A therapy planning system and method generate an optimal treatment plan accounting for changes in anatomy. Therapy is delivered to the subject according to a first auto-planned optimal treatment plan based on a first image of a subject. A second image of the subject is received after a period of time. The second image is registered with the first image to generate a deformation map accounting for physiological changes. The second image is segmented into regions of interest using the deformation map. A mapped delivered dose is computed for each region of interest using the dose delivery goals and the deformation map. The first treatment plan is merged with the segmented regions of the second image and the mapped delivered dose during optimization.
