The long-term objective of this research is to establish quantitative criteria for evaluating the potential effectiveness of altered fractionation schedules in radiotherapy. This is to be accomplished by developing models of tissue and tumor responses to repeated small doses of radiation, and by performing new experiments to test the models.
The specific aims of the project are to determine the influence of dose-fractionation patterns on recovery in late-responding tissues during interfraction intervals, and on the timing and severity of acute responses; a corollary aim is to determine the potential of tumors to accelerate their regrowth in response to radiation injury. Models of acute responses will be developed and tested experimentally. Emphasis is placed on the application of applied mathematics to problems in experimental design and analysis, and to experimental tests of the mathematical models. These studies will ultimately provide the radiotherapist with guidelines for the use of accelerated fractionation and hyperfractionation, by establishing the tumor sites where they might be most beneficial and by establishing limits on the number and size of daily treatments, based on both the necessity for complete Elkind repair in late-responding tissues and the timing and severity of reactions in early responding tissues.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA029026-12
Application #
3168476
Study Section
Radiation Study Section (RAD)
Project Start
1980-12-01
Project End
1992-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
12
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
Other Domestic Higher Education
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Thames, Howard D; Zhang, Ming; Tucker, Susan L et al. (2004) Cluster models of dose-volume effects. Int J Radiat Oncol Biol Phys 59:1491-504
Thames, Howard D; Petersen, Cordula; Petersen, Sven et al. (2002) Immunohistochemically detected p53 mutations in epithelial tumors and results of treatment with chemotherapy and radiotherapy. A treatment-specific overview of the clinical data. Strahlenther Onkol 178:411-21
Evans, S C; Mack, D C; Mason, K A et al. (2001) The proliferative response of mouse jejunal crypt cells to radiation-induced cell depletion is not mediated exclusively by transforming growth factor alpha. Radiat Res 155:866-9
Koscielny, S; Thames, H D (2001) Biased methods for estimating local and distant failure rates in breast carcinoma and a ""commonsense"" approach. Cancer 92:2220-7
Thames, H D; Ang, K K (1998) Altered fractionation: radiobiological principles, clinical results, and potential for dose escalation. Cancer Treat Res 93:101-28
Ruifrok, A C; Weil, M M; Thames, H D et al. (1998) Diurnal variations in the expression of radiation-induced apoptosis. Radiat Res 149:360-5
Powers, B E; Thames, H D; Gillette, S M et al. (1998) Volume effects in the irradiated canine spinal cord: do they exist when the probability of injury is low? Radiother Oncol 46:297-306
Ruifrok, A C; Weil, M M; Mason, K A et al. (1998) Induction of transforming growth factor alpha in irradiated mouse jejunum. Int J Radiat Oncol Biol Phys 42:1137-46
Ruifrok, A C; Mason, K A; Lozano, G et al. (1997) Spatial and temporal patterns of expression of epidermal growth factor, transforming growth factor alpha and transforming growth factor beta 1-3 and their receptors in mouse jejunum after radiation treatment. Radiat Res 147:1-12
Thames, H D; Ruifrok, A C; Mason, K A (1997) The effect of proliferative status and clonogen content on the response of mouse jejunal crypts to split-dose irradiation. Radiat Res 147:172-8

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