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RESEARCH PRODUCT

The Role of Oxygen Tension Distribution on the Radiation Response of Human Breast Carcinoma

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The response of tumors to radiation is heterogeneous even in animal tumor systems where tumors all originate from the same cell culture, are implanted in genetically similar age-matched animals in a constant anatomic locationl. Hence great heterogeneity of response exists even in situations where intrinsic genetic or epigenetic factors are minimally variable. Several metabolic factors are known to influence the probability of tumor control after radiation. These metabolic factors are also known to vary widely between tumors in humans2,3 and even in animal tumor models. Heterogeneous variables include tumor oxygen tension distribution, glutathione content, glucose delivery and utilization rate, pH, and blood flow. In addition, radiation response can be modified by intrinsic radiation sensitivity, rate of repopulation, and tumor size. The relative importance of oxygen in this list of modifiers of treatment response is unclear, but has been of major concern since the 1950’s4,5. In animal tumors treated with a few radiation fractions, oxygen tension distribution is probably the most powerful predictor of radiation response6. The impact of oxygen on human tumor response, however, is controversial particularly in the treatment of human disease wherein treatment is delivered in many fractions. Recently it has been pos-sible to measure the oxygen tension distributions of human breast carcinoma3,7. Using well established modeling techniques and classical radiation biology it is therefore possible to predict the heterogeneity of radiation treatment response expected secondary to the oxygen tension distribution. The purpose of this analysis is to determine to what extent the known shape of the radiation response curve for human breast cancers treated in situ can be predicted by the tumor oxygenation status.