Cone-beam computed tomography-based online adaptive radiotherapy of esophageal cancer in the neoadjuvant setting: Dosimetric analysis, toxicity and treatment response.

Background And Purpose Chemoradiotherapy (CRT) followed by surgery is a treatment option for esophageal cancer (EC). However, concerns persist regarding cardiopulmonary toxicity and inconsistent daily target coverage due to anatomical changes. To address these challenges, we implemented a CBCT-based online adaptive radiotherapy (oART) workflow for EC. This study provides updated dosimetric results and evaluates toxicity and treatment response using daily oART on the Ethos™ platform for EC in the neoadjuvant setting. Materials And Methods We analyzed 26 EC patients treated with oART and concurrent chemotherapy, comparing dosimetric data from scheduled and adapted treatment plans. Esophagectomy was performed 8-12 weeks post-CRT, and treatment response was evaluated using Becker tumor regression grading (Grades 1a and 1b indicating pathologic major response, pMR). We documented Grade ≥3 toxicities (CTCAE v5) and analyzed associations between target volume parameters, pMR, and toxicity. Results Adapted plans improved PTVD99 % and CTVD99 % by 20.6 % (absolute: 15.6 %, p < 0.001) and 6.1 % (absolute: 5.4 %, p < 0.001), respectively, compared to scheduled plans. Mean heart dose decreased by 3.8 % (0.8 Gy, p = 0.038), and mean lung V20Gy reduced by 3.3 % (0.7 %, p = 0.049). Acute Grade ≥3 CRT-related toxicities occurred in 7 (27 %) patients, and Grade ≥3 post-operative complications in 17 (65.4 %). A pMR was achieved in 18 (69.2 %) patients. No significant correlation was found between target dose parameters and toxicity or pMR. Conclusion This study confirms dosimetric improvements and high pMR rates with manageable toxicity following neoadjuvant CBCT-based oART in EC, suggesting oART could enhance treatment outcomes and support non-operative strategies for selected patients.