A Review of the Robust Optimization Process and Advances with Monte Carlo in the Proton Therapy Management of Head and Neck Tumors.

In intensity-modulated proton therapy, robust optimization processes have been developed to manage uncertainties associated with (1) range, (2) setup, (3) anatomic changes, (4) dose calculation, and (5) biological effects. Here we review our experience using a robust optimization technique that directly incorporates range and setup uncertainties into the optimization process to manage those sources of uncertainty. We also review procedures for implementing adaptive planning to manage the anatomic uncertainties. Finally, we share some early experiences regarding the impact of uncertainties in dose calculation and biological effects, along with techniques to manage and potentially reduce these uncertainties.