Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2024; 16(2): 386-397
Published online Feb 15, 2024. doi: 10.4251/wjgo.v16.i2.386
Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial
Vilma Pacheco-Barcia, Sara Custodio-Cabello, Fatima Carrasco-Valero, Magda Palka-Kotlowska, Axel Mariño-Mendez, Alberto Carmona-Bayonas, Javier Gallego, A J Muñoz Martín, Paula Jimenez-Fonseca, Luis Cabezon-Gutierrez
Vilma Pacheco-Barcia, Sara Custodio-Cabello, Magda Palka-Kotlowska, Luis Cabezon-Gutierrez, Department of Medical Oncology, Hospital Universitario de Torrejon, Madrid 28850, Spain
Fatima Carrasco-Valero, Department of Internal Medicine, Hospital Universitario de Torrejon, Madrid 28850, Spain
Axel Mariño-Mendez, Paula Jimenez-Fonseca, Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo 33011, Spain
Alberto Carmona-Bayonas, Department of Medical Oncology, Hospital Universitario Morales Meseguer, University of Murcia, Murcia 30001, Spain
Javier Gallego, Department of Medical Oncology, Hospital General Universitario de Elche, Elche 03202, Spain
A J Muñoz Martín, Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Universidad Complutense Madrid, Madrid 28007, Spain
Luis Cabezon-Gutierrez, Universidad Francisco de Vitoria, Madrid 28223, Spain
Author contributions: Pacheco-Barcia V, Mariño-Mendez A, and Jimenez-Fonseca P contributed to the conceptualization and project administration; Pacheco-Barcia V, Mariño-Mendez A, Jimenez-Fonseca P, and Cabezon-Gutierrez L were involved in the methodology and validation; Pacheco-Barcia V participated in the software, formal analysis, and data curation; Pacheco-Barcia V, Custodio-Cabello S, Carrasco-Valero F, Palka-Kotlowska M, Mariño-Mendez A, Carmona-Bayonas A, Gallego J, Martín AJM, Jimenez-Fonseca P, and Cabezon-Gutierrez L took part in the investigation of this study; Pacheco-Barcia V and Carrasco-Valero F contributed to the resources of this article; Pacheco-Barcia V, Jimenez-Fonseca P, and Cabezon-Gutierrez L wrote original draft; Pacheco-Barcia V, Carrasco-Valero F, and Jimenez-Fonseca P contributed to the writing, review and editing of this article; Custodio-Cabello S and Palka-Kotlowska M were involved in the visualization of this manuscript; Mariño-Mendez A, Jimenez-Fonseca P, and Cabezon-Gutierrez L participated in the supervision; and all authors have read and agreed to the published version of the manuscript.
Institutional review board statement: The study adhered to the ethical standards of the committee responsible for human experimentation (both institutional and national) and aligned with the 1975 Helsinki Declaration, as updated in 2008. The local ethics committee and Institutional Review Board approved the study under version 3.5, code PANT-SP-2023-01.
Informed consent statement: Consent was obtained from all patients who were alive at the time of data collection.
Conflict-of-interest statement: Pacheco-Barcia V: Advisory role: Advanced accelerator applications, a Novartis company. Speakers’ bureau: Merck, Eli Lilly, Eisai, Pierre Fabre. Congress attendance: Merck, Amgen, Merck Sharp and Dhome, Nutricia. Grant support: FSEOM and Merck. Other: Amgen. Martín AJM: Consultant or advisory role: GSK, Sanofi, Pfizer-BMS, Celgene, Leo Pharma, Incyte, Astra Zeneca, MSD, Lilly, Servier, Bayer, Roche. Research funding: Leo Pharma, Sanofi, Celgene. Speakers’ bureau: Rovi, Bayer, Menarini, Stada, Daichii Sankyo. Patents, Royalties. Other intellectual property: Risk assessment model in venous thromboembolism in cancer patients. Other authors declare no conflicts of interest related to this study.
Data sharing statement: Data supporting reported results can be requested from the authors.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Vilma Pacheco-Barcia, MD, MSc, PhD, Doctor, Department of Medical Oncology, Hospital Universitario de Torrejon, C/Mateo Inurria S/N, Madrid 28850, Spain. vepacheco@torrejonsalud.com
Received: October 26, 2023
Peer-review started: October 26, 2023
First decision: December 2, 2023
Revised: December 14, 2023
Accepted: January 10, 2024
Article in press: January 10, 2024
Published online: February 15, 2024
Processing time: 98 Days and 12.5 Hours
ARTICLE HIGHLIGHTS
Research background

Cancer-related inflammation manifests both at the site of the tumor and systemically, releasing acute phase proteins and circulating immune cells into the bloodstream. Against this inflammatory backdrop, the systemic inflammatory response index (SIRI) based on neutrophil, monocyte, and lymphocyte counts, has emerged as a prognostic factor in pancreatic cancer. Its utility extends to predicting overall survival (OS) in those undergoing chemotherapy, reflecting the status of both the immune response and systemic inflammation. One of the most conspicuous and clinically evident outcomes of the pro-inflammatory state is the anorexia-cachexia syndrome. While malnutrition and cachexia are acknowledged as adverse prognostic factors, the correlation between serum pro-inflammatory mediators and nutritional parameters, as well as the combined or individual contribution of each to prognosis, has yet to be clearly defined.

Research motivation

For patients with advanced pancreatic cancer, the systemic inflammatory response triggered by the disease often precipitates malnutrition. This is evident in cancer cachexia, a multifactorial hypermetabolic state characterized by involuntary weight loss, skeletal muscle depletion, and potentially, reduction in body fat. Unfortunately, traditional nutritional interventions might not effectively counteract this condition.

Research objectives

The primary objective of this pilot study, conducted as part of the PANTHEIA-Spanish Society of Medical Oncology (SEOM) initiative, is to analyze the utility of SIRI as a prognostic factor for response in patients with metastatic pancreatic cancer and to investigate its association with weight loss.

Research methods

This study included patients with pathologically confirmed metastatic pancreatic adenocarcinoma, treated from January 2020 to January 2023. The index was calculated using the product of neutrophil and monocyte counts, divided by lymphocyte counts, obtained 15 d before initiation chemotherapy. Originating from the PANTHEIA-SEOM initiative, a multicentric, observational, study promoted by the SEOM Real World-Evidence work group, our pilot research seeks to bridge this knowledge gap. Specifically, we focused on the interplay between weight loss and the inflammatory state as demarcated by SIRI.

Research results

We examined the survival outcomes of patients based on weight loss prior to diagnosis. The median OS for patients who experienced a weight loss > 5% in the three months before diagnosis was notably shorter than for those who did not, 6 mo compared to 19 mo, respectively, P = 0.003. However, within the low SIRI subgroup (< 2.3 × 10³/L), patients with low albumin levels (< 3.5 g/dL) tended to have worse OS (9 mo) compared to those with higher albumin levels (16 mo, P = 0.869). In patients with high SIRI values, albumin levels did not significantly affect survival outcomes. In the exploratory analysis of survival outcomes based on weight loss and SIRI values, the most striking difference was among patients with low SIRI levels (< 2.3 × 103/L): Those without weight loss of > 5% had a median OS of 20 mo compared to 11 mo for those who did have a weight loss of > 5%. In this pilot study, an elevated SIRI was suggested to be predictive of lower OS, progression free survival, and increased weight loss.

Research conclusions

Our findings indicate a significant correlation between elevated SIRI levels and decreased survival in patients with metastatic pancreatic cancer, with a notable association with weight loss. Furthermore, SIRI emerges as an independent prognostic factor of survival. By viewing SIRI as an emblem of systemic inflammation, we shed light on its potential link with the nutritional trajectories of these patients.

Research perspectives

This revelation is paramount, as discerning the intricate web of systemic inflammation, weight loss and the cachexia-anorexia syndrome could pave the way for early interventions, potentially enhancing patient prognosis.