Trial Information

The Effect of Experience and Training on the Accuracy of CT (Computed Tomography) Colonography in Comparison With Optical Colonoscopy in the Detection of Colonic Neoplasia

1. Purpose To study the Effect of Experience and Training on the Accuracy of CT (Computed
Tomography) Colonography in Comparison with Optical Colonoscopy in the Detection of Colonic
Neoplasia

2. Hypotheses

1. The accuracy (sensitivity and specificity) of interpretation of the CTC images will
improve with each 100 scans examined. Less time will be required to interpret the CTC
images after each successive 100 scans. The accuracy of each of the observers will be
similar.

2. The sensitivity and specificity will be similar for CTC and OC for the last 100
patients undergoing both examinations.

3. Patients will prefer CTC to OC based on comfort and ease of the procedure.

4. CTC will have the added benefit of identifying extra-colonic findings which will not be
found on OC. CTC will be performed at a lower cost per patient with a lower
complication rate than for OC and will take a similar amount of time to perform.

3. Justification Screening is believed to decrease the incidences of colorectal cancer and
death as a result of the detection of both precancerous lesions and cancers at early
stages4-6. Fecal occult blood testing and flexible sigmoidoscopy can miss a substantial
number of significant lesions7. Despite its risk, inconvenience, and cost, optical
colonoscopy is the primary screening tool for colorectal cancer when performed every 10
years, beginning at 50 years of age in people who are at average risk8,9. Screening is also
recommended at a younger age for populations at increased risk10.

Virtual colonoscopy is a rapidly evolving technique in which data from computed tomography
(CT) is used to generate both two-dimensional and three-dimensional displays of the colon
and rectum. This minimally invasive method for the examination of the colon, also referred
to as CT colonography (CTC), is a promising alternative to optical colonoscopy for use in
widespread screening, as it requires no intravenous administration of sedatives or analgesia
and little recovery time.

Many studies have sought to compare the utility of CTC and optical colonoscopy (OC) in the
detection of colonic polyps and adenocarcinomas in various patient populations.

Before CTC can be used in usual practice the training required by those interpreting the
studies needs to be further studied so that guidelines can be created defining requirements
necessary prior to implementation of this screening strategy.

4. Study Objectives: To determine the effects of previous training and experience on the
accuracy of polyp and cancer detection for CTC in patients at above average risk for
colorectal cancer.

1. To assess the learning curve of GI radiologists (experienced and not experienced with
CTC interpretation), a GI fellow and a family physician as they acquire experience in
reading CTC datasets by measuring the detection rates, miss rates and the amount of
time needed to read images for the 1st, 2nd and 3rd set of 100 CTC's which they
interpret.

2. The study will also determine the sensitivity and specificity of CTC compared with OC
for the detection of colonic polyps (of various sizes) and adenocarcinoma in patients
at high risk for colorectal cancer (those over 45 years of age with a family history of
colorectal cancer, those with positive screening tests and those with suggestive
symptoms).

3. Patient satisfaction with both CTC and OC will be evaluated by means of a patient
questionnaire.

4. The two procedures will be compared in terms of complication rates, the time required
to perform each test, extra-colonic findings and the cost to perform each procedure per
patient.

5. Research Method A non-randomized, evaluator blinded study of 300 consecutive patients at
high risk for colonic neoplasia referred for colonoscopy. Each patient is to undergo
standard colonoscopy preparation on the day prior to CT Colonography (CTC) followed within 2
hours by optical colonoscopy (OC). Patients will be men and women aged 19 - 65 years who
were scheduled to undergo elective colonoscopy referred from a suburban primary care
setting.

Study population The study participants will consist of two main populations. The first will
include patients at average to high risk of colonic neoplasia who are eligible for screening
colonoscopy. Average risk patients are those aged 45-65 who wish to undergo screening for
colorectal cancer. High risk patients include those with a family history of colorectal
cancer, previous colorectal cancer or neoplasia, positive screening tests (Fecal Occult
Blood (FOBT), flexible sigmoidoscopy, digital rectal exam or air contrast barium enema) and
patients with gastrointestinal symptoms and signs (abdominal pain, rectal bleeding, anemia).
Patients will be recruited from a suburban primary care medical clinic in Coquitlam, B.C.
(North Road Medical Centre) and referred to a gastroenterology clinic in downtown Vancouver
(Pacific Gastroenterology Associates) or recruited from the gastroenterology clinic
directly.

Ethical approval will be obtained from the University of British Columbia and the St. Paul's
Hospital Institutional Review Boards. A study investigator will obtain informed consent from
potential study participants.

Design After obtaining informed consent, participants will be instructed to consume a clear
liquid diet for the 24 hours prior to the exam. Patients will receive detailed instructions
regarding bowel preparation using oral Picosalax and Bisacodyl suppositories to be taken on
the day prior to their procedures (see Appendix 2). Instructions will also be provided
regarding the intake of oral barium and gastrograffin which will be used as stool tagging
agents (see Appendix 2). As both CTC and OC will take place on the same day, the preparation
will be identical for both procedures. No sedative agents will be administered during CTC.
Colonic distention for CTC will be achieved with automated low-pressure delivery of carbon
dioxide. Patients will be allowed sips of clear fluid on the morning of the examinations and
will then be kept without oral intake until after both CTC and OC are completed.

CT Colonography Patients will be given an appointment time for presentation to St. Paul's
Hospital radiology department. After reporting, they will be asked to change into a hospital
gown and CT scanning will be performed. Images will be acquired using the GE Lightspeed 64
row multidetector CT scanner. Slices will be obtained at 0.75mm resolution and will be
reconstructed using GE Healthcare software at a resolution of 1.25mm. Scans will be obtained
during a single breath hold using a low radiation exposure protocol (~30-50 mAs which
corresponds to an absorbed radiation dose of 3-5 mSv). The quality and adequacy of the
images will be assessed before patients leave the radiology department to await colonoscopy
which will be performed within 2 hours.

Interpretation There will be 2 radiologist readers both experienced in gastrointestinal
imaging and one of whom is experienced in CTC interpretation. The Radiologists will review
the scans and record their findings in 4 separate envelopes, one for each section of the
colon (rectum and sigmoid, descending, transverse and right colon). The size of lesions
found will be recorded from the optimum view using electronic callipers. Finally, the
radiologists will review the films for any extra-colonic findings that will be recorded
separately. Similarly, a GI Fellow and a Family Physician will review the scans recording
their findings in the same manner. However, at least one Radiologist will review the films
at the time of the examination to ensure that they are of adequate quality and to provide
their interpretation prior to OC. The amount of time taken to read the films for each
reviewer will be recorded as a total time to read all views for each patient. Observers will
be made aware of optical colonoscopy results after each 100 procedures.

Optical Colonoscopy Within 2 hours of finishing the CTC imaging, participants will undergo
OC with conscious sedation using a combination of midazolam and Demerol or fentanyl to
achieve patient comfort. An experienced gastroenterologist using an Olympus colonoscope will
perform the colonoscopies. The endoscopist, blinded to the CTC results will examine the
colon on withdrawal of the endoscope, recording findings for each of the four segments of
the colon. Each segment is then to be sequentially unblinded allowing the endoscopist to
review the Radiologists findings for each colonic segment on CTC. Polyps detected at
endoscopy will be removed using standard techniques (biopsy forceps or snare cautery) and
submitted for pathological assessment.

Advanced neoplasms will be divided by pathology into adenocarcinomas and polyps. Polyps will
be further categorized according to size (≤5mm, 6-9mm and ≥10mm). Morphologic
characteristics of the lesions will also be recorded by viewers as sessile, pedunculated or
flat. Lesion size is to be determined by measurement of removed lesions (before fixation) or
estimated at endoscopy by comparison to the biopsy forceps, for those lesions that are not
removed.

Patient Questionnaires Following endoscopy, patients will be transferred to recovery area
where they will undergo monitoring of their vital signs following standard practice
guidelines, until they are ready for discharge. Immediately prior to discharge, patients
will be given a 10 question written survey, for self-completion (see appendix 1). The
recovery room nurse will give this to them after final consultation with the
Gastroenterologist while in the recovery room. Patients will be given as much time as
necessary to complete the survey and instruction to seal the survey in an envelope and
return it to the nurse prior to leaving the recovery room.

In order to assess the test/retest reliability of the survey, a random sample of patients
will be mailed a second survey (identical to the first) 3 - 4 weeks after the day of
examination. Enclosed will be instructions for self-completion of the survey and a self
addressed, postage paid, return envelope to allow for its return.

6. Statistical Analysis The reference standard of polyp detection will be the results of OC
after each colonic segment is re-examined once the CTC results are known. Tests of accuracy
will be sensitivity, specificity, true positive and true negative results with comparison to
the reference standard. ROC curves for CTC and OC will be derived after all tests are
completed. The AUC for each tests' ROC curve will be used to compare accuracy between these
two tests. ROC curves and the AUC statistic will be derived from the dataset once divided
according to each 100 CTC performed and by each reader to evaluate the learning curve of
this test. Tests of significance will be McNemar's test, paired t-tests, and chi-square
tests as appropriate. Interobserver reliability will be reported as a kappa statistic.