ADIPOSE TISSUE METABOLISM IN RECTAL CANCER PATIENTS WITH CACHEXIA

Adipose tissue (AT) glucose uptake, assessed by Fludeoxyglucose F-18 (FDG) positron emission tomography/computed tomography (PET/CT), reflects tissue metabolic activity and may be linked to both glucose metabolism by adipocytes and inflammatory cell activity. Additionally, adipose tissue radiodensity, measured by computed tomography (CT), has emerged as a promising metabolic biomarker. Increased AT radiodensity may indicate inflammation or the presence of brown adipose tissue (BAT), providing insights into pathophysiological processes underlying cancer cachexia. The purpose of this study was to evaluate adipose tissue metabolism, assessed by the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) glucose uptake through ¹⁸F-FDG PET/CT analysis and VAT and SAT radiodensity assessed by CT in cachexia (C) and non-cachexia (NC) rectal cancer patients. This is a cross-sectional study involving patients diagnosed with rectal cancer. Cachexia was categorized according to Fearon's criteria, being defined as weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] < 20 kg/m 2 ) or low skeletal muscle mass (defined according to Martin's criteria). Body composition and tissue radiodensity was analyzed using computed tomography (CT) images processed with the SliceOmatic software based on the difference in tissue measurements by Hounsfield Units (HU). The segmentation and data collection of PET/CT images are performed in FIJI and the Beth Israel Plugin for FIJI. In the segmented areas (VAT and SAT), glucose uptake values (¹⁸F-FDG) are collected, represented by the Standard Uptake Value (SUV) variable. M-value was determined using euglycemic hyperinsulinemic clamp. Demographics characteristics, disease-related data, and biochemical test results were collected from medical records. Statistical analyses were performed using Jamovi® version 2.3. This study protocol was approved by the Institutional Review Board (CAAE: 91217418.2.0000.5404). A total of 36 patients were included in the analysis. Cachexia was diagnosed in 25 patients (69.4%). The median age was 64 years (range: 43-74) in the C group and 62 years (range: 47-72) in the NC group. Weight loss greater than 5% occurred in all C patients, and low muscularity in 36.4% of this group. Cachexia patients had a higher VAT SUV mean (0.815 ± 0.184) compared to NC (0.644 ± 0.148), p = 0.005. VAT glucose uptake was correlated with VAT radiodensity (rho = 0.678, p < 0.001) and weight loss (rho = 0.434, p = 0.015) while it was negatively correlated with VAT area (rho = -0.412, p = 0.021). Additionally, VAT radiodensity showed a negative correlation with VAT area (rho = -0.452, p = 0.008), SAT area (rho = -0.465, p = 0.006), and BMI (rho = -0.695, p = 0.015). Positive correlations were observed between VAT radiodensity and SAT radiodensity (rho = 0.633, p < 0.001) and SAT SUV mean (rho = 0.532, p = 0.002). No significant correlation was found between VAT SUV mean and M-value; however, M-value-TBW correlated with VAT radiodensity (rho = 0.369, p = 0.03). These findings suggest that VAT metabolism may serve as a potential biomarker in cachexia and underscore the need to expand investigations into the metabolic alterations that influence the pathophysiology of cachexia.