title: Prognostic value of the proliferation marker Ki-67 in laryngeal carcinoma: results of the accelerated radiotherapy with carbogen breathing and nicotinamide phase III randomized trial.
abstract: BACKGROUND
  The prognostic and predictive value of the proliferation marker Ki-67 was investigated in a randomized trial comparing accelerated radiotherapy with carbogen breathing and nicotinamide (ARCON) to accelerated radiotherapy in laryngeal carcinoma.
  
  
  METHODS
  Labeling index of Ki-67 (Li Ki-67) in immunohistochemically stained biopsies and the colocalization with carbonic anhydrase IX (CAIX) were related to tumor control and patient survival.
  
  
  RESULTS
  On average, node-positive patients had a higher Li Ki-67 (median 14% vs 8%; p < .01). In patients with a high Li Ki-67, the 5-year regional control and metastases-free survival were 79% versus 96% (p < .01) and 71% versus 88% (p = .05) for accelerated radiotherapy and ARCON, respectively. The 5-year local control and disease-specific survival were not significantly different. Patients with low Ki-67 expression had an excellent outcome with accelerated radiotherapy alone.
  
  
  CONCLUSIONS
  Patients with laryngeal carcinomas with high proliferative activity are at increased risk of regional and distant metastases formation. This risk can be reduced by treatment with ARCON.
authors.affiliation: Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
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: 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: 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: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D002245:Carbon Dioxide / Q000627:therapeutic use; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D007822:Laryngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000627:therapeutic use; D010100:Oxygen / Q000627:therapeutic use; D011379:Prognosis; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D000951:Antigens, Neoplasm; D019394:Ki-67 Antigen; D011838:Radiation-Sensitizing Agents; D014803:Vitamin B Complex; D002245:Carbon Dioxide; D009536:Niacinamide; C011700:carbogen; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D010100:Oxygen
keywords: hypoxia; laryngeal carcinoma; prognostic; proliferation; radiotherapy