Cachectic Body Composition and Inflammatory Markers Portend a Poor Prognosis in Patients with Locally Advanced Pancreatic Cancer Treated with Chemoradiation.

Stephanie E Combs,Jürgen Debus,Jonathan Eberlein,Jakob Liermann,Thilo Hackert,Benjamin Farnia,Patrick Naumann

doi:10.3390/cancers11111655

Abstract

Background: Patients with pancreatic cancer often develop cancer cachexia, a complex multifactorial syndrome with weight loss, muscle wasting and adipose tissue depletion with systemic inflammation causing physical impairment. In patients with locally advanced pancreatic cancer (LAPC) neoadjuvant treatment is routinely performed to allow a subsequent resection. Herein, we assess body composition and laboratory markers for cancer cachexia both before and after neoadjuvant chemoradiation (CRT). Methods: Subcutaneous fat (SCF), visceral fat (VF), skeletal muscle (SM), weight and laboratory parameters were determined longitudinally in 141 LAPC patients treated with neoadjuvant CRT. Changes during CRT were statistically analyzed and correlated with outcome and Kaplan–Meier curves were plotted. Different prognostic factors linked to cachexia were assessed by uni- and multivariable cox proportional hazards models. Results: There was a significant decrease in weight as well as SCF, VF and SM during CRT. The laboratory parameter C-reactive protein (CRP) increased significantly, whereas there was a significant decrease in leukocyte count, hemoglobin, albumin and cholinesterase as well as in the tumor marker CA 19.9. Cachectic weight loss, sarcopenia, reductions in body compartments SCF, VF and SM, and changes in laboratory markers as well as resection affected survival in univariable analysis. In multivariable analysis, weight loss >5% (HR 2.8), reduction in SM >5% (HR 5.5), an increase in CRP (HR 2.2) or CA 19.9 (HR 1.9), and resection (HR 0.4) remained independently associated with survival, whereas classical cachexia and sarcopenia did not. Interestingly, the subgroup of patients with cachectic weight loss >5% or SM reduction >5% during CRT did not benefit from resection (median survival 12 vs. 27 months). Conclusions: Persistent weight loss and muscle depletion during CRT as well as systemic inflammation after CRT impacted survival more than cachexia or sarcopenia according classical definitions.

Highlights

Cancer cachexia is defined as a multifactorial syndrome with ongoing loss of skeletal mass, termed sarcopenia, leading to fatigue and physical impairment
We previously reviewed evidence on the prognostic significance of continued weight loss and muscle depletion during CRT [25]; additional body composition markers such as subcutaneous fat, visceral fat, visceral obesity, sarcopenic visceral obesity as well as laboratory parameters associated with cachexia are the scope of the current retrospective analysis
Achieving a complete surgical resection after neoadjuvant treatment is crucial for prolonged survival in patients with locally advanced pancreatic cancer

Summary

Introduction

Cancer cachexia is defined as a multifactorial syndrome with ongoing loss of skeletal mass, termed sarcopenia, leading to fatigue and physical impairment. Patients with pancreatic cancer often develop cancer cachexia, a complex multifactorial syndrome with weight loss, muscle wasting and adipose tissue depletion with systemic inflammation causing physical impairment. In patients with locally advanced pancreatic cancer (LAPC) neoadjuvant treatment is routinely performed to allow a subsequent resection. We assess body composition and laboratory markers for cancer cachexia both before and after neoadjuvant chemoradiation (CRT). Methods: Subcutaneous fat (SCF), visceral fat (VF), skeletal muscle (SM), weight and laboratory parameters were determined longitudinally in 141 LAPC patients treated with neoadjuvant CRT. Sarcopenia, reductions in body compartments SCF, VF and SM, and changes in laboratory markers as well as resection affected survival in univariable analysis. Weight loss >5% (HR 2.8), reduction in SM >5% (HR 5.5), an increase in CRP (HR 2.2) or CA 19.9 (HR 1.9), and resection (HR 0.4)

Methods

Discussion

Conclusion