Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): Study protocol for an international multicentre prospective diagnostic accuracy study

- Methods: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy.
- Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI..
- Liver MRI is increasingly used as an additional im- aging modality for staging of CRLM since it is consid- ered to be more accurate for detection of CRLM as compared to CT [23 – 26].
- Although previous literature suggests that liver MRI is superior in detection and characterization of CRLM compared to CT, it is not known whether the higher diagnostic accuracy of MRI has sufficient impact on pa- tient management in terms of additional clinically sig- nificant CRLM (CS-CRLM) that actually change the local therapy plan.
- Hence, the actual role of liver MRI for manage- ment of patients with CRLM remains unclear.
- Until now, no definitive evidence has been provided on the impact of liver MRI on finding CS-CRLM as compared to CT for patients with primary or recurrent CRLM..
- The aim of the present CAMINO study is to evaluate whether diffusion-weighted and gadoxetic acid enhanced liver MRI has sufficient clinical added value to CT in order to be routinely performed in the staging of CRLM..
- This is an international multicentre prospective diagnos- tic accuracy study assessing the proportion of patients with CRLM scheduled for local therapy in which liver MRI finds additional CS-CRLM as compared to CT.
- The hypothesis is that the higher accuracy of liver MRI will lead to finding of at least 10% additional CS-CRLM compared to CT, resulting in improved decision-making on the local therapy plan, such as additional surgery or ablation and potentially preventing unnecessary surgical exploration or ablative treatment.
- The secondary aim of this study is to identify subgroups which benefit most from additional liver MRI..
- The CAMINO study is an international multicentre pro- spective incremental diagnostic accuracy study on the added value of liver MRI including DWI and gadoxetic acid enhanced T1-weighted sequence in patients with CRLM who are considered candidates for local therapy based on CT.
- Patients will be recruited in 17 liver sur- gery centres in the Netherlands, Belgium, Norway and Italy: Amsterdam UMC, Amsterdam.
- Due to the large number of participating centres, a phased implementa- tion of the start of the study will be used..
- This study will be conducted in accordance with the guidelines of Good Clinical Practice and in agreement with the Declaration of Helsinki (64th version, October 2013).
- The main objective of this study in patients with CRLM is to identify the proportion of patients in which liver MRI including DWI and gadoxetic acid enhanced T1- weighted sequence finds CS-CRLM in addition to an ab- dominal portal venous phase CT.
- The local therapy plan proposed by the MDT based on CT only will be compared to the local therapy plan based on CT and liver MRI.
- It is hypothe- sized that liver MRI will lead to the detection of CS- CRLM in at least 10% of patients which is considered the minimal clinically important difference.
- The findings of this study – whether or not liver MRI including DWI and gadoxetic acid enhanced T1-weighted sequence has clinical added value on local therapy strategy of CRLM patients – will determine the role of liver MRI in the sta- ging of CRLM and will provide international guidelines with data for a scientifically based recommendation on the implementation of liver MRI in the pre- interventional workup..
- The secondary aim is to identify which subgroups benefit most from the additional liver MRI by perform- ing a logistic regression analysis and developing a clinical prediction model..
- Consecutive adult patients with primary or recurrent CRLM who are considered candidates for curative sur- gery, thermal ablation or a combination of curative sur- gery and intra-operative ablation, based on abdominal CT will be invited to the study.
- Patients who receive neoadjuvant or induction chemotherapy and are subse- quently eligible for local curative therapy will be invited as well..
- Patients fulfilling one or more of the following criteria will be excluded:.
- Patients with contra-indications for liver MRI..
- Informed consent will be obtained for the use of individ- ual patient data for study purposes.
- The formal written informed consent will be obtained during the outpatient clinic visit by a member of the study team.
- Before patients agree to participate in this study, they will be provided with written information in the form of a Patient Information Sheet.
- Participants will be told that they may withdraw from the study at any time for any reason.
- Patients withdrawing permission will be replaced..
- Liver MRI is a non-invasive imaging method used in daily clinical practice and under intensive quality control as part of its clinical applications.
- In this study, all participants will undergo both abdom- inal CT and liver MRI.
- Liver MRI includes at least T2-weighted se- quence, T1-weighted sequence with gadoxetic acid as contrast agent (i.e.
- plain, arterial, portal venous, early de- layed and late delayed phase) as previous studies showed that gadoxetic acid has become the preferred contrast agent in liver MRI for CRLM, and DWI [24, 30].
- Since gadoxetic acid will be administered immediately before the start of MRI, the duration of the scan will not exceed the standard duration with any other contrast agent.
- In every participating centre there is substantial experience with the use of gadoxetic acid and also with interpret- ation and assessment of gadoxetic acid enhanced liver MRI..
- Both CT and liver MRI will be performed according to the imaging protocols from the Radiological Society of.
- All pre-interventional imaging will be assessed by an experienced abdominal radiologist.
- Liver MRI will be assessed by a radiologist who is not blinded to CT re- sults since liver MRI is performed in addition to CT in daily clinical practice.
- The radiologist has access to in- formation about previous CT results and the interpret- ation of the liver MRI may be influenced by this additional information.
- However, we aim to evaluate the clinical added value of liver MRI in addition to CT and.
- The time interval between CT and liver MRI is 4 weeks at maximum.
- This time interval for CT and MRI is based on the rapid growth potential of CRLM and the importance of CT and MRI being per- formed within a sufficiently short time interval while taking into account the feasibility of arranging liver MRI in participating centres..
- If there are contraindications for gadoxetic acid, liver MRI is performed with another routinely used extracel- lular contrast medium at the participating center or – when contraindicated– no contrast medium is used.
- In all participating centres, potentially eligible patients will be discussed during a formal regular MDT meeting (Fig.
- First, the CT will be presented by the radiologist and indication for local therapy will be determined by the MDT.
- therapy, the exact surgical or ablative plan based on CT only will be decided and documented in the electronic case report form (eCRF).
- After finalizing and document- ing the CT-based local therapy plan, the findings of liver MRI are disclosed as a second step.
- This will be either – if directly available – at the same MDT meeting, or at the next MDT meeting, after liver MRI has been per- formed (no longer than 4 weeks after CT).
- CS-CRLM found at liver MRI with the exact change in the local therapy plan will be documented in the eCRF.
- Additionally, we will strive to report whether post- operative histopathology reports were in accordance with findings of the pre-operative CT, liver MRI and IOUS..
- All patients who underwent surgical and/or ablative treatment will be assessed in the local follow-up sched- ule of the study site.
- Ideally, patients will be seen with a CT-chest/abdomen at 3 to 4 months and 6 to 8 months after surgery and/or thermal ablation.
- Patients who are no longer considered as candidates for local curative therapy based on the additional liver MRI findings will have at least 6 months follow-up by CT, as stated in ESMO guidelines 13 .
- In addition to the primary outcome measure which will be determined in the daily clinical workflow of the par- ticipating centres, a fixed central independent, blinded.
- These are recruited from participating centres and will post-hoc evaluate step-by-step the additional value of liver MRI as compared to CT only on the local therapy plan.
- The participating radiologists have extensive ex- perience with CT and liver MRI and have assessed at least 500 abdominal CT scans and 500 liver MRI scans for focal liver lesions.
- The CT and liver MRI of each patient will be assessed by one radiologist only since all radiologists have extensive experience in assessing abdominal CT scans for focal liver lesions and liver MRI scans.
- Based on CT and liver MRI findings of the radiologist, each interventional radiologist and surgeon will get the findings presented and will indi- cate independently whether they would change their ini- tial local therapeutical plan based on the liver MRI results.
- Agreement of 4/5 expert panel members (agree- ment rate of 80% or more) will be considered as consen- sus.
- The local therapy plan proposed by the MDT based on CT only will be com- pared to the local therapy plan based on CT and liver MRI..
- Secondary outcomes include a prediction model to evaluate the probability of finding CS-CRLM on liver MRI and the proportion of patients with a change in local therapy plan based on the occurrence of CS-CRLM on liver MRI, as identified by the expert panel in the post hoc evaluation..
- All parameters will be collected prospectively.
- abdomen and liver MRI in order to be assessed by the expert panel.
- All patient data and imaging will be coded by an individual study number and saved in the eCRF..
- No identifying data will be entered into the database.
- Since the CAMINO study has a pragmatic design and should represent daily clinical practice, the main analysis of the primary outcome will be based on the intention- to-imaging (ITI) population.
- The ITI population will consist of all included patients fulfilling the inclusion cri- teria of the CAMINO study, regardless of any study protocol violation such as an extended time interval of more than 4 weeks between CT and MRI and liver MRI performed with another contrast agent then Gadoxetic acid.
- The incremental accuracy in the ITI analysis will be calculated as the number of included participants with a clinically significant CRLM (CS-CRLM) detected by liver MRI and not seen on CT, as identified by the local MDT, relative to the total number of included participants..
- Additionally, the main analysis will be complemented by an imaging-per-protocol (IPP) analysis.
- The incremental accur- acy in the IPP analysis will be calculated as the number of included participants with a clinically significant.
- CRLM (CS-CRLM) detected by liver MRI and not seen on CT, relative to the total number of included partici- pants without.
- Three subgroup analyses will be performed: first, in the groups of patients who did and did not receive pre- operative chemotherapy.
- A prediction model will be developed using multivari- able relaxed lasso logistic regression modelling, to evalu- ate the probability based on patient, tumor and procedural variables of finding CS-CRLM on liver MRI..
- This exploratory model will be used for identifying sub- groups in whom the probability of finding CS-CRLM is less than 10%.
- All baseline variables will be considered for the regression model..
- All baseline, clinicopathological and procedural vari- ables will be described and analysed.
- Continuous, not normally distributed variables will be expressed as me- dian with interquartile range (IQR).
- In case variables are normally distributed they will be reported as mean with standard deviation (SD).
- A Mann-Whitney U test will be used to compare continuous, not normally distributed variables between groups.
- Normally distributed, continu- ous variables will be compared using an Independent samples T-test.
- P-values below 0.05 will be considered significant.
- Sample size calculation and statistical considerations The literature on the clinical impact of additional liver MRI in patients with primary or recurrent CRLM is very limited and consists of primarily small retrospective studies [26, 35].
- Our estimate of the chances of finding CS-CRLM on liver MRI is based on literature, clinical experience and practicality..
- Based on these consider- ations, the proportion of patients in which liver MRI finds CS-CRLM is postulated to be 10%.
- The primary outcome measure, the proportion of pa- tients with CS-CRLM on liver MRI not identified on CT, guides the sample size for this incremental diagnos- tic accuracy study.
- If a participant withdraws consent, a new one will be recruited..
- It is unknown to what extent liver MRI may result in a change in clinical management in patients with CRLM scheduled for local therapy based on staging with CT..
- The present international multicentre prospect- ive study will determine the clinical added value of liver MRI to CT in patients with CRLM scheduled for local curative therapy including liver resection and/or thermal ablation..
- A non-randomized design was chosen since a random- ized controlled trial comparing abdominal CT and liver MRI versus CT was considered not feasible due to the high use of MRI in current daily practice.
- A retrospect- ive analysis to document the incremental value of liver MRI compared to CT is not reliable, since a regular MDT meeting structure does not include a consistent step-by-step documentation of the added value of MRI on final patient management..
- In contrast, it is also important to acknowledge the burden of performing an additional liver MRI in the workup of patients with CRLM.
- Performing routine liver MRI in all CRLM patients may add diagnostic delay due to waiting lists and limited MRI-capacity.
- Indeterminate lesions at liver MRI could make it more difficult to de- cide on an accurate surgical or ablative strategy.
- In addition, CT in combination with surgical exploration and IOUS is considered as the standard for CRLM de- tection and is performed in all patients, questioning the added value of liver MRI and its associated costs.
- As adding routine liver MRI to the workup of CRLM pa- tients may cause additional pre-interventional delays and increases healthcare costs, any recommendation about its use should be guided by high quality studies which determine its exact added value..
- with CRLM will be outlined.
- In summary, this prospective international multicentre study will provide the required evidence to decide on the routine use of liver MRI during the preoperative workup of patients with primary and recurrent CRLM considered candidates for local therapy.
- BG will be the study coordinator of the CAMINO study and contributed to the design of the study, collecting data and writing of the manuscript.
- Bayer Schering Pharma® (Berlin, Germany) co-funded the CAMINO study by providing gadoxetic acid for the liver MRI of all included patients.
- 3 Department of.
- Prospective comparison of gadoxetic acid-enhanced liver MRI and contrast-enhanced CT with histopathological correlation for preoperative detection of colorectal liver metastases following chemotherapy and potential impact on surgical plan

Xem thử không khả dụng, vui lòng xem tại trang nguồn
hoặc xem Tóm tắt