Baseline Low-dose Computed Tomography Research Articles

Lung cancer screening by low-dose CT scan in France: final results of the DEP KP80 study after three rounds

In prior randomised controlled trials, lung cancer screening using low-dose computed tomography (LDCT) has been shown to reduce lung cancer mortality and overall mortality. Despite these results, organised screening in France remains a challenge. This study assessed the feasibility and efficacy of lung cancer screening within a real-life context in a French administrative territory. DEP KP80 was a single-arm prospective study. Participants aged between 55 and 74 years, smokers or former smokers of ≥30 pack-years, were recruited. An annual LDCT scan was scheduled and three rounds were performed. Subjects were selected by general practitioners or pulmonologists, who checked the inclusion criteria and prescribed the CT scan. Between March 2016 and February 2020, 1254 participants were enrolled. Overall, 945 (75.4%) participants underwent baseline LDCT (T0), 376 (42.8%) completed the first round (T1) and 270 (31%) the second (T2) one. Forty-two lung cancers were diagnosed, 30 cancers (71.4%) were stage I or II and 34 cancers (80.9%) were treated surgically. In this study, the overall positive predictive value for a positive screening was 48% (95% CI 37-59) and the negative predictive value 100% (95% CI 100-100). This study demonstrated the feasibility and efficacy of lung cancer screening in a real-life context with most lung cancers diagnosed at an early stage and surgically removed. Our results also highlighted the importance of participation in each round, underlining the fact that optimising organisation is a major goal. Agence Régionale de Santé de Picardie, La Ligue contre le cancer, le Conseil Départemental de la Somme, and AstraZeneca.

Coronary artery calcification detected on low-dose computed tomography in high-risk participants of an Australian lung cancer screening program: A prospective observational study.

Coronary artery calcification (CAC) is a frequent additional finding on lung cancer screening (LCS) low-dose computed tomography (LDCT). Cardiovascular disease (CVD) is a major cause of death in LCS participants. We aimed to describe prevalence of incidental CAC detected on LDCT in LCS participants without prior history of coronary artery disease (CAD), evaluate their CVD risk and describe subsequent investigation and management. Prospective observational nested cohort study including all participants enrolled at a single Australian site of the International Lung Screen Trial. Baseline LDCTs were reviewed for CAC, and subsequent information collected regarding cardiovascular health. 5-year CVD risk was calculated using the AusCVD risk calculator. 55% (226/408) of participants had CAC on LDCT and no prior history of CAD, including 23% with moderate-severe CAC. Mean age of participants with CAC was 65 years, 68% were male. 53% were currently smoking. Majority were high risk (51%) or intermediate risk (32%) of a cardiovascular event in 5 years. 21% of participants were re-stratified to a higher CVD risk group when CAC detected on LCS was incorporated. Only 10% of participants with CAC received lifestyle advice (only 3% currently smoking received smoking cessation advice). 80% of participants at high-risk did not meet guideline recommendations, with 47% of this group remaining without cholesterol lowering therapy. LCS with LDCT offers the potential to identify and communicate CVD risk in this population. This may improve health outcomes for high-risk LCS participants and further personalize management once screening results are known.

Assessing Bronchiectasis Progression in Low-dose Screening for Lung Cancer: Frequency and Predictors.

Bronchiectasis is associated with loss of lung function, substantial use of health care resources, and increased morbidity and mortality in people with cardiopulmonary diseases. We assessed the frequency of progression or new development of bronchiectasis and predictors of progression in participants in low-dose computed tomography (CT) screening programs. We reviewed our prospectively enrolled screening cohort in the Early Lung and Cardiac Action Program cohort of smokers, aged 40 to 90, between 2010 and 2019, and medical records to assess the progression of bronchiectasis after five or more years of follow-up after baseline low-dose CT. Logistic and multivariate-analysis-of-covariance regression analyses were used to examine factors associated with bronchiectasis progression. Among 2182 baseline screening participants, we identified 534 (mean age: 65±9y; 53.6% women) with follow-up screening of 5+ years (median follow-up: 103.2mo). Of the 534 participants, 34 (6.4%) participants had progressed (25/126, 19.8%) or newly developed (9/408, 2.2%) bronchiectasis. Significant predictors of progression (progressed+newly developed) were: age (P=0.03), pack-years of smoking (P=0.004), baseline components of the ELCAP Bronchiectasis Score, including the severity of bronchial dilatation (P=0.01), its extent (P=0.01), bronchial wall thickening (P=0.04), and mucoid impaction (P<0.001). Assuming similar progression rates, ~136 out of 2182 participants are expected to progress on follow-up screening. This study sheds light on bronchiectasis progression and its significant predictors in a low-dose CT screening program. We recommend reporting bronchiectasis as participants who have smoked are at increased risk, and continued assessment over the entire period of participation in the low-dose CT screening program would allow for the identification of possible causes, early warning, and even early treatment.

Opportunistic lung cancer screening with low-dose computed tomography in National Cancer Center of China: The first 14 years' experience.

In China, over 50% of lung cancer cases occur in nonsmokers. Thus, identifying high-risk individuals for targeted lung cancer screening is crucial. Beyond age and smoking, determining other risk factors for lung cancer in the Asian population has become a focal point of research. Using 30,000 participants in the prospectively enrolled cohort at China's National Cancer Center (NCC) over the past 14 years, we categorized participants by risk, with an emphasis on nonsmoking females. Between November 2005 and December 2019, 31,431 individuals voluntarily underwent low-dose computed tomography (LDCT) scans for lung cancer screening at the NCC. We recorded details like smoking history, exposure to hazards, and family history of malignant tumors. Using the 2019 NCCN criteria, participants were categorized into high-, moderate-, and low-risk groups. Additionally, we separated non-high-risk groups into female never smokers (aged over 40) exposed to second-hand smoke (SHS) and others. Any positive results from initial scans were monitored per the I-ELCAP protocol (2006), and suspected malignancies were addressed through collaborative decisions between patients and physicians. We analyzed and compared the detection rates of positive results, confirmed lung cancers, and cancer stages across risk, age, and gender groups. Out of 31,431 participants (55.9% male, 44.1% female), 3695 (11.8%) showed positive baseline LDCT scans with 197 (0.6%; 106 females, 91 males) confirmed as lung cancer cases pathologically. Malignancy rate by age was 0.1% among those aged under 40 years, 0.4% among those aged 40-49 years, 0.8% among those aged 50-59 years, and 1.2% among those aged 60 years and older. From the 25,763 participants (56.9% male, 43.1% female) who completed questionnaires, 1877 (7.3%) were categorized as high risk, 6500 (25.2%) as moderate risk, and 17,386 (67.5%) as low risk. Of the 23,886 in the non-high-risk category, 8041 (33.7%) were females over 40 years old exposed to SHS. The high-risk group showed the highest lung cancer detection rate at 1.4%. However, females exposed to SHS had a notably higher detection rate than the rest of the non-high-risk group (1.1% vs. 0.5%; p < 0.0001). In this cohort, 84.8% of the detected lung cancers were at an early stage. In our study, using LDCT for lung cancer screening proved significant for high-risk individuals. For non-high-risk populations, LDCT screening could be considered for nonsmoking women with exposure to SHS.

Lung Cancer Yield Among Those Undergoing Lung Cancer Screening in Community-based Healthcare Systems

Purpose: Lung cancer screening (LCS) via low-dose computed tomography (LDCT) for those with a high risk of lung cancer based on age and smoking history has been recommended in the United States for almost a decade, but performance of LCS in community-based settings is unclear. We aimed to estimate the proportion of those screened who were diagnosed with lung cancer across five healthcare systems in the United States. Methods: Study participants were LCS-eligible individuals who received care and a baseline LCS LDCT within the five healthcare systems in the Population-based Research to Optimize the Screening Process Lung Consortium (PROSPR-Lung). We collected data on LDCT utilization and results, as well as patient characteristics and smoking history, via electronic health records. LCS LDCT findings were categorized using Lung-RADS [negative (1), benign (2), probably benign (3), or suspicious (4)]. Lung cancer diagnoses occurring within 12 months of a baseline LDCT were ascertained via cancer registry data. Our preliminary analyses, presented here, includes estimates of lung cancer yield, overall, and by Lung-RADS category, among those receiving a baseline LDCT 2014–2018. Data collection through 2021 is underway and final analyses will include data through 2021. Results: There were 8,682 patients with a baseline scan included in analyses. Of these, 47% were female, 52% were ages 65+, and the ethnic and racial distribution was: 4% Hispanic, 2% Hawaiian/Pacific Islander, 4% Asian, 14% Black, and 74% White. There were 142 (1.6%) patients diagnosed with lung cancer within 12-months of their baseline LDCT. Among those with negative LCS LDCT findings, Lung-RADS 1 (n = 1,987) or Lung-RADS 2 (n = 5,232), there were 1 and 8 lung cancer diagnoses, respectively. Among those with positive LCS LDCT findings, Lung-RADS 3 (n = 906), Lung-RADS 4/4A (n = 363), or Lung-RADS 4B/4X (n = 194), 10 (1%), 35 (10%), and 88 (45%) were diagnosed with lung cancer, respectively. Conclusions: The proportion of those diagnosed with lung cancer within 12 months of a baseline LDCT within community settings is similar to clinical trials settings, and use of Lung-RADS categorization in community settings appropriately stratifies patients into those with a low- vs. high-risk of prevalent lung cancer.

The probability of lung cancer in patients with incidentally detected pulmonary nodules detected via low-dose computed tomography screening in China.

10569 Background: Low dose computed tomography (LDCT) screening has been proven to be effective in reducing lung cancer mortality, but the ensuing high false-positive and overdiagnosis rates shackle the effectiveness of lung cancer screening (LCS) in China. Nodule malignancy prediction models may be an applicable solution. Methods: We developed and internally validated the model using data from the ongoing Henan province Cancer Screening Program in Urban China (CanSPUC). From 2013 to 2021, 23031 heavy smokers underwent baseline screening with LDCT; 2553 participants were diagnosed with pulmonary nodules. Detailed questionnaire, physical assessment and follow-up were completed for all participants. We then externally validated the model using the National Lung Screening Trial (NLST) dataset consisting of 10485 lung nodules in 4660 participants. Multivariable Cox proportional risk regression models were used. Data analysis was performed from July 1, 2022, through December 31, 2022. Results: A total of 111 and 1089 lung cancer cases with a median follow-up duration of 3.7 years occurred in the Henan CanSPUC and NLST study, respectively. Age, gender, physical activity, consumption of pickled food, history of silicosis or pneumoconiosis, nodule type, size, calcification, and pleural retraction sign were included into the model. The AUC (95% CI) of the model for 5-year lung cancer risk was 0.857 (0.801, 0.914) and 0.847 (0.829, 0.881) in the training set and validation set, respectively. Compared with Mayo model, VA model, PKU model, and Brock model, the Henan CanSPUC model yield statistically better discriminatory performance (all P values &lt; 0.05). The model calibrated well across the deciles of predicted risk in both the overall population and all subgroups. Conclusions: The model developed and validated in this study may be used to estimate the probability of lung cancer in nodules detected at baseline LDCT, allowing more efficient risk-adapted follow-up in population-based LCS programs.

Fully automated calcium scoring predicts all-cause mortality at 12 years in the MILD lung cancer screening trial.

Coronary artery calcium (CAC) is a known risk factor for cardiovascular (CV) events and mortality but is not yet routinely evaluated in low-dose computed tomography (LDCT)-based lung cancer screening (LCS). The present analysis explored the capacity of a fully automated CAC scoring to predict 12-year mortality in the Multicentric Italian Lung Detection (MILD) LCS trial. The study included 2239 volunteers of the MILD trial who underwent a baseline LDCT from September 2005 to January 2011, with a median follow-up of 190 months. The CAC score was measured by a commercially available fully automated artificial intelligence (AI) software and stratified into five strata: 0, 1-10, 11-100, 101-400, and > 400. Twelve-year all-cause mortality was 8.5% (191/2239) overall, 3.2% with CAC = 0, 4.9% with CAC = 1-10, 8.0% with CAC = 11-100, 11.5% with CAC = 101-400, and 17% with CAC > 400. In Cox proportional hazards regression analysis, CAC > 400 was associated with a higher 12-year all-cause mortality both in a univariate model (hazard ratio, HR, 5.75 [95% confidence interval, CI, 2.08-15.92] compared to CAC = 0) and after adjustment for baseline confounders (HR, 3.80 [95%CI, 1.35-10.74] compared to CAC = 0). All-cause mortality significantly increased with increasing CAC (7% in CAC ≤ 400 vs. 17% in CAC > 400, Log-Rank p-value <0.001). Non-cancer at 12 years mortality was 3% (67/2239) overall, 0.8% with CAC = 0, 1.0% with CAC = 1-10, 2.9% with CAC = 11-100, 3.6% with CAC = 101-400, and 8.2% with CAC > 400 (Grey's test p < 0.001). In Fine and Gray's competing risk model, CAC > 400 predicted 12-year non-cancer mortality in a univariate model (sub-distribution hazard ratio, SHR, 10.62 [95% confidence interval, CI, 1.43-78.98] compared to CAC = 0), but the association was no longer significant after adjustment for baseline confounders. In conclusion, fully automated CAC scoring was effective in predicting all-cause mortality at 12 years in a LCS setting.

Accuracy of baseline low-dose computed tomography lung cancer screening: a systematic review and meta-analysis.

Screening using low-dose computed tomography (LDCT) is a more effective approach and has the potential to detect lung cancer more accurately. We aimed to conduct a meta-analysis to estimate the accuracy of population-based screening studies primarily assessing baseline LDCT screening for lung cancer. MEDLINE, Excerpta Medica Database, and Web of Science were searched for articles published up to April 10, 2022. According to the inclusion and exclusion criteria, the data of true positives, false-positives, false negatives, and true negatives in the screening test were extracted. Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the literature. A bivariate random effects model was used to estimate pooled sensitivity and specificity. The area under the curve (AUC) was calculated by using hierarchical summary receiver-operating characteristics analysis. Heterogeneity between studies was measured using the Higgins I2 statistic, and publication bias was evaluated using a Deeks' funnel plot and linear regression test. A total of 49 studies with 157,762 individuals were identified for the final qualitative synthesis; most of them were from Europe and America (38 studies), ten were from Asia, and one was from Oceania. The recruitment period was 1992 to 2018, and most of the subjects were 40 to 75 years old. The analysis showed that the AUC of lung cancer screening by LDCT was 0.98 (95% CI: 0.96-0.99), and the overall sensitivity and specificity were 0.97 (95% CI: 0.94-0.98) and 0.87 (95% CI: 0.82-0.91), respectively. The funnel plot and test results showed that there was no significant publication bias among the included studies. Baseline LDCT has high sensitivity and specificity as a screening technique for lung cancer. However, long-term follow-up of the whole study population (including those with a negative baseline screening result) should be performed to enhance the accuracy of LDCT screening.

Stratification of Lung Cancer Risk with Thoracic Imaging Phenotypes.

In lung cancer screening, estimation of future lung cancer risk is usually guided by demographics and smoking status. The role of constitutional profiles of human body, a.k.a. body habitus, is increasingly understood to be important, but has not been integrated into risk models. Chest low dose computed tomography (LDCT) is the standard imaging study in lung cancer screening, with the capability to discriminate differences in body composition and organ arrangement in the thorax. We hypothesize that the primary phenotypes identified using lung screening chest LDCT can form a representation of body habitus and add predictive power for lung cancer risk stratification. In this pilot study, we evaluated the feasibility of body habitus image-based phenotyping on a large lung screening LDCT dataset. A thoracic imaging manifold was estimated based on an intensity-based pairwise (dis)similarity metric for pairs of spatial normalized chest LDCT images. We applied the hierarchical clustering method on this manifold to identify the primary phenotypes. Body habitus features of each identified phenotype were evaluated and associated with future lung cancer risk using time-to-event analysis. We evaluated the method on the baseline LDCT scans of 1,200 male subjects sampled from National Lung Screening Trial. Five primary phenotypes were identified, which were associated with highly distinguishable clinical and body habitus features. Time-to-event analysis against future lung cancer incidences showed two of the five identified phenotypes were associated with elevated future lung cancer risks (HR=1.61, 95% CI = [1.08, 2.38], p=0.019; HR=1.67, 95% CI = [0.98, 2.86], p=0.057). These results indicated that it is feasible to capture the body habitus by image-base phenotyping using lung screening LDCT and the learned body habitus representation can potentially add value for future lung cancer risk stratification.

Pulmonary emphysema and coronary artery calcifications at baseline LDCT and long-term mortality in smokers and former smokers of the ITALUNG screening trial

ObjectivesCardiovascular disease (CVD), lung cancer (LC), and respiratory diseases are main causes of death in smokers and former smokers undergoing low-dose computed tomography (LDCT) for LC screening. We assessed whether quantification of pulmonary emphysematous changes at baseline LDCT has a predictive value concerning long-term mortality.MethodsIn this longitudinal study, we assessed pulmonary emphysematous changes with densitometry (volume corrected relative area below − 950 Hounsfield units) and coronary artery calcifications (CAC) with a 0–3 visual scale in baseline LDCT of 524 participants in the ITALUNG trial and analyzed their association with mortality after 13.6 years of follow-up using conventional statistics and a machine learning approach.ResultsPulmonary emphysematous changes were present in 32.3% of subjects and were mild (6% ≤ RA950 ≤ 9%) in 14.9% and moderate-severe (RA950 > 9%) in 17.4%. CAC were present in 67% of subjects (mild in 34.7%, moderate-severe in 32.2%). In the follow-up, 81 (15.4%) subjects died (20 of LC, 28 of other cancers, 15 of CVD, 4 of respiratory disease, and 14 of other conditions). After adjusting for age, sex, smoking history, and CAC, moderate-severe emphysema was significantly associated with overall (OR 2.22; 95CI 1.34–3.70) and CVD (OR 3.66; 95CI 1.21–11.04) mortality. Machine learning showed that RA950 was the best single feature predictive of overall and CVD mortality.ConclusionsModerate-severe pulmonary emphysematous changes are an independent predictor of long-term overall and CVD mortality in subjects participating in LC screening and should be incorporated in the post-test calculation of the individual mortality risk profile.Key Points• Densitometry allows quantification of pulmonary emphysematous changes in low-dose CT examinations for lung cancer screening.• Emphysematous lung density changes are an independent predictor of long-term overall and cardio-vascular disease mortality in smokers and former smokers undergoing screening.• Emphysematous changes quantification should be included in the post-test calculation of the individual mortality risk profile.

Characteristics of Persons Screened for Lung Cancer in the United States : A Cohort Study.

Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was recommended by the U.S. Preventive Services Task Force (USPSTF) in 2013, making approximately 8 million Americans eligible for screening. The demographic characteristics and adherence of persons screened in the United States have not been reported at the population level. To define sociodemographic characteristics and adherence among persons screened and entered into the American College of Radiology's Lung Cancer Screening Registry (LCSR). Cohort study. United States, 2015 to 2019. Persons receiving a baseline LDCT for LCS from 3625 facilities reporting to the LCSR. Age, sex, and smoking status distributions (percentages) were computed among persons who were screened and among respondents in the 2015 National Health Interview Survey (NHIS) who were eligible for screening. The prevalence between the LCSR and the NHIS was compared with prevalence ratios (PRs) and 95% CIs. Adherence to annual screening was defined as having a follow-up test within 11 to 15 months of an initial LDCT. Among 1159092 persons who were screened, 90.8% (n = 1052591) met the USPSTF eligibility criteria. Compared with adults from the NHIS who met the criteria (n = 1257), screening recipients in the LCSR were older (34.7% vs. 44.8% were aged 65 to 74 years; PR, 1.29 [95% CI, 1.20 to 1.39]), more likely to be female (41.8% vs. 48.1%; PR, 1.15 [CI, 1.08 to 1.23]), and more likely to currently smoke (52.3% vs. 61.4%; PR, 1.17 [CI, 1.11 to 1.23]). Only 22.3% had a repeated annual LDCT. If follow-up was extended to 24 months and more than 24 months, 34.3% and 40.3% were adherent, respectively. Underreporting of LCS and missing data may skew demographic characteristics of persons reported to be screened. Underreporting of adherence may result in underestimates of follow-up. Approximately 91% of persons who had LCS met USPSTF eligibility criteria. In addition to continuing to target all eligible adults, men, those who formerly smoked, and younger eligible patients may be less likely to be screened. Adherence to annual follow-up screening was poor, potentially limiting screening effectiveness. None.

906P A pilot study of a lung cancer screening program with low-dose computed tomography in high-risk individuals in Greece

Greece is one of the European countries with the highest prevalence of smoking. Low-dose computed tomography (LDCT) has been proposed as a useful tool for the early detection of lung cancer, with the potential to reduce death rates. Given the fact that Greece has no National Lung Cancer Screening program, the pilot REGISTRY study was designed to assess the effects of baseline screening with LDCT in high-risk individuals. From January 2016 to March 2022, 1500 individuals aged > 45 years with smoking history of at least 15 pack-years, were recruited in the study. Former smokers needed to quit within 15 years from study entry to be eligible. Each participant was advised to undergo annual screening with LDCT for ten years and the evaluation was based on the updated NCCN guidelines. A high rate of adherence to screening (90.1%) was reported. The median age of participants was 63 years and the number of pack years ranged from 15 to 72 (median 30 years). In total, 697 subjects (46,4%) reported at least one comorbidity including hypertension, diabetes mellitus, COPD and/or prior cancer. The rate of positive screening tests was 0,66% (10 of 1500 patients). Eight patients were diagnosed with cancer at baseline LDCT, while the rest within two years from initiation of screening. All ten patients were diagnosed with non-small cell lung cancer (adenocarcinoma=5 and squamous cell carcinoma N=5). All patients underwent surgery. Seven patients were diagnosed with stage I, two with stage II and one with stage III disease. Real-world data from this pilot study in Greece are concordant with large randomized phase III screening trials and confirm the utility of LDCT as a potent strategy for the early detection of lung cancer. A National Lung Cancer screening program should become a priority for Greek health policy makers.

EP01.05-005 The Accuracy of Baseline Low-dose CT Lung Cancer Screening: A Systematic Review and Meta-analysis

Screening using low-dose computed tomography (LDCT) is a more effective approach and has the potential to detect the lung cancer more accurately. We aimed to conduct a meta-analysis to estimate the accuracy from population-based screening studies primarily assessing baseline LDCT screening for lung cancer.

Detection of COPD in the SUMMIT Study lung cancer screening cohort using symptoms and spirometry.

COPD is a major comorbidity in lung cancer screening (LCS) cohorts, with a high prevalence of undiagnosed COPD. Combining symptom assessment with spirometry in this setting may enable earlier diagnosis of clinically significant COPD and facilitate increased understanding of lung cancer risk in COPD. In this study, we wished to understand the prevalence, severity, clinical phenotype and lung cancer risk of individuals with symptomatic undiagnosed COPD in a LCS cohort. 16 010 current or former smokers aged 55-77 years attended a lung health check as part of the SUMMIT Study. A respiratory consultation and spirometry were performed alongside LCS eligibility assessment. Those with symptoms, no previous COPD diagnosis and airflow obstruction were labelled as undiagnosed COPD. Baseline low-dose computed tomography (LDCT) was performed in those at high risk of lung cancer (PLCOm2012 score ≥1.3% and/or meeting USPSTF 2013 criteria). Nearly one in five (19.7%) met criteria for undiagnosed COPD. Compared with those previously diagnosed, those undiagnosed were more likely to be male (59.1% versus 53.2%; p<0.001), currently smoking (54.9% versus 47.6%; p<0.001) and from an ethnic minority group (p<0.001). Undiagnosed COPD was associated with less forced expiratory volume in 1 s impairment (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1 and 2: 85.3% versus 68.4%; p<0.001) and lower symptom/exacerbation burden (GOLD A and B groups: 95.6% versus 77.9%; p<0.001) than those with known COPD. Multivariate analysis demonstrated that airflow obstruction was an independent risk factor for lung cancer risk on baseline LDCT (adjusted OR 2.74, 95% CI 1.73-4.34; p<0.001), with a high risk seen in those with undiagnosed COPD (adjusted OR 2.79, 95% CI 1.67-4.64; p<0.001). Targeted case-finding within LCS detects high rates of undiagnosed symptomatic COPD in those most at risk. Individuals with undiagnosed COPD are at high risk for lung cancer.

Participation in community-based lung cancer screening: the Yorkshire Lung Screening Trial.

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. Individuals aged 55-80 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. 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. 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.

Baseline computed tomography screening and blood microRNA predict lung cancer risk and define adequate intervals in the BioMILD trial

Large randomized trials have demonstrated that lung cancer (LC) screening with low-dose computed tomography (LDCT) reduces LC mortality in heavy smokers. We previously showed in the MILD screening trial that the combination of a prespecified circulating microRNA (miRNA) signature classifier (MSC) and LDCT improves the accuracy of LDCT alone. The primary aim of the prospective BioMILD study was to assess the additional value of the blood MSC assay at the time of baseline LDCT with the goal of personalizing LC screening intervals. The study enrolled 4119 volunteers from January 2013 to March 2016, with a median follow-up of 5.3 years. Baseline LDCT and miRNAs stratified participants into four groups: CT-/MSC- (n= 2664; 64.7%); CT-/MSC+ (n= 800; 19.4%); CT+/MSC- (n= 446; 10.8%); and CT+/MSC+ (n= 209; 5.1%). As per the protocol, those in the CT-/MSC- and CT-/MSC+ groups were allocated to LDCT repeat at 3-year and 1-year intervals; CT+ participants were allocated for 1-year or earlier intervals on the basis of LDCT features independent of MSC results. CT+ participants had a 15.8-fold higher 4-year LC incidence than CT- participants (95% confidence interval 10.34-24.05), and MSC+ participants had a 2.0-fold higher 4-year LC incidence than MSC- participants (95% confidence interval 1.40-2.90); there was no evidence that the MSC effect differed between CT+ and CT- participants. LC incidence at 4 years was 0.8% in CT-/MSC-, 1.1% in CT-/MSC+, 10.8% in CT+/MSC-, and 20.1% in CT+/MSC+ participants. LC mortality rates at 5 years in the four risk groups were 0.5 in CT-/MSC-, 1.5 in CT-/MSC+, 4.2 in CT+/MSC-, and 10.1 in CT+/MSC+. The combined use of LDCT and blood miRNAs at baseline predicts individual LC incidence and mortality, with a major effect of MSC for LDCT-positive individuals. These findings may have important implications in personalizing screening intervals.

Moderate-severe coronary calcification predicts long-term cardiovascular death in CT lung cancer screening: The ITALUNG trial

PurposeCoronary artery calcifications (CAC) are very strong indicators for increased cardio-vascular (CV) risk and can be evaluated also in low-dose computed tomography (LDCT) for lung cancer screening. We assessed whether a simple and fast CAC visual score is associated with CV mortality. MethodsCAC were retrospectively assessed by two observers using a 4-score (absent, mild, moderate and severe) scale in baseline LDCT obtained in 1364 participants to the ITALUNG trial who had 55–69 years of age and a smoking history ≥20 pack–years. Correlations with CV risk factors at baseline and with CV mortality after 11 years of follow-up were investigated. ResultsCAC were absent in 470 (34.5%), mild in 433 (31.7%), moderate in 357 (26.2%) and severe in 104 (7.6%) subjects. CAC severity correlated (≤0.001) with age, male sex, pack-years, history of arterial hypertension or diabetes, obesity and treated hypercholesterolemia. Twenty-one CV deaths occurred. Moderate or severe CAC were significantly associated with higher CV mortality after adjustment for all other known risk factors (ARR = 2.72; 95 %CI:1.04–7.11). Notably, also in subjects with none or one only additional CV risk factor, the presence of moderate-severe CAC allowed to identify a subgroup of subjects with higher CV death risk (RR = 3.66; CI95%:1.06–12.6). ConclusionsModerate or severe CAC visually assessed in LDCT examinations for lung cancer screening are independently associated with CV mortality.

The BUILT study: a single-center 5-year experience of Lung Cancer screening in Taiwan.

Background: There are no uniform guidelines on low-dose computed tomography (LDCT) follow-up in lung cancer screening. Few studies have analyzed the incidental abnormalities and role of tumor markers in lung cancer screening. The purpose of this study was to investigate the diagnostic performance of LDCT, optimal follow-up duration, incidental findings, and role of tumor markers in diagnosing lung cancer.Methods: We retrospectively analyzed subjects who underwent their first LDCT in Taipei Tzu Chi Hospital between September 1, 2015, and August 31, 2016. All chest CT scans until August 31, 2020, were recorded. A non-calcified nodule with a diameter ≥2 mm on LDCT was defined as a positive result. We extracted the data, including possible risk factors of lung cancer and follow-up outcomes.Results: A total of 1502 subjects were recruited. Of the 38 subjects who underwent biopsy, 31 had confirmed lung cancer. Lung cancer in all patients was diagnosed within 4 years. Univariate logistic regression analysis revealed that a family history of lung cancer in first-degree relatives and abnormal serum carcinoembryonic antigen (CEA) levels were the significant risk factors for lung cancer. A cumulative lung cancer incidence of 54.7 patients per 1000 person-years was determined solely via radiological follow-up. In total, 271 (18%) subjects exhibited incidental findings on baseline LDCT.Conclusion: The overall lung cancer detection rate in this study was 2.1% in the 5-year study period. A family history of lung cancer and abnormal serum CEA levels are important risk factors for lung cancer. A minimum of 4-year follow-up is required to track suspicious nodules. A purely radiological follow-up detects a high incidence of lung cancer.

Organized Lung Cancer Screening Pilot: Informing a Province-Wide Program in Ontario, Canada

Lung cancer is the leading cause of cancer deaths in Ontario. The National Lung Screening Trial demonstrated that screening with low-dose computed tomography (LDCT) reduces lung cancer mortality. In June 2017, Ontario Health (Cancer Care Ontario) initiated a pilot for lung cancer screening to inform implementation of a province-wide initiative. The screening pathway includes targeted recruitment strategies, the Tammemägi risk prediction model (PLCOm2012) to determine eligibility, opt-out smoking cessation services for all current smokers, use of the Lung-RADS scoring system to guide abnormal results management, and screening navigators providing end-to-end support. Referral criteria include being 55 years of age to 74 years of age and a current or former daily cigarette smoker for greater than or equal to 20 years, while the screening eligibility criterion is a PLCOm2012 risk greater than or equal to 2% in 6 years. Selected results of the interim pilot evaluation are presented. Four hospitals contributed data in the first year of the pilot. During 2017 to 2018, 4205 Ontarians were recruited, 3234 risk assessments were conducted, and 2151 (66.5%) individuals were eligible for screening. Baseline LDCT scans were performed in 1624 (50.2%) individuals. Diagnostic evaluation in 120 (7.4%) individuals identified 28 (1.7%) with lung cancer, and proportions of stage I to II and stage III to IV were 71% and 29%, respectively. Of those recruited, 1443 (34.3%) individuals were smokers and 1326 (91.9%) accepted smoking cessation services. The pilot is the largest in Canada and aligns with International Agency for Research on Cancer standards for population-based, organized cancer screening. Recruitment of high-risk individuals, high rates of smoking cessation program acceptance, and detection of early-stage cancers are demonstrated.

Prevalence and burden of bronchiectasis in a lung cancer screening program.

The prevalence of bronchiectasis in the general population and in individuals undergoing lung cancer screening with low dose computed tomography (LDCT) is unknown. The aim of this study is to estimate the prevalence and impact of bronchiectasis in a screening lung cancer program. 3028 individuals participating in an international multicenter lung cancer screening consortium (I-ELCAP) were selected from 2000 to 2012. Patients with bronchiectasis on baseline CT were identified and compared to selected controls. Detection of nodules, need for additional studies and incidence of cancer were analyzed over the follow-up period. The prevalence of bronchiectasis was 11.6%(354/3028). On the baseline LDCT, the number of subjects with nodules identified was 189(53.4%) in patients with bronchiectasis compared to 63(17.8%) in controls (p<0.001). The occurrence of false positives was higher in subjects with bronchiectasis (26%vs17%;p = 0.003). During follow-up, new nodules were more common among subjects with bronchiectasis (17%vs.12%; p = 0.008). The total number of false positives during follow-up was 29(17.06%) for patients with bronchiectasis vs. 88(12.17%) for controls (p = 0.008).The incidence rate of lung cancer during follow-up was 6.8/1000 and 5.1/1000 person-years for each group respectively (p = 0.62). Bronchiectasis are common among current and former smokers undergoing lung cancer screening with LDCT. The presence of bronchiectasis is associated with greater incidence of new nodules and false positives on baseline and follow-up screening rounds. This leads to an increase need of diagnostic tests, although the lung cancer occurrence is not different.