A therapy planning system (18) and method generate an optimal treatment plan. A plurality of objectives are automatically formulated (154) based on a plurality of clinical goals including dose profiles and priorities. The dose profiles and the priorities correspond to a plurality of structures including a plurality of target and/or critical structures identified within a planning image. Further, a plurality of treatment plan parameters are optimized (156) based on the plurality of objectives to generate a treatment plan. The plurality of objectives are reformulated (162) and the plurality of treatment plan parameters are reoptimized (156) based on the reformulated plurality of objectives to generate a reoptimized treatment plan. The optimizing (156) is repeated based on the reformulated plurality of objectives to generate a reformulated treatment plan.
