## 1 Introduction
An IMRT gamma analysis study [18] evaluated the dose difference for 34 cancer patients, and results indicated no significant changes in dose distribution between NCCT- and CCT-based plans for targets and critical structures except the lower thoracic esophagus segment. Another study [19] examined 20 thorax cancer patients because of the abundance of large blood vessels that may emphasize the effect of contrast agents; differences were found, however negligible. In a recent VMAT study, [PERSON] et al. [20] investigated images from 47 rectal cancer patients. The study concluded that contrast material has a significant effect on calculated doses for the target volumes and critical structures. Different results were reported by IMRT and VMAT studies [21] for head and neck cancer patients, where no significant dose differences between NCCT and CCT plans were found for both critical structures and target volumes. These results were echoed in another study [22] where 11 pelvic treatment plans were calculated based on NCCT and CCT image sets; differences were within 2%. In a virtual study [23] on 10 head and neck cancer patients, vessel densities in CCT images were corrected manually. In IMRT plans based on both CCT and manually created NCCT, dose differences were insignificant for targets and critical structures. In another virtual CCT study, [PERSON] et al. [24] replaced blood vessels and heart HU values in NCCT images of 22 esophageal cancer patients with higher values up to 445 HU. IMRT and 3 DCRT plans were recalculated for comparison. Results suggest a linear increase in calculated dose with increase in HU values. Although the authors recommended replacing contrast material in the heart with a constant value of 45 HU, no significant dose differences were reported. This was also the finding in a more recent artificial intelligence-based study [25] where 40 patients' CCT images were used to generate virtual NCCT images. VMAT plans based on three image sets, NCCT, virtual NCCT, and CCT, were used to evaluate the effect on dose calculations. Results showed no significant dose difference between the image sets for targets and critical structures. Similarly, [PERSON] et al. [26] used CCT images of nine non-small-cell lung cancer patients to calculate 3 DCRT and IMRT treatment plans. Virtual non-contrast images were generated by altering HU values in blood vessels. Dose distributions based on the virtual NCCT were compared to those based on CCT images in target volumes, and results suggested no significant differences. [PERSON] et al. [27] also reported no significant change in dose calculations for the PTV and organs at risk. The 2001 results indicated that dose differences for targets and critical structures were within 2.5%. A similar study by [PERSON] et al. [28] for five stomach cancer patients in which the visible contrast material had a HU value of 500 was assigned 0 HU value. To mimic non-contrast images, the stomach density was altered virtually to water equivalent density. Treatment plans were calculated based on both CCT and virtual NCCT, and average dose differences for both were within 2%. A similar approach was used also in a prostate cancer study [29] which included CCT images for 10 patients. Densities in bladder and rectum were altered to water density. Box treatment technique plans were created using CCT and virtual NCCT image sets. No significant differences were reported for both target volumes and critical structures. However, statistically significant dose differences were reported in some virtual studies. [PERSON] et al. [30] evaluated the dosimetric differences between two treatment plans based on CCT and virtual NCCT images for ten patients and reported significant statistical dose differences. An artefact masking study evaluated the effect of a contrast agent on dose calculation for 17 thoracic cancer patients and reported dose differences within 3% except in two patients [31]. The authors recommended masking CCT artefacts prior to dose calculation.