Association between age and lung cancer risk: evidence from lung lobar radiomics.

Abstract

Background: Previous studies have highlighted the prominent role of age in lung cancer risk, with signs of lung aging visible in computed tomography (CT) imaging. This study aims to characterize lung aging using quantitative radiomic features extracted from five delineated lung lobes and explore how age contributes to lung cancer development through these features.

Methods: We analyzed baseline CT scans from the Wenling lung cancer screening cohort, consisting of 29,810 participants. Deep learning-based segmentation method was used to delineate lung lobes. A total of 1,470 features were extracted from each lobe. The minimum redundancy maximum relevance algorithm was applied to identify the top 10 age-related radiomic features among 13,137 never smokers. Multiple regression analyses were used to adjust for confounders in the association of age, lung lobar radiomic features, and lung cancer. Linear, Cox proportional hazards, and parametric accelerated failure time models were applied as appropriate. Mediation analyses were conducted to evaluate whether lobar radiomic features mediate the relationship between age and lung cancer risk.

Results: Age was significantly associated with an increased lung cancer risk, particularly among current smokers (hazard ratio = 1.07, P = 2.81 × 10^- 13). Age-related radiomic features exhibited distinct effects across lung lobes. Specifically, the first order mean (mean attenuation value) filtered by wavelet in the right upper lobe increased with age (β = 0.019, P = 2.41 × 10^- 276), whereas it decreased in the right lower lobe (β = -0.028, P = 7.83 × 10^- 277). Three features, namely wavelet_HL_firstorder_Mean of the right upper lobe, wavelet_LH_firstorder_Mean of the right lower lobe, and original_shape_MinorAxisLength of the left upper lobe, were independently associated with lung cancer risk at Bonferroni-adjusted P value. Mediation analyses revealed that density and shape features partially mediated the relationship between age and lung cancer risk while a suppression effect was observed in the wavelet first order mean of right upper lobe.

Conclusions: The study reveals lobe-specific heterogeneity in lung aging patterns through radiomics and their associations with lung cancer risk. These findings may contribute to identify new approaches for early intervention in lung cancer related to aging.

Clinical trial number: Not applicable.