Radiotherapy is an important component of multi-modality treatment strategies for childhoodcancers. However, radiotherapy it is known to cause a diverse spectrum of side-effects includingsecond cancers, which can be physically and emotionally devastating. Our long term goal toreduce the incidence of second cancers by developing a user-friendly model that will enableclinicians to select the type of radiotherapy with the lowest risk of second cancer. It is ourhypothesis that using proton therapy instead of photon therapy will significantly reduce thepredicted risk of second cancers that develop in the breast and thyroid of children treated forHodgkin's disease and medulloblastoma, respectively. Testing this hypothesis requiresknowledge of the radiation exposures to organs at risk from contemporary, multi-modalitytreatments. An innovative contribution of this project is the development of models to predict strayradiation exposures incurred during proton therapy, a problem that is not well understood. Thefollowing Specific Aims will test the hypothesis:1.) Identify the dosimetric factors that govern the stray radiation exposures to individual patients. We will use the method of Monte Carlo simulation to determine how strongly each parameter influences the stray radiation exposures.2.) Establish the confidence interval that can be achieved with an integrated dose/risk model for predicting second cancer development for individual patients. The methods to validate organ doses from analytical-model predictions will include comparison with Monte Carlo simulations and measurements. We will also carry out a comprehensive uncertainty analysis of the risk predictions.3.) In virtual clinical trials comparing photon therapy versus proton therapy, establish the integrated dose/risk model's ability to detect a significant difference in the predicted incidence of second cancer. To achieve this aim, we will perform virtual clinical trials (for the treatment of medulloblastoma and Hodgkin's disease) that compare the risk of developing second cancers of the thyroid and breast after proton therapy versus photon therapy.
Today approximately 80% of children survive their initial cancer but are at elevated risk for developing second cancers later in life. The proposed research will lead to individualized treatment strategies that will reduce second-cancer risks. In the future, we expect that the lower-risk treatments will result in fewer second cancers and this will translate into longer, higher-quality lives for survivors of childhood cancer (presently 270,000 persons in the United States).
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