High Systemic Immune Inflammation Index Is Associated With Low Skeletal Muscle Quantity in Resectable Pancreatic Ductal Adenocarcinoma.

Jelle C. van Dongen,Claudia J. Lucassen,Dana A. M. Mustafa,Casper J. van Eijck,J. Sven D. Mieog,Jeroen L. A. van Vugt,Bas Groot Koerkamp,Kostandinos Sideras,Lawlaw Saida,Anneke Droop,Yordi van Putten,Jesse V. Groen,Mustafa Suker,Shirin Shahbazi Feshtali,Katya Mauff,Mohammad Hosein Aziz

doi:10.3389/fonc.2022.827755

Jelle C. van Dongen, Claudia J. Lucassen + Show 14 more

Open Access

https://doi.org/10.3389/fonc.2022.827755

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Abstract

Background and AimsFailing immune surveillance in pancreatic ductal adenocarcinoma (PDAC) is related to poor prognosis. PDAC is also characterized by its substantial alterations to patients’ body composition. Therefore, we investigated associations between the host systemic immune inflammation response and body composition in patients with resected PDAC.MethodsPatients who underwent a pancreatectomy for PDAC between 2004 and 2016 in two tertiary referral centers were included. Skeletal muscle mass quantity and muscle attenuation, as well as subcutaneous and visceral adipose tissue at the time of diagnosis, were determined by CT imaging measured transversely at the third lumbar vertebra level. Baseline clinicopathological characteristics, laboratory values including the systemic immune inflammation index (SIII), postoperative, and survival outcomes were collected.ResultsA total of 415 patients were included, and low skeletal muscle mass quantity was found in 273 (65.7%) patients. Of the body composition indices, only low skeletal muscle mass quantity was independently associated with a high (≥900) SIII (OR 7.37, 95% CI 2.31-23.5, p=0.001). The SIII was independently associated with disease-free survival (HR 1.86, 95% CI 1.12-3.04), and cancer-specific survival (HR 2.21, 95% CI 1.33-3.67). None of the body composition indices were associated with survival outcomes.ConclusionThis study showed a strong association between preoperative low skeletal muscle mass quantity and elevated host systemic immune inflammation in patients with resected PDAC. Understanding how systemic inflammation may contribute to changes in body composition or whether reversing these changes may affect the host systemic immune inflammation response could expose new therapeutic possibilities for improving patients’ survival outcomes.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal, with mortality rates being overlapped by its incidence rates [1]
Adipose tissue can contribute to carcinogenesis and PDAC pathobiology, as this organ can alter the systemic release of adipokines, growth factors, and multiple cytokines [16]
Seventeen patients died from causes other than pancreatic cancer (13 treatmentrelated, 1 due to a cerebrovascular accident, 1 due to a myocardial infarction, and two from an unknown cause), and were excluded from survival analysis

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal, with mortality rates being overlapped by its incidence rates [1]. The host systemic immune inflammation response [5], and alterations of the body composition [6] have received increasing attention in cancer prognostic studies, their combined associations in PDAC have not yet been considered. Cancer cachexia is known to affect a complex network of inflammatory mediators, such as tumor necrosis factor-alpha (TNF-a), interleukins (ILs) like IL-6 and IL-1, and C-reactive protein [11–14]. These mediators in their turn can affect skeletal muscle through direct (receptormediated) and indirect mechanisms (cytokine-induced dysregulation of other organs and tissue systems) [15].

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