It has long been accepted that hypoxia in solid tumors may contribute to radio resistance, and a number of means of detecting and quantitating tumor hypoxia are under investigation. With the advent of the novel bioreductive cytotoxic agent tirapazamine for clinical trials, there will soon be a real need to identify tumors whose hypoxia is sufficient to justify the use of this agent (with its associated side effects). At present, the most relied upon technique for quantifying tumor hypoxia involves an invasive polarographic needle probe electrode (the Eppendorf pO2 histograph). However, this technique has yet to be validated as a reliable prognostic indicator. Moreover, because it is both invasive and can only be used with accessible tumors, a less invasive (or noninvasive) method of measuring hypoxia would be a significant advantage. The overall objective of this project is to compare results obtained with the Eppendorf pO2 histograph, with those of a noninvasive technique for detecting tumor hypoxia based on magnetic resonance spectroscopy (MRS) of lactate, and those from a third technique which uses the Comet Assay to assess single-strand breaks in the DNA of individual cells following a test dose of 5 Gy. In addition to the intercomparison of techniques, results will also be used to test the hypothesis that it is the hypoxic tumors that respond best to tirapazamine. A specific group of patients, with advanced stage head and neck cancers, will allow a comparison of results from the polarographic electrode technique with those of the Comet Assay, and magnetic resonance spectroscopy. Investigators will be blinded to the oxygen assessment made by the other techniques, and patients will be randomized with regard to treatment. This will allow a non-biased evaluation of these novel ways of measuring oxygen in solid tumors. The ability of the oxygen electrode to predict prognosis (based on oxygenation) will also be assessed.
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