Oligometastatic Disease, Liver Metastases, Colorectal Cancer
Conditions
Brief summary
If an abbreviated hepatobiliary phase (HBP) protocol liver MR with gadobenate dimeglumine is shown clinically comparable to standard of care liver MR with gadoxetate disodium for detecting hepatic metastasis from colorectal cancer, its use will save time, cost, and patients' effort.
Detailed description
The goal is to: * Estimate and compare the diagnostic performance, including sensitivity, specificity, positive/negative predictive value, and area under the receiver operating characteristics (AUROC), of abbreviated protocol liver magnetic resonance (MR) with hepatobiliary phase (HBP) using gadobenate dimeglumine for detecting liver metastases, with 1) abbreviated protocol liver MR with HBP using gadoxetate disodium, 2) standard of care complete protocol liver MR using gadoxetate disodium, and 3) complete protocol liver MR using gadobenate dimeglumine. * Estimate and compare quantitative measures of HBP images (liver enhancement ratio, lesion contrast to noise and signal to noise ratios \[CNR and SNR\]) for both gadobenate dimeglumine and gadoxetate disodium. * Qualitatively assess the preference, or lack thereof, of radiologists regarding the images generated by abbreviated protocol liver MR with HBP using gadobenate dimeglumine versus abbreviated protocol liver MR with HBP using gadoxetate disodium.
Interventions
Gadoxetate disodium MR contrast is now mainly used for the purpose of HBP liver MR imaging to save MR scanner time and total examination time.
The most commonly used MR contrast agent in abdominal imaging is gadobenate dimeglumine, which has mainly the characteristics of an extracellular agent used for most indications of MR examinations.
Sponsors
University of Colorado, Denver
Bracco Diagnostics, Inc
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Masking description
We have attempted to mitigate any potential conflict of interest through randomization of the order of exams and blinding the image evaluators to contrast agents.
Intervention model description
This is a prospective study. The subjects will be randomized into two groups. Both groups will undergo two complete protocol liver MRs for known or suspected colorectal cancer (CRC) metastasis, one exam with gadoxetate disodium and the other exam with gadobenate dimeglumine, within an interval of 3-20 days, but in opposite order, determined randomly. From the complete protocol liver MR with both contrast agents, an image set of abbreviated HBP protocol liver MR for each agent will be obtained (Fig.1).Two week-intervals will be placed between the evaluations of different image sets of a patient, and the images will be presented in a different random order to each evaluating radiologist. The schedule of random order of protocol liver MRs and presentation of images to radiologists will be determined by the project biostatistician.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Colorectal cancer patients * Age 18-80 years * No prior treatment including surgery * Prior imaging with suspected liver metastasis
Exclusion criteria
* Age \< 18 years or \> 80 years * eGFR \< 30 ml/min/1.73 m2 * Previous reaction to gadolinium contrast agents * History of claustrophobia or movement disorders likely to impact image quality * Non-MR safe implants or metallic foreign bodies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Preference of Radiologists for the Hepatobiliary Phase Images Generated by MultiHance (amHBP) Versus Eovist (aeHBP). | 1 month | The quality of amHBP and aeHBP images was assessed using ordinal response mixed effect models that included right/left image position as a covariate. For each paired comparison, radiologists indicated their preferred hepatobiliary phase image. |
| Quantitative Timing Measures for Hepatobiliary Phase MRI | 1 month | Measures of timing used to obtain hepatobiliary phase images. |
| Estimate and Compare Quantitative Measures of HBP Images (Liver Enhancement Ratio, Lesion Contrast to Noise and Signal to Noise Ratios [CNR and SNR]) for Both Gadobenate Dimeglumine and Gadoxetate Disodium. | 1 month | A single reader analyzed paired Eovist and MultiHance hepatobiliary phase images (N=10 paired datasets). Quantitative metrics included liver-to-metastasis, liver-to-spleen, liver-to-muscle, and liver-to-blood contrast ratios (CNR's), as well as liver signal-to-noise ratio (SNR). All CNR's were calculated as signal intensity of liver relative to the reference tissue, with liver SNR liver signal/liver noise. Higher contrast ratios and higher SNR values indicate greater liver enhancement and improved lesion conspicuity. |
| Estimate and Compare Qualitative Measures of HBP Images for Both Gadobenate Dimeglumine and Gadoxetate Disodium. | 1 month | A single reader performed a qualitative assessment of Dynamic and Hepatobiliary Phase Image Quality (Likert scale 1-5) for both Eovist and MultiHance Hepatobiliary Phase images (N=10 paired data). Higher scores indicate better image quality. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic Performance of Gadobenate Dimeglumine | 1 year | The primary performance diagnostic will be sensitivity, similar to the recently published retrospective study by Canellas et al. (2019). In addition to other diagnostic performance metrics of interest (e.g., specificity, AUROC), lesions will be analyzed descriptively in terms of number of metastases detected and lesion size. |
| Compare Sensitivity and Specificity, | 17 months | The primary analysis will use pathology as the gold standard, if available, but will revert to long term imaging in the absence of pathology. To address the potential impact of this limitation, we will also conduct an exploratory analysis to compare the sensitivity and specificity of the imaging methods by each gold standard. |
| Test Validity of Imaging Methods | 17 months | We will also conduct an exploratory analysis to test the validity of long term imaging as a gold standard against available pathology reports. |
| Compare Patient Time Associated With Imaging Method | 17 months | In addition to analyses for the primary aims, additional analyses will be conducted to examine patient time associated with each imaging method; time metrics can be compared between imaging methods in absolute terms, but also proportionally to sensitivity. |
| Compare Cost Associated With Imaging Method | 17 months | In addition to analyses for the primary aims, additional analyses will be conducted to examine cost associated with each imaging method; cost metrics can be compared between imaging methods in absolute terms, but also proportionally to sensitivity. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNikhil Madhuripan, MD
University of Colorado, Denver
Participant flow
Pre-assignment details
Up to 15 subjects who meet study eligibility criteria and who have exceptional circumstances will be evaluated as part of the PI Discretion Cohort. These subjects may bypass randomization and proceed with gadoxetate disodium scan followed by gadobenate dimeglumine to minimize clinical disruption.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 46.33 years STANDARD_DEVIATION 6.43 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Pathology distribution Adenocarcinoma | 2 Participants |
| Pathology distribution Neuroendocrine Tumor | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 3 |
| other Total, other adverse events | 0 / 7 | 0 / 3 |
| serious Total, serious adverse events | 0 / 7 | 0 / 3 |
Outcome results
None listed