Relation between Carbonic Anhydrase IX Serum Level, Hypoxia and Radiation Resistance of Head and Neck Cancers

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Klin Onkol 2014; 27(4): 269-275. DOI: 10.14735/amko2014269.

Summary

Background: Hypoxia of locally advanced head and neck cancers is one of the main causes of their radiation resistance that presents clinically as a persistence of residual tumor disease after radiation therapy. Therefore, detection of tumor hypoxia could be an important predictor of treatment efficacy. Carbonic anhydrase IX (CA IX) is a protein, coded by a homonymous gene, the expression of which increases in tumor tissues at hypoxic conditions. Hence, CA IX represents an endogenic marker of tumor hypoxia, identifi able in tumor tissues, and its soluble extracellular domain can also be detected in body fluids of the patient. The primary endpoint of this study was to explore whether a correlation exists between CA IX serum level and the residual tumor disease after therapy. The secondary endpoint was to find out how the serum concentration of CA IX changes during the course of fractionated radiation therapy. Materials and Methods: The presented prospective monocentric clinical study evaluated a population of 30 patients with locally advanced squamous cell head and neck cancers, treated by radiation therapy or concurrent chemo-radiation therapy with a curative intent. The serum concentration of the soluble form of CA IX was examined from a venous blood sample, using sandwich enzyme-linked immunosorbent assay (ELISA). The blood samples were obtained before the treatment initiation, in the middle of radiation therapy, at the time of finishing radiation therapy and six weeks after the treatment completion. Results: We found a substantial variability in the CA IX levels measured in the examined population, ranging 0– 1,696 pg/ ml. We found no significant changes in the mean value of CA IX concentration during the course of radiation therapy and after the treatment completion. In 11 patients (36.7%), the treatment resulted in complete remission of the disease. In these patients, lower average pre-treatment levels of CA IX were noted when compared to patients with persistence of residual tumor disease (37.57 vs 77.47; p = 0.154). Conclusion: The results indicate that serum level of CA IX in patients with locally advanced head and neck cancers does not change significantly during the course of fractionated radiation therapy. The relation between CA IX serum level and residual tumor disease after radiation therapy requires verification on a larger population of patients.

http://dx.doi.org/10.14735/amko2014269

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