Sarcopenic obesity exacerbates gastric cancer prognosis via increased intermuscular and visceral fat accumulation

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BACKGROUND: Ectopic fat distribution reflects patient's metabolic profile, shaping the tumor microenvironment, which may be a key prognostic indicator. Our study pursues to explore the independent and combined effects of muscle atrophy and abnormal fat distribution on survival in gastric cancer patients. METHOD: , assessing muscle mass, intermuscular, and visceral fat. Ectopic fat phenotypes included visceral obesity (increased visceral adipose tissue, VAT) and myosteatosis (reduced skeletal muscle density, SMD). Associations between body composition parameters/phenotypes and progression-free survival (PFS), overall survival (OS), and cachexia-related survival (CRS) were evaluated using Kaplan-Meier analysis with log-rank tests and Cox proportional hazards regression. RESULTS: Of the 283 patients, 32 patients (11.3%) were BMI-define obese, 139 patients (49.1%) showed visceral obesity, and 176 patients (62.2%) presented with myosteatosis. Sarcopenia was present in 234 patients (82.7%), and 151 patients (53.4%) presented with a combination of sarcopenia and myosteatosis. During a median follow-up of 41 months (2-108 months), 53 patients developed metastasis, 6 relapse, and 142 died. Skeletal muscle mass (Normal Attenuation Muscle Area, NAMA, HR = 0.989, 95% CI 0.980-0.998, P = 0.022, for PFS) and quality (SMD, HR = 0.975, 95% CI 0.955-0.995, P = 0.013, for PFS) serve as protective prognostic factors after multiple covariate adjustments. Multivariate analyses identified all adiposity-related parameters, including Low Attenuation Muscle Area (LAMA, HR = 1.015, 95% CI 1.003-1.026, P = 0.012, for PFS), intermuscular adipose tissue (IMAT, HR = 1.018, 95% CI 1.002-1.034, P = 0.027, for PFS), and VFI (HR = 1.008, 95% CI 1.001-1.015, P = 0.042) as negative indicators for survival. Sensitivity analyses confirmed these associations. Besides, IMAT, LAMA, and VFI significantly influence prognosis in advanced patients (TNM stage III-IV). Kaplan-Meier survival analysis revealed sarcopenic visceral obesity markedly reduces survival; when combined with myosteatosis (SMVO), this combined phenotype further exacerbated CRS (5-year CRS: 74.7% in SMVO, P = 0.019) beyond the effects of individual phenotypes. CONCLUSION: Sarcopenic obesity (myosteatosis/visceral obesity) can identify poorer prognosis in gastric cancer patients, especially male patients. It is crucial for obese gastric cancer patients to evaluate their body composition, specifically focusing on fat distribution. TRIAL REGISTRATION: Registered in August 2016, NCT02873676 at www. CLINICALTRIALS: gov .

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