Abstract 3403: Disentangling the obesity paradox in high-grade serous epithelial ovarian cancer

Abstract

Abstract Background: Previously published evidence suggests an 'obesity paradox' in epithelial ovarian cancer, where excess adiposity is linked to better survival. However, prior studies did not jointly consider skeletal muscle, a key prognostic factor in cancer. Addressing this gap, our study examines the combined effects of adiposity and muscle phenotypes on mortality in high-grade serous epithelial ovarian cancer (HGSOC), offering novel insights into the role of body composition in patient outcomes. Methods: 343 HGSOC patients from the Body Composition and Epithelial Ovarian Cancer (BComES) Cohort at Roswell Park were included in this analysis. Body composition was derived from sliceOmatic software using computed tomography images obtained prior to chemotherapy. Body composition was quantified as surface area (cm2) at L3 for intermuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), total adipose tissue (TAT), and skeletal muscle index (SMI). SMI<38.5 cm2/m2 was defined as low SMI, a proxy for sarcopenia. For each adipose depot, phenotypes were categorized as: 1) low adiposity/high SMI (optimal/referent); 2) high adiposity/high SMI; 3) high adiposity/low SMI (e.g., sarcopenic obesity); and 4) low adiposity/low SMI (e.g., cancer cachexia). Multivariable Cox models adjusted for age, tumor stage, and surgical debulking status were used to estimate Hazard Ratios (HR) and 95% Confidence Intervals (CI) representing associations of each body composition phenotype with mortality. Results: High IMAT and VAT were associated with increased mortality in patients with high SMI (HR=1.80, 95% CI: 1.18-2.74 and HR=1.96, 95% CI: 1.27-3.04, respectively) and low SMI (HR=1.65, 95% CI: 1.05-2.61 and HR=1.70, 95% CI: 1.04-2.80). High SAT and TAT were also associated with increased mortality in patients with high SMI (HR=1.74, 95% CI: 1.14-2.67 and HR=2.04, 95% CI: 1.31-3.18), but associations were shy of significance for patients with low SMI (HR=1.37, 95% CI: 0.85-2.23 and HR=1.58, 95% CI: 0.95-2.61). Lastly, low SMI and low adiposity was associated with increased mortality for VAT (HR= 1.65, 95% CI: 1.01-2.70), SAT (HR=1.88, 95% CI: 1.14-3.10), TAT (HR=1.97, 95% CI:1.19-3.26) and IMAT (HR=1.46, 95% CI: 0.85-2.53). Conclusions: In this study, we observed no support for an obesity paradox. Rather, we observed compelling evidence linking high adiposity phenotypes with striking increases in HGSOC mortality, regardless of SMI. Notably, as the cachectic phenotype was also linked to substantial increases in mortality, unwittingly assigning patients with low adiposity and low muscle to a reference group in adiposity research could falsely induce an ‘obesity paradox’. Importantly, as body composition can be modified through diet and exercise, our data establishes it as a potential therapeutic target alongside chemotherapy to improve outcomes in this deadly disease. Citation Format: Evan W. Davis, Nancy Barone, Charles Roche, Gyorgy Paragh, André Klein, Rikki Cannioto. Disentangling the obesity paradox in high-grade serous epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3403.