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Purpose: The study evaluates the efficacy of cone-beam computed tomography (CBCT)-based synthetic CTs (sCT) as a potential alternative to verification CT (vCT) for enhanced treatment monitoring and early adaptation in proton therapy. Methods: Seven common treatment sites were studied. Two sets of sCT per case were generated: direct-deformed (DD) sCT and image-correction (IC) sCT. The image qualities and dosimetric impact of the sCT were compared to the same-day vCT. Results: The sCT agreed with vCT in regions of homogeneous tissues such as the brain and breast; however, notable discrepancies were observed in the thorax and abdomen. The sCT outliers existed for DD sCT when there was an anatomy change and for IC sCT in low-density regions. The target coverage exhibited less than a 5% variance in most DD and IC sCT cases when compared to vCT. The Dmax of serial organ-at-risk (OAR) in sCT plans shows greater deviation from vCT than small-volume dose metrics (D0.1cc). The parallel OAR volumetric and mean doses remained consistent, with average deviations below 1.5%. Conclusion: The use of sCT enables precise treatment and prompt early adaptation for proton therapy. The quality assurance of sCT is mandatory in the early stage of clinical implementation.

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