Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

CRC diagnosed by screening was defined as cancer diagnosed by primary screening colonoscopy, or colonoscopy after a positive immunochemical based faecal occult blood test i(FOBT) in patients without symptoms invited to examination according to the national screening programme policy

Symptomatic CRC was defined as cancer diagnosed in symptomatic patients.

Jan Král, M.D.

The purpose of this study is to determine whether colorectal cancer diagnosed by screening (primary screening colonoscopy, colonoscopy after immunochemical based faecal occult blood test) has more favourable clinical-pathological characteristics than colorectal cancer diagnosed for symptoms. We aimed to compare these two groups of patients at the time of diagnosis and confirm the efficiency of the screening programme.

Multicentre prospective observational study. 12 centres across the Czech rep. included. Study approved by Ethical Committee.

All participants gave their informed signed consent. Each centre was assigned a unique ID number to distinguish between the locations in which patients were enrolled.

Patients informations were stored under identification number in secure internet database (RedCap) run by The International Clinical Research Center of St. Anne's University Hospital Brno.REDCap is a secure, web-based application designed to support data capture for research studies.

Statistical analysis was done with SAS, ver. 9.3. Descriptive statistics such as absolute and relative frequencies and median with 95 % confidence intervals were used. Differences between the screening and non-screening groups were compared using the Chi-square test or Fisher's exact test (categorical parameters) and Mann-Whitney test (continuous parameters). Results with a p-value \< 0.05 were considered statistically significant

Colorectal Cancer: Screening vs. Non-Screening

Colorectal Cancer Screening Detects Tumors at Earlier Stages Improving Clinical Outcomes

Differences between colorectal cancer stage (0,I,II) in screening vs. non-screening group.

* 0. stage (Tis N0 M0)
* I. stage (T1-2 N0 M0)
* II. stage (T3-4 N0 M0)
* III. stage (T1-4 N1-2 M0)
* IV. stage (T1-4 N1-2 M1)

Stages 0,I II were considered to have better outcome

Differences between colorectal cancer grade in screening vs. non-screening group.

* GX (cannot be identified)
* G1 (well diff.)
* G2 (moderately diff.)
* G3 (poorly diff.)
* G4 (undifferentiated)

Grades 1,2 were considered to have connection with lower stage

Difference between colorectal cancer resection margins (RX, R0, R1, R2) in screening vs. non-screening group.

* RX: cannot be identified
* R0: no cancer cells seen microscopically at the resection margin
* R1: cancer cells present microscopically at the resection margin (microscopic positive margin)
* R2: gross examination by the naked eye shows tumor tissue present at the resection margin (macroscopic positive margin)

Differences between occurrence of colorectal cancer metastasis (MX, M0, M1) between screening vs. non-screening group.

* MX: cannot be measured
* M0: cancer has not spread to other parts of the body
* M1: cancer has spread to other parts of the body

Median time between diagnosis and surgery.

Differences between neoadjuvant, adjuvant and systemic palliative therapy in screening vs. non-screening group.

Number of patients treated with palliative therapy in both groups.

Private practice at Hluboká nad Vltavou

Klaudian Hospital Mladá Boleslav

Masaryk Hospital Usti nad Labem

Brno University Hospital

Medic Kral Ltd.

Chomutov Hospital

Tomas Bata Hospital, Czech Republic

Military University Hospital, Prague

Frýdek-Místek Hospital

The University Hospital Plzeň

Vitkovice Hospital

Institute for Clinical and Experimental Medicine

M.D.

Adverse event data were not collected because data were mainly obtained at the time of diagnosis or at the time of treatment plan setting.

Study was focused on comparing screening group and non-screening group at the time of diagnosis and confirm the efficiency of the screening programme.

Patients with colorectal cancer diagnosed by screening (primary screening colonoscopy, colonoscopy after FOBT).

Screening Group

Symptomatic CRC was defined as carcinoma detected by CT, MR or sonography and then verified by colonoscopy.

Non-screening Group

Patients with colorectal cancer diagnosed by screening procedures (primary screening colonoscopy, colonoscopy after FOBT).

Screening

Patients with colorectal cancer diagnosed by other diagnostic procedures (diagnostic colonoscopy, CT, magnetic resonance, ultrasonography, urgent surgery, etc.)

Others

Total

Age (years, median)

Age, Customized

Sex: Female, Male

Jan Král

Patients with colorectal cancer diagnosed by screening procedures (primary screening colonoscopy, colonoscopy after iFOBT).

Symptomatic CRC was defined as cancer diagnosed in symptomatic patients by colonoscopy, or by CT, MRI or ultrasonography before verification by colonoscopy.

Non-Screening Group

Colorectal Cancer Stage (pTNM)

Patients with colorectal cancer diagnosed by screening (primary screening colonoscopy, colonoscopy after iFOBT).

Symptomatic CRC (non-screening group) was defined as cancer diagnosed in symptomatic patients by colonoscopy, or by CT, MRI or ultrasonography before verification by colonoscopy.

Colorectal Cancer Grade

Colorectal Cancer Resection Margins

Colorectal Cancer Metastasis

Colorectal Cancer Surgery

Colorectal Cancer and Palliative Therapy

CRC diagnosed by screening was defined as cancer diagnosed by primary screening colonoscopy, or colonoscopy after a positive immunochemical based faecal occult blood test (iFOBT) in patients without symptoms invited to examination according to the national screening programme policy

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

This group of patients are allocated to a supplementary preoperative breast Magnetic Resonance Imaging (MRI) in addition to standard preoperative breast imaging (ultrasound and mammography).

This groups of patients are allocated to receive standard preoperative breast imaging only (ultrasound and mammography).

Breast Magnetic Resonance Imaging prior to breast conserving surgery with and without intravenous contrast agent.

Breast MRI

The control group that receives standard preoperative imaging only (breast ultrasound and mammography)

standard breast imaging

Irina Manhoobi, MD

Peer Christiansen, MD, DMSc

Peer Christiansen

Irina P Manhoobi

Inge Andersen, MD, PhD

The goal of this randomised study is to investigate if a supplementary preoperative breast Magnetic Resonance Imaging (MRI) improves the assessment of breast cancer and can help surgical planning such that sufficient resection margins can be obtained during breast conserving surgery.

The main questions are:

1. Is preoperative breast MRI in addition to the currently used standard imaging methods ultrasound and mammography more accurate to detect Ductal Carcinoma in Situ and the invasive breast tumor compared to standard methods only?
2. Does preoperative breast MRI reduce the number of involved histological margins after breast conserving surgery in the MRI-group versus the control group?

Magnetic Resonance Imaging (MRI) of the breast preoperatively is a well-known imaging method in primary breast cancer and is only used as a complement to the standard imaging methods in complex cases, lobular cancer, patients with large tumors that need preoperative neoadjuvant therapy or for patients with dense breast tissue where the tumor is difficult to detect with the standard imaging methods. The MRI is not used as a standard diagnostic method, because of its lower specificity that may result in a higher false-positivity rate.

The advantage of the MRI with use of intravenously contrast agent (also called dynamic enhanced MRI), is its ability to simultaneously assess the tumor morphology and semiquantitative enhancement kinetics that evaluate the newly formed vessels as a tumor-specific feature. A fast-initial enhancement and wash-out (type III) is typically seen in malignancies, due to increased vascular permeability, density, and interstitial fluid. Furthermore, the breast MRI can identify preinvasive malignant lesions such as Ductal Carcinoma in Situ (DCIS) in the breast with a much higher sensitivity than mammography and most commonly manifests as non-mass-enhanced lesion on an MRI with intravenous contrast agent. Less frequently the DCIS manifests as a mass or a focus on MRI and is usually not visible on non-contrast enhanced MRI, because it is masked by the normal breast parenchyma. Few larger randomized trials have investigated the efficacy of preoperative MRI in breast cancer and its effect on involved histological margins after breast conserving surgery that lead to repeat surgery. Controversy still exists whether preoperative MRI of the breast can reduce the number of repeat surgery in breast cancer. We aim to investigate in this randomised study if a supplementary breast MRI preoperatively with an optimised MRI scan protocol can help surgical planning to detect the DCIS and invasive cancer such that tumor free resection margins can be obtained during breast conserving surgery (BCS) and the patients can avoid repeat surgery.

Methods:

The study will be performed as a clinical, open-label, prospective and randomized study. We will include 440 breast cancer patients, randomized to either MRI of the breast prior to BCS together with the standard methods: Ultrasound and mammography (220) or to standard methods only (220) at two different breast centers, Aarhus University Hospital (AUH) and Viborg Regional Hospital (VRH).

The MRI of the breast: Will be performed with a protocol with intravenous contrast agent, Dotarem on a 3 Tesla Siemens MRI at the Department of Radiology at AUH and a 1.5 Tesla Siemens MRI System at VRH, with breast adaptive coils and diffusions sequences. The MRI of the breast will be performed soon after the patient is included in this study and will not delay surgery. The MRI protocol consists of T2- and T1-weighted spin-echo sequences in the axial plane, a T2-weighted sequence, dynamic contrast enhanced subtracted series with intravenous contrast agent Dotarem and diffusions-sequences, with breast adaptive coils at each institution. The MRI images of the breast from VRH for each patient will be sent to AUH, where the images will be interpreted by an experienced breast radiologist, using the same picture archiving and communication system from Siemens Healthcare. The tumor and DCIS will be measured, localized anatomically and presented for the breast surgeon at each institution at Multi-Disciplinary-Team conferences at each institution. The size of the invasive tumor and the DCIS in the breast will be recorded and compared to the corresponding size on the standard methods with mammography and ultrasound.

Ultrasound and mammography of the breast: Are routine methods at both institutions that are used as part of the triple diagnosis of breast cancer (palpation of the breast, ultrasound and mammography of the breast and ultrasound-guided core biopsy of the tumor). Ultrasound and mammography are performed and interpreted at both institutions by dedicated and specialized breast radiologists.

Final histopathology: The final microscopical assessment of the margins are the reference method for the final status of the margins and will be performed by experienced breast pathologists. According to the Danish Health Board´s recommendations, a final pathology report should be available after 7 workdays.

Statistical Analysis:

Power calculation: The number of repeat surgery for positive margins after BCS is in average 20%. A sample size of at least 219 patients was calculated as necessary to detect a reduction from 20% in the non-MRI group to 10% in the MRI-group with a statistical power of 80% and a 5% level of significance. We expect that few patients may drop-out for different reasons, and we estimated that a total number of 440 patients are enough to be included. Chi-square test will be used to compare outcomes with categorical variables. Regression analysis will be used for adjusted analysis. A p-value of less than 0.05 will be considered statistically significant.

Safety:

Allergic reactions to contrast intravenous contrast Dotarem with Gadolinium that we plan to use are very rare, approximately 0,1 %, where most are mild with skin rash.

Should an allergic reaction happen during contrast administration to the study patient, the radiologist will examine the patient and initiate medical treatment according to the severity of the adverse event and according to local instruction at each department. During the first consultation with the surgeon, the patient will be asked about previous allergic reactions towards contrast agents. If the patient has previously had severe allergic reaction towards the MRI contrast agent Dotarem, the patient will not be included in the study.

Randomized, open-label, double-center trial including female participants with early breast cancer planned for breast conserving surgery randomised 1:1 in a Magnetic Resonance Imaging, MRI-group (preoperative MRI, ultrasound and mammography) and a control group (preoperative ultrasound and mammography).

Preoperative Magnetic Resonance Imaging to Obtain Adequate Resection Margins in Breast Conserving Surgery, (PRIMAR) Trial

Preoperative Magnetic Resonance Imaging to Obtain Adequate Resection Margins (PRIMAR) Trial

The plan is to share participant data when the inclusion ends and data analysis is final and the final manuscript is published.

The number of involved (positive) resection margins in the final histopathology after breast conserving surgery that lead to repeat surgery.

The number of patients where additional breast tissue is removed during initial breast conserving surgery.

The number of additional malignant tumors and DCIS in the breast detected (MRI vs. standard methods)

Type of repeat surgery: Breast conserving surgery or mastectomy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Colorectal Cancer: Screening vs. Non-Screening	NCT02727894	Colorectal Canc... Screening		-	Institute for Clinical and Experimental Medicine
Preoperative Magnetic Resonance Imaging to Obtain Adequate Resection Margins in Breast Conserving Surgery, (PRIMAR) Trial	NCT05825768	Breast Cancer	Breast MRI standard breast...	18 Years -	Aarhus University Hospital

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