A system and method of performing prospective and retrospective on-line adaptive radiotherapy. The method includes performing, during a treatment delivery session, delivery of a dose of radiation to an anatomical volume. The method includes detecting, during the treatment delivery session, a current state of the anatomical volume. The method includes predicting a future change in the current state of the anatomical volume during the treatment delivery session. The method includes adjusting, while the anatomical volume is in the current state, the treatment delivery to anticipate the future change in the anatomical volume.