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In patients with head and neck cancer, the presence of proteins indicating low oxygen levels in tumor cells is linked with worse survival after radiation therapy. These results were published in the Journal of Clinical Oncology.

Approximately 40,000 people in the U.S. are diagnosed with head and neck cancer every year. Cancers of the head and neck include cancers of the nasal cavity and sinuses, mouth, and throat.

Among head and neck cancer patients who receive radiation therapy, the oxygen level in cancer cells influences the success of treatment: Radiation therapy is less successful when cancer cells have low oxygen levels. Unfortunately, many cancers, including head and neck cancers, tend to be hypoxic (lacking in oxygen).

To explore the relationship between two markers of tumor hypoxia and response to either standard or accelerated radiation therapy, researchers evaluated tumor tissue from 198 patients with head and neck cancer. The tumor tissue was tested for two proteins that indicate hypoxia: HIF-2 and CA9.

This study was originally designed to compare two different approaches to radiation therapy for head and neck cancer: standard and accelerated. The study failed to find a benefit of accelerated therapy, and the researchers hypothesized that accelerated radiation therapy may only benefit those patients whose tumors have adequate oxygen levels.

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Fifty-nine percent of subjects were classified as HIF-2 positive and 58% of subjects were classified as CA9 positive. Forty percent of subjects were positive for both markers.

The presence of either marker was linked with worse survival after radiation therapy, and the presence of both reduced survival to a greater extent than the presence of only one.

Among subjects with neither marker (suggesting adequate tumor oxygen levels), there was some evidence that accelerated radiation therapy produced better treatment outcomes than standard radiation therapy.

The researchers conclude that patients with markers of tumor hypoxia have a worse response to radiation therapy for head and neck cancer. Patients with these markers may be good candidates for clinical trials of hypoxia-targeting drugs.

Patients with head or neck cancer may wish to talk with their doctor about the risks and benefits of participating in a clinical trial evaluating new treatment approaches. Sources of information regarding ongoing clinical trials include the National Cancer Institute (

Reference: Koukourakis MI, Bentzen SM, Giatromanolaki A et al. Endogenous Markers of Two Separate Hypoxia Response Pathways (Hypoxia Inducible Factor 2 Alpha and Carbonic Anhydrase 9) Are Associated with Radiotherapy Failure in Head and Neck Cancer Patients Recruited in the CHART Randomized Trial. Journal of Clinical Oncology. 2006;24:727-735.