Neutrophile-to-lymphocyte, lymphocyte-to-monocyte, and platelet-to-lymphocyte ratios as prognostic and response biomarkers for resectable locally advanced gastric cancer

Abstract

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.

Prognostic significance of post-preoperative tumor markers increments in patients with non-metastatic gastric cancer

“…Based on previous research (Sturgeon et al 2010 ), the cutoff value of CEA and CA199 was 5 ng/ml and 37 U/ml, respectively. Besides, we calculated the prognostic nutritional index (PNI) and tumor-related inflammatory indicators, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR) in accordance with previous literature (Tomás et al 2022 ; Pikuła et al 2022 ; Gao et al 2018 ; Liu et al 2017 ). Patients were divided into three groups respectively according to the number of positive tumor markers (CEA and CA199) before surgery and the number of incremental tumor markers after surgery.…”

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as biomarkers to prognosticate survival in advanced gastric cancer patients in the era of immunotherapy: a systematic review and meta-analysis

“…A 2021 Italian study with a cohort of locally advanced patients treated with neoadjuvant chemotherapy demonstrated that baseline high NLR is significantly correlated with worse OS and PFS ( 3 ). A 2022 study also investigated patients with locally advanced disease receiving preoperative chemotherapy, finding a significant association between higher values of NLR and decreased OS ( 68 ). These results are in concordance with our findings and suggest the utility of novel biomarkers to prognosticate survival across the landscape of GC scenarios.…”

Prognostic significance of post-preoperative tumor markers increments in patients with non-metastatic gastric cancer

“…Besides, we calculated the prognostic nutritional index (PNI) and tumor related in ammatory indicators, including neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR) in accordance with previous literature. (Tomás TC et al 2022;Pikuła A et al 2022;Gao ZM et al 2018;Liu X et al 2017) Patients were divided into three groups respectively according to the number of positive tumor markers (CEA and CA199) before surgery and the number of incremental tumor markers after surgery. To further compare the predictive superiority between preoperative tumor markers levels and post-preoperative tumor markers increments, we divided patients into four groups based on whether preoperative tumor markers were positive and whether postoperative tumor markers were elevated.…”