Virtual Lung Screening Trial (VLST): An In Silico Replica of the National Lung Screening Trial for Lung Cancer Detection.

Importance: Clinical imaging trials are crucial for evaluation of medical innovations, but the process is inefficient, expensive, and ethically-constrained. Virtual imaging trial (VIT) approach addresses these limitations by emulating the components of a clinical trial. An in silico rendition of the National Lung Screening Trial (NCLS) via Virtual Lung Screening Trial (VLST) demonstrates the promise of VITs to expedite clinical trials, reduce risks to subjects, and facilitate the optimal use of imaging technologies in clinical settings.

Objectives: To demonstrate that a virtual imaging trial platform can accurately emulate a major clinical trial, specifically the National Lung Screening Trial (NLST) that compared computed tomography (CT) and chest radiography (CXR) imaging for lung cancer screening.

Design setting and participants: A virtual patient population of 294 subjects was created from human models (XCAT) emulating the NLST, with two types of simulated cancerous lung nodules. Each virtual patient in the cohort was assessed using simulated CT and CXR systems to generate images reflecting the NLST imaging technologies. Deep learning models trained for lesion detection, AI CT-Reader, and AI CXR-Reader served as virtual readers.

Main outcomes and measures: The primary outcome was the difference in the Receiver Operating Characteristic Area Under the Curve (AUC) for CT and CXR modalities.

Results: The study analyzed paired CT and CXR simulated images from 294 virtual patients. The AI CT-Reader outperformed the AI CXR-Reader across all levels of analysis. At the patient level, CT demonstrated superior diagnostic performance with an AUC of 0.92 (95% CI: 0.90-0.95), compared to CXR's AUC of 0.72 (0.67-0.77). Subgroup analyses of lesion types revealed CT had significantly better detection of homogeneous lesions (AUC 0.97, 95% CI: 0.95-0.98) compared to heterogeneous lesions (0.89; 0.86-0.93). Furthermore, when the specificity of the AI CT-Reader was adjusted to match the NLST sensitivity of 94% for CT, the VLST results closely mirrored the NLST findings, further highlighting the alignment between the two studies.

Conclusion and relevance: The VIT results closely replicated those of the earlier NLST, underscoring its potential to replicate real clinical imaging trials. Integration of virtual trials may aid in the evaluation and improvement of imaging-based diagnosis.