title: Neutrophil-lymphocyte ratio as a predictive biomarker for response to high dose interleukin-2 in patients with renal cell carcinoma.
abstract: BACKGROUND
  Immunotherapy with high-dose interleukin-2 (HD-IL2) results in long-term survival in some metastatic renal cell carcinoma (mRCC) patients but has significant acute toxicities. Biomarkers predicting response to therapy are needed to better select patients most likely to benefit. NLR (absolute neutrophil count (ANC)/absolute lymphocyte count (ALC)) is a prognostic and predicative biomarker in various malignancies. The goal was to determine whether NLR can predict response to HD-IL2 in this setting.
  
  
  METHODS
  Patients with clear cell mRCC treated with HD-IL2 were identified from an institutional database from 2003-2012. Baseline variables for the assessment of IMDC risk criteria, and neutrophil and lymphocyte count, were collected. Best response criteria were based on RECIST 1.0. Wilcoxon rank-sum test was used to evaluate the association of continuous baseline variables with disease control. NLR was stratified by ≤4 or >4. Progression free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and Cox proportional hazard models assessed associations of NLR with survival.
  
  
  RESULTS
  In 71 eligible patients, median NLR in those with an objective response (n = 14, 20%) was 2.3 vs 3.4 in those without (n = 57, 80%, p = 0.02). NLR ≤4 was associated with improved progression free and overall survival. After adjustment for IMDC risk criteria, NLR remained a significant predictor of OS (ANC/ALC ≤4 vs >4, HR 0.41, 95% CI 1.09-5.46, p = 0.03; ANC/ALC continuous variable per unit change in NLR, HR 1.08, 95% CI 1.01-1.14, p = 0.03).
  
  
  CONCLUSIONS
  In this discovery set, NLR predicts overall survival in patients treated with HD-IL2 in mRCC, and may allow better patient selection in this setting. Data needs validation in an independent cohort.
authors.affiliation: University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Kuzman
authors.affiliation: University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.|Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.
authors.forename: David D
authors.initials: DD
authors.lastname: Stenehjem
authors.affiliation: University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Merriman
authors.affiliation: Department of Pathology and ARUP Laboratories, University of Utah, Salt Lake City, UT, USA.
authors.forename: Archana M
authors.initials: AM
authors.lastname: Agarwal
authors.affiliation: University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
authors.forename: Shiven B
authors.initials: SB
authors.lastname: Patel
authors.affiliation: University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Hahn
authors.affiliation: University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
authors.forename: Anitha
authors.initials: A
authors.lastname: Alex
authors.affiliation: University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Albertson
authors.affiliation: University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Gill
authors.affiliation: University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA. neeraj.agarwal@hci.utah.edu.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D007958:Leukocyte Count; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D007376:Interleukin-2
keywords: High dose interleukin-2; Neutrophil lymphocyte ratio; Renal cell carcinoma