells.

Malignant mesothelioma (MM) is poorly responsive to systemic cytotoxic chemotherapy and invariably fatal. Here we describe a screen of 94 drugs in 15 exome-sequenced MM lines and the discovery of a subset defined by loss of function of the nuclear deubiquitinase BRCA associated protein-1 (BAP1) that demonstrate heightened sensitivity to TRAIL (tumour necrosis factor-related apoptosis-inducing ligand). This association is observed across human early passage MM cultures, mouse xenografts and human tumour explants. We demonstrate that BAP1 deubiquitinase activity and its association with ASXL1 to form the Polycomb repressive deubiquitinase complex (PR-DUB) impacts TRAIL sensitivity implicating transcriptional modulation as an underlying mechanism. Death receptor agonists are well-tolerated anti-cancer agents demonstrating limited therapeutic benefit in trials without a targeting biomarker. We identify BAP1 loss-of-function mutations, which are frequent in MM, as a potential genomic stratification tool for TRAIL sensitivity with immediate and actionable therapeutic implications.