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The purpose of this study is to investigate whether quality assurance (QA) for cone-beam computed tomography (CBCT) image rotation is necessary in order to ensure the accuracy of CBCT based image-guided radiation therapy (IGRT) and adaptive radiotherapy (ART). Misregistration of angular coordinates duringCBCTacquisitionmay lead to a rotated reconstructed image. If target localization is performed based on this image, an under- or over-dosage of the target volume (TV) and organs at risk (OARs) may occur. Therefore, patient CT image sets were rotated by 1° up to 3° and the treatment plans were recalculated to quantify changes in dose-volume histograms. A computer code in C++ was written to model the TV displacement and overlap area of an ellipse shape at the target and dose prescription levels corresponding to the image rotation. We investigated clinical scenarios in IGRT and ART in order to study the implications of image rotation on dose distributions for: (1) lateral TV and isocenter (SBRT), (2) central TV and isocenter (IMRT), (3) lateral TV and isocenter (IMRT). Mathematical analysis showed the dose coverage of TV depends on its shape, size, location, and orientation relative to the isocenter. Evaluation of three first scenario for θ = 1° showed variations in TV D95 in the context of IGRT and ART when compared to the original plan were within 2.7 ± 2.6% and 7.7 ± 6.9% respectively while variations in the second and third scenarios were less significant (<0.5%) for the angular range evaluated. However a larger degree of variation was found in terms of minimum and maximum doses for target and OARs. The rotation of CBCT image data sets may have significant dosimetric consequences in IGRT and ART. The TV's location relative to isocenter and shape determine the extent of alterations in dose indicators. Our findings suggest that a CBCT QA criterion of 1? would be a reasonable action level to ensure accurate dose delivery. [ABSTRACT FROM AUTHOR]