Statistical Methods--3D Conformal Radiation Therapy Data

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DESCRIPTION (provided by applicant): The advancement in technology has enabled radiation oncologists to deliver higher doses of radiation to a defined region of cancer using 3D conformal radiation therapy techniques. A consequence of higher doses to the tumor can also be a higher dose to critical normal tissue and organs. However, the advancement in the technology has for the most part preceded a proper quantitative understanding of the relationship between the delivered dose distribution within the critical organs and the observed functional complication. Mathematical models, based on either radiobiological phenomena or chosen for their mathematical convenience, have been suggested to describe the relationship. Although a number of models have been suggested there have been few published studies in which these models have been successfully fit to data using modern statistical methods which make efficient use of the data. The research in this proposal is an integration of concepts in statistics, radiation biology and biomathematics. The aims are to develop appropriate biomathematical models to describe the relationship between the dose distribution and the complication and to develop efficient statistical estimation methods. The specific goals are (i) to develop mathematical models for the effect of the dose distribution on the injury to the organ; (ii) to develop efficient statistical methods to estimate the relationship and (iii) to apply the statistical methods to data from head and neck cancer and to evaluate them in simulation studies. Three different types of models will be developed and investigated, beginning with radiobiologically motivated dose-damage-injury models, then general parsimonious parametric and semi-parametric adaptations will be considered. Estimation methods will be based on Markov chain Monte Carlo methods. Methods of assessing goodness of fit and for representing the results will be developed. The methods will be applied to repeated measures saliva flow measurements from the parotid for patients treated with 3D conformal radiation therapy for head and neck cancer.