Association of Progressive PPFE and Mortality in Lung Cancer Screening Cohorts

Background: Pleuroparenchymal fibroelastosis (PPFE) is an upper lobe predominant fibrotic lung abnormality associated with increased mortality in established interstitial lung disease. However, the clinical significance of radiologic PPFE progression in lung cancer screening (LCS) populations remains unclear. Methods: We analysed longitudinal low-dose CT scans and clinical data from two LCS studies: National Lung Screening Trial (NLST; n=7,980); SUMMIT study (n=8,561). An automated algorithm quantified PPFE volume on baseline and follow-up scans. Annualised change in PPFE was derived and dichotomised using a distribution-based threshold to define progressive PPFE. Associations between progressive PPFE and mortality were evaluated using Cox proportional hazards models adjusted for demographic and clinical variables. In SUMMIT cohort, associations between progressive PPFE and clinical outcomes were assessed using incidence rate ratios (IRR) and odds ratios (OR). Findings: Progressive PPFE independently associated with mortality in both LCS cohorts (NLST: Hazard Ratio (HR)=1.25, 95% Confidence Interval (CI): 1.01--1.56, p=0.042; SUMMIT: HR=3.14, 95% CI: 1.66--5.97, p<0.001). Within SUMMIT, progressive PPFE was strongly associated with higher respiratory admissions (IRR=2.79, p<0.001), increased antibiotic and steroid use (IRR=1.55, p=0.010), and showed a trend towards higher modified medical research council scores (OR=1.40, p=0.055). Interpretation: Radiologic PPFE progression independently associates with mortality across two large LCS cohorts, and associates with adverse clinical outcomes. Quantitative assessment of PPFE progression may provide a clinically relevant imaging biomarker to identify individuals at increased risk of respiratory morbidity within LCS programmes.

Association of Radiologic PPFE Change with Mortality in Lung Cancer Screening Cohorts

Background: Pleuroparenchymal fibroelastosis (PPFE) is an upper lobe predominant fibrotic lung abnormality associated with increased mortality in established interstitial lung disease. However, the clinical significance of radiologic PPFE progression in lung cancer screening populations remains unclear. We investigated whether longitudinal change in PPFE quantified on low dose CT independently associates with mortality and respiratory morbidity. Methods: We analysed longitudinal low-dose CT scans and clinical data from two lung cancer screening studies: the National Lung Screening Trial (NLST; n=7980) and the SUMMIT study (n=8561). An automated algorithm quantified PPFE volume on baseline and follow up scans. Annualised change in PPFE (dPPFE) was derived and dichotomised using a distribution based threshold to define progressive PPFE. Associations between dPPFE and mortality were evaluated using Cox proportional hazards models adjusted for demographic and clinical variables. In the SUMMIT cohort, dPPFE was also examined in relation to clinical outcomes. Findings: dPPFE independently associated with mortality in both cohorts (NLST: HR 1.25, 95% CI 1.01-1.56, p=0.042; SUMMIT: HR 3.14, 95% CI 1.66-5.97, p<0.001). Kaplan-Meier curves showed reduced survival among participants with progressive PPFE in both cohorts. In SUMMIT, dPPFE was associated with higher respiratory admissions (IRR 2.79, p<0.001), increased antibiotic and steroid use (IRR 1.55, p=0.010), and a trend towards higher mMRC scores (OR 1.40, p=0.055). Interpretation: Radiologic PPFE progression independently associates with mortality across two large lung cancer screening cohorts and with adverse clinical outcomes. Quantitative assessment of PPFE progression may provide a clinically relevant imaging biomarker for identifying individuals at increased respiratory risk within screening programmes.

A data-centric deep learning approach to airway segmentation

The morphology and distribution of airway tree abnormalities enables diagnosis and disease characterisation across a variety of chronic respiratory conditions. In this regard, airway segmentation plays a critical role in the production of the outline of the entire airway tree to enable estimation of disease extent and severity. In this study, we propose a data-centric deep learning technique to segment the airway tree. The proposed technique utilises interpolation and image split to improve data usefulness and quality. Then, an ensemble learning strategy is implemented to aggregate the segmented airway trees at different scales. In terms of segmentation performance (dice similarity coefficient), our method outperforms the baseline model by 2.5% on average when a combined loss is used. Further, our proposed technique has a low GPU usage and high flexibility enabling it to be deployed on any 2D deep learning model.

Enhancing Cancer Prediction in Challenging Screen-Detected Incident Lung Nodules Using Time-Series Deep Learning

Lung cancer is the leading cause of cancer-related mortality worldwide. Lung cancer screening (LCS) using annual low-dose computed tomography (CT) scanning has been proven to significantly reduce lung cancer mortality by detecting cancerous lung nodules at an earlier stage. Improving risk stratification of malignancy risk in lung nodules can be enhanced using machine/deep learning algorithms. However most existing algorithms: a) have primarily assessed single time-point CT data alone thereby failing to utilize the inherent advantages contained within longitudinal imaging datasets; b) have not integrated into computer models pertinent clinical data that might inform risk prediction; c) have not assessed algorithm performance on the spectrum of nodules that are most challenging for radiologists to interpret and where assistance from analytic tools would be most beneficial. Here we show the performance of our time-series deep learning model (DeepCAD-NLM-L) which integrates multi-model information across three longitudinal data domains: nodule-specific, lung-specific, and clinical demographic data. We compared our time-series deep learning model to a) radiologist performance on CTs from the National Lung Screening Trial enriched with the most challenging nodules for diagnosis; b) a nodule management algorithm from a North London LCS study (SUMMIT). Our model demonstrated comparable and complementary performance to radiologists when interpreting challenging lung nodules and showed improved performance (AUC=88\%) against models utilizing single time-point data only. The results emphasise the importance of time-series, multi-modal analysis when interpreting malignancy risk in LCS.