Pretreatment Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Unresectable or Metastatic Esophageal Cancer Patients With Anti-PD-1 Therapy

Abstract

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) is an inflammatory index calculated by the absolute neutrophil count dividing the absolute lymphocyte count, and its prognostic role in esophageal cancer (EC) patients with anti-PD-1 therapy remains unclear.MethodsA total of 140 unresectable or metastatic EC patients receiving PD-1 inhibitor treatment were included from Jan 2016 to Mar 2020. Kaplan–Meier method and log-rank test were used for comparing overall survival (OS) and progression-free survival (PFS) between groups. Multivariate Cox analysis was performed to assess the prognostic value of NLR.ResultsThe cutoff value of NLR was set at 5, and the median follow-up time was 20.0 months. Patients with pretreatment NLR <5 had higher ORR (46.7% vs. 12.1%; p < 0.001) and DCR (85.0% vs. 69.7%; p = 0.047) than those with NLR ≥5. Kaplan–Meier curves showed that pretreatment NLR <5 was associated with longer PFS (median: 10.0 vs. 3.5 months, p < 0.0001) and OS (median: 22.3 vs. 4.9 months, p < 0.0001). Multivariate analysis demonstrated that pretreatment NLR ≥5 independently and significantly increased the risk of disease progression (hazard ratio (HR), 1.77 (95% confidence interval (CI), 1.12–2.82); p = 0.015) and death (HR, 4.01 (95% CI, 2.28–7.06); p < 0.001). Subgroup analysis showed that pretreatment NLR ≥5 was associated with poor efficacy and survival in most subsets.ConclusionsOur findings showed that pretreatment NLR was independently and significantly associated with the efficacy and prognosis of EC patients treated with PD-1 inhibitors. NLR could serve as a convenient and useful prognostic biomarker for EC patients with anti-PD-1 therapy.

Prognostic value of inflammatory markers and clinical features for survival in advanced or metastatic esophageal squamous cell carcinoma patients receiving anti-programmed death 1 treatment

“…Previous researches revealed that high NLR level has been consistently linked to a worse prognosis in EC when patients were treated with either topical therapies or systemic chemotherapy ( 34 , 35 ). Our results, consistent with these researches ( 29 , 30 ), showed that a high baseline NLR was in line with inferior survival in ESCC receiving immunotherapy. Multivariate cox analysis indicated that baseline NLR was an independent prognostic indicator for both PFS and OS.…”

“…Our results revealed that the survival of patients with low ECOG PS score significantly improved after anti-PD-1 therapy, and was therefore considered a significant prognostic indicator for PFS and OS. In accordance to our findings, patients with ECOG PS≥2 had poorer PFS and OS than those with ECOG PS ≤ 1 ( 30 ). Regarding treatment lines, we found that the PFS and OS of patients accepting first-line anti-PD-1 treatment were significantly longer than those accepting second-line or posterior treatment.…”

“…For example, Liu et al revealed that PLR, NLR, and SII at baseline were significantly linked to PFS and OS (29). Previous researches suggested that pretreatment high NLR was correlated with inferior PFS and OS (30)(31)(32). However, another retrospective study indicated that NLR at 6 weeks post-treatment but not at baseline was related to poor PFS (33).…”

Ability of Blood Cell Parameters to Predict Clinical Outcomes of Nivolumab Monotherapy in Advanced Esophageal Squamous Cell Carcinoma

“…The reported cutoffs of pretreatment NLRs required to significantly stratify survival range from 3 to 7 in these studies, [11][12][13]18 and 3.84, 5.0 and 6.0 for unresectable advanced and recurrent esophageal cancer, although the reports [11][12][13] included patients with esophageal adenocarcinoma treated by some types of ICI or by combination chemotherapies. [27][28][29] The optimal cutoff for pretreatment NLRs required to significantly stratify the survival of patients with ESCC who underwent nivolumab monotherapy in the present study was 4.9. Our cutoff value of NLR was within the range for those of esophageal and other types of cancer.…”

Nomogram Based on Monocyte-to-Lymphocyte Ratio to Predict Survival of Unresectable Esophageal Squamous Cell Carcinoma Who Receive First-Line PD-1/PD-L1 Inhibitors Combined with Chemotherapy

“…The neutrophil-to-lymphocyte ratio (NLR) and the monocyte-to-lymphocyte ratio (MLR) are recognized as the hallmarks of systemic inflammatory status that can reflect the prognosis of ICIs-received solid tumors: non-small-cell lung cancer (NSCLC) [ 21 ], melanoma [ 22 ], and gastric cancer (GC) [ 23 , 24 ]. Recent research has looked into the prognostic value of inflammatory indicators in ESCC patients who have received the anti-PD-1 immunotherapy [ 25 , 26 , 27 ]. In their studies, patients in the second or later lines make up a large proportion.…”