Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2022; 14(7): 1307-1323
Published online Jul 15, 2022. doi: 10.4251/wjgo.v14.i7.1307
Neutrophile-to-lymphocyte, lymphocyte-to-monocyte, and platelet-to-lymphocyte ratios as prognostic and response biomarkers for resectable locally advanced gastric cancer
Tiago Cruz Tomás, Inês Eiriz, Marina Vitorino, Rodrigo Vicente, João Gramaça, Alicia Guadalupe Oliveira, Paulo Luz, Mafalda Baleiras, Ana Sofia Spencer, Luísa Leal Costa, Patrícia Liu, Joana Mendonça, Magno Dinis, Teresa Padrão, Marisol Correia, Gonçalo Atalaia, Michelle Silva, Teresa Fiúza
Tiago Cruz Tomás, Inês Eiriz, Marina Vitorino, Rodrigo Vicente, Gonçalo Atalaia, Michelle Silva, Teresa Fiúza, Department of Medical Oncology, Hospital Professor Doutor Fernando Fonseca EPE, Amadora 2720-276, Portugal
João Gramaça, Department of Medical Oncology, Centro Hospitalar Barreiro-Montijo EPE, Barreiro 2830-003, Portugal
Alicia Guadalupe Oliveira, Department of Medical Oncology, Hospital do Espírito Santo de Évora EPE, Évora 7000-811, Portugal
Paulo Luz, Department of Medical Oncology, Centro Hospitalar Universitário do Algarve EPE, Algarve 8000-386, Portugal
Mafalda Baleiras, Department of Medical Oncology, Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental EPE, Lisboa 1449-005, Portugal
Ana Sofia Spencer, Department of Medical Oncology, Hospital Santo António dos Capuchos, Centro Hospital Lisboa Central EPE, Lisboa 1169-050, Portugal
Luísa Leal Costa, Department of Medical Oncology, Hospital Beatriz Ângelo, Loures 2674-514, Portugal
Patrícia Liu, Department of Medical Oncology, Centro Hospitalar de Trás-os-Montes e Alto Douro EPE, Vila Real 5000-508, Portugal
Joana Mendonça, Department of Medical Oncology, Hospital da Senhora da Oliveira EPE, Guimarães 4835-044, Portugal
Magno Dinis, Department of Medical Oncology, Hospital Garcia de Orta EPE, Almada 2805-267, Portugal
Teresa Padrão, Department of Medical Oncology, Hospital da Luz, Lisboa 1500-650, Portugal
Marisol Correia, Department of Medical Oncology, Hospital Distrital de Santarém EPE, Santarém 2005-177, Portugal
Author contributions: Tomás TC designed and conducted the research, formally processed the statistical data, and wrote the paper; Vitorino M, Vicente R, Gramaça J, Oliveira AG, Luz P, Spencer AS, Eiriz I, Liu P, Mendonça J, Costa LL, Baleiras M, Dinis M, Correia M, and Padrão T performed the investigation and data collection; Atalaia G, Silva M, and Fiúza T supervised and validated the report.
Institutional review board statement: The study was reviewed and approved by the Ethical Committee for Health of Hospital Professor Doutor Fernando Fonseca (approval No. 045/2021).
Informed consent statement: The informed consent statement was waived.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No data are available.
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:
Corresponding author: Tiago Cruz Tomás, MD, Doctor, Department of Medical Oncology, Hospital Professor Doutor Fernando Fonseca EPE, IC 19, Amadora 2720-276, Portugal.
Received: August 2, 2021
Peer-review started: August 2, 2021
First decision: September 5, 2021
Revised: September 19, 2021
Accepted: June 23, 2022
Article in press: June 23, 2022
Published online: July 15, 2022
Processing time: 344 Days and 3.5 Hours
Research background

Fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) perioperative regimen became the standard of care in resectable locally advanced gastric cancer (LAGC), but there is still a need for prognostic and predictive response biomarkers. Blood ratios, such as neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR) and platelet-to-lymphocyte (PLR) ratios are known prognostic biomarkers in several solid tumors. Tumor regression grade (TRG) is a system used to evaluate residual tumor in patients submitted to preoperative therapies, providing information on the response to therapies and predicting prognosis.

Research motivation

This study investigated the prognostic and predictive significance of pre-treatment blood ratios in resectable LAGC.

Research objectives

This study assessed the potential value of NLR, LMR, and PLR in predicting survival outcomes and response to preoperative FLOT (preFLOT) regimen in resectable LAGC.

Research methods

We retrospectively analyzed patients with resectable LAGC treated with at least one preFLOT cycle, from 12 Portuguese hospitals. NLR, LMR, and PLR pre-treatment values were exploratory correlated with different variables, and with those statistically significant pre-treatment values were divided according to into high or low groups, determined by receiver operating characteristic curve, and evaluated regarding association to survival outcomes and response prediction. Relative risks and hazard ratios were calculated, with NLR, pathological complete response, T stage regression (TSR) and TRG as independent variables, and overall survival (OS) the dependent variable.

Research results

We included 295 patients in this study. NLR was correlated with time of survival (r = 0.143; P = 0.014). High PLR was defined as > 141 for progression and > 144 for mortality; high LMR was defined as > 3.56 for TSR. PLR was associated with systemic progression during FLOT (P = 0.022) and mortality (P = 0.013), with high PLR patients having 2.2 times higher risk of progression [95% confidence interval (CI): 0.89-5.26] and 1.5 times higher risk of mortality (95%CI: 0.92-2.55). LMR was associated with TSR and high LMR patients have 1.4 times higher risk of achieving TSR (95%CI: 1.01-1.99). OS benefit was found with TSR (P = 0.015) and partial/complete TRG (P < 0.001). Patients without TSR as well as no evidence of pathological response have 2.1 (95%CI: 1.14-3.96) and 2.8-times (95%CI: 1.6-5) higher risk of death.

Research conclusions

NLR, LMR, and PLR are significant biomarkers that are potential indicators for prognosis and treatment response prediction.

Research perspectives

In further investigation, validation of these blood ratios is important, as well as integration into risk scores that could help clinicians in the decision-making strategy in the clinical management of patients with resectable LAGC.