Body composition changes in patients with lung cancer prior to diagnosis: a secondary analysis of National Lung Screening Trial data

The majority of patients with lung cancer are afflicted with cancer cachexia (CC), a syndrome characterized by wasting of muscle and fat tissues, associated with poor treatment response and increased mortality. Despite its prevalence, no effective treatments have been developed. Very little is known about early manifestations of the disease prior to diagnosis, which may provide insight into mechanistic drivers of CC and allow for the identification of novel therapeutics. We recently developed a preclinical model that better recapitulates several characteristics of human lung CC, and our findings suggest that early adipose tissue loss may be an important characteristic of the disease and an effector of pathological consequence. To better understand early body composition changes in human lung CC, we conducted a secondary analysis using body composition data collected from low dose computed tomography scans collected during the National Lung Screening Trial (NLST; NCT00047385). We selected patients diagnosed with lung cancer with ≥ 2 computed tomography scans before diagnosis (n=436) and, for controls, pairing one NLST participant who remained lung cancer-free after the same follow-up time as the cognate case (n=436). Cases were indexed to the date of their diagnosis scan and controls had an index date equal to the date of diagnosis of their matched case. Body composition from scans was measured using a novel, AI-based analysis of imaging. We fit crude and multivariable-adjusted hierarchical linear models to estimate changes in adipose and muscle tissue depot size and density, with adjustment for race/ethnicity, BMI, and age. Because males and females exhibit sex dimorphisms in lean body mass and adiposity, particularly in the anatomical region examined (thoracic region), all analyses were stratified by biological sex. Females diagnosed with advanced-stage cancer (stage 3-4) exhibited a reduction in visceral adipose tissue (VAT) cross-sectional area indexed to height and an increase in VAT density (indicating reduced adipocyte size) as they approached diagnosis compared with controls. In males, those diagnosed with advanced-stage cancer (stage 3-4) showed a decrease in SAT density and loss of skeletal muscle leading up to diagnosis compared with controls. These findings show that both males and females experience changes to adipose tissue size and composition, with males also showing reductions in muscle size. Because of sex differences in the anatomic localization of fat in the thoracic compartment where CT scans were conducted, it is challenging to draw conclusions about biological sex-specific CC-associated body composition changes. Further studies will be needed to evaluate other adipose tissue depots and/or whole-body adiposity to fully characterize early body composition changes during the development of lung cancer. NIH R01 AR065826(MJT), NCI R21 CA283492(MJT), T32- HL076122-18(DBS), R01 CA253923 (BJL) and the University of Vermont Cancer Center. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.