Quantitative use of cone-beam computed tomography in proton therapy: challenges and opportunities

The fundamental goal in radiation therapy (RT) is to simultaneously maximize tumor cell killing and healthy tissue sparing. Reducing uncertainty margins improves normal tissue sparing, but generally requires advanced techniques. Adaptive RT (ART) is a compelling technique that leverages daily imaging and anatomical information to support reduced margins and to optimize plan quality for each treatment fraction. An especially exciting avenue for ART is proton therapy (PT), which aims to combine daily plan re-optimization with the unique advantages provided by protons, including reduced integral dose and near-zero dose deposition distal to the target along the beam direction. A core component for ART is onboard image guidance, and currently two options are available on proton systems, including cone-beam computed tomography (CBCT) and CT-on-rail (CToR) imaging. While CBCT suffers from poorer image quality compared to CToR imaging, CBCT platforms can be more easily integrated with PT systems and thus may support more streamlined adaptive proton therapy (APT). In this review, we present current status of CBCT application to proton therapy dose evaluation and plan adaptation, including progress, challenges and future directions.