title: Derived neutrophil lymphocyte ratio may predict benefit from cisplatin in the advanced biliary cancer: the ABC-02 and BT-22 studies.
abstract: BACKGROUND
  The superiority of cisplatin and gemcitabine (CisGem) chemotherapy over gemcitabine (Gem) alone in patients with advanced biliary tract cancer (ABC) has been demonstrated in two randomised trials; ABC02 and the Biliary Tract (BT) 22 study. We used a combined dataset from these two trials to investigate the derived neutrophil-to-lymphocyte ratio (dNLR), which is thought to be a prognostic factor associated with clinical outcomes in several solid tumours, including ABC.
  
  
  METHODS
  White blood cell (WBC) and absolute neutrophil count (ANC) were available for 379 of 410 patients from ABC-02 and all 83 patients in BT-22. The dNLR was calculated as ANC/(WBC-ANC), as previously specified. We examined the association between dNLR and overall survival (OS) and progression-free survival (PFS), as well as comparing the treatment effect in two patient groups defined by their dNLR level. A high dNLR was defined as ≥3.0, which was approximately the upper tertile value.
  
  
  RESULTS
  A total of 462 individual patient records were analysed, 328 with baseline dNLR <3 and 134 with dNLR ≥3. There were 443 deaths in the cohort, and all surviving patients had a dNLR <3. There was strong evidence that dNLR was closely associated with both OS [hazard ratio (HR), 1.62; 95% confidence interval (CI) 1.32-2.01] and PFS (HR, 1.40; 95% CI 1.13-1.72). There was limited evidence (P = 0.10) of a differential effect of CisGem on OS between the two dNLR groups, but this was clearest in the ABC-02 dataset (P = 0.06). There was good evidence (P = 0.008) of an association between low baseline dNLR and long-term survival on a CisGem regimen. There was also good evidence of an association between ECOG performance status (split at 0 and 1 versus 2) on both OS (P < 0.001) and PFS (P = 0.01), but no evidence of a differential treatment effect, with both groups receiving benefit from the addition of cisplatin.
  
  
  CONCLUSIONS
  These data confirm that high dNLR is associated with worse OS and PFS, and suggests it may also be predictive of benefit for the addition of cisplatin to gemcitabine in European patients with ABC. Incorporating dNLR into the clinical context may better inform prognosis and chemotherapy decisions in ABC patients.
authors.affiliation: Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: T
authors.initials: T
authors.lastname: Grenader
authors.affiliation: Cancer Research UK and UCL Clinical Trials Centre, UCL, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Nash
authors.affiliation: Department of Oncology, Soroka Medical Center, Be'er Sheva, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Plotkin
authors.affiliation: Department of Oncology, Kyorin University School of Medicine, Tokyo.
authors.forename: J
authors.initials: J
authors.lastname: Furuse
authors.affiliation: Department of Oncology, Aichi Cancer Center Hospital, Nagoya.
authors.forename: N
authors.initials: N
authors.lastname: Mizuno
authors.affiliation: Department of Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okusaka
authors.affiliation: Department of Oncology, Imperial Healthcare, London.
authors.forename: H
authors.initials: H
authors.lastname: Wasan
authors.affiliation: Institute of Cancer Sciences, University of Manchester, Manchester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Valle
authors.affiliation: Shaare Zedek Medical Center, Jerusalem, Israel. Electronic address: j.bridgewater@ucl.ac.uk.
authors.forename: J
authors.initials: J
authors.lastname: Bridgewater
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000401:mortality; D014408:Biomarkers, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D009504:Neutrophils / Q000166:cytology*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine
keywords: biliary tract cancer; cisplatin and gemcitabine; neutrophil lymphocyte ratio; predictive; prognostic