title: Differential risk assessments from five hypoxia specific assays: The basis for biologically adapted individualized radiotherapy in advanced head and neck cancer patients.
abstract: OBJECTIVE
  Hypoxia adversely relates with prognosis in human tumours. Five hypoxia specific predictive marker assays were compared and correlated with definitive radiotherapy.
  
  
  METHODS
  Sixty-seven patients with advanced head and neck carcinomas were studied for pre-treatment plasma osteopontin measured by ELISA, tumour oxygenation status using pO(2) needle electrodes and tumour osteopontin, hypoxia inducible factor 1alpha (HIF-1alpha) and carboxyanhydrase 9 (CA9) by immunohistochemistry. The primary treatment was radiotherapy and the hypoxic radiosensitizer nimorazole. Loco-regional tumour control was evaluated at 5 years.
  
  
  RESULTS
  All five markers showed inter-tumour variability. Inter-marker correlations were inconsistent. Only plasma osteopontin inversely correlated with median tumour pO(2), (p=0.02, r=0.28) and CA9 correlated with HIF-1alpha (p<0.01, r=0.45). In Kaplan-Meier analysis high plasma osteopontin, high HIF-1alpha and high proportion of tumour pO(2)2.5mmHg (HP(2.5)) related significantly with poorer loco-regional control, whereas CA9 and tumour osteopontin failed to predict loco-regional control in this set dataset. When analyzing Hb, stage, and the five markers by competing risks HP(2.5) was the strongest variable to predict for loco-regional tumour control.
  
  
  CONCLUSIONS
  There was diversity and lack of correlation among five different hypoxia assays within individual tumours. High plasma osteopontin, high HIF-1alpha and high proportion of tumour pO(2)2.5mmHg (HP(2.5)) related significantly with poorer loco-regional control, whereas CA9 and tumour OPN failed to predict local control.
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark. marianne@oncology.dk
authors.forename: Marianne
authors.initials: M
authors.lastname: Nordsmark
authors.forename: Jesper Grau
authors.initials: JG
authors.lastname: Eriksen
authors.forename: Val
authors.initials: V
authors.lastname: Gebski
authors.forename: Jan
authors.initials: J
authors.lastname: Alsner
authors.forename: Michael R
authors.initials: MR
authors.lastname: Horsman
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000097:blood / Q000378:metabolism*; D015687:Cell Hypoxia / Q000187:drug effects; D003131:Combined Modality Therapy; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000097:blood / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009554:Nimorazole / Q000494:pharmacology*; D053495:Osteopontin / Q000097:blood / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D018570:Risk Assessment
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011838:Radiation-Sensitizing Agents; D053495:Osteopontin; D009554:Nimorazole; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D010100:Oxygen