Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study.
OBJECTIVE
To analyze the relationship between pre-treatment measurements of tumor oxygen tension (pO2) and survival in advanced head and neck cancer.


METHODS
Eppendorf pO2 measurements in 397 patients from seven centers were analyzed using the fraction of pO2 values < or =2.5 mmHg (HP2.5), < or =5 mmHg (HP5) and median tumor pO2 (mmHg) as descriptors. All patients had intended curative radiation therapy alone or as pre- or post-operative radiotherapy or radio-chemotherapy according to the practice at each center.


RESULTS
The degree of hypoxia varied between tumors with an overall median tumor pO2=9 mmHg (range 0-62 mmHg), a median HP2.5=19% (range 0-97%) and HP5=38%, (range 0-100%). By quadratic regression median tumor pO2 correlated with Hb (2P=0.026, n=357), while HP2.5 or HP5 did not. HP2.5 above the population median was the only parameter that associated with poor overall survival (Kaplan Meier analysis, P=0.006). In a multivariate Cox Proportional Hazards analysis, stratified according to institution HP2.5 was by far the most statistically significant factor in explaining the variability in survival. After adjusting for HP2.5, clinical stage, radiation dose and surgery hemoglobin concentration was not significant in the model. The prognostic model shows that the 5-year survival is almost constant for HP2.5 values in the range from 0 to 20%, whereas the 5-year survival approaches 0% in the most hypoxic tumors.


CONCLUSIONS
This study provides evidence that tumor hypoxia is associated with a poor prognosis in patients with advanced head and neck cancer.
Nordsmark
Marianne
M
Department of Experimental Clinical Oncology, Aarhus University Hospital, DK, Denmark. marianne@oncology.dk
Bentzen
Søren M
SM
Rudat
Volker
V
Brizel
David
D
Lartigau
Eric
E
Stadler
Peter
P
Becker
Axel
A
Adam
Markus
M
Molls
Michael
M
Dunst
Juergen
J
Terris
David J
DJ
Overgaard
Jens
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015687:Cell Hypoxia; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012044:Regression Analysis; D016019:Survival Analysis; D016896:Treatment Outcome
D010100:Oxygen