Lung cancer screening with low-dose computed tomography (LDCT) has been recommended, based primarily on the results of the NLST (National Lung Screening Trial). The American College of Radiology ...recently released Lung-RADS, a classification system for LDCT lung cancer screening.
To retrospectively apply the Lung-RADS criteria to the NLST.
Secondary analysis of a group from a randomized trial.
33 U.S. screening centers.
Participants were randomly assigned to the LDCT group of the NLST, were aged 55 to 74 years, had at least a 30-pack-year history of smoking, and were current smokers or had quit within the past 15 years.
3 annual LDCT lung cancer screenings.
Lung-RADS classifications for LDCT screenings. Lung-RADS categories 1 to 2 constitute negative screening results, and categories 3 to 4 constitute positive results.
Of 26 722 LDCT group participants, 26 455 received a baseline screening; 48 671 screenings were done after baseline. At baseline, the false-positive result rate (1 minus the specificity rate) for Lung-RADS was 12.8% (95% CI, 12.4% to 13.2%) versus 26.6% (CI, 26.1% to 27.1%) for the NLST; after baseline, the false-positive result rate was 5.3% (CI, 5.1% to 5.5%) for Lung-RADS versus 21.8% (CI, 21.4% to 22.2%) for the NLST. Baseline sensitivity was 84.9% (CI, 80.8% to 89.0%) for Lung-RADS versus 93.5% (CI, 90.7% to 96.3%) for the NLST, and sensitivity after baseline was 78.6% (CI, 74.6% to 82.6%) for Lung-RADS versus 93.8% (CI, 91.4% to 96.1%) for the NLST.
Lung-RADS criteria were applied retrospectively.
Lung-RADS may substantially reduce the false-positive result rate; however, sensitivity is also decreased. The effect of using Lung-RADS criteria in clinical practice must be carefully studied.
National Institutes of Health.
Quantitative analysis of thin-section CT of the chest has a growing role in the clinical evaluation and management of diffuse lung diseases. This heterogeneous group includes diseases with markedly ...different prognoses and treatment options. Quantitative tools can assist in both accurate diagnosis and longitudinal management by improving characterization and quantification of disease and increasing the reproducibility of disease severity assessment. Furthermore, a quantitative index of disease severity may serve as a useful tool or surrogate endpoint in evaluating treatment efficacy. The authors explore the role of quantitative imaging tools in the evaluation and management of diffuse lung diseases. Lung parenchymal features can be classified with threshold, histogram, morphologic, and texture-analysis-based methods. Quantitative CT analysis has been applied in obstructive, infiltrative, and restrictive pulmonary diseases including emphysema, cystic fibrosis, asthma, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, connective tissue-related interstitial lung disease, and combined pulmonary fibrosis and emphysema. Some challenges limiting the development and practical application of current quantitative analysis tools include the quality of training data, lack of standard criteria to validate the accuracy of the results, and lack of real-world assessments of the impact on outcomes. Artifacts such as patient motion or metallic beam hardening, variation in inspiratory effort, differences in image acquisition and reconstruction techniques, or inaccurate preprocessing steps such as segmentation of anatomic structures may lead to inaccurate classification. Despite these challenges, as new techniques emerge, quantitative analysis is developing into a viable tool to supplement the traditional visual assessment of diffuse lung diseases and to provide decision support regarding diagnosis, prognosis, and longitudinal evaluation of disease.
RSNA, 2019.
•The presence of nodules on low-dose CT screening was associated with increased risk of lung cancer up to 12 years later.•Lung cancers diagnosed even more than 4 years after nodule detection tended ...to occur in the same lung lobe as the nodule.•Long-term lung cancer risk differed based on the size and attenuation of nodules.
Non-calcified nodules (NCNs) associated with false positive low-dose CT (LDCT) lung cancer screens have been attributed to various causes. Some, however, may represent lung cancer precursors. An association of NCNs with long-term lung cancer risk would provide indirect evidence of some NCNs being cancer precursors.
LDCT arm participants in the National Lung Screening Trial (NLST) received LDCT screens at baseline and years 1-2. The relationship between NCNs found on LDCT screens and subsequent lung cancer diagnosis over different time periods was examined at the person and lobe level. For the latter, a lobe had a cancer outcome only if the cancer was located in the lobe. Separate analyses were performed on baseline and post-baseline LDCT findings; for the latter, those with baseline NCNs were excluded and only new (non-pre-existing) NCNs examined. Raw and adjusted rate-ratios (RRs) were computed for presence of NCNs and subsequent lung cancer risk; adjusted RRs controlled for demographic and smoking factors.
26,309 participants received the baseline LDCT screen. Over median 11.3 years follow-up, 1675 lung cancers were diagnosed. Adjusted RRs for time periods 0–4, 4–8 and 8−12 years following the baseline screen were 5.1 (95 % CI:4.4–5.9), 1.5 (95 % CI:1.3–1.9) and 1.5 (95 % CI:1.2-1.8) at the person-level and 14.7 (95 % CI:12.6–17.2), 2.6 (95 % CI: 2.0–3.4) and 2.2 (95 % CI:1.6–2.9) at the lobe-level. 18,585 participants were included in the post-baseline analysis. Adjusted RRs for periods 0–4, 4–8 and 8−11 years were 5.6 (95 % CI: 4.5–7.0), 1.9 (95 % CI: 1.3–2.7) and 1.6 (95 % CI: 0.9–2.9) at the person-level and 19.6 (95 % CI:14.9–25.3), 2.5 (95 % CI:1.3–4.7) and 3.3 (95 % CI:1.4–7.6) at the lobe-level. Raw RRs were similar.
NCNs are associated with excess long-term lung cancer risk, suggesting that some may be lung cancer precursors.
There is limited information about survival of stage I lung cancer diagnosed by screening.
What was the survival rate of screen-detected stage I lung cancer in the National Lung Screening Trial ...(NLST), and was it affected by screening method, patient or tumor characteristics, or treatment method?
The study cohort consisted of all NLST participants with screen-detected stage I lung cancer. Lung cancer-specific survival for stage I overall and for IA and IB substages were compared in the low-dose CT and chest radiography (CXR) screening randomization arms and with an analogous cohort from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute; the cumulative incidence competing risk method was used for analysis. Cox proportional hazards models were used to evaluate the association between lung cancer-specific survival and screening arm, patient factors, primary tumor size, and treatment.
There were 324 screen-detected stage I lung cancers in the low-dose CT arm and 125 in the CXR arm. The 10-year survival in the low-dose CT arm was greater than in the CXR arm (73.4% vs 64.6%; P = .05), and both were greater than in the Surveillance, Epidemiology, and End Results cohort (55.6%; P < .001 vs low-dose CT arm, P = .04 vs CXR arm). Proportional hazards models revealed a greater likelihood of survival in the low-dose CT arm (hazard ratio HR, 0.69; 95% CI, 0.5-0.98) and with primary tumor size below the median of 17 mm (HR, 0.61; 95% CI, 0.42-0.88). There was no survival difference between treatment with limited resection vs full resection (HR, 1.11; 95% CI, 0.6-1.9), whereas nonsurgical treatment was associated with a reduced likelihood of survival compared with full resection (HR, 3.1; 95% CI, 1.6-6.0).
Long-term lung cancer-specific survival of stage I lung cancer was greater with low-dose CT imaging than with CXR screening or in the general population, for smaller primary tumor size, and with surgical treatment.
Incidental respiratory disease-related findings are frequently observed on low-dose CT (LDCT) lung cancer screenings. This study analyzed data from the National Lung Screening Trial (NLST) to assess ...the relationship between such findings and respiratory disease mortality (RDM), excluding lung cancer.
Are incidental respiratory findings on LDCT scanning associated with increased RDM?
Subjects in the NLST LDCT arm received three annual screens. Trial radiologists noted findings related to possible lung cancer, as well as respiratory-related incidental findings. Demographic characteristics, smoking history, and medical history were captured in a baseline questionnaire. Kaplan-Meier curves were used to assess cumulative RDM. Multivariate proportional hazards models were used to assess risk factors for RDM; in addition to incidental CT scan findings, variables included respiratory disease history (COPD/emphysema, and asthma), smoking history, and demographic factors (age, race, sex, and BMI).
Of 26,722 subjects in the NLST LDCT arm, 25,002 received the baseline screen and a subsequent LDCT screen. Overall, 59% were male, 26.5% were aged ≥ 65 years at baseline, and 10.6% reported a history of COPD/emphysema. Emphysema on LDCT scanning was reported in 30.7% of subjects at baseline and in 44.2% at any screen. Of those with emphysema on baseline LDCT scanning, 18% reported a history of COPD/emphysema. Median mortality follow-up was 10.3 years. There were 3,639 deaths, and 708 were from respiratory diseases. Among subjects with no history of COPD/emphysema, 10-year cumulative RDM ranged from 3.9% for subjects with emphysema and reticular opacities to 1.1% for those with neither condition; the corresponding range among subjects with a COPD/emphysema history was 17.3% (both) to 3.7% (neither). Emphysema on LDCT imaging was associated with a significantly elevated RDM hazard ratio (2.27; 95% CI, 1.92-2.7) in the multivariate model. Reticular opacities (including honeycombing/fibrosis/scar) also had a significantly elevated hazard ratio (1.39; 95% CI, 1.19-1.62).
Incidental respiratory disease-related findings observed on NLST LDCT screens were frequent and associated with increased mortality from respiratory diseases.
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An analysis of the results of this trial, which compared low-dose CT with chest radiography, showed that CT had a lower positive predictive value for a positive screening result but detected more ...lung cancers at earlier stages.
The National Lung Screening Trial (NLST) was a randomized trial of lung-cancer–specific mortality among participants in an asymptomatic high-risk cohort who underwent screening with the use of low-dose helical computed tomography (CT) as compared with screening with the use of single-view posteroanterior chest radiography. The NLST showed a 20% relative reduction in mortality from lung cancer with three rounds of low-dose CT screening (rounds T0, T1, and T2) as compared with radiography.
1
In this article, we present more detailed findings from the two incidence screenings (rounds T1 and T2), including information on rates of positive screening tests, performance characteristics of . . .
Idiopathic pulmonary fibrosis (IPF) is a progressive inflammatory lung disease without effective molecular markers of disease activity or treatment responses. Monocyte and interstitial macrophages ...that express the C-C motif CCR2 (chemokine receptor 2) are active in IPF and central to fibrosis.
To phenotype patients with IPF for potential targeted therapy, we developed
Cu-DOTA-ECL1i, a radiotracer to noninvasively track CCR2
monocytes and macrophages using positron emission tomography (PET).
CCR2
cells were investigated in mice with bleomycin- or radiation-induced fibrosis and in human subjects with IPF. The CCR2
cell populations were localized relative to fibrotic regions in lung tissue and characterized using immunolocalization, single-cell mass cytometry, and
RNA
hybridization and then correlated with parallel quantitation of lung uptake by
Cu-DOTA-ECL1i PET.
Mouse models established that increased
Cu-DOTA-ECL1i PET uptake in the lung correlates with CCR2
cell infiltration associated with fibrosis (
= 72). As therapeutic models, the inhibition of fibrosis by IL-1β blockade (
= 19) or antifibrotic pirfenidone (
= 18) reduced CCR2
macrophage accumulation and uptake of the radiotracer in mouse lungs. In lung tissues from patients with IPF, CCR2
cells concentrated in perifibrotic regions and correlated with radiotracer localization (
= 21). Human imaging revealed little lung uptake in healthy volunteers (
= 7), whereas subjects with IPF (
= 4) exhibited intensive signals in fibrotic zones.
These findings support a role for imaging CCR2
cells within the fibrogenic niche in IPF to provide a molecular target for personalized therapy and monitoring.Clinical trial registered with www.clinicaltrials.gov (NCT03492762).
The link between mucus plugs and airflow obstruction has not been established in chronic severe asthma, and the role of eosinophils and their products in mucus plug formation is unknown.
In clinical ...studies, we developed and applied a bronchopulmonary segment-based scoring system to quantify mucus plugs on multidetector computed tomography (MDCT) lung scans from 146 subjects with asthma and 22 controls, and analyzed relationships among mucus plug scores, forced expiratory volume in 1 second (FEV1), and airway eosinophils. Additionally, we used airway mucus gel models to explore whether oxidants generated by eosinophil peroxidase (EPO) oxidize cysteine thiol groups to promote mucus plug formation.
Mucus plugs occurred in at least 1 of 20 lung segments in 58% of subjects with asthma and in only 4.5% of controls, and the plugs in subjects with asthma persisted in the same segment for years. A high mucus score (plugs in ≥ 4 segments) occurred in 67% of subjects with asthma with FEV1 of less than 60% of predicted volume, 19% with FEV1 of 60%-80%, and 6% with FEV1 greater than 80% (P < 0.001) and was associated with marked increases in sputum eosinophils and EPO. EPO catalyzed oxidation of thiocyanate and bromide by H2O2 to generate oxidants that crosslink cysteine thiol groups and stiffen thiolated hydrogels.
Mucus plugs are a plausible mechanism of chronic airflow obstruction in severe asthma, and EPO-generated oxidants may mediate mucus plug formation. We propose an approach for quantifying airway mucus plugging using MDCT lung scans and suggest that treating mucus plugs may improve airflow in chronic severe asthma.
Clinicaltrials.gov NCT01718197, NCT01606826, NCT01750411, NCT01761058, NCT01761630, NCT01759186, NCT01716494, and NCT01760915.
NIH grants P01 HL107201, R01 HL080414, U10 HL109146, U10 HL109164, U10 HL109172, U10 HL109086, U10 HL109250, U10 HL109168, U10 HL109257, U10 HL109152, and P01 HL107202 and National Center for Advancing Translational Sciences grants UL1TR0000427, UL1TR000448, and KL2TR000428.
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