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

Purpose: To analyze the relationship between pre-treatment measurements of tumor oxygen tension (pO₂) and survival in advanced head and neck cancer. Patients and methods: Eppendorf pO₂ measurements in 397 patients from seven centers were analyzed using the fraction of pO₂ values ≤2.5 mmHg (HP_2.5), ≤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 HP_2.5=19% (range 0-97%) and HP ₅=38%, (range 0-100%). By quadratic regression median tumor pO ₂ correlated with Hb (2P=0.026, n=357), while HP_2.5 or HP₅ 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.