PROJECT SUMMARY Approximately half of all cancer patients in the United States are treated with external beam radiotherapy (RT), with approximately 40% of all curative treatment being attributed to it. Modern treatment planning systems (TPS) are designed to optimize the target dose distribution such that the dose to the tumor volume is maximized and doses to surrounding organs at risk are minimized. While this approach is successful in reducing the severity of deterministic organ toxicities, there is mounting evidence to suggest that stochastic, radiation-induced second primary cancer (SPC) risks are a serious concern following RT treatment and should be considered in TPS dose engines. This is presently impractical due to the limited anatomical information present in the patient’s planning computed tomography (CT) image studies. Furthermore, TPS that do compute doses to near- and out-of-field organs either grossly underestimate their magnitudes or neglect to compute them entirely. A whole-body computational phantom, with anthropometric parameters based on the patient’s demographic, could supplement the limited geometric information present in the planning image. Implementing this model into a system-specific Monte Carlo radiation transport simulation would then provide a practical means to compute doses to organs distal to the treatment field with a high degree of accuracy. Previous work at the University of Florida has produced the largest adult and pediatric computational phantom libraries to date, representing individuals of both biological sexes over a wide range of heights, weights, and ages. Given this information, I hypothesize that computational phantoms produced by merging CT planning images with patient-matched tetrahedral mesh-type phantoms can be used to compute accurate near- and out-of-field organ doses and concomitant SPC risks following RT, with potential for clinical implementation, medical record supplementation, prospective TPS dose optimization, and future epidemiological studies. The proposed project will achieve this through the completion of the following Specific Aims: Aim 1: Develop a system for generation of whole-body patient-specific mesh phantoms from radiation therapy treatment planning CT images. Aim 2: Construct Monte Carlo radiation transport source terms for external beam radiotherapy systems and assess normal organ doses and concomitant SPC risks following radiotherapy treatment. The development of this system will fulfill an urgent need for RT dosimetry methods which compute dose and SPC risk for all organs in the body post-treatment.