Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study

Abstract Purpose To analyze the relationship between pre-treatment measurements of tumor oxygen tension (pO 2 ) and survival in advanced head and neck cancer. Patients and methods Eppendorf pO 2 measurements in 397 patients from seven centers were analyzed using the fraction of pO 2 values ≤2.5mmHg (HP 2.5 ), ≤5mmHg (HP 5 ) and median tumor pO 2 (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 pO 2 =9mmHg (range 0–62mmHg), a median HP 2.5 =19% (range 0–97%) and HP 5 =38%, (range 0–100%). By quadratic regression median tumor pO 2 correlated with Hb (2 P =0.026, n =357), while HP 2.5 or HP 5 did not. HP 2.5 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 HP 2.5 was by far the most statistically significant factor in explaining the variability in survival. After adjusting for HP 2.5 , 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 HP 2.5 values in the range from 0 to 20%, whereas the 5-year survival approaches 0% in the most hypoxic tumors. Conclusion This study provides evidence that tumor hypoxia is associated with a poor prognosis in patients with advanced head and neck cancer.