CT-Derived Muscle and Adipose Tissue Characteristics and Survival in Advanced NSCLC Treated with First-Line Immunotherapy-Based Regimens.

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Abstract

Host-related factors such as skeletal muscle and adipose tissue characteristics are increasingly recognized as determinants of outcome in advanced non-small cell lung cancer (aNSCLC). However, the prognostic relevance of integrated body composition phenotypes in patients receiving first-line immunotherapy-based treatment remains unclear. We retrospectively analyzed patients with aNSCLC treated with first-line immune checkpoint inhibitors (ICI) alone or combined with chemotherapy (ICI-CT) between October 2018 and December 2023 at LMU University Hospital. AI-derived CT biomarkers included skeletal muscle volume index (SMVI), skeletal muscle density (SMD), visceral adipose volume index (VAVI), and subcutaneous adipose volume index (SAVI), normalized for height. Individual body composition parameters were analyzed as standardized continuous variables. For exploratory phenotype analyses, SMVI and VAVI were categorized using cohort-specific sex-stratified median values. An integrated body composition phenotype was defined as "high-muscle/low-visceral-adiposity" (high SMVI/low VAVI) or "low-muscle/high-visceral-adiposity" (low SMVI/high VAVI), with patients not meeting either definition classified as having an intermediate phenotype. Multivariable Cox regression adjusted for age, sex, treatment modality, and metastatic burden evaluated associations with progression-free survival (PFS) and overall survival (OS). Of 116 screened patients, 103 with evaluable baseline CT imaging were included. The cohort predominantly comprised ever-smokers (81.6%) and patients with adenocarcinoma (62.1%). Higher SMD (per one standard deviation increase) was associated with improved overall survival (HR 0.72, 95% CI 0.52-1.00; <i>p</i> = 0.047), and higher VAVI was associated with a higher risk of death (HR 1.29, 95% CI 1.00-1.65; <i>p</i> = 0.048). Neither SMD nor VAVI was significantly associated with PFS, and SMVI and SAVI were not significantly associated with OS or PFS. In the exploratory integrated phenotype analysis, median OS was 29.5 months in the high-muscle/low-visceral-adiposity group, 16.2 months in the intermediate group, and 19.3 months in the low-muscle/high-visceral-adiposity group; however, the overall Kaplan-Meier comparison was not statistically significant (log-rank <i>p</i> = 0.385). AI-derived CT body composition assessment may provide complementary prognostic information in patients with aNSCLC receiving first-line immunotherapy-based treatment. Higher skeletal muscle density was associated with a lower risk of death, whereas higher visceral adiposity was associated with a higher risk of death. The exploratory integrated phenotype analysis did not demonstrate a consistent risk gradient across phenotype categories. These findings require validation in larger prospective cohorts before clinical implementation.

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