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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Tiago Cruz Tomás, MD, Doctor, Department of Medical Oncology, Hospital Professor Doutor Fernando Fonseca EPE, IC 19, Amadora 2720-276, Portugal. tiago.tomas@campus.ul.pt
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
BACKGROUND
Perioperative fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) improves prognosis in locally advanced gastric cancer (LAGC). Neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR), and platelet-to-lymphocyte (PLR) ratios are prognostic biomarkers but not predictive factors.
AIM
To assess blood ratios’ (NLR, LMR and PLR) potential predictive response to FLOT and survival outcomes in resectable LAGC patients.
METHODS
This was a multicentric retrospective study investigating the clinical potential of NLR, LMR, and PLR in resectable LAGC patients, treated with at least one preoperative FLOT cycle, from 12 Portuguese hospitals. Means were compared through non-parametric Mann-Whitney tests. Receiver operating characteristic curve analysis defined the cut-off values as: High PLR > 141 for progression and > 144 for mortality; high LMR > 3.56 for T stage regression (TSR). Poisson and Cox regression models the calculated relative risks/hazard ratios, using NLR, pathologic complete response, TSR, and tumor regression grade (TRG) as independent variables, and overall survival (OS) as the dependent variable.
RESULTS
This study included 295 patients (mean age, 63.7 years; 59.7% males). NLR was correlated with survival time (r = 0.143, P = 0.014). PLR was associated with systemic progression during FLOT (P = 0.022) and mortality (P = 0.013), with high PLR patients having a 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 had a 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 and with no evidence of pathological response had 2.1-times (95%CI: 1.14-3.96) and 2.8-times (95%CI: 1.6-5) higher risk of death.
CONCLUSION
Higher NLR is correlated with longer survival time. High LMR patients have a higher risk of decreasing T stage, whereas high PLR patients have higher odds of progressing under FLOT and dying. Patients with TSR and a pathological response have better OS and lower risk of dying.
Core Tip: Fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) perioperative regimen has become the standard of care for resectable locally advanced gastric cancer, but there is a need for prognostic and predictive biomarkers. Neutrophil-to-lymphocyte (NLR), lymphocyte-to-monocyte (LMR), and platelet-to-lymphocyte (PLR) ratios are useful in solid tumors. We performed exploratory analyses regarding pathological response prediction and survival outcomes. NLR is weakly correlated with overall survival, high LMR patients have higher risk of T stage regression, high PLR patients have higher odds of progressing under FLOT and higher risk of mortality, and patients without T stage or pathological regression have higher risk of dying.
