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.

The role of computer-assisted radiographer reporting in lung cancer screening programmes.

OBJECTIVES: Successful lung cancer screening delivery requires sensitive, timely reporting of low-dose computed tomography (LDCT) scans, placing a demand on radiology resources. Trained non-radiologist readers and computer-assisted detection (CADe) software may offer strategies to optimise the use of radiology resources without loss of sensitivity. This report examines the accuracy of trained reporting radiographers using CADe support to report LDCT scans performed as part of the Lung Screen Uptake Trial (LSUT). METHODS: In this observational cohort study, two radiographers independently read all LDCT performed within LSUT and reported on the presence of clinically significant nodules and common incidental findings (IFs), including recommendations for management. Reports were compared against a 'reference standard' (RS) derived from nodules identified by study radiologists without CADe, plus consensus radiologist review of any additional nodules identified by the radiographers. RESULTS: A total of 716 scans were included, 158 of which had one or more clinically significant pulmonary nodules as per our RS. Radiographer sensitivity against the RS was 68-73.7%, with specificity of 92.1-92.7%. Sensitivity for detection of proven cancers diagnosed from the baseline scan was 83.3-100%. The spectrum of IFs exceeded what could reasonably be covered in radiographer training. CONCLUSION: Our findings highlight the complexity of LDCT reporting requirements, including the limitations of CADe and the breadth of IFs. We are unable to recommend CADe-supported radiographers as a sole reader of LDCT scans, but propose potential avenues for further research including initial triage of abnormal LDCT or reporting of follow-up surveillance scans. KEY POINTS: • Successful roll-out of mass screening programmes for lung cancer depends on timely, accurate CT scan reporting, placing a demand on existing radiology resources. • This observational cohort study examines the accuracy of trained radiographers using computer-assisted detection (CADe) software to report lung cancer screening CT scans, as a potential means of supporting reporting workflows in LCS programmes. • CADe-supported radiographers were less sensitive than radiologists at identifying clinically significant pulmonary nodules, but had a low false-positive rate and good sensitivity for detection of confirmed cancers.

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.

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).

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.

Lung Screen Uptake Trial: results from a single lung cancer screening round.

The Lung Screen Uptake Trial tested a novel invitation strategy to improve uptake and reduce socioeconomic and smoking-related inequalities in lung cancer screening (LCS) participation. It provides one of the first UK-based 'real-world' LCS cohorts. Of 2012 invited, 1058 (52.6%) attended a 'lung health check'. 768/996 (77.1%) in the present analysis underwent a low-dose CT scan. 92 (11.9%) and 33 (4.3%) participants had indeterminate pulmonary nodules requiring 3-month and 12-month surveillance, respectively; 36 lung cancers (4.7%) were diagnosed (median follow-up: 1044 days). 72.2% of lung cancers were stage I/II and 79.4% of non-small cell lung cancer had curative-intent treatment.

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.

Evaluation of cardiovascular risk in a lung cancer screening cohort.

INTRODUCTION: Lung cancer screening (LCS) by low-dose computed tomography (LDCT) offers an opportunity to impact both lung cancer and coronary heart disease mortality through detection of coronary artery calcification (CAC). Here, we explore the value of CAC and cardiovascular disease (CVD) risk assessment in LCS participants in the Lung Screen Uptake Trial (LSUT). METHODS: In this cross-sectional study, current and ex-smokers aged 60-75 were invited to a 'lung health check'. Data collection included a CVD risk assessment enabling estimation of 10 year CVD risk using the QRISK2 score. Participants meeting the required lung cancer risk underwent an ungated, non-contrast LDCT. Descriptive data, bivariate associations and a multivariate analysis of predictors of statin use are presented. RESULTS: Of 1005 individuals enrolled, 680 were included in the final analysis. 421 (61.9%) had CAC present and in 49 (7.2%), this was heavy. 668 (98%) of participants had a QRISK2≥10% and QRISK2 was positively associated with increasing CAC grade (OR 4.29 (CI 0.93 to 19.88) for QRISK2=10%-20% and 12.29 (CI 2.68 to 56.1) for QRISK2≥20% respectively). Of those who qualified for statin primary prevention (QRISK2≥10%), 56.8% did not report a history of statin use. In the multivariate analysis statin use was associated with age, body mass index and history of hypertension and diabetes. CONCLUSIONS: LCS offers an important opportunity for instituting CVD risk assessment in all LCS participants irrespective of the presence of LDCT-detected CAC. Further studies are needed to determine whether CAC could enhance uptake and adherence to primary preventative strategies.

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 Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and 'hard-to-reach' patients.

BACKGROUND: Participation in low-dose CT (LDCT) lung cancer screening offered in the trial context has been poor, especially among smokers from socioeconomically deprived backgrounds; a group for whom the risk-benefit ratio is improved due to their high risk of lung cancer. Attracting high risk participants is essential to the success and equity of any future screening programme. This study will investigate whether the observed low and biased uptake of screening can be improved using a targeted invitation strategy. METHODS/DESIGN: A randomised controlled trial design will be used to test whether targeted invitation materials are effective at improving engagement with an offer of lung cancer screening for high risk candidates. Two thousand patients aged 60-75 and recorded as a smoker within the last five years by their GP, will be identified from primary care records and individually randomised to receive either intervention invitation materials (which take a targeted, stepped and low burden approach to information provision prior to the appointment) or control invitation materials. The primary outcome is uptake of a nurse-led 'lung health check' hospital appointment, during which patients will be offered a spirometry test, an exhaled carbon monoxide (CO) reading, and an LDCT if eligible. Initial data on demographics (i.e. age, sex, ethnicity, deprivation score) and smoking status will be collected in primary care and analysed to explore differences between attenders and non-attenders with respect to invitation group. Those who attend the lung health check will have further data on smoking collected during their appointment (including pack-year history, nicotine dependence and confidence to quit). Secondary outcomes will include willingness to be screened, uptake of LDCT and measures of informed decision-making to ensure the latter is not compromised by either invitation strategy. DISCUSSION: If effective at improving informed uptake of screening and reducing bias in participation, this invitation strategy could be adopted by local screening pilots or a national programme. TRIAL REGISTRATION: This study was registered with the ISRCTN (International Standard Registered Clinical/soCial sTudy Number: ISRCTN21774741) on the 23rd September 2015 and the NIH ClinicalTrials.gov database (NCT0255810) on the 22nd September 2015.

Drug-induced chylothorax as a rare pleural complication in dasatinib therapy for chronic myeloid leukaemia.

Chylothorax is a lymphatic chylous pleural effusion typically associated with traumatic (iatrogenic, non-iatrogenic) and non-traumatic (infections, malignancy, lymphatic disorders) aetiologies. Drug-induced chylothorax is uncommon and mostly reported in association with BCR-ABL tyrosine kinase inhibitor therapy.

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.

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.

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.