An Uncertainty-Guided Digital Twin Framework for Online Adaptive Proton Therapy in Head and Neck Cancer: A Feasibility Study

Yizhou Wu, Ryan J. Sanford, Huiqiao Xie, Jie Ding, Shupeng Chen +10

Objective: Head and neck (HN) proton therapy spans six to seven weeks of anatomical change, while offline replanning takes about a week. We present an uncertainty-guided digital twin (UGDT) framework that forecasts treatment-day anatomy before treatment and evaluate whether it generates online adaptive proton therapy (APT) plans of clinical quality. Approach: A library of 302 longitudinal deformations from 88 previously treated HN patients was transported onto each new patient's treatment planning CT (TPCT) using two-step multi-atlas deformable image registration (DIR) built on a pretrained CT foundation model, generating about 284 predicted CTs (pdCTs) with contours per patient. Dispersion of propagated clinical target volume (CTV) contours defined a patient-specific robust margin. In ten patients, the quality assurance CT (QACT) triggering a replan represented treatment-day anatomy, and the physician-approved replan was the baseline. The pdCT most similar to the QACT (pdCT-H) and one from the lowest quartile (pdCT-L) were planned to within about 5% of baseline plan quality, forward-calculated on the QACT, and reoptimized to generate online APT plans. Main results: pdCT plans…