## 1 Introduction  
In clinical radiation therapy, the accuracy of radiotherapy treatment planning and dose calculations requires high-quality medical images to delineate and define planning target volumes (PTV) and critical structures of interests, or organs at risk (OAR). CT is the most suitable modality for radiotherapy treatment planning and dose calculation algorithms due to its geometrical accuracy and tissue density information. In addition, CT data is essential for the treatment planning dose calculation algorithms, as these are dependent on the electron density information embedded in CT images. CT, however, may suffer imaging artifacts due to the presence of high-density materials such as dental fillings,prosthetic implants, and contrast agents. The latter are iodine-based agents introduced intentionally to opacify vascular structures and other organs. Contrast agents may also alter the apparent Hounsfield Unit (HU) values. Non-contrast CT imaging (NCCT) has been the modality of choice for three-dimensional conformal radiotherapy (3 DCRT) dose calculations since the introduction of algorithms-based computerized treatment planning systems. However, visualization of anatomy in CT images generally could be improved by taking advantage of contrast agents [1] to differentiate organs, and enhance lesion detection and characterization, thus, improving the delineation accuracy of PTVs and OARs. International recommendations, such as the American Association of Physicists in Medicine (AAPM) Task Group 179 [2] and the Institute of Physicists and Engineers in Medicine (IPEM) Report No. 81 [3], recommend CT number values to be within \(\pm\)30 HU for soft tissues and within \(\pm\)50 HU and \(\pm\)150 HU for lung and bony structures, respectively, from reference values to maintain acceptable dosimetric accuracy of dose calculations [4; 5; 6; 7]. This is particularly relevant for intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) where both dose calculation and plan optimization are dependent on the CT images. Currently, IMRT and VMAT are predominantly the treatment delivery techniques for managing cancer patients worldwide [8; 9; 10]. It is a common practice in radiotherapy settings to acquire two sets of CT images in the same CT simulation session, one without a contrast agent (NCCT) for TPS dose calculation, and another with a contrast agent (CCT) for delineation of PTVs and OAR. There are some obvious drawbacks for acquiring two sets of CT images for each patient. First, the inconvenience for the patient, then the additional cost of the procedure, added workload, and increased low level radiation exposure to the patient. Thus, it would be practical and convenient if CCT imaging alone could be used for both structure delineation and dose calculations. A number of studies have addressed this issue. Phantom studies [11; 12; 13; 14] investigated changes in dosimetry due to contrast materials for different energies and concentrations. Results show a significant change in the dose calculations between NCCT and CCT dose calculations plans up to 7% [13]. [PERSON] et al. [15] retrospectively evaluated 22 treatment plans for seven different sites. Mean dose differences between NCCT and CCT image sets-based plans were within 2% with a maximum of 20%. The authors recommended careful consideration of target volume proximity and calculation algorithm factors when CCT images are used. [PERSON] et al. [16] found no significant effect on dose calculations, except that machine monitor units (MU) settings were increased by more than 2% in upper-abdominal irradiations. [PERSON] et al. [17] reported no statistically significant dose difference in the rectal region between NCCT- and CCT-based plans, while a statistically significant dose difference was reported in the lower esophageal region. Additionally, no significant dose differences were reported in all critical structures.