title: Association between sex, cachexia status, and muscle wasting in pancreatic cancer
title: a retrospective study
titleType: Subtitle
Creators: name: Freeman, Ashley
Publisher: name: University of Iowa
Year: 2023
Subjects: cachexia
cancer
skeletal muscle
weight loss
public abstract
Pancreatic Cancer

description: Background: Cachexia is a complex metabolic disease consisting of progressive and unintentional weight loss from the depletion of skeletal muscle and adipose tissue. Cancer cachexia is formally defined through consensus definition as a weight loss of greater than 5% in six months. In pancreatic ductal adenocarcinoma (PDAC), up to 80% of patients have cachexia at the time of their diagnosis. Cachexia is associated with several negative outcomes, including reduced survival, greater treatment toxicity, worse post-surgical outcomes, and lower quality of life due to progressive functional impairment. Emerging evidence suggests sex is a critical variable in the pathophysiology of cancer cachexia. Objective: To investigate the sex difference in body composition in patients with PDAC and, subsequently, advance how cachexia clinical trials and therapeutics are used clinically. Methods: Body composition was assessed on CT images of PDAC patients taken during routine care. Total cross-sectional area of skeletal muscle (SKM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were assessed at the third lumbar vertebrae. Clinical data were extracted from patient medical records. Survival data were analyzed for 192 PDAC patients. To understand differences in body composition at the time of diagnosis, scans closest to diagnosis were analyzed for the 176 treatment-naïve patients. Results: 72% of patients had cachexia at the time of diagnosis. Mean weight loss in cachectic patients at the time of diagnosis was 13.19%, compared to the mean weight loss of 1.84% in non-cachectic patients. Cachectic males had lower SKM indices at the time of diagnosis compared to their non-cachectic counterparts (83.78 ± 14.15 cm^2/m cachectic vs. 90.39 ± 14.90 cm^2/m non-cachectic, p=0.047), but females had no such association (69.76 ±10.60 cm^2/m cachectic vs. 70.07 ± 10.59 cm^2/m non-cachectic, p=0.90). Cachectic females had lower SAT indices at the time of diagnosis (75.09 ± 36.18 cm^2/m cachectic vs. 57.36 ± 30.77 cm^2/m non-cachectic, p=0.03), but no such differences were seen between cachectic and non-cachectic males (19.27 ± 8.71 cm^2/m vs. 23.03 ± 10.20 cm^2/m, respectively, p=0.08). Consistent with published data, patients with cachexia had significantly shorter median survival than those without cachexia (1.96 years non-cachectic vs. 1.46 years cachectic, p=0.009). Separate analyses revealed that a BMI-adjusted weight loss grading system referred to as cachexia grade significantly associated with survival in males (1.93 years low-grade vs. 1.56 years high-grade, p=0.001) but not females (1.36 years low-grade vs. 1.40 years high-grade, p=0.58). These sex differences remained after adjustment for age and metastatic disease. Conclusions: Our data show distinct differences in the phenotype of males and females with pancreatic cancer-induced cachexia and necessitates exploration of sex-specific anti-cachexia therapeutic interventions.