br c Division of Hematology Medical Oncology Mayo

c Division of Hematology/Medical Oncology, Mayo Clinic, Phoenix, AZ, USA
d Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA
e 21st Century Oncology, Inc., Fort Meyers, FL, USA
f Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
g Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA
h Division of Biostatistics, The Ohio State University, Columbus, OH, USA
i Division of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
Article history:
Received in revised form
Available online 10 November 2018
Keywords:
Pancreatic ductal adenocarcinoma
Inflammation
Weight loss
Biomarker
Background: Cachexia is a wasting syndrome characterized by involuntary loss of >5% body weight due to depletion of adipose and skeletal muscle mass. In cancer, the pro-inflammatory cytokine interleukin-6 (IL-6) is considered a mediator of cachexia and a potential biomarker, but the relationship between IL-6, weight loss, and cancer stage is unknown. In this study we sought to evaluate IL-6 as a biomarker of cancer cachexia while accounting for disease progression.
Methods: We retrospectively studied 136 subjects with biopsy-proven pancreatic ductal adenocarcinoma (PDAC), considering the high prevalence of cachexia is this population. Clinical data were abstracted from subjects in all cancer stages, and BYL-719 IL-6 levels were measured using a multiplex array and a more sensitive ELISA. Data were evaluated with univariate comparisons, including Kaplan-Meier survival curves, and multivariate Cox survival models.
Results: On multiplex, a total of 43 (31.4%) subjects had detectable levels of plasma IL-6, while by ELISA all subjects had detectable IL-6 levels. We found that increased plasma IL-6 levels, defined as detectable for multiplex and greater than median for ELISA, were not associated with weight loss at diagnosis, but rather with the presence of metastasis (p < 0.001 for multiplex and p ¼ 0.007 for ELISA). Further, while >5% weight loss was not associated with worse survival, increased plasma IL-6 by either methodology was.
Conclusion: Circulating IL-6 levels do not correlate with cachexia (when defined by weight loss), but rather with advanced cancer stage. This suggests that IL-6 may mediate wasting, but should not be considered a diagnostic biomarker for PDAC-induced cachexia.
© 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.
* Corresponding author. Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University Wexner Medical Center, 410 West Tenth Avenue, Co-lumbus, OH 43210, USA. E-mail address: [email protected] (P.A. Hart).
Introduction
Pancreatic ductal adenocarcinoma (PDAC) is the second leading cause of cancer-related deaths with a poor 5-yr survival of <10% [1]. While these symptoms are due to local tumor effects, patients also
Abbreviations:
BMI body mass index
IL-6 Interleukin-6
PDAC pancreatic ductal adenocarcinoma
frequently present with systemic such as weight loss. Tumor-induced inflammation leads to anorexia and has been suggested as the cause of the hypermetabolic state observed in many cancer patients [2,3]. Additionally, anatomic compression from the mass can cause gastric outlet obstruction and/or exocrine pancreatic insufficiency leading to impaired oral intake and malabsorption, respectively. This combination of factors can lead to cachexia, which is characterized by weight loss due to the loss of adipose and skeletal muscle tissues. Although objective data are available for body weight in electronic medical records for patients, pre-morbid body weights are often unavailable, and self-reported weights are at risk for recall bias [4e6]. This is a key limitation in the field of cancer cachexia research and illustrates the need for a more objective disease biomarker.