Evaluation of Computed Tomography and Magnetic Diffusion Resonance Imaging in the Preoperative Staging of Colon Cancer
Phase: NA
Conditions: Colonic Neoplasms
Sponsor: Larissa University Hospital

COVER PAGE
Study Protocol
OFFICIAL  TITLE:  Evaluation  of  computed  tomography  and 
magnetic diffusion resonance imaging in the preoperative staging of 
colon cancer
BRIEF TITLE: CT and MRI in Preoperative Colon Cancer Staging 
UNIQUE PROTOCOL ID: CTMR 
DOCUMENT DATE: January 2023
Principal Investigator:
Effrosyni Bompou, MSc
Telephone: 00302413501000
Email: feybobou@hotmail.com
Sub-Investigators:
Ioannis Baloyiannis
Aikaterini Vassiou
Study Director
George Tzovaras, Professor of General Surgery
Telephone: 00302413502804
Email: gtzovaras@hotmail.com
Department of Surgery
University Hospital of Larissa
Mezourlo 41110 Larissa
Greece
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1. INTRODUCTION
1.1 Literature Review
Over the last years a significant improvement in the treatment of patients with colon cancer has 
been reported. This has been attributed to the improvement of the staging techniques, as well as the 
optimization of the surgical management. However, the current five-year survival rates of colon 
cancer patients in European countries ranges from 32% to 64%. [1]. This variation could be due to 
treatment discrepancies and the lack of adherence to the international guidelines [2].
Surgical treatment of colon cancer includes the radical resection of the tumour (colectomy). 
Following resection, the specimen is histopathologically examined, the disease is staged and further 
treatment is determined. Neoadjuvant treatment (radiotherapy or/and chemotherapy) for colon 
cancer  has  not  been  yet  approved,  unlike  rectal  cancer,  where  neoadjuvant  treatment  is 
recommended for specific disease stages [3]. 
Preoperative staging of colon cancer aims to identify those patients with remote metastatic 
disease, who will, more likely, not benefit from upward surgery. Recent developments in colon 
cancer management, demanding more precise local disease staging, to identify those patients who 
will likely benefit from neoadjuvant chemotherapy, are still at a clinical trial stage [4]. 
Preoperative treatment depends on the disease stage, which is defined by the tumour's invasion 
in the colonic wall, the dissemination in nearby organs or lymph nodes, and the presence of distal 
metastases. The stage is first evaluated radiologically and then confirmed via histopathological 
examination of the specimen. Imaging is an already approved tool for the staging of colonic cancer, 
while in some studies the combination of different imaging methods has been reported to improve 
the initial evaluation [5, 6, 7, 8, 9, 10]. 
Over  the  last  years,  evaluation  of  the  circumferential  resection  margin  (CRM)  is  also 
recommended  in  the  preoperative  staging  of  patients  with  colon  cancer.  This  assessment  is 
particularly important for tumours located at the cecum, right, or left colon, since these areas lack of 
mobile mesocolon and therefore it is possible to infiltrate the retroperitoneal resection margin.
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Nevertheless, the retroperitoneal invasion of these tumours has not been evaluated adequately 
as a preoperative marker for both local recurrence and for the selection of patients who may benefit 
from neoadjuvant treatment. In various studies the percentage of retroperitoneal resection margin's 
infiltration was between 7-10% for cecum and right colon adenocarcinomas, while its presence was 
identified  as  a  risk  factor  for  local  recurrence.  The  retroperitoneal  surface  infiltration  was 
preoperatively  evaluated  with  the  combination  of  imaging  methods  and  the  findings  were 
postoperatively compared with the histopathological features of the specimen [11, 12]. 
A more precise, imaging based, preoperative staging, could lead to a more targeted neoadjuvant 
treatment for patients with advanced disease, with the introduction of chemo- and/or radiotherapy. 
This approach could result to the downstaging of the tumour, with better short and long term 
oncological results.
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2. OBJECTIVE 
2.1 Description of the proposed project
The objective of this study is the evaluation of different imaging methods for the optimal 
preoperative  staging  of  colon  cancer  patients.  Imaging  findings  will  be  compared  with  the 
histopathologic results of the specimen following surgical resection.
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3. MATERIAL AND METHODS
3.1 Population
The sample will consist of males and females aged 18 to 90 years.
3.2 Diseases
The study will include patients with colon cancer that will meet the current criteria surgical 
resection based on the principles of complete mesocolic excision (CME).
3.3 Inclusion / Exclusion Criteria
Inclusion criteria are the following:
• Histologically confirmed colonic adenocarcinoma
• Patient 18 to 90 years old
• Abscence of comorbidities that may affect treatment
• Signed informed consent of the patient
Exclusion criteria are the following:
•   Inability to receive or contraindication for intravenous contrast 
•   Renal impairment 
•   Previous allergies to intravenous contrasts 
•   Incompatible implants with magnetic resonance imaging 
•   Claustrophobia 
•   Active sepsis or systemic infection 
•   Untreated physical and mental disability 
•   Lack of compliance with the protocol process 
•   Non-granting of signed informed consent
3.4 Study Arms
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In this study there will be one arm. All prospectively included patients with colon cancer will 
be preoperatively submitted to MRI for staging. The evaluation of the diagnostic accuracy will be 
based on the cross-examination with the CT scan and the pathology results.
The MRI protocol will include the following imaging series: T1 and T2 in axial and coronal 
plane before the administration of intravenous contrast, diffuse weight imaging in axial plane and 
T1 after the administration of intravenous contrast.
The CT scan protocol will include the following: per os and intravenous administration of 
contrast, axial slices of 0.3mm thickness and reconstruction per 1mm, multi-planar reformation 
and three-dimensional volume rendering.
3.5 Anesthesia
Patients will receive general anesthesia.
3.7 Primary endpoint
Diagnostic accuracy in T stage. Evaluation of diagnostic accuracy in the T stage assessment
[Time Frame: 1 month postoperatively]
3.8 Secondary endpoints
Secondary endpoints of the present study are:
    Diagnostic accuracy in N stage. Evaluation of diagnostic accuracy in the presence of local 
or distant metastatic lymph nodes
    [Time Frame: 1 month postoperatively]
    
Diagnostic accuracy in the retroperitoneal resection margin. Evaluation of diagnostic accuracy 
in the retroperitoneal resection margin
    [Time Frame: 1 month postoperatively]
    
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Diagnostic  accuracy  in  peritoneal  or nearby organ infiltration.  Evaluation of  diagnostic 
accuracy in the peritoneal or nearby organ infiltration
    [Time Frame: 1 month postoperatively]
3.9 Calculation of the sample size
The sample size calculation was based on the primary endpoint. According to the literature, the 
specificity of MRI of the T1/T2 vs T3/T4 differentiation is 84%. Therefore, for a prospective study 
with alpha: 5%, power: 80%, d=10% and dropout rate: 30%, the estimated number of patients is 
120.
3.10 Randomization
There will be no randomization or allocation concealment. 
3.11 Blindness
There will be no blindness at the level of the patient, the treating physicians (surgeon, 
oncologist, radiotherapist) and the researcher who will record the data.
3.12 Exit criteria
The patient will be discharged when it is ensured that is medically safe to be released. The exit 
time will be regarded as the time that the patient will fulfill the Clinical Discharge Criteria. More 
specifically, the patient should display the following: steady vital signs, fully oriented, without 
nausea or vomiting, mobilized with a steady gait and without a notable bleeding.
3.13 Monitoring
Following hospital discharge, the patient will be called for reassessment at one month after the 
operation. Patients will be included in the standard monitoring protocol (CT, MRI, cancer markers), 
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unless otherwise required. At the same time, the pathological assessment of the specimen will be 
recorded.
3.14 Medication
Both preoperative and postoperative patient treatment will be standardized. The principles of the 
ERAS protocols will be applied to patients. More specifically, antimicrobial prophylaxis will 
include the administration of intravenous antibiotics within 60 minutes prior to the onset of 
operation.  Patients  will  receive  preoperative,  mechanical  bowel  preparation  and  per-os 
antimicrobial prophylaxis. Prior to surgery, patients will abstain from solid and liquid foods for 6 
and 2 hours, respectively. The nasogastric tube will be removed postoperatively and repositioned 
only in case of ileus. Postoperative analgesia will include a multidisciplinary approach using 
analgesics (paracetamol, lornoxicam) in combination with dorsal or epidural analgesia. Opioid 
administration  will  be  avoided.  Postoperative  nausea  and  vomiting  prophylaxis  will  include 
granisetron 3mg / 3ml IV. Mechanical and pharmaceutical thromboprophylaxis will be used. A 
zero-balance approach to fluid losses will be applied. Mobilization will be initiated from the first 
postoperative day.  Feeding will be initiated on the basis of the intestinal function recovery.
3.15 Study Group
All participating members have years of experience in their field and have, therefore, completed 
the learning curve for the required techniques. Data collection and recording will be carried out by 
an independent, third party, researcher.
3.16 Conducting a Study
The study will be conducted in the Department of Surgery of University Hospital of Larissa in 
collaboration with the Radiology Department of University Hospital. Patient data will be recorded 
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both in the patient charts and in an electronic database. The required laboratory examinations will 
be defrayed by the patient insurance funds.
4. LITERATURE
1. Xynos E., Gouvas N., et al. Clinical practice guidelines for the surgical management of 
colon cancer: a consensus statement of the Hellenic and Cypriot Colorectal Cancer Study Group by 
the HeSMO. Annals of Gastroenterology (2016) 29, 3-17 
2. Nelson H, Petrelli N, Carlin A, et al.: Guidelines 2000 for colon and rectal cancer surgery. J 
Natl Cancer Inst 2001;93:583– 596. 
3. Jhaveri KS, Hooman HN, MRI of Rectal Cancer: An Overview and Update on Recent 
Advances. AJR 2015; 205:W42–W55 
4. FOxTROT Trial, Lancet Oncol. 2012 Nov;13(11):1152-60. doi: 10.1016/S1470-2045(12) 
70348-0. Epub 2012 Sep 25. 
5. Nerad E, Lambregts D et al, MRI for Local Staging of Colon Cancer: Can MRI Become the 
Optimal Staging Modality for Patients With Colon Cancer? Diseases of the Colon & Rectum, 2017: 
60; 4: 385–392, 
6. Jakobs MA, Macura KJ. Et al, Multiparametric Whole-body MRI with Diffusion-weighted 
Imaging and ADC Mapping for the Identification of Visceral and Osseous Metastases From Solid 
Tumors. Academic Radiology 2018 
7. Kijima S, Sasaki T, Nagata K et al, Preoperative evaluation of colorectal cancer using CT 
colonography, MRI, and PET/CT World J Gastroenterol 2014;20(45): 16964-16975. 
8. Antosh G, Vogt F, Freudenberg L et al, Whole body dual modality PET/CT and whole body 
MRI for tumor staging in oncology. JAMA 2003: 290, 24: 3199-3206, 
9. Hunter C, Blake H, Jeyadevan N, et al. Local staging and assessment of colon cancer with 
1.5-T magnetic resonance imaging. Br J Radiol 2016; 89: 0257. 
10.
Ellebæk  SB,  Fristrup  CW,  Bau  Mortensen  M.  Intraoperative  Ultrasound  as  a 
Screening Modality for the Detection of Liver Metastases during Resection of Primary Colorectal 
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Cancer - A Systematic Review. Ultrasound International Open 2017; 3: E60–E68. 
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12.
ElibolFD, ObuzF,SökmenS,Terzi C, CandaAE,Sağol Ö, Sarıoğlu S. The role of 
multidetector CT in local staging and evaluation of retroperitoneal surgical margin involvement in 
colon cancer. DiagnIntervRadiol 2016; 22:5–12 
13.
Bateman AC, Carr NJ, Warren BF. The retroperitoneal surface in distal caecal and 
proximalascending colon carcinoma: the Cinderella surgicalmargin?J ClinPathol2005;58:426–428. 
14.
Hajian-Tilaki  K,J  Biomed  Inform.  2014  Apr;  48:193-204.  doi  : 
10.1016/j.jbi.2014.02.013. Epub 2014 Feb 26. 
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Heald RJ, Husband EM, Ryall RD,1988 Sep; 81(9): 503–50 
16.
West NP, Hohenberger W, Weber K, Perrakis A, Finan PJ, Quirke P. Complete 
mesocolic excision with central vascular ligation produces an oncologically superior specimen 
compared with standard surgery for carcinoma of the colon. JClinOncol. 2010;28:272–278.
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