The 2023 American Association for Thoracic Surgery (AATS) Expert Consensus Document: Management of subsolid lung nodules.

OBJECTIVE: Lung cancers that present as radiographic subsolid nodules represent a subtype with distinct biological behavior and outcomes. The objective of this document is to review the existing literature and report consensus among a group of multidisciplinary experts, providing specific recommendations for the clinical management of subsolid nodules. METHODS: The American Association for Thoracic Surgery Clinical Practice Standards Committee assembled an international, multidisciplinary expert panel composed of radiologists, pulmonologists, and thoracic surgeons with established expertise in the management of subsolid nodules. A focused literature review was performed with the assistance of a medical librarian. Expert consensus statements were developed with class of recommendation and level of evidence for each of 4 main topics: (1) definitions of subsolid nodules (radiology and pathology), (2) surveillance and diagnosis, (3) surgical interventions, and (4) management of multiple subsolid nodules. Using a modified Delphi method, the statements were evaluated and refined by the entire panel. RESULTS: Consensus was reached on 17 recommendations. These consensus statements reflect updated insights on subsolid nodule management based on the latest literature and current clinical experience, focusing on the correlation between radiologic findings and pathological classifications, individualized subsolid nodule surveillance and surgical strategies, and multimodality therapies for multiple subsolid lung nodules. CONCLUSIONS: Despite the complex nature of the decision-making process in the management of subsolid nodules, consensus on several key recommendations was achieved by this American Association for Thoracic Surgery expert panel. These recommendations, based on evidence and a modified Delphi method, provide guidance for thoracic surgeons and other medical professionals who care for patients with subsolid nodules.

Subsolid Nodules: Significance and Current Understanding.

Subsolid nodules are heterogeneously appearing and behaving entities, commonly encountered incidentally and in high-risk populations. Accurate characterization of subsolid nodules, and application of evolving surveillance guidelines, facilitates evidence-based and multidisciplinary patient-centered management.

Single-Cell Characterization of Pulmonary Nodules Implicates Suppression of Immunosurveillance across Early Stages of Lung Adenocarcinoma.

A greater understanding of molecular, cellular, and immunological changes during the early stages of lung adenocarcinoma development could improve diagnostic and therapeutic approaches in patients with pulmonary nodules at risk for lung cancer. To elucidate the immunopathogenesis of early lung tumorigenesis, we evaluated surgically resected pulmonary nodules representing the spectrum of early lung adenocarcinoma as well as associated normal lung tissues using single-cell RNA sequencing and validated the results by flow cytometry and multiplex immunofluorescence (MIF). Single-cell transcriptomics revealed a significant decrease in gene expression associated with cytolytic activities of tumor-infiltrating natural killer and natural killer T cells. This was accompanied by a reduction in effector T cells and an increase of CD4+ regulatory T cells (Treg) in subsolid nodules. An independent set of resected pulmonary nodules consisting of both adenocarcinomas and associated premalignant lesions corroborated the early increment of Tregs in premalignant lesions compared with the associated normal lung tissues by MIF. Gene expression analysis indicated that cancer-associated alveolar type 2 cells and fibroblasts may contribute to the deregulation of the extracellular matrix, potentially affecting immune infiltration in subsolid nodules through ligand-receptor interactions. These findings suggest that there is a suppression of immune surveillance across the spectrum of early-stage lung adenocarcinoma. SIGNIFICANCE: Analysis of a spectrum of subsolid pulmonary nodules by single-cell RNA sequencing provides insights into the immune regulation and cell-cell interactions in the tumor microenvironment during early lung tumor development.

Analysis of Eligibility for Lung Cancer Screening by Race After 2021 Changes to US Preventive Services Task Force Screening Guidelines.

Importance: Lung cancer incidence and mortality have disproportionate consequences for racial and ethnic minority populations. The extent to which the 2021 changes to the US Preventive Services Task Force (USPSTF) screening guidelines have reduced the racial disparity gap in lung cancer screening eligibility is not known. Objective: To assess the consequences of the changes in USPSTF low-dose computed tomography eligibility criteria for lung cancer screening between 2013 and 2021 among Black and White community-dwelling adults. Design, Setting, and Participants: This cohort study analyzed data from the Reasons for Geographic and Racial Differences in Stroke study, a prospective longitudinal cohort study of community-dwelling Black and White adults 45 years and older who were initially recruited across the US between January 2003 and October 2007, with ongoing follow-up. All participants who would have been potentially eligible for lung cancer screening based on the 2021 USPSTF guidelines (N = 14 285) were included. Follow-up data for the current cohort study were collected and analyzed between January 2013 and December 2017, with final analysis performed in 2021. Exposures: Self-reported Black vs White race. Primary Outcomes and Measures: Differences in the proportion of Black vs White participants eligible for lung cancer screening according to 2013 and 2021 guidelines were assessed using modified Poisson models with robust SEs. Associations between important covariates (demographic characteristics and social factors associated with health), including interaction and dissimilarity indices (2 measures of residential segregation), and differences in screening eligibility were also examined. Results: Among 14 285 participants (mean [SD] age, 64.7 [7.5] years; 7675 men [53.7%]), 5787 (40.5%) self-identified as Black and 8498 (59.5%) as White. Based on the 2013 USPSTF guidelines, 1109 of 5787 Black participants (19.2%) and 2313 of 8498 White participants (27.2%) were eligible for lung cancer screening (difference, -8.06 percentage points; 95% CI, -9.44 to -6.67 percentage points). Based on the 2021 guidelines, 1667 of 5787 Black participants (28.8%) and 2940 of 8498 White participants (34.6%) were eligible for screening (difference, -5.73 percentage points; 95% CI, -7.28 to -4.19 percentage points). After adjustment for differences in individual characteristics and residential segregation, the 2013 difference in screening eligibility among Black vs White participants was -12.66 percentage points (95% CI, -14.71 to -10.61 percentage points), and the 2021 difference was -12.15 percentage points (95% CI, -14.37 to -9.93 percentage points). Conclusions and Relevance: In this study, 2021 changes to the USPSTF lung cancer screening guidelines were associated with reductions in but not elimination of existing eligibility disparities in lung cancer screening among Black and White adults. These findings suggest that accounting for factors beyond age and pack-years of smoking is needed when tailoring guidelines to improve screening eligibility among groups at high risk of lung cancer.

Capturing Demographic, Health-Related, and Psychosocial Variables in a Standardized Manner: Towards Improving Cancer Screening Adherence.

Determining factors influencing patient participation in and adherence to cancer screening recommendations is key to successful cancer screening programs. However, the collection of variables necessary to anticipate patient behavior in cancer screening has not been systematically examined. Using lung cancer screening as a representative example, we conducted an exploratory analysis to characterize the current representations of 18 demographic, health-related, and psychosocial variables collected as part of a conceptual model to understand factors for lung cancer screening participation and adherence. Our analysis revealed a lack of standardization in controlled terminologies and common data elements for these variables. For example, only eight (44%) demographic and health-related variables were recorded consistently in the electronic health record. Multiple survey instruments could collect the remaining variables but were highly inconsistent in how variables were represented. This analysis suggests opportunities to establish standardized data formats for psychological, cognitive, social, and environmental variables to improve data collection.

Generalizability and Transportability of the National Lung Screening Trial Data: Extending Trial Results to Different Populations.

BACKGROUND: Randomized controlled trials (RCT) play a central role in evidence-based healthcare. However, the clinical and policy implications of implementing RCTs in clinical practice are difficult to predict as the studied population is often different from the target population where results are being applied. This study illustrates the concepts of generalizability and transportability, demonstrating their utility in interpreting results from the National Lung Screening Trial (NLST). METHODS: Using inverse-odds weighting, we demonstrate how generalizability and transportability techniques can be used to extrapolate treatment effect from (i) a subset of NLST to the entire NLST population and from (ii) the entire NLST to different target populations. RESULTS: Our generalizability analysis revealed that lung cancer mortality reduction by LDCT screening across the entire NLST [16% (95% confidence interval [CI]: 4-24)] could have been estimated using a smaller subset of NLST participants. Using transportability analysis, we showed that populations with a higher prevalence of females and current smokers had a greater reduction in lung cancer mortality with LDCT screening [e.g., 27% (95% CI, 11-37) for the population with 80% females and 80% current smokers] than those with lower prevalence of females and current smokers. CONCLUSIONS: This article illustrates how generalizability and transportability methods extend estimation of RCTs' utility beyond trial participants, to external populations of interest, including those that more closely mirror real-world populations. IMPACT: Generalizability and transportability approaches can be used to quantify treatment effects for populations of interest, which may be used to design future trials or adjust lung cancer screening eligibility criteria.

Association of Inclusion of More Black Individuals in Lung Cancer Screening With Reduced Mortality.

Importance: The potential to achieve greater reductions in lung cancer mortality than originally estimated by the National Lung Screening Trial with the inclusion of more Black participants stresses the importance of improving access to lung cancer screening for Black current and former smokers, a population presently with the highest lung cancer morbidity and mortality. Objective: To estimate lung cancer and all-cause mortality reductions achievable with lung cancer screening via low-dose computed tomography (LDCT) of the chest in populations with greater proportions of Black screening participants than seen in the original NLST cohort. Design, Setting, and Participants: This cohort study was conducted as a secondary analysis of existing data from the National Lung Screening Trial, a large national randomized clinical trial conducted from 2002 through 2009. NLST participants were current or former smokers, aged between 55 and 74 years, with at least 30 pack-years of smoking history and less than 15 years since quitting. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% CIs of lung cancer mortality and all-cause mortality according to LDCT screening compared with chest radiograph screening. Using a transportability formula, we estimated outcomes for LDCT screening among hypothetical populations by varying the distributions of Black individuals, women, and current smokers. Data were analyzed between September 2020 and March 2021. Exposures: Lung screening with LDCT of the chest compared with chest radiography. Main Outcomes and Measures: Lung cancer mortality and all-cause mortality. Results: This study included a total of 53 452 participants enrolled in the NLST. Of 2376 Black individuals and 51 076 non-Black individuals, 21 922 (41.0%) were women and the mean (SD) age was 61.4 (5.0) years. Over a median (interquartile range) follow-up of 6.7 (6.2-7.0) years, LDCT screening among the synthesized population with a higher proportion of Black individuals (13.4%, mirroring US Census data) was associated with a greater relative reduction of lung cancer mortality (eg, Black individuals: HR, 0.82; 95% CI, 0.72-0.92; vs entire NLST cohort: HR, 0.84; 95% CI, 0.76-0.96). Further reductions in lung cancer mortality by LDCT screening were found among a hypothetical population with a higher proportion of men or current smokers, along with a higher proportion of Black individuals (ie, 60% Black participants; 20% to 40% women) (HR, 0.68; 95% CI, 0.48-0.97). Conclusions and Relevance: The potential to achieve greater reductions in lung cancer mortality than originally estimated by the NLST with the inclusion of more Black participants stresses the critical importance of improving access to lung cancer screening for Black current and former smokers.

Left atrial thrombus mimicking myxoma in a patient with hereditary hemorrhagic telangiectasia: Diagnostic and therapeutic dilemmas.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by the development of arteriovenous malformations. The arteriovenous shunts may result in high output heart failure, which predisposes to atrial dilatation and atrial fibrillation. Due to recurrent bleeding from epistaxis or the gastrointestinal tract, patients with HHT and atrial fibrillation are at high risk of bleeding if anticoagulated for stroke prevention. In this report, we present a case of a 74-year-old woman with a history of HHT and atrial fibrillation who developed a large left atrial thrombus that initially was thought to represent an atrial myxoma. The diagnosis was confirmed with cardiac magnetic resonance imaging, and the patient underwent surgical resection of the thrombus. This case demonstrates the role of different imaging modalities in the assessment of left atrial masses and presents an opportunity to review the data on safety of anticoagulation in patients with HHT.

Recent Innovations in Renal Vascular Imaging.

Noninvasive imaging of the vascular renal system is a common request in diagnostic radiology. Typical indications include suspected renovascular hypertension, vasculitis, neoplasm, vascular malformation, and structural diseases of the kidney. Profound knowledge of the renal anatomy, including vascular supply and variants, is mandatory for radiologists and allows for optimized protocolling and interpretation of imaging studies. Besides renal ultrasound, computed tomography and MR imaging are commonly requested cross-sectional studies for renal and renal vascular imaging. This article discusses basic renal vascular anatomy, common imaging findings, and current and potential future imaging protocols for various renovascular pathologic conditions.

Forward-Projected Model-Based Iterative Reconstruction in Screening Low-Dose Chest CT: Comparison With Adaptive Iterative Dose Reduction 3D.

OBJECTIVE: The objective of this study is to compare forward-projected model-based iterative reconstruction solution (FIRST), a newer fully iterative CT reconstruction method, with adaptive iterative dose reduction 3D (AIDR 3D) in low-dose screening CT for lung cancer. Differences in image noise, image quality, and pulmonary nodule detection, size, and characterization were specifically evaluated. MATERIALS AND METHODS: Low-dose chest CT images obtained for 50 consecutive patients between December 2015 and January 2016 were retrospectively reviewed. Images were reconstructed using FIRST and AIDR 3D for both lung and soft-tissue reconstruction. Images were independently reviewed to assess image noise, subjective image quality (with use of a 5-point Likert scale, with 1 denoting far superior image quality; 2, superior quality; 3, equivalent quality; 4, inferior quality; and 5, far inferior quality), pulmonary nodule count, size of the largest pulmonary nodule, and characterization of the largest pulmonary nodule (i.e., solid, part solid, or ground glass). RESULTS: Across all 50 cases, measured image noise was lower with FIRST than with AIDR 3D (lung window, 44% reduction, 41 ± 7 vs 74 ± 8 HU, respectively; soft-tissue window, 32% reduction, 11 ± 2 vs 16 ± 2 HU, respectively). Readers subjectively rated images obtained with FIRST as comparable to images obtained with AIDR 3D (mean [± SD] Likert score for FIRST vs AIDR 3D, 3.2 ± 0.3 for soft-tissue reconstructions and 3.0 ± 0.3 for lung reconstructions). For each reader, very good agreement regarding nodule count was noted between FIRST and AIDR 3D (interclass correlation coefficient [ICC], 0.83 for reader 1 and 0.78 for reader 2). Excellent agreement regarding nodule size (ICC, 0.99 for reader 1 and 0.99 for reader 2) and characterization of the largest nodule (kappa value, 0.92 for reader 1 and 0.82 for reader 2) also existed. CONCLUSION: Images reconstructed with FIRST are superior to those reconstructed AIDR 3D with regard to image noise and are equivalent with regard to subjective image quality, pulmonary nodule count, and nodule characterization.