title: Neutrophil-to-lymphocyte ratio as a prognostic marker in locally advanced nasopharyngeal carcinoma: A pooled analysis of two randomised controlled trials.
abstract: To assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with International Union Against Cancer (UICC)-staged III/IVA,B nasopharyngeal carcinoma (NPC), who were enrolled into two randomised controlled trials of concurrent/adjuvant chemotherapy when added to radiotherapy (SQNP01), and induction chemotherapy when added to chemoradiotherapy (NCC0901).
  
  
  
  A post hoc analysis of pooled cohorts from SQNP01 (N = 221) and NCC0901 (N = 172) was performed. We employed a threshold of pre-treatment NLR = 3.0 (median) to stratify patients. Survival outcomes were compared using log-rank test. Multivariable Cox regression analyses were performed to assess association between NLR and overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS).
  
  
  
  High NLR (≥3.0) was associated with advanced T-status (p = 0.002), N-status (p = 0.002), overall UICC stage (p = 0.004), and high pre-treatment Epstein-Barr virus DNA titre (p = 0.001). High NLR was not associated with OS (0.94 [0.67-1.32], p = 0.7), DFS (0.98 [0.73-1.33], p = 0.9), DMFS (1.02 [0.66-1.57], p = 0.9), and LRFS (1.37 [0.84-2.22], p = 0.2) on univariable and multivariable analyses, while conventional clinical indices (T-status, N-status, and overall UICC stage) were prognostic of clinical outcomes. High NLR also did not predict for a treatment effect with the experimental arms in both trials.
  
  
  
  Our pooled analyses that were confined to a homogenous patient population of locally advanced NPC do not suggest that NLR adds prognostic value to conventional clinical indices in identifying patients with unfavourable disease.
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore. Electronic address: Melvin.chua.l.k@singhealth.com.sg.
authors.forename: Melvin Lee Kiang
authors.initials: ML
authors.lastname: Chua
authors.affiliation: Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore, Singapore.
authors.forename: Sze Huey
authors.initials: SH
authors.lastname: Tan
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore.
authors.forename: Grace
authors.initials: G
authors.lastname: Kusumawidjaja
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore.
authors.forename: Ma Than Than
authors.initials: MT
authors.lastname: Shwe
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore.
authors.forename: Shie Lee
authors.initials: SL
authors.lastname: Cheah
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Kam Weng
authors.initials: KW
authors.lastname: Fong
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Yoke Lim
authors.initials: YL
authors.lastname: Soong
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Joseph Tien Seng
authors.initials: JT
authors.lastname: Wee
authors.affiliation: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Terence Wee Kiat
authors.initials: TW
authors.lastname: Tan
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma / Q000097:blood* / Q000473:pathology / Q000628:therapy / Q000821:virology; D002945:Cisplatin / Q000008:administration & dosage; D004279:DNA, Viral / Q000097:blood; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000097:blood; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy / Q000821:virology; D009367:Neoplasm Staging; D009504:Neutrophils; D011379:Prognosis; D016016:Proportional Hazards Models; D011878:Radiotherapy; D016032:Randomized Controlled Trials as Topic; D012846:Singapore; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D004279:DNA, Viral; D003841:Deoxycytidine; D016190:Carboplatin; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine
keywords: Biomarker; Locally advanced; Nasopharyngeal carcinoma; Neutrophil-to-lymphocyte ratio; Prognosis