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Cancer Epidemiol Biomarkers Prev. 2019 Sep 18. pii: cebp.0370.2019. doi: 10.1158/1055-9965.EPI-19-0370. [Epub ahead of print]

Post diagnosis loss of skeletal muscle, but not adipose tissue, is associated with shorter survival of patients with advanced pancreatic cancer.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute ababic1@partners.org.
2
Department of Imaging, Dana-Farber Cancer Institute and Harvard Medical School.
3
Health Sciences Research, Mayo Clinic.
4
Mayo Clinic.
5
Department of Hepatobiliary and Pancreatic Surgery division, National Cancer Center Hospital East.
6
University of Massachusetts Amherst.
7
Department of Medical Oncology, Dana-Farber Cancer Institute.
8
Internal Medicine, Division of Gastroenterology, Baylor College of Medicine.
9
Wilmot Cancer Institute, University of Rochester Medical Center.
10
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School.
11
Dana-Farber Cancer Institute.
12
Metabolomics, Broad Institute of MIT and Harvard University.
13
Children's Hospital Boston.
14
University of Alberta.
15
Division of Research, Kaiser Permanente Northern California.
16
Medical Oncology, Kaiser Permanente.
17
Metabolomics Platform, Broad Institute of Massachusetts Institute of Technology and Harvard.
18
Koch Institute/Biology, Massachusetts Institute of Technology.
19
Department of Health Sciences Research, Mayo Clinic College of Medicine.

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 at diagnosis and 50-120 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 to 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% CI, 1.12-3.62). Patients in the top quartile of muscle attenuation change (average decrease of 4.9 ± 2.4 Hounsfield units) had a HR of 2.19 (95% CI, 1.18-4.04) compared to 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 (BCAAs; 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 two to four 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.

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