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.

Assessing the impact of nodule features and software algorithm on pulmonary nodule measurement uncertainty for nodules sized 20 mm or less.

Background: Measurements are not exact, so that if a measurement is repeated, one would get a different value each time. The spread of these values is the measurement uncertainty. Understanding measurement uncertainty of pulmonary nodules is important for proper interpretation of size and growth measurements. Larger amounts of measurement uncertainty may require longer follow-up intervals to be confident that any observed growth is due to actual growth rather than measurement uncertainty. We examined the influence of nodule features and software algorithm on measurement uncertainty of small, solid pulmonary nodules. Methods: Volumes of 107 nodules were measured on 4-6 repeated computed tomography (CT) scans (Siemens Somatom AS, 100 kVp, 120 mA, 1.0 mm slice thickness reconstruction) prospectively obtained during CT-guided fine needle aspiration biopsy between 2015-2021 at Department of Diagnostic, Molecular, and Interventional Radiology in Icahn School of Medicine at Mount Sinai, using two different automated volumetric algorithms. For each, the coefficient of variation (standard deviation divided by the mean) of nodule volume measurements was determined. The following features were considered: diameter, location, vessel and pleural attachments, nodule surface area, and extent of the nodule in the three acquisition dimensions of the scanner. Results: Median volume of 107 nodules was 515.23 and 535.53 mm3 for algorithm #1 and #2, respectively with excellent agreement (intraclass correlation coefficient =0.98). Median coefficient of variation of nodule volume was low for the two algorithms, but significantly different (4.6% vs. 8.7%, P<0.001). Both algorithms had a trend of decreasing coefficient of variation of nodule volume with increasing nodule diameter, though only significant for algorithm #2. Coefficient of variation of nodule volume was significantly associated with nodule volume (P=0.02), attachment to blood vessels (P=0.02), and nodule surface area (P=0.001) for algorithm #2 using a multiple linear regression model. Correlation between the coefficient of variation (CoV) of nodule volume and the CoV of the x, y, z measurements for algorithm #1 were 0.29 (P=0.0021), 0.25 (P=0.009), and 0.80 (P<0.001) respectively, and for algorithm #2, 0.46 (P<0.001), 0.52 (P<0.001), and 0.58 (P<0.001), respectively. Conclusions: Even in the best-case scenario represented in this study, using the same measurement algorithm, scanner, and scanning protocol, considerable measurement uncertainty exists in nodule volume measurement for nodules sized 20 mm or less. We found that measurement uncertainty was affected by interactions between nodule volume, algorithm, and shape complexity.

Timeliness of surgery for early-stage lung cancer: Patient factors and predictors.

Objectives: Time-to-treatment initiation is an important consideration for patients undergoing thoracic surgery for early-stage lung cancer because delays have the potential to adversely affect outcomes. This study seeks to quantify time-to-treatment initiation for patients with clinical stage I lung cancer, explore patient factors and predictors that lead to an increased time-to-treatment initiation, and compare surgeon perception of appropriate time-to-treatment initiation to the results. Methods: Time-to-treatment initiation was determined for patients enrolled in the Mount Sinai Initiative for Early Lung Cancer Research on Treatment study who underwent surgical resection for clinical stage I lung cancer between March 2016 and December 2021. The following dates were determined: (1) date of first suspicious radiologic imaging, (2) date of first biopsy, and (3) date of surgery. A total of 15 thoracic surgeons who participated in the Mount Sinai Initiative for Early Lung Cancer Research on Treatment were assessed on their perception on time-to-treatment initiation. Results: For 638 patients, median time from first suspicious imaging findings to biopsy was 40 days, biopsy to surgery was 37 days, and suspicious imaging to surgery was 84 days. Significant factors that resulted in longer time-to-treatment initiation in the multivariate analysis were African American or Black race (P = .005), vascular disease (P = .01), and median household income less than $75,000 (P = .04). Although the surgeon's perception was that the average time from biopsy to surgery was 28 days, it was longer for 63.5% of participants; surgeon perception of maximum time between diagnosis and surgery was 84 days and longer for 28.7% of participants. Conclusions: Patient factors such as race, income, and comorbidities were found to have differences in time-to-treatment initiation. Delays to surgery exceeded the expectations of thoracic surgeons.

Thyroid abnormalities identified on CT screening for lung cancer.

PURPOSE: Because incidental thyroid nodules (ITNs) are common extrapulmonary findings in low-dose computed tomography (LDCT) scans for lung cancer screening, we aimed to investigate the frequency of ITNs on LDCT scans separately on baseline and annual repeat scans, the frequency of malignancy among the ITNs, and any association with demographic, clinical, CT characteristics. METHODS: Retrospective case series of all 2309 participants having baseline and annual repeat screening in an Early Lung and Cardiac Action Program (MS-ELCAP) LDCT lung screening program from January 2010 to December 2016 was performed. Frequency of ITNs in baseline and annual repeat rounds were determined. Multivariable regression analysis was performed to identify significant predictors. RESULTS: Dominant ITNs were seen in 2.5 % of 2309 participants on baseline and in 0.15 % of participants among 4792 annual repeat LDCTs. The low incidence of new ITNs suggests slow growth as it would take approximately an average of 16.8 years for a new ITN to be detected on annual rounds of screening. Newly detected ITNs on annual repeat LDCT were all smaller than 15 mm. Regression analysis showed that the increasing of age, coronary artery calcifications score and breast density grade were significant predictors for females having an ITN. No significant predictors were found for ITNs in males. CONCLUSION: ITNs are detected at LDCT however, no malignancy was found. Certain predictors for ITNs in females have been identified including breast density, which may point towards a common causal pathway.

Visual scoring of osteoporosis on low-dose CT in lung cancer screening population.

OBJECTIVES: The risk factors for lung cancer screening eligibility, age as well as smoking history, are also present for osteoporosis. This study aims to develop a visual scoring system to identify osteoporosis that can be applied to low-dose CT scans obtained for lung cancer screening. MATERIALS AND METHODS: We retrospectively reviewed 1000 prospectively enrolled participants in the lung cancer screening program at the Mount Sinai Hospital. Optimal window width and level settings for the visual assessment were chosen based on a previously described approach. Visual scoring of osteoporosis and automated measurement using dedicated software were compared. Inter-reader agreement was conducted using six readers with different levels of experience who independently visually assessed 30 CT scans. RESULTS: Based on previously validated formulas for choosing window and level settings, we chose osteoporosis settings of Width = 230 and Level = 80. Of the 1000 participants, automated measurement was successfully performed on 774 (77.4 %). Among these, 138 (17.8 %) had osteoporosis. There was a significant correlation between the automated measurement and the visual score categories for osteoporosis (Kendall's Tau = -0.64, p < 0.0001; Spearman's rho = -0.77, p < 0.0001). We also found substantial to excellent inter-reader agreement on the osteoporosis classification among the 6 radiologists (Fleiss κ = 0.91). CONCLUSIONS: Our study shows that a simple approach of applying specific window width and level settings to already reconstructed sagittal images obtained in the context of low-dose CT screening for lung cancer is highly feasible and useful in identifying osteoporosis.

Change in quality of life of stage IA non-small cell lung cancer after surgery or radiation therapy.

Background: Few studies have examined the differential impact of stereotactic body radiotherapy (SBRT) and surgery for early-stage non-small cell lung cancer (NSCLC) on quality of life (QoL) during the first post-treatment year. Methods: A prospective cohort of stage IA NSCLC patients undergoing surgery or SBRT at Mount Sinai Health System had QoL measured before treatment, and 2, 6, and 12 months post-treatment using: 12-item Short Form Health Survey version 2 (SF-12v2) [physical component summary (PCS) and mental component summary (MCS)], Functional Assessment of Cancer Therapy-Lung Cancer Subscale (FACT-LCS), and the Patient Health Questionnaire-4 (PHQ-4) measuring depression and anxiety. Locally weighted scatterplot smoothing (LOWESS) was fitted to identify the best interval knot for the change in the QoL trends post-treatment, adjusted piecewise linear mixed effects model was developed to estimate differences in baseline, 2- and 12-month scores, and rates of change. Results: In total, 503 (88.6%) patients received surgery and 65 (11.4%) SBRT. LOWESS plots suggested QoL changed at 2 months post-surgery. Worsening in PCS was observed for both surgery and SBRT within 2 months after treatment but was only significant for surgical patients (-2.11, P<0.001). Two months later, improvements were observed for surgical but not SBRT patients (0.63 vs. -0.30, P<0.001). Surgical patients had significantly better PCS (P<0.001) and FACT-LCS (P<0.001) scores 1-year post-treatment compared to baseline, but not SBRT patients. Both surgical and SBRT patients reported significantly less anxiety 1-year post-treatment compared to baseline (P<0.001 and P=0.03). Decrease in depression from baseline to 1-year post-treatment was only significant for surgical patients (P<0.001). Conclusions: Post-treatment, surgical patients exhibited improvements in physical health and reductions in lung cancer symptoms following initial deterioration within the first two months; in contrast, SBRT patients showed persistent decline in these areas throughout the year. Nonetheless, improved mental health was noted across both patient categories post-treatment. Targeted interventions and continuous monitoring are recommended during the initial 2 months post-surgery and throughout the year post-SBRT to alleviate physical and mental distress in patients.

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.

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.

Prospective Cohort Study to Compare Long-Term Lung Cancer-Specific and All-Cause Survival of Clinical Early Stage (T1a-b; ≤20 mm) NSCLC Treated by Stereotactic Body Radiation Therapy and Surgery.

INTRODUCTION: We aimed to compare outcomes of patients with first primary clinical T1a-bN0M0 NSCLC treated with surgery or stereotactic body radiation therapy (SBRT). METHODS: We identified patients with first primary clinical T1a-bN0M0 NSCLCs on last pretreatment computed tomography treated by surgery or SBRT in the following two prospective cohorts: International Early Lung Cancer Action Program (I-ELCAP) and Initiative for Early Lung Cancer Research on Treatment (IELCART). Lung cancer-specific survival and all-cause survival after diagnosis were compared using Kaplan-Meier analysis. Propensity score matching was used to balance baseline demographics and comorbidities and analyzed using Cox proportional hazards regression. RESULTS: Of 1115 patients with NSCLC, 1003 had surgery and 112 had SBRT; 525 in I-ELCAP in 1992 to 2021 and 590 in IELCART in 2016 to 2021. Median follow-up was 57.6 months. Ten-year lung cancer-specific survival was not significantly different: 90% (95% confidence interval: 87%-92%) for surgery versus 88% (95% confidence interval: 77%-99%) for SBRT, p = 0.55. Cox regression revealed no significant difference in lung cancer-specific survival for the combined cohorts (p = 0.48) or separately for I-ELCAP (p = 1.00) and IELCART (p = 1.00). Although 10-year all-cause survival was significantly different (75% versus 45%, p < 0.0001), after propensity score matching, all-cause survival using Cox regression was no longer different for the combined cohorts (p = 0.74) or separately for I-ELCAP (p = 1.00) and IELCART (p = 0.62). CONCLUSIONS: This first prospectively collected cohort analysis of long-term survival of small, early NSCLCs revealed that lung cancer-specific survival was high for both treatments and not significantly different (p = 0.48) and that all-cause survival after propensity matching was not significantly different (p = 0.74). This supports SBRT as an alternative treatment option for small, early NSCLCs which is especially important with their increasing frequency owing to low-dose computed tomography screening. Furthermore, treatment decisions are influenced by many different factors and should be personalized on the basis of the unique circumstances of each patient.

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.

Predictors of pulmonary embolism in hospitalized patients with COVID-19.

BACKGROUND: High venous thromboembolism (VTE) rates have been described in critically ill patients with COVID-19. We hypothesized that specific clinical characteristics may help differentiate hypoxic COVID-19 patients with and without a diagnosed pulmonary embolism (PE). METHODS: We performed a retrospective observational case-control study of 158 consecutive patients hospitalized in one of four Mount Sinai Hospitals with COVID-19 between March 1 and May 8, 2020, who received a Chest CT Pulmonary Angiogram (CTA) to diagnose a PE. We analyzed demographic, clinical, laboratory, radiological, treatment characteristics, and outcomes in COVID-19 patients with and without PE. RESULTS: 92 patients were negative (CTA-), and 66 patients were positive for PE (CTA+). CTA + had a longer time from symptom onset to admission (7 days vs. 4 days, p = 0.05), higher admission biomarkers, notably D-dimer (6.87 vs. 1.59, p < 0.0001), troponin (0.015 vs. 0.01, p = 0.01), and peak D-dimer (9.26 vs. 3.8, p = 0.0008). Predictors of PE included time from symptom onset to admission (OR = 1.11, 95% CI 1.03-1.20, p = 0.008), and PESI score at the time of CTA (OR = 1.02, 95% CI 1.01-1.04, p = 0.008). Predictors of mortality included age (HR 1.13, 95% CI 1.04-1.22, p = 0.006), chronic anticoagulation (13.81, 95% CI 1.24-154, p = 0.03), and admission ferritin (1.001, 95% CI 1-1.001, p = 0.01). CONCLUSIONS: In 158 hospitalized COVID-19 patients with respiratory failure evaluated for suspected PE, 40.8% patients had a positive CTA. We identified clinical predictors of PE and mortality from PE, which may help with early identification and reduction of PE-related mortality in patients with COVID-19.

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.

Environmental exposures are important risk factors for advanced liver fibrosis in African American adults.

Background & Aims: The prevalence and aetiology of liver fibrosis vary over time and impact racial/ethnic groups unevenly. This study measured time trends and identified factors associated with advanced liver fibrosis in the United States. Methods: Standardised methods were used to analyse data on 47,422 participants (≥20 years old) in the National Health and Nutrition Examination Survey (1999-2018). Advanced liver fibrosis was defined as Fibrosis-4 ≥2.67 and/or Forns index ≥6.9 and elevated alanine aminotransferase. Results: The estimated number of people with advanced liver fibrosis increased from 1.3 million (95% CI 0.8-1.9) to 3.5 million (95% CI 2.8-4.2), a nearly threefold increase. Prevalence was higher in non-Hispanic Black and Mexican American persons than in non-Hispanic White persons. In multivariable logistic regression analysis, cadmium was an independent risk factor in all racial/ethnic groups. Smoking and current excessive alcohol use were risk factors in most. Importantly, compared with non-Hispanic White persons, non-Hispanic Black persons had a distinctive set of risk factors that included poverty (odds ratio [OR] 2.09; 95% CI 1.44-3.03) and susceptibility to lead exposure (OR 3.25; 95% CI 1.95-5.43) but did not include diabetes (OR 0.88; 95% CI 0.61-1.27; p =0.52). Non-Hispanic Black persons were more likely to have high exposure to lead, cadmium, polychlorinated biphenyls, and poverty than non-Hispanic White persons. Conclusions: The number of people with advanced liver fibrosis has increased, creating a need to expand the liver care workforce. The risk factors for advanced fibrosis vary by race/ethnicity. These differences provide useful information for designing screening programmes. Poverty and toxic exposures were associated with the high prevalence of advanced liver fibrosis in non-Hispanic Black persons and need to be addressed. Impact and Implications: Because liver disease often produces few warning signs, simple and inexpensive screening tests that can be performed by non-specialists are needed to allow timely diagnosis and linkage to care. This study shows that non-Hispanic Black persons have a distinctive set of risk factors that need to be taken into account when designing liver disease screening programs. Exposure to exogenous toxins may be especially important risk factors for advanced liver fibrosis in non-Hispanic Black persons.

Evaluation of emphysema on thoracic low-dose CTs through attention-based multiple instance deep learning.

In addition to lung cancer, other thoracic abnormalities, such as emphysema, can be visualized within low-dose CT scans that were initially obtained in cancer screening programs, and thus, opportunistic evaluation of these diseases may be highly valuable. However, manual assessment for each scan is tedious and often subjective, thus we have developed an automatic, rapid computer-aided diagnosis system for emphysema using attention-based multiple instance deep learning and 865 LDCTs. In the task of determining if a CT scan presented with emphysema or not, our novel Transfer AMIL approach yielded an area under the ROC curve of 0.94 ± 0.04, which was a statistically significant improvement compared to other methods evaluated in our study following the Delong Test with correction for multiple comparisons. Further, from our novel attention weight curves, we found that the upper lung demonstrated a stronger influence in all scan classes, indicating that the model prioritized upper lobe information. Overall, our novel Transfer AMIL method yielded high performance and provided interpretable information by identifying slices that were most influential to the classification decision, thus demonstrating strong potential for clinical implementation.

Impact of Duration of Diagnostic Workup on Prognosis for Early Lung Cancer.

INTRODUCTION: Growth assessment for pulmonary nodules is an important diagnostic tool; however, the impact on prognosis due to time delay for follow-up diagnostic scans needs to be considered. METHODS: Using the data between 2003 and 2019 from the International Early Lung Cancer Action Program, a prospective cohort study, we determined the size-specific, 10-year Kaplan-Meier lung cancer (LC) survival rates as surrogates for cure rates. We estimated the change in LC diameter after delays of 90, 180, and 365 days using three representative LC volume doubling times (VDTs) of 60 (fast), 120 (moderate), and 240 (slow). We then estimated the decrease in the LC cure rate resulting from time between computed tomography scans to assess for growth during the diagnostic workup. RESULTS: Using a regression model of the 10-year LC survival rates on LC diameter, the estimated LC cure rate of a 4.0 mm LC with fast (60-d) VDT is 96.0% (95% confidence interval [CI]: 95.2%-96.7%) initially, but it would decrease to 94.3% (95% CI: 93.2%-95.0%), 92.0% (95% CI: 90.5%-93.4%), and 83.6%(95% CI: 80.6%-86.6%) after delays of 90, 180, and 365 days, respectively. A 20.0-mm LC with the same VDTs has a lower LC cure rate of 79.9% (95% CI: 76.2%-83.5%) initially and decreases more rapidly to 71.5% (95% CI: 66.4%-76.7%), 59.8% (95% CI: 52.4%-67.1%), and 17.9% (95% CI: 3.0%-32.8%) after the same delays of 90, 180, and 365 days, respectively. CONCLUSIONS: Time between scans required to measure growth of lung nodules affects prognosis with the effect being greater for fast growing and larger cancers. Quantifying the extent of change in prognosis is required to understand efficiencies of different management protocols.

New or enlarging hiatal hernias after thoracic surgery for early lung cancer.

Objective: The study objective was to determine the relationship between lung resection and the development of postoperative hiatal hernia. Methods: Preoperative and postoperative computed tomography imaging from 373 patients from the International Early Lung Cancer Action Program and the Initiative for Early Lung Cancer Research on Treatment were compared at a median of 31.1 months of follow-up after resection of clinical early-stage non-small cell lung cancer. Incidence of new hiatal hernia or changes to preexisting hernias were recorded and evaluated by patient demographics, surgical approach, extent of resection, and resection site. Results: New hiatal hernias were seen in 9.6% of patients after lung resection (5.6% after wedge or segmentectomy and 12.4% after lobectomy; P = .047). The median size of new hernias was 21 mm, and the most commonly associated resection site was the left lower lobe (24.2%; P = .04). In patients with preexisting hernias, 53.5% demonstrated a small but significant increase in size from 21 to 22 mm (P < .0001). All hernias persisted through the latest postoperative computed tomography scan. When 110 surgical patients without preexisting hernia were matched by sex, age, and smoking to nonoperative controls, the incidence of new hernia at follow-up was significantly higher among those who underwent surgery (17.3% vs 2.7%, P = .0003). Conclusions: Both open and minimally invasive lung resection for clinical early-stage lung cancer are associated with new or enlarging postoperative hiatal hernia, especially after resections involving the left lower lobe.

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.

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.