Radiologic Features of Nodules Attached to the Mediastinal or Diaphragmatic Pleura at Low-Dose CT for Lung Cancer Screening.

Background Pulmonary noncalcified nodules (NCNs) attached to the fissural or costal pleura with smooth margins and triangular or lentiform, oval, or semicircular (LOS) shapes at low-dose CT are recommended for annual follow-up instead of immediate workup. Purpose To determine whether management of mediastinal or diaphragmatic pleura-attached NCNs (M/DP-NCNs) with the same features as fissural or costal pleura-attached NCNs at low-dose CT can follow the same recommendations. Materials and Methods This retrospective study reviewed chest CT examinations in participants from two databases. Group A included 1451 participants who had lung cancer that was first present as a solid nodule with an average diameter of 3.0-30.0 mm. Group B included 345 consecutive participants from a lung cancer screening program who had at least one solid nodule with a diameter of 3.0-30.0 mm at baseline CT and underwent at least three follow-up CT examinations. Radiologists reviewed CT images to identify solid M/DP-NCNs, defined as nodules 0 mm in distance from the mediastinal or diaphragmatic pleura, and recorded average diameter, margin, and shape. General descriptive statistics were used. Results Among the 1451 participants with lung cancer in group A, 163 participants (median age, 68 years [IQR, 61.5-75.0 years]; 92 male participants) had 164 malignant M/DP-NCNs 3.0-30.0 mm in average diameter. None of the 164 malignant M/DP-NCNs had smooth margins and triangular or LOS shapes (upper limit of 95% CI of proportion, 0.02). Among the 345 consecutive screening participants in group B, 146 participants (median age, 65 years [IQR, 59-71 years]; 81 female participants) had 240 M/DP-NCNs with average diameter 3.0-30.0 mm. None of the M/DP-NCNs with smooth margins and triangular or LOS shapes were malignant after a median follow-up of 57.8 months (IQR, 46.3-68.1 months). Conclusion For solid M/DP-NCNs with smooth margins and triangular or LOS shapes at low-dose CT, the risk of lung cancer is extremely low, which supports the recommendation of Lung Imaging Reporting and Data System version 2022 for annual follow-up instead of immediate workup. © RSNA, 2024 See also the editorial by Goodman and Baruah in this issue.

Bronchiectasis in Low-Dose CT Screening for Lung Cancer.

Background Bronchiectasis is associated with loss of lung function, substantial use of health care resources, and increased morbidity and mortality in people with cardiopulmonary diseases. Purpose To assess the frequency and severity of bronchiectasis and related clinical findings of participants in a low-dose CT (LDCT) screening program. Materials and Methods The Early Lung and Cardiac Action Program (ELCAP) bronchiectasis score (range, 0-42; higher values indicate more severe bronchiectasis) was developed to facilitate bronchiectasis assessment. This quantitative scoring system screened participants based on accumulated knowledge and improved CT imaging capabilities. Secondary review of LDCT studies from smokers aged 40-90 years was performed when they were initially enrolled in the prospective Mount Sinai ELCAP screening study between 2010 and 2019. Medical records were reviewed to identify associated respiratory symptoms and acute respiratory events during the 2 years after LDCT. Logistic regression analysis was performed to examine factors associated with bronchiectasis. Results LDCT studies of 2191 screening participants (mean age, 65 years ± 9; 1140 [52%] women) were obtained, and bronchiectasis was identified in 504 (23%) participants. Median ELCAP bronchiectasis score was 12 (interquartile range, 9-16). Bronchiectasis was most common in the lower lobes for all participants, and lower lobe prevalence was greater with higher ELCAP score (eg, 91% prevalence with an ELCAP score of 16-42). In the fourth quartile, however, midlung involvement was higher compared with lower lung involvement (128 of 131 participants [98%] vs 122 of 131 participants [93%]). Bronchiectasis was more frequent with greater age (odds ratio [OR] = 2.0 per decade; 95% CI: 1.7, 2.4); being a former smoker (OR = 1.33; 95% CI: 1.01, 1.73); and having self-reported chronic obstructive pulmonary disease (OR = 1.38; 95% CI: 1.02, 1.88), an elevated hemidiaphragm (OR = 4; 95% CI: 2, 11), or consolidation (OR = 5; 95% CI: 3, 11). It was less frequent in overweight (OR = 0.7; 95% CI: 0.5, 0.9) or obese (OR = 0.6; 95% CI: 0.4, 0.8) participants. Two years after baseline LDCT, respiratory symptoms, acute respiratory events, and respiratory events that required hospitalization were more frequent with increasing severity of the ELCAP bronchiectasis score (P < .005 for all trends). Conclusion Prevalence of bronchiectasis in smokers undergoing low-dose CT screening was high, and respiratory symptoms and acute events were more frequent with increasing severity of the Early Lung and Cardiac Action Program Bronchiectasis score. © RSNA, 2022 See also the editorial by Verschakelen in this issue.

Race, age at diagnosis and histological characteristics of lung cancer in never-smokers (LCINS) and ever-smokers in low-dose computed tomography (LDCT) screening: a systematic review and meta-analysis.

Background: We previously demonstrated in a meta-analysis there was no difference in risk ratio (RR) of lung cancer detected by low-dose computed tomography (LDCT) screening among female never-smokers (NS) and male ever-smokers (ES) in Asia. LDCT screening significantly decreased lung cancer death among Asian NS compared to Asian ES (RR =0.27, P<0.001). Methods: We investigated if race, age at diagnosis, and histology further differentiate lung cancer diagnosed by LDCT among in NS and ES using the 14 studies from our previous meta-analysis. Results: Twelve publications reported relevant data utilized in this study. From five Asian and one international studies, Asian ES had similar risk of lung cancer diagnosed at baseline screening as Asian NS [RR =0.96; 95% confidence interval (CI): 0.74-1.24] but among non-Asian ES had a 4.56 times significantly higher risk than non-Asian NS (RR =4.56; 95% CI: 2.85-7.28). The baseline incidence of lung cancer in never-smoker (LCINS) was approximately 2.3 times higher among Asian NS than non-Asian NS (0.62% vs. 0.27%, P=0.001). Asian ES had about half the baseline incidence of lung cancer diagnosed as non-Asian ES (0.65% vs. 1.26%). LCINS was diagnosed at 1.98 years younger than ES (95% CI: -3.38 to -0.58) (four studies) and exhibited a higher proportion of adenocarcinoma (ADC) (96.58% vs. 70.37%). Conclusions: Among normal-risk individuals, LCINS had a significantly higher likelihood of being diagnosed among Asians than non-Asians, predominantly manifesting as ADC and diagnosed approximately 2 years younger than ES suggesting that the age limit to initiate lung cancer screening in NS may be set lower compared to LDCT lung cancer screening among ES.

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

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: Among 2182 baseline screening participants, we identified 534 (mean age: 65±9 y; 53.6% women) with follow-up screening of 5+ years (median follow-up: 103.2 mo). 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). CONCLUSIONS: 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.

Current and Future Perspectives on Computed Tomography Screening for Lung Cancer: A Roadmap From 2023 to 2027 From the International Association for the Study of Lung Cancer.

Low-dose computed tomography (LDCT) screening for lung cancer substantially reduces mortality from lung cancer, as revealed in randomized controlled trials and meta-analyses. This review is based on the ninth CT screening symposium of the International Association for the Study of Lung Cancer, which focuses on the major themes pertinent to the successful global implementation of LDCT screening and develops a strategy to further the implementation of lung cancer screening globally. These recommendations provide a 5-year roadmap to advance the implementation of LDCT screening globally, including the following: (1) establish universal screening program quality indicators; (2) establish evidence-based criteria to identify individuals who have never smoked but are at high-risk of developing lung cancer; (3) develop recommendations for incidentally detected lung nodule tracking and management protocols to complement programmatic lung cancer screening; (4) Integrate artificial intelligence and biomarkers to increase the prediction of malignancy in suspicious CT screen-detected lesions; and (5) standardize high-quality performance artificial intelligence protocols that lead to substantial reductions in costs, resource utilization and radiologist reporting time; (6) personalize CT screening intervals on the basis of an individual's lung cancer risk; (7) develop evidence to support clinical management and cost-effectiveness of other identified abnormalities on a lung cancer screening CT; (8) develop publicly accessible, easy-to-use geospatial tools to plan and monitor equitable access to screening services; and (9) establish a global shared education resource for lung cancer screening CT to ensure high-quality reading and reporting.

Low-Dose Computed Tomography (LDCT) Lung Cancer Screening in Asian Female Never-Smokers Is as Efficacious in Detecting Lung Cancer as in Asian Male Ever-Smokers: A Systematic Review and Meta-Analysis.

INTRODUCTION: Lung cancer in never-smokers is the major cancer cause of death globally. We compared the efficacy of low-dose computed tomography (LDCT) lung cancer screening among never-smokers versus ever-smokers using systematic review and meta-analysis. METHODS: LDCT lung cancer screening studies that simultaneously included both ever-smoker and never-smoker participants published by April 30, 2021, were searched through PubMed and Scopus. Primary outcome measure was relative risk (RR) of lung cancer diagnosed among never-smokers versus ever-smokers. RESULTS: A total of 14 studies (13 from Asia) were included (141,396 ever-smokers, 109,251 never-smokers, 1961 lung cancer cases diagnosed). RR of lung cancer diagnosed between ever-smokers versus never-smokers overall was 1.21 (95% confidence interval [CI]: 0.89-1.65), 1.37 (95% CI: 1.08-1.75) among males, and 0.88 (95% CI: 0.59-1.31) among females. RR was 1.78 (95% CI: 1.41-2.24) and 1.22 (95% CI: 0.89-1.68) for Asian female never-smokers versus male never-smokers and versus male ever-smokers, respectively, and 0.99 (95% CI: 0.65-1.50) versus high-risk ever-smokers (≥30 pack-years). Proportional meta-analysis revealed significantly more lung cancers diagnosed at first scan (95.4% [95% CI: 84.9-100.0] versus 70.9% [95% CI: 54.6-84.9], p = 0.010) and at stage 1 (88.5% [95% CI: 79.3-95.4] versus 79.7% [95% CI: 71.1-87.4], p = 0.071) among never-smokers versus ever-smokers, respectively. RR of lung cancer death and 5-year all-cause mortality in never-smokers versus ever-smokers was 0.27 (95% CI: 0.1-0.55, p < 0.001) and 0.13 (95% CI: 0.05-0.33, p < 0.001), respectively. CONCLUSIONS: The RR of lung cancer detected by LDCT screening among female never-smokers and male ever-smokers in Asia was statistically similar. Overall and lung cancer specific mortality from the lung cancer diagnosed from LDCT screening was significantly reduced among never-smokers compared to ever-smokers.

Comparison of lung cancer aggressiveness in patients who never smoked compared to those who smoked.

OBJECTIVES: To determine whether radiographic measures of tumor aggressiveness differ by smoking status. MATERIALS AND METHODS: All patients diagnosed with non-small-cell lung cancer(NSCLC) ≤ 30 mm in maximum diameter, without clinical evidence of metastasis who had both pre-treatment PET scans and two CT scans at least 90 days apart in a prospective cohort, the Initiative for Early Lung Cancer Research on Treatment(IELCART) at Mount Sinai between 2016 and 2020 were identified. Comparison of two measures of tumor aggressiveness, positron emission tomography(PET) SUVmax and tumor volume doubling time(VDT) by smoking status was performed. RESULTS: Of 417 patients identified, 158 patients had pre-treatment PET scans and at least two CT scans available. The two measures of tumor aggressiveness, SUVmax and VDT values were significantly different between patients who had never smoked and those who smoked: patients who never smoked had lower median SUVmax[2.5(IQR: 1.1-4.8) vs. 4.2(IQR:2.1-9.2),p = 0.002] and longer median VDT[(372.6 days vs. 225.6 days,p = 0.001)] compared to those who smoked. Using multivariable analyses, when adjusting for age and sex alone, SUVmax(p = 0.004) and VDT(p = 0.0001) remained significantly different by smoking status. The final multivariable analysis, adjusted for all three co-variates(sex, age and tumor histology) showed no significant difference in SUVmax and VDT by smoking status [SUVmax(p = 0.25) and VDT(p = 0.06)]. CONCLUSION: Smoking history does not influence VDT or PET SUVmax measures of lung cancer aggressiveness.

Opportunistic CT screening of osteoporosis on thoracic and lumbar spine: a meta-analysis.

BACKGROUND: Osteoporotic fractures are a major contributor to late life morbidity and mortality, and impose a substantial societal cost, yet osteoporosis remains substantially underdiagnosed and undertreated. The purpose of this meta-analysis was to assess the pooled diagnostic sensitivity and specificity of computed tomography (CT) images for diagnosing osteoporosis in patients who meet WHO dual X-ray absorptiometry (DXA) osteoporosis criteria using specific Hounsfield unit (HU) values as a threshold. METHODS: Systematic literature searches in PubMed, Embase, Web of Science and Google Scholar were performed from the earliest available date through 1 July 2018, restricted to publications in English. Participants in all studies underwent CT scans that included the lumbar and/or thoracic spine for different indications and HU measurements were used to identify osteoporosis. DXA scans served as the reference standard. RESULTS: Ten eligible studies were identified. The mean area under the hierarchical summary receiver operating characteristic (ROC) curve for diagnosis osteoporosis was 0.84 (95% CI: 0.81, 0.87). The pooled diagnostic sensitivity and specificity of CT images to identify osteoporosis were 0.83 (95% CI: 0.73, 0.90) and 0.74 (95% CI: 0.69, 0.79). The positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio were 3.4 (95% CI: 2.7, 4.5), 0.21 (95% CI: 0.12, 0.36), and 16.4 (95% CI: 7.8, 34.3), respectively. The bias-adjusted sensitivity and specificity of CT were 0.73 and 0.71. Meta-regression demonstrated that country of study, DXA criteria and scanner manufacturer were significant factors associated with the sensitivity of CT in detecting osteoporosis while scanner manufacturer was the only factor associated with specificity of CT. CONCLUSIONS: This meta-analysis showed reasonable pooled sensitivity and specificity for using threshold values measured on CT scans to identify osteoporosis opportunistically.

Recommendations for Implementing Lung Cancer Screening with Low-Dose Computed Tomography in Europe.

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

Landscape on CT screening for lung cancer in Asia.

Lung cancer remains the leading cause of cancer incidence and mortality worldwide. Approximately 60% of the world's new cases of lung cancer and deaths from it are expected in Asia in 2018. Currently, lung cancer screening using low-dose computed tomography (LDCT) is recommended for heavy smokers in North America, Europe and some countries in Asia. Tobacco smoking being the major risk factor for lung cancer, but in Asia, lung cancer in never-smokers (LCINS) is also a concern. This paper reviews on lung cancer incidence, mortality, etiology, smoking in Asia, and systematic reviews on LDCT lung cancer screening studies, including ongoing projects and recommendation on lung cancer screening in Asia. Some of the earliest studies of LDCT lung cancer screening worldwide were in Asia. Many countries in Asia have developed LDCT screening studies in various high-risk participants. Currently, there are several ongoing large-scale lung cancer screening trials to evaluate the efficacy of LDCT screening for never-smokers and light smokers, as well as heavy smokers, and to evaluate the feasibility of population-based LDCT lung cancer screening.

Screening values of carcinoembryonic antigen and cytokeratin 19 fragment for lung cancer in combination with low-dose computed tomography in high-risk populations: Initial and 2-year screening outcomes.

OBJECTIVES: To assess added screening value of Carcinoembryonic Antigen (CEA) and Cytokeratin 19 Fragment (CYFRA 21-1) in combination with LDCT beyond LDCT alone and likelihood ratio of positive (LHR+) of their combination for lung cancer in high-risk populations with indeterminate and positive LDCT after initial screening and 2-year follow up. MATERIALS AND METHODS: LDCT was performed annually at baseline and for 2 years in 634 heavy smokers (>30 pack-years) who were aged 50-70 years, and it was classified as negative, indeterminate, or positive (suspicious for lung cancer). Serum CEA and CYFRA 21-1 were examined and followed with LDCT in the indeterminate and positive LDCT groups and defined as positive with an abnormal level of either CEA or CYFRA 21-1. RESULTS: A total of 17 lung cancer cases were diagnosed (9 from initial screening and 8 from follow-up cycles). Seventy and 22 patients had indeterminate and positive baseline LDCT, respectively. Among indeterminate baseline LDCT, the LHR+ for lung cancer diagnosed after initial screening with a positive marker was 6.61 (p = .039) and 1.51 (p = .502) with a negative marker. After 2 years follow up, the LHR+ was 6.31 (p = .004) and 0.86 (p = .677), respectively. Among positive baseline LDCT, the LHR+ for lung cancer diagnosed after initial round with positive and negative markers was 69.44 (p < 0.001) and 11.57 (p = .015), respectively. The corresponding LHR+ after 2-year round was 13.61 (p = .002) and 18.15 (p = .001), respectively. The combinations of CEA/CYFRA 21-1 and LDCT, and CEA and LDCT had crude and adjusted added value beyond LDCT alone (crude: 8%, p = .033 and 7%, p = .038; adjusted: 4%, p = .019 and 4%, p = .029, respectively). CONCLUSIONS: CEA in combination with LDCT significantly increases the value of lung cancer screening compared with using LDCT alone particularly in participants with indeterminate baseline LDCT in both initial and 2-year screening outcomes.