**6. Radiation exposure**

Radiation exposure at the time of CTC screening leads to a slight but increased risk of devel‐ oping cancer at a future time [94]. Therefore, reducing radiation exposure is a major chal‐ lenge for CTC screening.Currently, CTC scanning delivers a significant amount of X-ray radiation exposure to the patient [95]. In 2004, a survey of 28 institutions revealed the me‐ dian effective dose of radiation was 5.1 mSv (range 1.2 mSv - 11.7 mSv) per position and the median mAs value was 67 mAs[96].

Given current CT technology, a simple and effective strategy to reduce radiation would be to lower the mAs level (i.e. deliver less X-ray photons to the body) during the data acquisi‐ tion. This strategy would however, lead to a higher noise signal in the acquired data. Recent efforts on modeling a solution to avoid this noise artifact are aimed at minimizing the noise prior or during image reconstruction. Despite the great effort on this solution in the past decade, CTC still faces challenges at a mAs level lower than 50 [97].

A feasibility study examined low radiation doses from 10mAs to 40 mAs using adaptive statistical iterative reconstruction (ASIR) models [98]. Eighteen patients were scanned with a standard 50 mAs CTC dose in the supine position and a reduced dose of 25 mAs with 40% ASIR in the prone position. No significant image quality differences were seen between standard-and low-dose images using 40% ASIR. The results of this pilot study show that the radiation dose during CTC can be reduced 50% below currently accepted low-dose techni‐ ques without significantly affecting image quality when ASIR is used [98]. Larger studies are needed to confirm this observation. Despite the increasing use of multi-slice scanners, which are slightly less dose-efficient, the median effective dose remained approximately constant between 1996 and 2004 [96]. Of 83 institutions, 62% used 64-detector row CT and 17 (50%) used dose modulation [99].

tions. Of the 68 patients who favored one examination, 56 [82%) preferred CTC (P < 0.00001). CTC was regarded as "not painful" by 62 (57%) of 108 patients compared with 28

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Intuitively we may believe that CTC, being a noninvasive test, would be preferred to OC by most patients. However, when the risks of finding lesions that require follow-up and other factors are taken into account, patient preferences may change. In one study, OC was preferred over CTC as the need for a follow-up test increased, as the likelihood of missing cancers or polyps increased, and as the cost for CTC increased (the odds rato of preferring CTC to OC ranged from 0.65 to 0.80)[106]. Therefore, an informed decision re‐ garding CTC vs. OC should include a discussion of the benefits, risks, costs and associat‐ ed uncertainties of the tests. In summary, patients usually prefer CTC to OC but the preference is most likely dependent on a number of other factors such as insurance cover‐ age, type of sedation used locally for OC, and the risk of finding a significant polyp on

Extracolonic findings are an important issue for CTC as they increase costs and patient risk by incurring addition tests. The frequency of extracolonic findings in the literature varies considerably as there are no standards for their reporting nor what constitutes a clinically significant extra-colonic finding. Some of the extracolonic lesions found are clinically impor‐ tant although most of them are incidental. In addition to increasing costs of CTC screening

The prevalence of extracolonic findings can be as high as 40% - 75% and are increased with patient age [107-109]. Most extracolonic findings are incidental and not clinically important. The most common extracolonic findings causing further evaluation in one study were lung nodules and indeterminate kidney lesions adding a cost of \$248 dollars per patient enrolled

In general, significant extracolonic findings are found in about 10 - 23% of patients undergo‐ ing CTC [111-113]. Potentially important extracolonic findings were seen in 15.4% (89 of 577) of patients in one study, with a work-up rate of 7.8% (45 of 577)[114]. In another study only 4.4% - 6.0% of patients required follow-up radiologic testing for the extracolonic findings [109]. Another study showed that 10% of 681 patients screened for colon cancer had extraco‐

Although extracolonic finding add cost to CTC screening programs, they may benefit pa‐ tients by diagnosing other potentially malignant lesions [112]. Unsuspected cancers (colonic and extra-colonic) are found in about 0.5% of screening cases [116]. In a large study, 36/10,286 patients (0.35%) undergoing a screening examination had an unsuspected extraco‐ lonic cancer which included renal cell carcinoma (n = 11), lung cancer (n = 8), non-Hodgkin lymphoma (n = 60, and a variety of other tumors (n = 11)[116). Other studies report a higher

programs, they may cause undue worry and anxiety for the patient.

(26%) for colonoscopy [15].

CTC thereby requiring a follow-up OC.

**8. Extracolonic findings**

for CTC screening [110].

lonic findings of high clinical importance [115].

rate of 2.7% of extracolonic cancer detection [107].

If the current CTC standards for radiation exposure are used for colorectal cancer screening, CTC is still be a viable screening tool, even after taking into account the increased risks of developing future cancers. Using a Monte Carlo simulation, it was found that for every 1 radiation-related cancer caused by CTC screening, 24 – 35 colorectal cancers would be pre‐ vented, implying a favorable risk to benefit ratio in favor of using CTC as a screening tool [100]. This model assumed using CTC every 5 years in patients aged 50 – 80 years old and using an estimated mean effective dose per CTC screening study of 8 mSv for women and 7 mSv for men.

An alternative solution to minimize the radiation is to use magnetic resonance imaging (MRI) instead of CT for virtual colonoscopy, i.e., MR colonography (MRC) [101]. However, this MRC alternative solution has several limitation compared to CTC. Currently it is more costly, more sensitive to motion and other artifacts, and has lower spatial resolution but with improvements with technology these disadvantages may be minimized.
