Postdiagnosis Loss of Skeletal Muscle, but Not Adipose Tissue, Is Associated with Shorter Survival of Patients with Advanced Pancreatic Cancer
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nihms-1539040.pdf
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Accepted version
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Author(s)
Babic, Ana
Rosenthal, Michael H.
Bamlet, William R.
Takahashi, Naoki
Sugimoto, Motokazu
Danai, Laura V.
Morales-Oyarvide, Vicente
Khalaf, Natalia
Dunne, Richard F.
Brais, Lauren K.
Date Issued
September 2019
Journal
Cancer Epidemiology Biomarkers and Prevention
Publisher
American Association for Cancer Research (AACR)
Citation
Babic, Ana et al. "Postdiagnosis Loss of Skeletal Muscle, but Not Adipose Tissue, Is Associated with Shorter Survival of Patients with Advanced Pancreatic Cancer." Cancer Epidemiology Biomarkers and Prevention 28, 12 (December 2019): 2062–2069 © 2019 American Association for Cancer Research
Version
Author's final manuscript
Abstract
Background: Pancreatic cancer is associated with development of cachexia, a wasting syndrome thought to limit survival. Few studies have longitudinally quantified peripheral tissues or identified biomarkers predictive of future tissue wasting. Methods: Adipose and muscle tissue were measured by computed tomography (CT) at diagnosis and 50 to 120 days later in 164 patients with advanced pancreatic cancer. Tissue changes and survival were evaluated by Cox proportional hazards regression. Baseline levels of circulating markers were examined in relation to future tissue wasting. Results: Compared with patients in the bottom quartile of muscle change per 30 days (average gain of 0.8 ± 2.0 cm2), those in the top quartile (average loss of 12.9 ± 4.9 cm2) had a hazard ratio (HR) for death of 2.01 [95% confidence interval (CI), 1.12-3.62]. Patients in the top quartile of muscle attenuation change (average decrease of 4.9 ± 2.4 Hounsfield units) had an HR of 2.19 (95% CI, 1.18-4.04) compared with those in the bottom quartile (average increase of 2.4 ± 1.6 Hounsfield units). Changes in adipose tissue were not associated with survival. Higher plasma branched chain amino acids (BCAA; P = 0.004) and lower monocyte chemoattractant protein-1 (MCP-1; P = 0.005) at diagnosis were associated with greater future muscle loss. Conclusions: In patients with advanced pancreatic cancer, muscle loss and decrease in muscle density in 2 to 4 months after diagnosis were associated with reduced survival. BCAAs and MCP-1 levels at diagnosis were associated with subsequent muscle loss. Impact: BCAAs and MCP-1 levels at diagnosis could identify a high-risk group for future tissue wasting.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1158/1055-9965.epi-19-0370
