Quantitative imaging workshop XIX: Utilizing quantitative thoracic imaging to optimize population health final summary.

Lung cancer screening involves the use of thoracic CT for both detection and measurements of suspicious lung nodules to guide the screening management. Since lung cancer screening eligibility typically requires age over 50 years along with >20 pack-year tobacco exposure, thoracic CT scans also frequently reveal evidence for pulmonary emphysema as well as coronary artery calcification. These three thoracic diseases are collectively three of the leading causes of premature death across the world. Screening for the major thoracic diseases in this heavily tobacco-exposed cohort is broadening the focus of lung cancer screening to a more comprehensive health evaluation including discussing the relevance of screen-detected findings of the heart and lung parenchyma. The status and implications of these emerging issues were reviewed in a multidisciplinary workshop focused on the process of quantitative imaging in the lung cancer screening setting to guide the evolution of this important new area of public health.

CT Predictors of Visceral Pleural Invasion in Patients with Non-Small Cell Lung Cancers 30 mm or Smaller.

Background CT-defined visceral pleural invasion (VPI) is an important indicator of prognosis for non-small cell lung cancer (NSCLC). However, there is a lack of studies focused on small subpleural NSCLCs (≤30 mm). Purpose To identify CT features predictive of VPI in patients with subpleural NSCLCs 30 mm or smaller. Materials and Methods This study is a retrospective review of patients enrolled in the Initiative for Early Lung Cancer Research on Treatment (IELCART) at Mount Sinai Hospital between July 2014 and February 2023. Subpleural nodules 30 mm or smaller were classified into two groups: a pleural-attached group and a pleural-tag group. Preoperative CT features suggestive of VPI were evaluated for each group separately. Multivariable logistic regression analysis adjusted for sex, age, nodule size, and smoking status was used to determine predictive factors for VPI. Model performance was analyzed with the area under the receiver operating characteristic curve (AUC), and models were compared using Akaike information criterion (AIC). Results Of 379 patients with NSCLC with subpleural nodules, 37 had subsolid nodules and 342 had solid nodules. Eighty-eight patients (22%) had documented VPI, all in solid nodules. Of the 342 solid nodules (46% in male patients, 54% in female patients; median age, 71 years; IQR: 66, 76), 226 were pleural-attached nodules and 116 were pleural-tag nodules. VPI was more frequent for pleural-attached nodules than for pleural-tag nodules (31% [69 of 226] vs 16% [19 of 116], P = .005). For pleural-attached nodules, jellyfish sign (odds ratio [OR], 21.60; P < .001), pleural thickening (OR, 6.57; P < .001), and contact surface area (OR, 1.05; P = .01) independently predicted VPI. The jellyfish sign led to a better VPI prediction (AUC, 0.84; 95% CI: 0.78, 0.90). For pleural-tag nodules, multiple tags to different pleura surfaces enabled independent prediction of VPI (OR, 9.30; P = .001). Conclusions For patients with solid NSCLC (≤30 mm), CT predictors of VPI were the jellyfish sign, pleural thickening, contact surface area (pleural-attached nodules), and multiple tags to different pleura surfaces (pleural-tag nodules). © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Nishino in this issue.

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.

A 20-year Follow-up of the International Early Lung Cancer Action Program (I-ELCAP).

Background The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer Action Program (ELCAP) participants in 1999 led to the International ELCAP (I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the 10-year lung cancer-specific survival of 80% for 484 participants diagnosed with a first primary lung cancer through annual screening, with a high frequency of clinical stage I lung cancer (85%). Purpose To update the cure rate by determining the 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening in the expanded I-ELCAP cohort. Materials and Methods For participants enrolled in the HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed until December 30, 2022, Kaplan-Meier survival analysis was used to determine the 10- and 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening. Eligible participants were aged at least 40 years and had current or former cigarette use or had never smoked but had been exposed to secondhand tobacco smoke. Results Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61-72), with a median smoking history of 43.0 pack-years (IQR, 29.0-60.0). Median follow-up duration was 105 months (IQR, 41-182). The frequency of clinical stage I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer-specific survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung cancer-specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91, 98) for 181 participants with pathologic T1aN0M0 lung cancer. Conclusion The 10-year lung cancer-specific survival of 80% reported in 2006 for I-ELCAP participants enrolled in annual low-dose CT screening and diagnosed with a first primary lung cancer has persisted, as shown by the updated 20-year lung cancer-specific survival for the expanded I-ELCAP cohort. © RSNA, 2023 See also the editorials by Grenier and by Sequist and Olazagasti in this issue.

The presence of circulating genetically abnormal cells in blood predicts risk of lung cancer in individuals with indeterminate pulmonary nodules.

PURPOSE: Computed tomography is the standard method by which pulmonary nodules are detected. Greater than 40% of pulmonary biopsies are not lung cancer and therefore not necessary, suggesting that improved diagnostic tools are needed. The LungLB™ blood test was developed to aid the clinical assessment of indeterminate nodules suspicious for lung cancer. LungLB™ identifies circulating genetically abnormal cells (CGACs) that are present early in lung cancer pathogenesis. METHODS: LungLB™ is a 4-color fluorescence in-situ hybridization assay for detecting CGACs from peripheral blood. A prospective correlational study was performed on 151 participants scheduled for a pulmonary nodule biopsy. Mann-Whitney, Fisher's Exact and Chi-Square tests were used to assess participant demographics and correlation of LungLB™ with biopsy results, and sensitivity and specificity were also evaluated. RESULTS: Participants from Mount Sinai Hospital (n = 83) and MD Anderson (n = 68), scheduled for a pulmonary biopsy were enrolled to have a LungLB™ test. Additional clinical variables including smoking history, previous cancer, lesion size, and nodule appearance were also collected. LungLB™ achieved 77% sensitivity and 72% specificity with an AUC of 0.78 for predicting lung cancer in the associated needle biopsy. Multivariate analysis found that clinical and radiological factors commonly used in malignancy prediction models did not impact the test performance. High test performance was observed across all participant characteristics, including clinical categories where other tests perform poorly (Mayo Clinic Model, AUC = 0.52). CONCLUSION: Early clinical performance of the LungLB™ test supports a role in the discrimination of benign from malignant pulmonary nodules. Extended studies are underway.

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.

Measuring the margin distance in pulmonary wedge resection.

BACKGROUND: Margin distance contributes to survival and recurrence during wedge resections for early-stage non-small cell lung cancer. The Initiative for Early Lung Cancer Research on Treatment sought to standardize a surgeon-measured margin intraoperatively. METHODS: Lung cancer patients who underwent wedge resection were reviewed. Margins were measured by the surgeon twice as per a standardized protocol. Intraobserver variability as well as surgeon-pathologist variability were compared. RESULTS: Forty-five patients underwent wedge resection. Same-surgeon measurement analysis indicated good reliability with a small mean difference and narrow limit of agreement for the two measures. The median surgeon-measured margin was 18.0 mm, median pathologist-measured margin was 16.0 mm and the median difference between the surgeon-pathologist margin was -1.0 mm, ranging from -18.0 to 12.0 mm. Bland-Altman analysis for margin measurements demonstrated a mean difference of 0.65 mm. The limit of agreement for the two approaches were wide, with the difference lying between -16.25 and 14.96 mm. CONCLUSIONS: A novel protocol of surgeon-measured margin was evaluated and compared with pathologist-measured margin. High intraobserver agreement for repeat surgeon measurements yet low-to-moderate correlation or directionality between surgeon and pathologic measurements were found. DISCUSSION: A standardized protocol may reduce variability in pathologic assessment. These findings have critical implications considering the impact of margin distance on outcomes.

Characterization of Newly Detected Costal Pleura-attached Noncalcified Nodules at Annual Low-Dose CT Screenings.

Background Solid costal pleura-attached noncalcified nodules (CP-NCNs) less than 10.0 mm with lentiform, oval, or semicircular (LOS) or triangular shapes and smooth margins on baseline low-dose CT scans from the Mount Sinai Early Lung and Cardiac Action Program (MS-ELCAP) were reviewed, and it was determined that they can be followed up at the first annual screening rather than having a shorter-term work-up. Purpose To determine whether the same criteria could be used for solid CP-NCNs newly identified at annual screening examinations. Materials and Methods With use of the same MS-ELCAP database, all new solid CP-NCNs measuring 30.0 mm or less were identified at 4425 annual screening examinations between 2010 and 2019. In addition, to ensure that no malignant CP-NCNs met the criteria, all solid malignant CP-NCNs of 30.0 mm or less in the International Early Lung Cancer Action Program, or I-ELCAP, database of 111 102 annual screening examinations from the 76 participating institutions between 1992 and 2019 were identified; Mount Sinai is one of these institutions. All identified solid CP-NCNs were reviewed-with the radiologists blinded to diagnosis-for shape (triangular, LOS, polygonal, round, or irregular), margin (smooth or nonsmooth), pleural attachment (broad or narrow), and the presence of emphysema and/or fibrosis within 10.0 mm of each CP-NCN. Intra- and interreader readings were performed, and agreements were determined by using the B-statistic. Results Of the 76 new solid CP-NCNs, 21 were lung cancers. Benign CP-NCNs were smaller than malignant ones (median diameter, 4.2 mm vs 11 mm; P < .001), had a different shape distributions, more frequently had smooth margins (67% vs 14%; P < .001), and less frequently had emphysema (38% vs 81%; P = .003) or fibrosis (3.6% vs 19%; P = .045) within a 10.0 mm radius. All 22 solid CP-NCNs less than 10.0 mm in average diameter with triangular or LOS shapes and smooth margins were benign, and none of the 21 solid malignant CP-NCNs had these characteristics. Intra- and interobserver agreement for triangular or LOS-shaped CP-NCNs with smooth margins was almost perfect (0.77 and 0.69, respectively). Conclusion The same follow-up recommendation developed for baseline costal pleura-attached noncalcified nodules (CP-NCNs) can be used for CP-NCNs newly identified at annual screening rounds. © RSNA, 2021.

Dose-response relationship between World Trade Center dust exposure and hepatic steatosis.

BACKGROUND: The World Trade Center (WTC) attack exposed thousands of workers to toxic chemicals that have been linked to liver diseases and cancers. This study examined the relationship between the intensity of WTC dust exposure and the risk of hepatic steatosis in the WTC General Responders Cohort (GRC). METHODS: All low-dose computed tomography (CT) scans of the chest performed on the WTC GRC between September 11, 2001 and December 31, 2018, collected as part of the World Trade Center Health Program, were reviewed. WTC dust exposure was categorized into five groups based on WTC arrival time. CT liver density was estimated using an automated algorithm, statistics-based liver density estimation from imaging. The relationship between the intensity of WTC dust exposure and the risk of hepatic steatosis was examined using univariate and multivariable regression analyses. RESULTS: Of the 1788 WTC responders, 258 (14.4%) had liver attenuation less than 40 Hounsfield units (HU < 40) on their earliest CT. Median time after September 11, 2001 and the earliest available CT was 11.3 years (interquartile range: 8.0-14.9 years). Prevalence of liver attenuation less than 40 HU was 17.0% for arrivals on September 11, 2001, 16.0% for arrivals on (September 12, 2001 or September 13, 2001), 10.9% for arrivals on September 14-30, 2001, and 9.0% for arrivals on January 10, 2001 or later (p = 0.0015). A statistically significant trend of increasing liver steatosis was observed with earlier arrival times (p < 0.0001). WTC arrival time remained a significant independent factor for decreased liver attenuation after controlling for other covariates. CONCLUSIONS: Early arrival at the WTC site was significantly associated with increasing hepatic steatosis.

Management of Nodules Attached to the Costal Pleura at Low-Dose CT Screening for Lung Cancer.

Background Pulmonary nodule features have been used to differentiate benign from malignant nodules. Purpose To determine the frequency of solid noncalcified nodules attached to the costal pleura (CP-NCNs) at baseline low-dose CT and to identify key features of benignity. Materials and Methods A retrospective review was performed of baseline low-dose CT scans obtained in 8730 participants in the Mount Sinai Early Lung and Cardiac Action Program screening cohort between 1992 and 2019. Participants with one or more solid CP-NCNs between 3.0 mm and 30.0 mm in average diameter were included. For each CP-NCN, the size, location, shape (lentiform, oval, or semicircular [LOS]; triangular; polygonal; round; or irregular), margin (smooth or nonsmooth), and attachment to the costal pleura (broad or narrow) were documented. The manifestation of emphysema and fibrosis within a 10-mm radius of the CP-NCN was determined. Multivariable logistic regression analysis, with synthetic minority oversampling techniques, was used. Results The 569 eligible participants (average age, 62 years ± 9 [standard deviation]; 343 women) had 943 solid CP-NCNs, of which 934 (99.0%) were benign and nine (1.0%) were malignant. Multivariable analysis showed that five shapes could be consolidated into three (LOS and/or triangular, round and/or polygonal, and irregular shape); pleural attachment was not a significant independent predictor (odds ratio, 1.24; P = .70); and interaction terms of size with shape (odds ratio, 0.73; P = .005) and margin were significant (odds ratio, 0.80; P = .001). All 603 CP-NCNs less than 10.0 mm with LOS or triangular shapes and smooth margins were benign. Conclusion All baseline noncalcified solid nodules attached to the costal pleura less than 10.0 mm in average diameter with lentiform, oval, semicircular, or triangular shapes and smooth margins were benign; thus, for these nodules, an annual repeat scan in 1 year, rather than a more immediate work-up, is recommended. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Godoy in this issue.