title: Change in platelet count as a prognostic indicator for response to primary tyrosine kinase inhibitor therapy in metastatic renal cell carcinoma.
abstract: OBJECTIVE
  To evaluate change in platelet count as an indicator of response to primary tyrosine kinase inhibitor (TKI) therapy for metastatic renal cell carcinoma (mRCC).
  
  
  METHODS
  We conducted a multicentre retrospective analysis of patients with mRCC undergoing primary TKI therapy from May 2005 to August 2014. Change in platelet count was defined as post-treatment platelet count after the first cycle of treatment minus the pretreatment platelet count. Response Evaluation Criteria in Solid Tumours were used to define partial response (PR), stable disease (SD) and progressive disease (PD). Analysis was conducted between subgroups with stable/increased (+ΔPlt) and decreased (-ΔPlt) counts. The primary outcome was overall survival (OS), determined using Kaplan-Meier analysis. Multivariable analysis was conducted for risk factors associated with PD.
  
  
  RESULTS
  A total of 115 patients with mRCC were analysed, of whom 19 (16.6%) had a +ΔPlt and 96 (83%) a -ΔPlt. More patients with a +ΔPlt had a Karnofsky score <80 (42.1 vs 14.6%; P = 0.005) and >2 metastatic sites (78.9 vs 51%; P = 0.041). More patients with +ΔPlt than with -ΔPlt had PD (89.4 vs 19.1%; P < 0.001) and more of those with -ΔPlt than with +ΔPlt had SD/PR (80.9 vs 10.6%; P < 0.001). Multivariable analysis showed that +ΔPlt (odds ratio [OR] 5.36, P < 0.001), Karnofsky score < 80 (OR 2.96, P = 0.002) and >2 metastatic sites at presentation (OR 1.87, P = 0.013) were risk factors for PD. Kaplan-Meier analysis showed a lower 5-year OS in patients with +ΔPlt than in those with -ΔPlt (23 vs 53%; P < 0.0001). +ΔPlt had a sensitivity of 48.6%, a specificity of 97.4%, a positive predictive value of 89.5% and a negative predictive value of 80.9% for PD.
  
  
  CONCLUSIONS
  Patients with a -ΔPlt were more likely to respond to TKI therapy and had longer OS. +ΔPlt above baseline had a high specificity for PD after primary TKI. Further investigation is required to determine the utility of ΔPlt.
authors.affiliation: Department of Urology, UC San Diego Health System, La Jolla, CA, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Hamilton
authors.affiliation: Department of Urology, UC San Diego Health System, La Jolla, CA, USA.
authors.forename: Hak J
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Jimenez
authors.affiliation: Department of Urology, Spectrum Health, Grand Rapids, MI, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Lane
authors.affiliation: Department of Urology, UC San Diego Health System, La Jolla, CA, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Urology, UC San Diego Health System, La Jolla, CA, USA.
authors.forename: Alp T
authors.initials: AT
authors.lastname: Beksac
authors.affiliation: Department of Urology, UC San Diego Health System, La Jolla, CA, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Gillis
authors.affiliation: Department of Urology, UC San Diego Health System, La Jolla, CA, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Alagh
authors.affiliation: Department of Urology, Spectrum Health, Grand Rapids, MI, USA.
authors.forename: Conrad
authors.initials: C
authors.lastname: Tobert
authors.affiliation: Department of Urology, UC San Diego Health System, La Jolla, CA, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Randall
authors.affiliation: Department of Urology, UC San Diego Health System, La Jolla, CA, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kane
authors.affiliation: Department of Urology, UC San Diego Health System, La Jolla, CA, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Millard
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Campbell
authors.affiliation: Department of Urology, UC San Diego Health System, La Jolla, CA, USA.
authors.forename: Ithaar H
authors.initials: IH
authors.lastname: Derweesh
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077210:Sunitinib; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib
keywords: Response Evaluation Criteria in Solid Tumours; Survival; carcinoma renal cell; metastasis; molecular targeted therapy; platelet count