Report on the IBBT ICA4DT WP5 Colon CAD software validation in CT colonography in a clinical setting.

Didier Bielen, PhD, MD

Feng Chen, PhD, MD

Hilde Vandenhout, PhD, MSc

Frederik De Keyser, MSc

Guy Marchal, PhD, MD

Report on the IBBT ICA4DT WP5 Colon CAD software validation in CT colonography in a clinical setting.

Didier Bielen, PhD, MD Feng Chen, PhD, MD Hilde Vandenhout, PhD, MSc Frederik De Keyser, MSc Guy Marchal, PhD, MD

Leuven, November 4th 2008.

3

1 Table of content

Report on the IBBT ICA4DT WP5 Colon CAD software validation

in CT colonography in a clinical setting. ...................................... 1 

1  Table of content ................................................................................. 3 

2  Introduction ........................................................................................ 3 

3  Materials and methods ....................................................................... 7 

3.1  Patient selection and CTC procedure ............................................ 7 

3.2  Establishing the enhanced reference standard ............................. 10 

3.3  Evaluation of CTC and CAD accuracy ....................................... 11 

4  Results .............................................................................................. 15 

5  Conclusion ....................................................................................... 19 

6  Acknowledgements ......................................................................... 19 

7  References ........................................................................................ 21 

Introduction

2 Introduction

In Western Europe and the United States, colorectal carcinoma (CRC) remains the second leading cause

of cancer related death(1-4). In Belgium, each year 7700 new colorectal cancers are diagnosed(5). The ma-

jority of these cancers originate from pre-existing benign lesions from the mucosal lining of the bowel

wall. These ‘adenomatous polyps’ have the potential to progress into a malignant lesion, a carcinoma,

over a period of ten year, the dwelling time(6, 7). According to results from endoscopy series the preva-

lence of such adenomas in persons aged ≥60 is 20-40%(8-10). Once a cancer has been diagnosed, the 5-

year survival declines significantly.

Given the fact that CRC is a common disease, with serious morbidity and mortality rates, and that effec-

tive treatment can be offered in case of early detection, attention should be drawn to secondary preven-

tion or screening1. Such screening tests should be sufficiently accurate for detecting polyps ≥10mm, ac-

ceptable to the otherwise healthy persons to be screened, feasible in clinical practice, not harmful nor

too expensive: the test should be cost-effective where the potential benefits must outweigh the costs.

Large scale detection and subsequent removal of lesions in an early stage, especially the advanced ade-

nomas2, may lead to a significant decrease in the incidence of CRC and a reduced cancer related mor-

bidity and mortality(11, 12).

However, the risk of cancer transformation is variable and associated with either the histological polyp

characteristics, in particular the villous component of a lesion, either the flat aspect of a lesion. But since

these histological characteristics can only be determined after the removal of a lesion, either surgical or

after an endoscopy, it would be more convenient to determine this risk prior to removal. Fortunately, the

main determinant of the risk for CRC is believed to be the polyp’s size(13, 14), that might be measured or

estimated in a non invasive way.

Up to today conventional colonoscopy (CC) is the most accurate technique, because if offers a high sen-

sitivity for polyp detection. Although the CC has the possibility for polyp removal, this might not be

taken into account in a screening setting since polyp removal will only be performed in a second thera-

peutic session. Further, the majority of lesions are not advanced adenomas and can be left in place if not

detected.

On the other hand, optical colonoscopy has some disadvantages, being especially the laxative bowel

preparation which is experienced as unpleasant since it causes a lot of patient discomfort, and the rather

high cost. Although there is a risk of bowel perforation, in particular in case of polyp removal, this

might not be taken into account in case of a screening program, since polyp removal will only be per-

formed in a second therapeutic session.

1 Secondary prevention activities are aimed at early disease detection, thereby increasing opportunities for interven-tions to prevent progression of the disease and emergence of symptoms 2 Advanced adenoma is a polyp with a diameter ≥1cm, and/or ≥20% villous component and/or high grade dysplasia, leading to a significant increased cancer risk

3

Introduction

Mass screening for polyps and small tumours by computed tomographic (CT) colonography (CTC), also

known as virtual colonoscopy, promises to become a short term alternative or at least a complementary

non-invasive screening tool(15-22). Since its introduction in 1994(23) many papers on the CTC technique

and its reliability have been published in both radiology and gastroenterology related journals. Although

the participation rate for a screening program using CTC can be compared to that of similar screening

programs(24), CTC did just recently became an accepted screening tool according to the guidelines of the

American Cancer Society(25, 26). The fact that it took so long was due to a number of reasons.

To become accepted and be able to compete with the CC, CTC should be sufficiently accurate, i.e. able

to detect at least significant polyps. Although there is no consensus on what should be targets, guide-

lines recommend to target on the advanced adenomas, whereas the importance of lesions 6-9mm re-

mains controversial(27). Especially this topic gives rise to a lot of controversy. One study, examining a

large patient population resembling the target population for a screening program, proved that CTC with

the use of a 3D approach is an accurate screening method in an average risk population and compared

favourably with optical colonoscopy, with a sensitivity for lesions >10mm that was >90%(28). Another

study stated that the sensitivity for lesions >10mm was only 55% and that the accuracy varied consid-

erably between centres, leading to the conclusion that CTC by these methods is not yet ready for wide-

spread use; techniques and training need to be improved(29). An explanation for these different conclu-

sions might be found in the fact that the first study was performed under optimal conditions with a stan-

dardized CTC technique and reading conditions, whereas the latter study grouped different centres, dif-

ferent CTC techniques and readers’ experiences, very close to what might be found in daily practice.

A recent publication(22) and findings presented at the latest RSNA conference(30, 31) are more optimistic,

indicating that primary screening strategies with CTC and CC resulted in similar detection rates for ad-

vanced neoplasias.

The clinically important polyp seems to be a lesion measuring at least 6mm. The rationale behind this is

the fact that the majority of polyps ≤5mm are hyperplastic and harbour a risk of malignancy of less than

1%, requesting only regular screening at an interval of 10 or fewer years. Intermediate lesions 6-9mm

are almost all benign in nature, 30% of these lesions are not adenomas, and the majority lack high-grade

dysplasia. For patients with no elevated risk interval surveillance, interval surveillance after 2-3 years

can be recommended in case there are no more than 2 lesions. Patients with 3 or more lesions 6-9mm

have an increased risk of developing advanced adenomas and these patients can be offered either sur-

veillance (i.e. control after 3 years) or polypectomy, depending on the patient’s and/or physician’s pref-

erences. Patients with lesions ≥10mm should be referred to colonoscopy with polyp removal, since 10-

25% of these lesions demonstrate high-grade dysplasia or carcinoma. The American Cancer Society

guidelines on the other hand recommend CC for any lesion >6mm detected until there is more evidence

on the safety of observation of these lesions.

The success of the patient’s risk stratification, as proposed by the by the Working Group on Virtual

Colonoscopy(32) based on the size of the largest lesion detected, will be the criterion to judge the accu-

racy of our CTC technique.

4

Introduction

5

Another aspect regarding CTC is that it is unclear whether CTC might benefit from the use of computer

aided detection (CAD). In the area of medical imaging, first CAD experiments involved the identifica-

tion and classification of micro calcifications in mammography(33). Positive results encouraged the de-

velopment of algorithms to identify lung nodules on chest radiographs(34) and helical CT images(35).

Whereas the idea behind CAD in CTC is quite simple — ‘Look for polyps and present them to the radi-

ologist’ — CAD is a multi step procedure typically consisting of (1) segmentation of the colonic wall,

(2) generation of intermediate polyp candidates, (3) classification for detection of final candidates and

(4) presentation of the polyp candidates.

To be feasible in daily practice, state-of-the-art CAD systems should require minimal or even no user

interaction for the extraction of the colonic wall, reasonable computation time (less than 10-20 min),

high sensitivity and specificity for different polyp sizes and shapes, with a low number of false posi-

tives. It remains unclear whether these systems will be clinically implemented as first(36), second or con-

comitant reader in CTC(37).

For these reasons, we evaluated in the study the added value of a prototype CAD program as a second

reader, this for the three different bowel preparation regimens. The same criteria, i.e. the patient’s risk

stratification, as proposed by the by the Working Group on Virtual Colonoscopy(32) based on the size of

the largest lesion detected, were used to judge the accuracy of this CAD technique.

Whereas conventional colonoscopy (CC) can only be performed with a high degree of specificity and

sensitivity if the colon wall is free of faecal residues, this requirement has been considered even more

stringent for CTC, due to the lack of direct visual control. However, if an onerous preparation must be

performed, it is doubtful that a significant impact from this technique would be observed(38). It is known

that especially a conventional wet bowel preparation with laxatives might compromise the acceptance of

the screening test by the target population, which are healthy persons aged 50-70 instead of patients and

consequently the participation rate of this target population(39-41). In general, the larger the amount of

preparation fluid, the higher the likelihood of a poor acceptance rate. Different preparation regimens

were discussed in literature, using either laxatives, laxatives combined with faecal and/or fluid tagging,

or tagging-only preparation(39, 40, 42-50).

The purpose of the study will be the evaluation of the effect of three different bowel preparation regi-

mens on the accuracy of the CAD software in CTC. Therefore we evaluated preparation regimens with a

decreasing proportion of laxatives, i.e. with the intention to reduce patient discomfort i.c. diarrhoea.

The validation objectives will the per patient results, since these results are (even more) important than

the per polyp results: missing a lesion of <5mm is not of clinical importance if this patient has also a

polyp of ≥12mm. These results might be influenced by the acquisition position or the patient’s prepara-

tion.

Materials and methods

3 Materials and methods

3.1 Patient selection and CTC procedure

From January 2004 through October 2006, an outpatient population was invited to undergo CTC prior to

the scheduled CC. The first 305 persons who agreed to take part were included in the study. The group

consisted of 170 men and 135 women (mean age 57; ranging 28-75 years). All patients were recruited

ambulatory and were active at the time of the examinations.

Indications for the colonoscopy were increased risk for colorectal cancer due to first degree relative un-

der the age of 60 with CRC or advanced adenoma, i.e. a familial elevated risk (n=57), follow-up for co-

lorectal tumour or advanced adenoma (n=137), or suspicion of colonic pathology necessitating CC (e.g.

anal bleeding, change in stool habit, n=111). Exclusion criteria were inflammatory bowel disease

(Crohn disease or ulcerative colitis) and pregnancy. The institutional ethics committee approved of all

the study protocols described in present chapter, and a written informed consent was obtained from all

patients.

Prior to the exam, all patients received diet recommendations. Two days prior to the exam, patients were

only allowed to eat food with a low fibre content (cheese, eggs, meat and fish, milk, pasta, white bread,

etc), while high fibre content food was prohibited (all kinds of dark bread, fruits and vegetables, whole-

wheat pasta, unpeeled rice, etc). The evening prior to the exam, patients were allowed to have only a

liquid meal. They were encouraged to drink at least 2 litres a day, but to restrict the use of sparkling

drinks, fruit juice, alcohol, coffee and tea.

To evaluate the effect of different preparation regimens, patients underwent, besides dietary restrictions,

one of three different bowel preparation regimens for which they received recommendations. Prepara-

tions contained a decreasing proportion of laxatives, with the intention to reduce patient discomfort i.c.

diarrhoea.

To evaluate the effect of a standard laxative bowel preparation, patients in “Group 1”, the laxative-only

group (n=102, with timeline 1/2004 to 2/2005), had to drink 4-5 litres electrolyte solution the morning

of the colonoscopy (Na+ 141meq, K+ 10meq, Cl- 121meq, HCO3- 30meq per litre water). This group

consisted of 60 men and 42 women (mean age 55, ranging 28-75 years). Indications for the colonoscopy

were familial elevated risk (n=43) or personal follow-up (n=59) (Table 1 – Group 1).

7

Materials and methods

TotalM W M W M W

Elevated familial risk 17 26 7 4 1 2 57Personnal follow-up 43 16 26 16 20 16 137No elevated risk 0 0 34 38 22 17 111

60 42 67 58 43 35 305

Group 1 Group 2 Group 3

Total102 125 78

Table 1 Indications for CC per study group and gender

To evaluate the effect of tagging, patients in “Group 2”, the laxative-and-tagging group (n=125, with

timeline 3/2004 to 4/2006), had to drink a low volume laxative preparation with two doses (45ml each)

sodium phosphate (Fleet Phospho Soda®, Wolfs, Belgium) the afternoon and evening prior to the

colonoscopy. Since the examinations of Group 1 and Group 2 were characterized by a partial overlap in

time, assignment to Group 2 was based on patients’ willingness and/or ability to undergo preparation at

home.

For tagging purposes, patients had to drink 100ml of a water-soluble iodinated contrast medium (me-

glumine ioxitalamate 3% - Telebrix Gastro® Guerbet/Codali Belgium): 10ml diluted in a standard glass

of water (250ml) together with the three principle meals (breakfast, lunch, dinner) the day prior to the

exam, 25ml diluted in a standard glass of water together with each dose of the laxative and 20ml diluted

in a standard glass of water the morning of the exam. The use of the contrast material is intended to en-

hance the density of possible residual stool (‘faecal tagging’)(42) allowing discrimination between non-

contrast containing polyps and contrast containing stool. This group consisted of 67 men and 58 women

(mean age 57; ranging 35-73 years). Indications for the colonoscopy were familial elevated risk (n=11),

personal follow-up (n=42) or suspicion of colonic pathology without an elevated risk for CRC (n=72)

(Table 1 – Group 2).

To evaluate the effects of a minimal preparation, patients in “Group 3”, the tagging-only group (n=78,

with timeline 11/2005 to 10/2006), received a minimal preparation of ‘faecal tagging’ only. Since also

Group 2 and Group 3 were characterized by a partial overlap in time, patients were assigned to Group 3

in case they were not willing and/or able to undergo preparation at home. The same tagging scheme as

used in Group 2 was applied, but patients had to drink 25ml of contrast medium diluted in a standard

glass of water (250ml) in the afternoon and in the evening i.e. without the laxatives. Group 3 consisted

of 43 men and 35 women (mean age 60; ranging 44-73 years). Indications for the colonoscopy were fa-

milial elevated risk (n=3), personal follow-up (n=36) or suspicion of colonic pathology without an ele-

vated risk for CRC (n=39) (Table 1 – Group 3).

Prior to the CTC, the radiologist informed all persons regarding the procedure and the possible compli-

cations (radiation exposure, discomfort, urge).

8

Materials and methods

All exams were performed with manual insufflation of the large bowel using a thin rectal cannula con-

nected to an enema bag containing an air-CO2 mixture (E-Z-EM Inc, Westbury, USA), where insuffla-

tion was sustained in accordance to the level of patient comfort. If any discomfort was reported, relief

could be obtained by releasing the pressure on the bag(40). Immediately prior to the CTC, a bowel relax-

ant (5ml butyl hyoscine bromide - Buscopan® Boehringer Ingelheim, Belgium, diluted in 10ml saline)

has been administered intravenously through an antecubital vein unless contra-indicated (patients with

prostatic enlargement or closed angle glaucoma). No intravenous contrast agent was given.

We planned all patients on a 16-row CT scanner (Sensation 16, Siemens, Germany). High resolution ex-

aminations were performed with thin collimation (16x0,75-1,5mm) and image reconstruction (slice

thickness 2mm and interval 1,5mm ). Supine scans were performed using 120kV and 55mAs. Prone

scans were performed using (a) 120kV and 55mAs; (b) 100kV and 50mAs or (c) 140kV and 15mAs.

Dose modulation was applied to reduce radiation dose. The CARE Dose technique (Combined Applica-

tion to Reduce Exposure Dose) allowed real-time in-plane dose modulation (x-y dose modulation) ac-

cording to patient’s body shape in the transverse plane, whereas CARE Dose4D allowed additional

through-plane dose modulation (z dose modulation) according to patient’s changing body shape in the

longitudinal plane. The abdomen was scanned from the diaphragmatic vault to the pubis in both supine

and prone position, this during one breath-hold per acquisition. Immediately after completion of the

CTC, the bag was disconnected to allow the gas to escape. The rectal cannula was removed and patients

could leave the CT suite; they were accompanied to the endoscopy department for their CC appoint-

ment.

The transversal CT images as well as coronal reformations of both supine and prone acquisition in

DICOM3 format were sent to a PACS4 workstation (Impax, Agfa, Belgium) for 2D reading and to a

dedicated workstation (syngo Colonography version VB20B, Siemens Medical Solutions, Forchheim

Germany) for 3D reading. The evaluation of all these images was done by a radiologist experienced in

abdominal CT and CTC in particular.

3 DICOM: “Digital Imaging and Communications in Medicine” – standard for distribution and viewing medical images, irrespective of their origin. 4 PACS: “Picture archiving and communication system” – the infrastructure of computers and networks for storage, distribution and presentation of images.

9

Materials and methods

3.2 Establishing the enhanced reference standard

All patients were examined by CC within three hours after the CTC examination. In case of the tagging-

only preparation (Group 3), an additional bowel preparation was performed prior to CC (4-5 litres of an

electrolyte solution i.e. Na+ 141meq, K+ 10meq, Cl- 121meq, HCO3- 30meq per litre of water).

For the CC, an experienced endoscopist gave information about discomfort, possible complications, etc.

All patients were examined with a standard endoscope (CF-100 MI, CF-130, CF-Q140, Olympus Opti-

cal Co., Hamburg, Germany). For sedation, pethidine (0-50mg) and midazolam (0-5mg) were routinely

used. The endoscopist was unaware of the CTC findings until he had examined a previously defined

colonic segment, called the “segmental unblinding” technique(28). These segments were: rectum, sig-

moid, descending colon, transverse colon, ascending colon and caecum. As a consequence of the blind-

ing, some lesions observed at CTC may not have been detected at CC causing an underestimation of the

sensitivity of CTC. Furthermore, it was not ethically acceptable that a patient who had a polyp recorded

at CTC and not detected at CC would have CC repeated in order to check for a possibly missed polyp.

To avoid the occurrence of this event, the endoscopist was assisted by an operator who was aware of the

CTC results, so that CC was performed in a “double check” fashion. After reaching the caecum, diag-

nostic assessment of each segment was performed sequentially during withdrawal of the endoscope. In

the event that a lesion detected by CTC was missed by CC, the assisting operator informed the endo-

scopist before the subsequent segment was visualized so that careful inspection of the segment could be

repeated. If a lesion was finally visualized, this was considered as a false-negative CC result; if no lesion

was visualized, this was recorded as a false-positive CTC finding. This technique resulted in an en-

hanced reference standard, the ground truth for further data analysis. Prior to removal, the endoscopist

measured each polyp using open biopsy forceps. A “polyp-matching algorithm” allowed to define a

CTC lesion as true positive in case the CC located that lesion in the same or adjacent segment and the

diameters were the same, within a 50 percent error margin.

10

Materials and methods

3.3 Evaluation of CTC and CAD accuracy

To be a valid tool, CTC should be able to accurately detect colon lesions, i.e. polyps and tumours. For

this purpose, the exams from Group 1 were evaluated on the PACS workstation; 3D reading was used

for problem solving only. The exams from Group 2 were evaluated on the dedicated colonography

workstation, and for Group 3, the radiologist chose the most efficient technique, depending on the pres-

ence of residual fluid and/or stool. No electronic cleansing, i.e. removal of high density fluid and resi-

dues by means of software tools, was applied.

Shape (sessile or pedunculated polyps, flat lesions, stenosing or vegetating tumours), size (in mm) and

location (rectum, sigmoid, descending colon, transverse colon, ascending colon, caecum) of all lesions

were registered.

For the definition of the lesion shape, we used the Paris Workshop 2002 definitions and recently pub-

lished radiological criteria concerning flat lesions(51, 52). Polypoid neoplasms protrude above the sur-

rounding surface at endoscopy, with a height that is double the lateral extension. Polyps are classified as

pedunculated in case the base is narrow or as sessile in case the base and the top of the lesion have the

same diameter. A lesion is considered a flat lesions in case the height of the lesion is less than the dou-

ble of the lateral extension.

All lesions were manually measured on the PACS workstation using a calliper, and this in the supine or

prone acquisition and the transversal or coronal plane containing the longest axis of the polyp. We did

not use additional multiplanar reformats. Window width (WW) and window level (WL) were 1700/-300

Hounsfield units (HU). Target lesions were those measuring ≥6mm; but whenever picked up, smaller

lesions were registered too. Findings were classified as normal, diminutive lesions (polyp size ≤5mm),

polyps 6-7mm, polyps 8-9mm, polyps ≥10mm and tumours.

For lesion location, we used following definitions: the rectum includes the part of the colon from the

dentate line to the most proximal transversal rectal fold, also known as valve of Houston; the sigmoid

colon extends from the most proximal transversal rectal fold to the inferior aspect of the vertical seg-

ment of descending colon; the latter extends to the most cephalic flexure of the transverse colon in the

left upper abdominal quadrant; the most cephalic curvatures of the flexures define the proximal and dis-

tal edges of the transverse colon; the ascending colon continues inferiorly from the proximal boundary

of the transverse colon until the ileocaecal valve, which defines the border between the caecum and the

ascending colon. The boundary between caecum and ascending colon can be established by drawing a

line from the valve perpendicular to the centreline of the colon(53). All the CTC results were summarized

in an Excel spread sheet.

The size of the polyps and tumours allow a patient risk stratification as proposed by the Working Group

on Virtual Colonoscopy(32). Patients with a tumour, a lesion ≥10mm or ≥3 lesions 6-9mm should be re-

ferred for polypectomy, whereas patients with <3 lesions 6-9mm might be eligible for short term follow-

up CC within three years; all other patients are eligible for long term surveillance CC after 5-10

years(32).

11

Materials and methods

For the evaluation of the CAD software, all DICOM data sets were send to a stand alone dedicated work

station. Whereas the idea behind CAD in CTC is quite simple — ‘Look for polyps and present them to

the radiologist’ — CAD is a multi step procedure typically consisting of (1) segmentation of the colonic

wall, (2) generation of intermediate polyp candidates, (3) classification for detection of final candidates

and (4) presentation of the polyp candidates. The Agfa CAD algorithm is based on robust sphere fitting

and searches for blobs in the colon wall that resemble a database of typical polyps. It has been integrated

into Agfa's Virtual Colonoscopy solution as a prototype for the clinical investigation. The CAD soft-

ware generated a list of polyp candidates. This way users can navigate through the CAD findings and

assess them for further reporting. The sphericity is a software setting which might influence the genera-

tion of polyp candidates. This setting was not tweaked during testing; testing will occur with a fixed pa-

rameter setting of the CAD software as determined during the software development. Datasets that were

used for the development of the CAD software were excluded.

To exclude the effect of reader experience, this list was evaluated by a surgeon with knowledge of radi-

ology but no experience in CTC. He was blinded to the results of the initial CTC and CC. Examinations

were evaluated in a random order, mixing the three different preparation regimens. All possible lesions

were measured manually. The total number of false positives per acquisition was noted. All the CAD

results were summarized in an Excel spread sheet, augmented with the statistical toolkit Analyse-it (ver-

sion 2.12). The CAD findings were compared with the enhanced reference standard based on the com-

bined findings of the original CTC and CC findings. This enhanced reference standard served as the

ground truth: a lesion found by CAD but not with the combined CTC/CC technique was considered a

false positive lesion, whereas a lesion not found by the CAD was considered a false negative. All lesions

found by CAD and confirmed by the combined CTC/CC technique was considered a true positive.

Given the need for the patient’s risk stratification by CTC, the per patient result was considered true

positive if a lesion was found by the CAD in at least one acquisition. Only the clinical significant lesions

as defined by the Working Group on Virtual Colonoscopy(32) were taken into consideration.

End point of this evaluation is to prove whether or not the CAD software has a performance comparable

to human readers in detecting polyps using CTC. Given the results of the CAD based on training data

sets, the per polyp sensitivity should be 100%, the per polyp specificity should be 83%, and the total

number of false positives should be 3,4 per case. At the moment of the CAD training, the software in-

cluded only the segmentation of the colonic wall and the generation step. Although an intermediate ver-

sion included the feature classification scheme, the software version used in this evaluation study did

not included the feature classification scheme algorithm.

All the CAD results were compared with the original CTC results as well as with the results of the CAD

software including the feature classification scheme.

The per patient sensitivity5 was calculated based on the true positives (TP), i.e. the correct assignment to

the correct risk group and the false negatives (FN). To evaluate which preparation group allowed best

polyp detection, the three groups were compared using the Pearson’s chi square test.

5 Sensitivity indicates how good a test is at detecting disease; Sens = TP/(TP+FN)

12

Materials and methods

13

The number of false positives was recorded for every acquisition and for the combined supine and prone

acquisition. The influence of the preparation on the total number of false positives was evaluated using

Analyse-it. A one-way Anova test was used to detect whether or not the differences induced by the

preparation were significant. Further paired t-test was used to evaluate if the acquisition position was

influencing the total number of false positives and if there was a correlation between the numbers of

false positives found in supine and prone acquisition.

Results

4 Results

The CAD evaluation could not be completed in the supine, the prone or both acquisitions in 23 patients.

For these reasons, only the results of the patients with a complete CAD evaluation in both the supine

and prone acquisition were taken into account for data analysis (n= 282): n=98 for Group 1; n=118 for

Group 2 and n=66 for Group 3.

Based on the enhanced reference standard (combined findings of CTC and CC, Table 2), 144 patients

(n=53 for Group 1, n=64 for Group 2 and n=27 for Group 3) had no lesions; 98 patients (n=32 for

Group 1, n=38 for Group 2 and n=28 for Group 3) had diminutive lesions ≤5mm; 19 patients (n=5 for

Group 1, n=6 for Group 2 and n=8 for Group 3) had <3 lesions 6-9mm (Figure 1); 1 patient (n=1 for

Group 3) had ≥3 lesions 6-9mm (Figure 2); 15 patients (n=7 for Group 1, n=7 for Group 2 and n=1 for

Group 3) had a lesion ≥10mm (Figure 3) and 5 patients (n=1 for Group 1, n=3 for Group 2 and n=1 for

Group 3) had a tumour (Figure 4).

Figure 1 Polyp 6-9mm in endoscopic and CTC endo view

15

Results

Figure 2 ≥3 Polyps 6-9mm in endoscopic and CTC endo view

Figure 3 Polyp ≥10mm in endoscopic and CTC endo view

Figure 4 Tumour in endoscopic and CTC endo view

This means that 40 patients had at least one significant lesion ≥6mm, of which 21 patients had at least

one lesion that needed referral to endoscopy or surgery. Three of these lesions were endoscopically clas-

sified as a flat lesion (n=1 for Group 1, n=1 for Group 2 and n=1 for Group 3).

16

Results

Group 1 Group 2 Group 3 All groupsNo lesions 53 64 27 144Polyps ≤5mm 32 38 28 98<3 Polyps 6-9mm 5 6 8 19≥3 Polyps 6-9mm 0 0 1 1Polyps ≥10mm 7 7 1 15Tumours 1 3 1 5

98 118 66 282 Table 2 Lesion types per study group (referral candidates in bold)

These significant lesions were located in the rectum (n=9), the sigmoid (n=16), the descending colon

(n=1), the transverse colon (n=7), the ascending colon (n=5), and the caecum (n=3).

Of the clinical relevant lesions, the CTC found 16/21 lesions (Table 3).

Group 1 Group 2 Group 3 All groups≥3 Polyps 6-9mm 0 0 1 1Polyps ≥10mm 4 6 1 11Tumours 1 2 1 4

5 8 3 16 Table 3 Lesion types found at CTC per study group

This corresponded to a per patient sensitivity of 62,5% for Group 1, 80,0% for Group 2 and 100,0% for

Group 3. For the three groups together, the per patient sensitivity was 76,1%.

The CAD found non of the ≥3 lesions 6-9mm in 1 patient (n=0 for Group 3); 7 lesions ≥10mm in 15

patients (n=1 for Group 1, n=5 for Group 2 and n=1 for Group 3) and a tumour in all 5 patients (n=1 for

Group 1, n=3 for Group 3 and n=1 for Group 3) (Table 4). None of the flat lesions was detected, even

not in retrospect.

Group 1 Group 2 Group 3 All groups≥3 Polyps 6-9mm 0 0 0 0Polyps ≥10mm 1 5 1 7Tumours 1 3 1 5

2 8 2 12 Table 4 Lesion types found at CAD per study group

This corresponded to a per patient sensitivity of 25,0% for Group 1, 80,0% for Group 2 and 66,6% for

Group 3. For the three groups together, the per patient sensitivity was 57,1%. Compared to CTC results,

the CAD software did not outperform the human reader.

17

Results

18

Comparing the feasibility to detect polyps in the three different preparation groups, the Pearson chi

square test showed that the results in Group 2 were significantly better compared to these in Group 1

(p=0,02). The difference between Group 1 and 3 and between Group 2 and 3 was not significant, but

this might be due to the fact that the total numbers of lesions in Group 3 were rather low.

Compared to the intermediate CAD software version including the feature classification scheme, there

was an improved detection only for the patients in Group 2.

The CAD software generated a total of 2347 false positive lesions in 472 acquisitions in the 282 patients

(n=593 in Group 1, n=997 in Group 2 and n=757 in Group 3). The number of false positive lesions per

acquisition ranged from 0-18 in Group 1, from 0-20 in Group 2 and from 0-21 in Group 3; the number

of false positive lesions per patient ranged from 0-21 in Group 1, from 0-28 in Group 2 and from 2-34 in

Group 3. The mean number of false positive lesions was 3,0 in Group 1, 4,2 in Group 2 and 5,7 in

Group 3. The differences between these groups was significant (p<0,0001).

The mean number of false positive lesions was 3,6 in the supine position and 4,7 in the prone position.

There was a weak correlation between the number of false positives in the supine and prone acquisition

(R2=0,18).

Given the huge amount of false positive lesions per patient and the limited information on these false

positive lesions (only the distance from rectum was generated automatically in the CAD report!), it was

not possible to measure nor to correlate these individual lesions with the original CTC or CC findings.

Conclusion

5 Conclusion

In conclusion, this study showed that the detection of significant lesions (a tumour, a lesion ≥10mm or

≥3 lesions 6-9mm) by means of CTC is feasible, even when using a reduced bowel preparation with

tagging but without laxatives, with good patient’s risk stratification based on the polyp size.

Unfortunately, the evaluated CAD software seems to be of limited added value, since the number of true

positive lesions is lower than the number of true positives found at the initial CTC, indicating the tested

CAD software does not outperform the human reader. The large amount of false positive lesions per pa-

tient and the limited automatically generated information on these false positive lesions poses a diagnos-

tic problem for the radiologist since he has to evaluate all the polyp candidates individually to decide

whether or not the candidate is a true or a false positive lesion.

These findings might indicate that the clinical environment in which the CAD software has been tested

differs significantly from the test environment.

6 Acknowledgements

Special thanks to Mr. Herman Pauwels and Mr. Tom Deprez for the PACS data management, data ano-

nymisation and randomisation.

19

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