Methods, systems and computer-readable storage media relate to image-guided treatment planning and treatment assessment. The methods, systems, and the computer-readable storage medias according to embodiments can analyze treatment response and can determine an accurate, outcome-based response assessment of treatment (e.g., radiation treatment). The methods may include a method for determining a treatment response. The method may include registering at least a first image data and a second image data of a subject, the first image data corresponding to a first time point, the second image data corresponding to a second time point, the first time point and the second time point being different with respect to a treatment session and/or treatment stage. The method may include processing the registered image to determine a treatment response. The registering may be based on deformable registration.