A comparative study on automatic treatment planning for online adaptive proton therapy of esophageal cancer: which combination of deformable registration and deep learning planning tools performs the best?

<i>Objective.</i>To demonstrate the feasibility of integrating fully-automated online adaptive proton therapy strategies (OAPT) within a commercially available treatment planning system and underscore what limits their clinical implementation. These strategies leverage existing deformable image registration (DIR) algorithms and state-of-the-art deep learning (DL) networks for organ segmentation and proton dose prediction.<i>Approach.</i>Four OAPT strategies featuring automatic segmentation and robust optimization were evaluated on a cohort of 17 patients, each undergoing a repeat CT scan. (1) DEF-INIT combines deformably registered contours with template-based optimization. (2) DL-INIT, (3) DL-DEF, and (4) DL-DL employ a nnU-Net DL network for organ segmentation and a controlling ROIs-guided DIR algorithm for internal clinical target volume (iCTV) segmentation. DL-INIT uses this segmentation alongside template-based optimization, DL-DEF integrates it with a dose-mimicking (DM) step using a reference deformed dose, and DL-DL merges it with DM on a reference DL-predicted dose. All strategies were evaluated on manual contours and contours used for optimization and compared with manually adapted plans. Key dose volume metrics like iCTV D98% are reported.<i>Main results.</i>iCTV D98% was comparable in manually adapted plans and for all strategies in nominal cases but dropped to 20 Gy in worst-case scenarios for a few patients per strategy, highlighting the need to correct segmentation errors in the target volume. Evaluations on optimization contours showed minimal relative error, with some outliers, particularly in template-based strategies (DEF-INIT and DL-INIT). DL-DEF achieves a good trade-off between speed and dosimetric quality, showing a passing rate (iCTV D98% > 94%) of 90% when evaluated against 2, 4 and 5 mm setup error and of 88% when evaluated against 7 mm setup error. While template-based methods are more rigid, DL-DEF and DL-DL have potential for further enhancements with proper DM algorithm tuning.<i>Significance.</i>Among investigated strategies, DL-DEF and DL-DL demonstrated promising within 10 min OAPT implementation results and significant potential for improvements.