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

https://doi.org/10.1016/j.radonc.2005.06.038Get rights and content

Abstract

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 (HP2.5), ≤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 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.

Conclusion

This study provides evidence that tumor hypoxia is associated with a poor prognosis in patients with advanced head and neck cancer.

Section snippets

Patient characteristics and inclusion criteria

The present study includes 397 patients with advanced head and neck cancer referred to the departments of Oncology, Aarhus University Hospital, DK; Radiation Oncology, University of Heidelberg, G; Institute Gustave Roussy, Villejuif, F; Radiotherapy and Radiation Oncology, Technical University, Münich, G; Radiotherapy, Martin Luther University, Halle-Wittenberg, G; Radiation Oncology, Division for Radiation Biology and Surgery, Stanford University, USA and Radiation Oncology, Duke University,

Oxygenation parameters

Distribution parameters of tumor oxygenation in the various centers are shown in Table 3. There was a substantial inter-individual heterogeneity in tumor hypoxia with an overall median tumor pO2=9 mmHg (range 0–62 mmHg), a median HP2.5 of 19% (range 0–97%) and HP5 of 38%, (range 0–100%). A statistically significant inter-institutional difference in the distribution of tumor oxygenation parameters was observed (HP2.5, P=0.02, HP5, P=0.001 and median tumor pO2, P=0.001, Kruskal–Wallis test) with

Discussion

The current study summarizes the World-wide experience with micro-electrode measurements of oxygen tension as a possible predictive assay for outcome after radiotherapy for advanced head and neck cancer. Data from seven institutions and 397 patients were analyzed using the Cox proportional hazards model. The pre-treatment tumor oxygenation status was found to be a highly significant prognostic factor for survival after radiotherapy alone or in combination with surgery, chemotherapy or a

Acknowledgements

Financial support was obtained from the Danish Cancer Society, the Research, the Development program at Mount Vernon Hospital, UK, Grants CA 67166 and DFG Ad123/1-1 and Ad123/1-2.

References (31)

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