Disclosed herein are systems and methods for adapting and/or updating radiotherapy treatment plans based on biological and/or physiological data and/or anatomical data extracted or calculated from imaging data acquired in real-time (e.g., during a treatment session). Functional imaging data acquired at the time of radiation treatment is used to modify a treatment plan and/or dose delivery instructions to provide a prescribed dose distribution to patient target regions. Also disclosed herein are methods for evaluating treatment plans based on imaging data acquired in real-time.