title: Class III beta-tubulin expression and benefit from adjuvant cisplatin/vinorelbine chemotherapy in operable non-small cell lung cancer: analysis of NCIC JBR.10.
abstract: OBJECTIVE
  High class III beta-tubulin (bTubIII) expression in advanced non-small cell lung cancer is known to correlate with reduced response rates and inferior survival with anti-microtubule agents. JBR.10 showed a 12% and 15% improvement in 5-year recurrence-free survival (RFS) and overall survival (OS), respectively, with the addition of cisplatin and vinorelbine following resection of stage IB-II non-small cell lung cancer. We sought to determine the effect of bTubIII on patient outcome and benefit from adjuvant chemotherapy in the JBR.10 trial.
  
  
  METHODS
  We did a semiquantitative immunohistochemical assay for bTubIII on primary tumor tissue available from 265 of the 482 patients in JBR.10. Tumors were classified as bTubIII "low" or "high" using a validated method. We examined the prognostic effect of bTubIII in patients treated with or without chemotherapy and the survival benefit from chemotherapy in low versus high bTubIII subgroups.
  
  
  RESULTS
  High bTubIII expression was associated with poorer RFS and OS in patients treated with surgery alone but not in patients treated with adjuvant chemotherapy. The RFS and OS benefits of adjuvant chemotherapy were greater in high versus low tubulin expressors. However, with Cox regression, the interaction between bTubIII status and chemotherapy treatment in predicting RFS or OS did not reach statistical significance.
  
  
  CONCLUSIONS
  Chemotherapy seemed to overcome the negative prognostic effect of high bTubIII expression. Greater benefit from adjuvant chemotherapy was seen in patients with high bTubIII expression. This is contrary to what has been seen in the setting of advanced disease; possible reasons for this difference are being explored.
authors.affiliation: Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sève
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.forename: Keyue
authors.initials: K
authors.lastname: Ding
authors.forename: Timothy
authors.initials: T
authors.lastname: Winton
authors.forename: Charles
authors.initials: C
authors.lastname: Butts
authors.forename: John
authors.initials: J
authors.lastname: Mackey
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
authors.forename: Laith
authors.initials: L
authors.lastname: Dabbagh
authors.forename: Sarit
authors.initials: S
authors.lastname: Aviel-Ronen
authors.forename: Lesley
authors.initials: L
authors.lastname: Seymour
authors.forename: Marlo
authors.initials: M
authors.lastname: Whitehead
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.forename: Frances A
authors.initials: FA
authors.lastname: Shepherd
authors.forename: Tony
authors.initials: T
authors.lastname: Reiman
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome; D014404:Tubulin / Q000096:biosynthesis*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: C498585:TUBB3 protein, human; D014404:Tubulin; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine