Abstract
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.
This work supported in part by NIH grants CA48096 and CA13311, and by the American Cancer Society Career Development Award.
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References
H.D. Suit, S. Skates, A. Taghian, P. Okunieff, et al, Clinical implications of heterogeneity of tumor response to radiation therapy, Radiother. Oncol. 25:251–260 (1992).
P. Vaupel, F. Kallinowski and P. Okunieff, Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review, Cancer Res. 49:6449 (1989).
P. Vaupel, K. Schlenger and M. Hoeckel, Blood flow and tissue oxygenation of human tumors: an update, Adv. Exp. Med. Biol. 277:895–906 (1990).
R.H. Thomlinson, Changes of oxygenation in tumors in relation to irradiation, Front. Radiat. Ther. Oncol. 3:109 (1968).
H.D. Suit, Hyperbaric oxygen in radiotherapy of four mouse tumors, Proc. Intern. Conf. Radiation Biology & Cancer 1:39 (1966).
H.D. Suit, R. Sedlacek, G. Silver, C-C. Hsieh, et al, Therapeutic gain factors to fractionated radiation treatment of spontaneous murine tumors using fast neutrons, photons plus O2 at 1 or 3 ATA, or photons plus misonidazole, Radiat. Res. 116:482 (1988).
P. Vaupel, K. Schlenger, C. Knoop and M. Hoeckel, Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements, Cancer Res. 51:3316 (1991).
S. Hellman, Improving the therapeutic index in breast cancer treatment: The Richard and Hinda Rosenthal Foundation Award lecture, Cancer Res. 40:4335 (1980).
H.D. Thames and H.D. Suit, Tumor radioresponsiveness versus fractionation sensitivity, Int. J. Radiat. Oncol. Biol. Phys. 12:687 (1986).
J.H. Hendry and H.D. Thames, Fractionation sensitivity and the oxygen effect, Br. J. Radiol. 63:79 (1992).
S.S. Tucker, H.D. Thames and J.M. Taylor, How well is the probability of tumor cure after fractionated irradiation described by Poisson statistics, Radiat. Res. 124:273 (1990).
J.E. Moulder and S. Rockwell, Hypoxic fractions of solid tumors: experimental techniques, methods of analysis and a survey of exist-ing data, Int. J. Radiat. Oncol. Biol. Phys. 10:695 (1984).
J. Denekamp, J.F. Fowler and S. Dische, The proportion of hypoxic cells in a human tumor, Int. J. Radiat. Oncol. Biol. Phys. 2:1227 (1977).
R.A. Gatenby, H.B. Kessler, J.S. Rosenblum, L.R. Coia, et al, Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy, Int. J. Radiat. Oncol. Biol. Phys. 14:831 (1988).
P. Okunieff, M. Urano, F. Kallinowski, P. Vaupel, et al, Tumors growing in irradiated tissue: Oxygenation, metabolic state, and pH, Int. J. Radiat. Oncol. Biol. Phys. 21:667 (1991).
P. Vaupel, P. Okunieff, F. Kallinowski and L.J. Neuringer, Correlations between 31P-NMR spectroscopy and tissue O2 tension measurements in a murine fibrosarcoma, Radiat. Res. 120:477 (1989).
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Okunieff, P., Dunphy, E.P., Hoeckel, M., Terris, D.J., Vaupel, P. (1994). The Role of Oxygen Tension Distribution on the Radiation Response of Human Breast Carcinoma. In: Vaupel, P., Zander, R., Bruley, D.F. (eds) Oxygen Transport to Tissue XV. Advances in Experimental Medicine and Biology, vol 345. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2468-7_65
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