Baseline derived neutrophil-to-lymphocyte ratio as a prognostic biomarker for non-colorectal gastrointestinal cancer patients treated with immune checkpoint blockade

Clin Immunol. 2020 Mar:212:108345. doi: 10.1016/j.clim.2020.108345. Epub 2020 Jan 15.

Abstract

Background: Biomarkers in non-colorectal gastrointestinal (GI) cancer patients receiving immune checkpoint blockades (ICBs) are still limited.

Methods: Data were prospectively collected from a discovery cohort (n = 53) and a validation cohort (n = 107) in patients with non-colorectal GI cancer receiving ICB, as well as a chemotherapy-only cohort (n = 171). System inflammatory markers and derived neutrophil-to-lymphocyte ratio (dNLR) were determined as biomarkers by univariate and multivariate analyses.

Results: A higher level of dNLR (cutoff = 3) was associated with shorter overall survival (OS) in discovery and validation cohorts. In pooled cohort, disease control rate (DCR) (28% vs. 48.1%) was associated with dNLR (p = .017). In univariate analysis, original tumor site, tumor histopathology, number of metastases, and dNLR were correlated with OS. In multivariate analysis, higher dNLR level was correlated with reduced OS (10.43 months vs. 4.20 months, p < .001). In chemotherapy-only cohort, dNLR was also correlated with DCR and OS.

Conclusion: Higher dNLR level was correlated with worse outcomes, suggesting that dNLR may help risk-group stratification and assist disease management strategies as a prognostic biomarker for non-colorectal GI patients receiving ICB.

Keywords: Immune checkpoint blockade; Inflammation; Non-colorectal GI cancer; Overall survival; dNLR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / metabolism
  • Biomarkers
  • CTLA-4 Antigen / antagonists & inhibitors
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Digestive System Neoplasms / blood
  • Digestive System Neoplasms / drug therapy
  • Digestive System Neoplasms / pathology
  • Esophageal Neoplasms / blood
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / pathology
  • Female
  • Gallbladder Neoplasms / blood
  • Gallbladder Neoplasms / drug therapy
  • Gallbladder Neoplasms / pathology
  • Humans
  • Leukocyte Count
  • Liver Neoplasms / blood
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology
  • Lymphocyte Count*
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neutrophils*
  • Prognosis
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Progression-Free Survival
  • Retrospective Studies
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Survival Rate
  • Young Adult

Substances

  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Biomarkers
  • CD274 protein, human
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor