title: Tumor hypoxia has independent predictor impact only in patients with node-negative cervix cancer.
abstract: OBJECTIVE
  This prospective clinical study was begun in 1994 to validate the independent prognostic impact of tumor hypoxia in patients with cervix cancer treated with definitive radiation therapy.
  
  
  METHODS
  Between May 1994 and January 1999, 106 eligible patients with epithelial cervix cancer had tumor oxygen pressure (PO(2)) measured using the Eppendorf probe. Oxygenation data are presented as the hypoxic proportion, defined as the percentage of PO(2) readings less than 5 mm/Hg (abbreviated as HP(5)) and the median PO(2).
  
  
  RESULTS
  The median HP(5) in individual patients was 48%, and the median PO(2) was HP(5). Progression-free survival (PFS) for patients with hypoxic tumors (HP(5) > 50%) was 37% at 3 years versus 67% in those patients with better oxygenated tumors (P =.004). In multivariate analysis, only tumor size (risk ratio [RR], 1.33; P =.0003) and evidence of pelvic nodal metastases on imaging studies (RR, 2.52; P =.0065) were predictive of PFS. However, an interaction between nodal status and oxygenation was observed (P =.006), and further analysis indicated that HP(5) was an independent predictor of outcome in patients with negative nodes on imaging (P =.007). There was a significant increase in the 3-year cumulative incidence of distant metastases in the hypoxic group (41% v 15% in those with HP(5) < 50%; P =.0023), but not in pelvic relapse (37% v 27%; P =.12).
  
  
  CONCLUSIONS
  Tumor hypoxia is an independent predictor of poor PFS only in patients with node-negative cervix cancer, in addition to tumor size. Its impact appears to be related to an increased risk of distant metastases rather than to an effect on pelvic control.
authors.affiliation: Department of Radiation Oncology, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network and University of Toronto, Toronto, Ontario, Canada. anthony.fyles@rmp.uhn.on.ca
authors.forename: A
authors.initials: A
authors.lastname: Fyles
authors.forename: M
authors.initials: M
authors.lastname: Milosevic
authors.forename: D
authors.initials: D
authors.lastname: Hedley
authors.forename: M
authors.initials: M
authors.lastname: Pintilie
authors.forename: W
authors.initials: W
authors.lastname: Levin
authors.forename: L
authors.initials: L
authors.lastname: Manchul
authors.forename: R P
authors.initials: RP
authors.lastname: Hill
mesh_terms: D015687:Cell Hypoxia / Q000502:physiology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D011379:Prognosis; D011446:Prospective Studies; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology / Q000503:physiopathology* / Q000532:radiotherapy