Thesis
Association between sex, cachexia status, and muscle wasting in pancreatic cancer: a retrospective study
University of Iowa
Master of Science (MS), University of Iowa
Spring 2023
DOI: 10.25820/etd.007136
Abstract
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.
Details
- Title: Subtitle
- Association between sex, cachexia status, and muscle wasting in pancreatic cancer: a retrospective study
- Creators
- Ashley Freeman
- Contributors
- Erin Talbert (Advisor)Jessica Gorzelitz (Committee Member)Jessica Sieren (Committee Member)
- Resource Type
- Thesis
- Degree Awarded
- Master of Science (MS), University of Iowa
- Degree in
- Health and Human Physiology
- Date degree season
- Spring 2023
- Publisher
- University of Iowa
- DOI
- 10.25820/etd.007136
- Number of pages
- x, 39 pages
- Copyright
- Copyright 2023 Ashley Freeman
- Language
- English
- Date submitted
- 04/25/2023
- Date approved
- 05/01/2023
- Description illustrations
- Illustrations, tables, graphs, charts
- Description bibliographic
- Includes bibliographical references (pages 36-39).
- Public Abstract (ETD)
Cachexia is a side effect of cancer that refers to unintentional loss of muscle and fat. Patients with pancreatic cancer experience the highest amount and greatest frequency of this cancer-induced weight loss. Patients with greater weight loss at the time of their cancer diagnosis have poorer outcomes than those with less weight loss. Emerging evidence suggests that despite similar amounts of weight loss between males and females, the contents of this weight loss might be vastly different. This type of distinct difference between sexes is referred to as a sexual dimorphism—something that we set out to investigate. We used CT scans, routine image assessments of cancer, to analyze the muscle and fat composition of male and female pancreatic cancer patients and examine the differences that appear. We found that sex has an important influence on cancer cachexia, and we hope to use these findings to improve cachectic patients’ treatments, quality of life, and survival.
- Academic Unit
- Health and Human Physiology
- Record Identifier
- 9984425198202771
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