Advancing proton therapy treatment plan optimization under uncertainties

Various sources of uncertainty affect proton radiation therapy planning, including anatomical changes, patient setup errors, and proton range uncertainties. These uncertainties can significantly compromise treatment quality by reducing target coverage and limiting the sparing of surrounding healthy tissues.
The overall objective of this thesis is to develop methodologies for proton radiation therapy planning that maintain treatment quality despite these uncertainties. To achieve this objective, the thesis first establishes the current state of the field through a systematic review of online adaptive radiation therapy planning. Building on this foundation, it develops an automated workflow for rapid online adaptive proton treatment planning to facilitate the clinical implementation of online adaptive proton therapy for managing anatomical changes. The thesis then proposes a novel robust treatment planning strategy for head and neck proton therapy to improve dosimetric outcomes in the presence of patient setup and proton range uncertainties. Finally, it investigates the optimal timing of offline adaptation for head and neck proton therapy to determine when adaptive replanning is most beneficial.