title: Pattern of CAIX expression is prognostic for outcome and predicts response to ARCON in patients with laryngeal cancer treated in a phase III randomized trial.
abstract: OBJECTIVE
  In a phase III trial in patients with advanced stage laryngeal carcinoma comparing ARCON (accelerated radiotherapy with carbogen breathing and nicotinamide) to accelerated radiotherapy alone (AR) the prognostic and predictive value of CAIX, a hypoxia-associated protein, was investigated.
  
  
  METHODS
  261 Paraffin embedded tumor biopsies and 79 fresh frozen biopsies from patients entered in the trial were immunohistochemically stained for CAIX. CAIX-fraction and CAIX expression pattern were related to tumor control and patient survival.
  
  
  RESULTS
  Low CAIX-fraction was prognostic for worse regional control and overall survival in patients treated with AR. Patients with a low CAIX-fraction treated with ARCON had better regional control and metastasis-free survival compared to AR (RC 97% vs 71%, p < 0.01 and MFS 92% vs 69%, p = 0.06). Patients with a perinecrotic CAIX staining pattern had a significantly worse local control, metastasis-free and overall survival compared to patients with a diffuse pattern (65% vs 84%, p = 0.01, 70% vs 96%, p < 0.01 and 42% vs 71%, p < 0.01 respectively), and this could not be improved with ARCON. After multivariate analysis CAIX pattern and N-stage emerged as significant predictors for metastasis-free survival and overall survival.
  
  
  CONCLUSIONS
  ARCON improves regional control and metastasis-free survival only in patients with low CAIX expression. The different patterns of CAIX expression suggest different mechanisms of upregulation and have important prognostic value.
authors.affiliation: Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, The Netherlands. Electronic address: s.rademakers@rther.umcn.nl.
authors.forename: Saskia E
authors.initials: SE
authors.lastname: Rademakers
authors.forename: Ilse J
authors.initials: IJ
authors.lastname: Hoogsteen
authors.forename: Paul F
authors.initials: PF
authors.lastname: Rijken
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.forename: Chris H
authors.initials: CH
authors.lastname: Terhaard
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Doornaert
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
authors.forename: Piet
authors.initials: P
authors.lastname: van den Ende
authors.forename: Robert
authors.initials: R
authors.lastname: Takes
authors.forename: Remco
authors.initials: R
authors.lastname: De Bree
authors.forename: Albert J
authors.initials: AJ
authors.lastname: van der Kogel
authors.forename: Johan
authors.initials: J
authors.lastname: Bussink
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Kaanders
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis*; D002245:Carbon Dioxide / Q000627:therapeutic use*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis*; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000201:enzymology / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000627:therapeutic use*; D009593:Nitroimidazoles / Q000494:pharmacology; D010100:Oxygen / Q000627:therapeutic use*; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D009593:Nitroimidazoles; D002245:Carbon Dioxide; D009536:Niacinamide; C033815:pimonidazole; C011700:carbogen; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D010100:Oxygen
keywords: ARCON; CAIX; Hypoxia; Laryngeal cancer