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 ≤2.5 mmHg (HP 2.5), ≤5 mmHg (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=9 mmHg (range 0–62 mmHg), 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.