Image-Guided Radiation Therapy System for Small Animals

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Radiation therapy is used to treat approximately 50% of all patients with cancer. To improve the cure rate with radiation therapy and to decrease the short- and long-term side effects of radiation, we have received multiple NIH grants to study radiation biology in small animals. Duke University was one of the first centers to obtain a first generation microCT/micro-irradiator for use in small animals (X-RAD 225Cx), which has supported one of the most successful research programs in the country in radiation therapy, radiation injury, and imaging. Major technological improvements in target localization, treatment planning, and radiation delivery in combination with functional imaging have occurred since that time, and these capabilities are essential for our radiation research to better mimic human radiation therapy and therefore have the most relevance and impact. To improve our ability to carry out clinically meaningful research in radiation biology, we request a shared instrument that combines on-board imaging capabilities (micro-CT), with conformal small beam radiation therapy and advanced treatment planning software that is capable of the same treatment planning approaches and metrics most commonly used today in the clinic. This is incorporated into the Xstrahl Small Animal Radiation Research Platform (SARRP). The proposed instrument uses state-of-the-art technology for small animals that rigorously simulates the radiation therapy planning and treatment conditions of our patients. We propose to use this technology to investigate (1) mechanisms of tumor control and (2) normal tissue injury by radiation therapy. We will utilize the on-board imaging and the custom collimators to safely deliver large doses of radiation with high precision and accuracy to dissect mechanisms of tumor control. This approach will allow us to study the clinically meaningful endpoint of tumor cure. Moreover, the ability to image small animals and localize the tumor target before each treatment will facilitate fractionated radiation therapy schedules for small animals, which are routinely used to treat patients in the clinic. The instrument will also allow us to have the unprecedented ability to focus radiation therapy on part of an organ, to create dose volume histograms (DVHs) to study mechanisms of normal tissue injury, and to model advanced approaches for cancer therapy (e.g. sparing lymph nodes for immunotherapy studies). This approach will avoid multi-organ injury by the radiation treatment and will thereby facilitate studies of radiation-induced normal tissue injury in small animals. In summary, this technology offers a dramatic improvement in our ability to study fundamental radiation biology questions using the same technology with which we treat patients. Combining this novel instrument with the extensive expertise in radiation research at Duke will bring about new discoveries and will facilitate their translation into improved cancer therapy.