The implementation of low-dose chest CT for lung screening presents a crucial opportunity to advance lung cancer care through early detection and interception. In addition, millions of pulmonary nodules are incidentally detected annually in the United States, increasing the opportunity for early lung cancer diagnosis. Yet, realization of the full potential of these opportunities is dependent on the ability to accurately analyze image data for purposes of nodule classification and early lung cancer characterization. This review presents an overview of traditional image analysis approaches in chest CT using semantic characterization as well as more recent advances in the technology and application of machine learning models using CT-derived radiomic features and deep learning architectures to characterize lung nodules and early cancers. Methodological challenges currently faced in translating these decision aids to clinical practice, as well as the technical obstacles of heterogeneous imaging parameters, optimal feature selection, choice of model, and the need for well-annotated image data sets for the purposes of training and validation, will be reviewed, with a view toward the ultimate incorporation of these potentially powerful decision aids into routine clinical practice.

Lung cancer is the third most common cancer in the US, and the leading cause of cancer-related death.¹ In the US, Black individuals are disproportionately affected by cancer, experiencing the highest rate of death and lowest rates of survival for most cancers. This statistic is particularly true of lung cancer, with Black men experiencing higher rates of lung cancer death than any other racial or ethnic group.²

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.

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 n...