Assessment of the Metabolic Profile in Gastric Cancer Associated Cachexia

Cancer-associated cachexia is a complex syndrome defined by the progressive loss of fat and skeletal muscle, resistant to conventionally used nutritional interventions. Recent evidence, however, points to adipose tissue not merely as an energy reservoir, but as a metabolically active and inflamed entity. 18F-FDG PET/CT allows for the measurement of this metabolic activity, offering a new pathophysiological perspective. In this context, studying metabolic changes in adipose tissues is fundamental for discovering new biomarkers for this syndrome. To characterize the tissue metabolic profile (adipose and muscular) and inflammatory status of patients with gastric cancer, comparing cachectic and non-cachectic individuals. A prospective study with 48 patients with gastric cancer. For cachexia diagnosis, Fearon's criteria were used (weight loss >5%, or >2% associated with low BMI or sarcopenia according to Martin). Body composition was quantified via computed tomography (CT) using an automated deep learning algorithm (U-Net + ResNet18). Metabolic activity (mean SUV) in subcutaneous (SAT) and visceral (VAT) adipose tissues was measured by 18F-FDG PET/CT, with segmentation performed in FIJI (Beth Israel Plugin). Laboratory data (CRP, CRP/albumin, and NLR) were collected via medical records and managed on the REDCap platform. Statistical analysis (Jamovi® 2.3) employed Chi-square, Fisher's Exact, Student's t, and Mann-Whitney U tests (p<0.05). The study was conducted with ethical approval (CAAE: 76237023.0.0000.5404). Of the 48 patients, 66.7% presented with cachexia according to Fearon. Cachexia was significantly associated with higher metabolic uptake in VAT and SAT, assessed by PET/CT, in both categorical and continuous analyses (mean VAT SUV: p=0.011; mean SAT SUV: p=0.002). Cachectic patients exhibited a higher frequency of severe weight loss (p<0.001), lower food intake (p<0.001), and a distinct distribution of BMI categories (p=0.011). Furthermore, an association was observed between cachexia and elevated neutrophil-to-lymphocyte ratio levels (categorical NLR, p=0.047), as well as inflammatory markers CRP (p=0.008) and CRP/albumin ratio (p=0.002). There was no significant association between cachexia and sarcopenia, myosteatosis, visceral obesity, insulin resistance, or skeletal muscle metabolic uptake. There was also no difference regarding tumor 18F-FDG uptake between the groups. Therefore, the data demonstrate that cachexia, in the context of gastric cancer, is marked by a hypermetabolic state of adipose tissue (VAT and SAT) and exacerbated systemic inflammation. This occurs independently of the tumor glycolytic avidity or of the patient's muscle depletion levels. Thus, the findings suggest that this metabolic activation of adipose tissue may be a crucial event in the energy wasting associated with cachexia, highlighting it as a potential marker of the syndrome's severity.