title: Gene expression classifier predicts for hypoxic modification of radiotherapy with nimorazole in squamous cell carcinomas of the head and neck.
abstract: OBJECTIVE
  To validate the predictive impact of a hypoxia gene expression classifier in identifying patients with head and neck squamous cell carcinoma (HNSCC) having benefit from hypoxic modification of radiotherapy.
  
  
  METHODS
  Gene expressions were quantified from formalin-fixed, paraffin-embedded tumour biopsies of 323 HNSCC patients randomized for placebo or nimorazole in conjunction with radiotherapy in the DAHANCA 5 study. Tumours were classified as either "more" or "less" hypoxic with a classifier constituting of 15 hypoxia responsive genes. The predictive impact was evaluated by analysing the response to nimorazole vs. placebo in terms of loco-regional tumour control (LRC) and disease-specific survival (DSS) in the two classified groups.
  
  
  RESULTS
  Hundred and fourteen patients (35%) were classified as having "more" hypoxic tumours. These patients had a significant benefit of hypoxic modification with nimorazole compared with placebo in terms of LRC (5-year actuarial values 49% vs. 18%; p=0.001) and DSS (48% vs. 30%; p=0.04). "Less" hypoxic tumours had no significant effect of hypoxic modification (LRC: 50% vs. 44%; p=0.39, DSS: 57% vs. 51%; p=0.49) and generally an outcome, which was similar to "more" hypoxic tumours treated with nimorazole. In contrast to HPV-negative tumours, HPV-positive tumours had a substantially better outcome in response to radiotherapy, which was irrespective of hypoxic modification.
  
  
  CONCLUSIONS
  A predictive 15-gene hypoxia classifier could identify patients associated with improved outcome after combining radiotherapy with hypoxic modification and underlines the relevance of such therapy. The impact of the classifier was limited to HPV-negative tumours.
authors: Department of Experimental Clinical Oncology, Aarhus University Hospital, Arahus C, Denmark. kasper@oncology.dk
authors: Kasper
authors: K
authors: Toustrup
authors: Brita Singers
authors: BS
authors: Sørensen
authors: Pernille
authors: P
authors: Lassen
authors: Carsten
authors: C
authors: Wiuf
authors: Jan
authors: J
authors: Alsner
authors: Jens
authors: J
authors: Overgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy*; D015687:Cell Hypoxia / Q000235:genetics* / Q000528:radiation effects*; D016009:Chi-Square Distribution; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009554:Nimorazole / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D011838:Radiation-Sensitizing Agents; D009554:Nimorazole