A method of minimizing radiation toxicity in image guided radiotherapy (IGRT) is provided that includes using a probabilistic prediction algorithm that is operated on a suitably programmed computer and includes multimodality inputs and provides real-time geometric and topological target estimates to compensate for system latency, using an online adaptive imaging system that provides radiographic images of the target when the geometric and topological target estimates are in a region of predefined uncertainty, and using an image dose control algorithm, operating on a suitably programmed computer, that includes parameters for controlling dose per image, where instances for image acquisition are optimized according to a planned dose pattern and delivery result.
