Toolkit for determination of dose-response relations, validation of radiobiological parameters and treatment plan optimization based on radiobiological measures

• Accurately determined dose-response relations of the different tumors and normal tissues should be estimated and used in the clinic. The aim of this study is to demonstrate developed tools that are necessary for determining the dose-response parameters of tumors and normal tissues, for clinically verifying already published parameter sets using local patient materials and for making use of all this information in the optimization and comparison of different treatment plans and radiation techniques. One of the software modules (the Parameter Determination Module) is designed to determine the dose-response parameters of tumors and normal tissues. This is accomplished by performing a maximum likelihood fitting to calculate the best estimates and confidence intervals of the parameters used by different radiobiological models. Another module of this software (the Parameter Validation Module) concerns the validation and compatibility of external or reported dose-response parameters describing tumor control and normal tissue complications. This is accomplished by associating the expected response rates, which are calculated using different models and published parameter sets, with the clinical follow-up records of the local patient population. Finally, the last module of the software (the Radiobiological Plan Evaluation Module) is used for estimating and optimizing the effectiveness a treatment plan in terms of complication-free tumor control, P+. The use of the Parameter Determination Module is demonstrated by deriving the dose-response relation of proximal esophagus from head & neck cancer radiotherapy. The application of the Parameter Validation Module is illustrated by verifying the clinical compatibility of those dose-response parameters with the examined treatment methodologies. The Radiobiological Plan Evaluation Module is demonstrated by evaluating and optimizing the effectiveness of head & neck cancer treatment plans. The results of the radiobiological evaluation are compared against dosimetric criteria. The presented toolkit appears to be very convenient and efficient for clinical implementation of radiobiological modeling. It can also be used for the development of a clinical data and health information database for assisting the performance of epidemiological studies and the collaboration between different institutions within research and clinical frameworks.

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