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; Tung-Ho Wu; Ping-Hsiu Wu; Justin Roper; Jun Zhou; Minglei Kang; Bill Stokes; Sibo Tian; David S. Yu; Xiaofeng Yang; Chih-Wei Chang

arXiv · 2609.39010

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·Tung-Ho Wu·Ping-Hsiu Wu·Justin Roper·Jun Zhou·Minglei Kang·Bill Stokes·Sibo Tian·David S. Yu·Xiaofeng Yang·Chih-Wei Chang

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Abstract

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 scored within -0.7% (pdCT-H) and -1.0% (pdCT-L) of baseline. Forward calculation on QACT reduced high-dose CTV D98% to 88.3% and 85.5%. After online reoptimization, D98% recovered to 98.3 +/- 0.3% and 98.2 +/- 0.3%, versus 98.5 +/- 0.4% at baseline. Spinal cord and brainstem doses remained below tolerance, and plan quality scores were within -1.1% (p = 0.19) and -1.7% (p = 0.01) of baseline. Significance: UGDT generated online APT plans comparable in quality to physician-approved offline replans using anatomy forecast before treatment, enabling a transition from reactive offline replanning toward anticipatory online adaptation.

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Yizhou Wu, Ryan J. Sanford, Huiqiao Xie, Jie Ding, Shupeng Chen, Tung-Ho Wu, Ping-Hsiu Wu, Justin Roper, Jun Zhou, Minglei Kang, Bill Stokes, Sibo Tian, David S. Yu, Xiaofeng Yang, Chih-Wei Chang. 2026-09-30. An Uncertainty-Guided Digital Twin Framework for Online Adaptive Proton Therapy in Head and Neck Cancer: A Feasibility Study. https://arxiv.org/abs/2609.39010

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