Liver Metastases From Colorectal Primary Cancer
Conditions
Keywords
Liver metastases, Colorectal primary cancer, Contrast-enhanced ultrasound, Sonovue®
Brief summary
Hypothesis: Use of contrast ultrasound showed interesting results, which can increase ultrasonography sensitivity performed during surgery in the evaluation of operable liver metastases. This study is a two-stage phase II multicenter study (Simon's two-stage).
Detailed description
Hypothesis: Use of contrast ultrasound showed interesting results, which can increase ultrasonography sensitivity performed during surgery in the evaluation of operable liver metastases. This study is a two-stage phase II multicenter study (Simon's two-stage).
Interventions
Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment: Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages
Sponsors
Institut Bergonié
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient with histological proven colorectal cancer. 2. Operable liver metastases according to preoperative imagery. Operability is the possibility of treatment by resection and/or local destruction (radiofrequency, cryotherapy…). 3. Patient treated or not with preoperative chemotherapy. 4. With or without extra-hepatic metastases 5. Age ≥ 18 years. 6. Radiological assessment by CT and MRI liver and positron emission tomography scan (PETscan) within six weeks before surgery. 7. Patient affiliated to the Social Security system. 8. Signed informed consent.
Exclusion criteria
1. Known hypersensitivity to sulfur hexafluoride or another component of SonoVue®. 2. Patients with recent acute coronary syndrome or suffering from unstable ischemic heart disease, especially: evolving myocardial infarction, unstable angina during the last 7 days, recent coronary intervention or another factor suggesting clinical instability, acute heart failure, class III or IV heart failure, severe arrhythmias. 3. Patients with right-to-left shunt, severe pulmonary arterial hypertension, uncontrolled systemic hypertension, as patients suffering from respiratory distress syndrome. 4. Pregnant and lactating women. 5. Patients with contraindication for a CT scan, a MRI or a positron emission tomography (PET) with contrast. 6. Patients with indication of two step liver surgery. 7. Patients already included in the study. 8. Patient who couldn't be treated or followed up according to study criteria for psychological, social, family or geographical reasons. Patient deprived of liberty or under guardianship.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Utility of Intraoperative Contrast Ultrasound in the Surgery of Colorectal Cancer Liver Metastases. | At time of surgery | The clinical utility will be evaluated in terms of justified modification of the surgical procedure following contrast-enhanced intra-operative ultrasound (CE-IOUS), compared to the surgical procedure following conventional intra-operative ultrasound. For each patient, we will consider CE-IOUS to be clinically useful: * if the surgical procedure envisaged at the end of the CE-IOUS is different from the surgical procedure envisaged at the end of the conventional ultrasound * and if the surgical procedure envisaged at the end of the CE-IOUS is justified We reported the percentage of patients for whom there was a modified and justified surgical gesture following CE-IOUS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Utility of CE-IOUS in Subgroup of Patients Who Received Preoperative Chemotherapy | at time of surgery | The primary endpoint will be assessed in the subgroup of patients who received preoperative chemotherapy. As for the primary outcome, the clinical utility is evaluated in terms of justified modification of the surgical gesture envisaged following CE-IOUS, compared to the surgical gesture envisaged following a conventional intraoperative ultrasound. We reported the percentage of patients for whom there was a modified and justified surgical gesture following CE-IOUS in the subgroup of patients who received preoperative chemotherapy. |
| Performance Evaluation of Intraoperative Ultrasound Contrast: Detection Rate Per Lesion | up to 3 months after surgery | Detection of malignant lesions by CE-IOUS in chemotherapy-free patients within 3 post-operative months. The detection rate is defined as the proportion of malignant lesions for which there is concordance between the diagnosis established by CE-IOUS and the reference examination. |
| Description of Technical Arrangements for the CE-IOUS | At time of contrast-enhanced IOUS | Description of technical arrangements for the CE-IOUS duration. The length of time during which contrast injection was useable. |
| Performance Evaluation of Intraoperative Ultrasound Contrast Per Lesion: Characterisation Rate | up to 3 months after surgery | Characterisation rate for focal liver lesions: the proportion of lesions whose nature on CE-IOUS is identical to the nature of the lesions defined by the reference examinations among all the lesions seen on CE-IOUS (malignant and benign) |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Contrast-enhanced Intraoperative Ultrasound Contrast-enhanced intraoperative ultrasound
Contrast-enhanced intraoperative ultrasound: Once the patient is included in the study, a staging procedure is performed in three stages before hepatic metastases treatment:
Step # 1 preoperative (maximum 8 weeks before surgery Steps # 2 and # 3 intraoperative performed by the same surgeon in 2 stages | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 14 |
| Overall Study | Simon's design requirements | 2 |
Baseline characteristics
| Characteristic | Contrast-enhanced Intraoperative Ultrasound | — |
|---|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 11 | — |
| Cancer localization Left Colon | 22 Participants | — |
| Cancer localization Rectum | 17 Participants | — |
| Cancer localization Right Colon | 11 Participants | — |
| Cancer localization Transverse Colon | 2 Participants | — |
| Liver metastases Metachronous | 23 Participants | — |
| Liver metastases Synchronous | 29 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 17 Participants | — |
| Sex: Female, Male Male | 35 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 54 |
| serious Total, serious adverse events | 11 / 54 |
Outcome results
Primary
Clinical Utility of Intraoperative Contrast Ultrasound in the Surgery of Colorectal Cancer Liver Metastases.
The clinical utility will be evaluated in terms of justified modification of the surgical procedure following contrast-enhanced intra-operative ultrasound (CE-IOUS), compared to the surgical procedure following conventional intra-operative ultrasound. For each patient, we will consider CE-IOUS to be clinically useful: * if the surgical procedure envisaged at the end of the CE-IOUS is different from the surgical procedure envisaged at the end of the conventional ultrasound * and if the surgical procedure envisaged at the end of the CE-IOUS is justified We reported the percentage of patients for whom there was a modified and justified surgical gesture following CE-IOUS.
Time frame: At time of surgery
Population: We used a 2-stage Simon's design with the following assumptions:~* maximum tolerated futility rate: 5%,~* expected minimum utility rate: 15%,~* Type I error of 10%,~* power of 85%. Thus, 52 eligible and evaluable patients were required (25 in the first stage). First stage: stop, if CE-IOUS is not deemed clinically useful for at least one patient (4.0%).~Second stage: CE-IOUS clinically useful if the planned surgical procedure is modified and justified for 5 or more patients (9.6%).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Contrast-enhanced Intraoperative Ultrasound | Clinical Utility of Intraoperative Contrast Ultrasound in the Surgery of Colorectal Cancer Liver Metastases. | 7.7 percentage of patients |
Secondary
Clinical Utility of CE-IOUS in Subgroup of Patients Who Received Preoperative Chemotherapy
The primary endpoint will be assessed in the subgroup of patients who received preoperative chemotherapy. As for the primary outcome, the clinical utility is evaluated in terms of justified modification of the surgical gesture envisaged following CE-IOUS, compared to the surgical gesture envisaged following a conventional intraoperative ultrasound. We reported the percentage of patients for whom there was a modified and justified surgical gesture following CE-IOUS in the subgroup of patients who received preoperative chemotherapy.
Time frame: at time of surgery
Population: Subgroup of patients with preoperative chemotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Contrast-enhanced Intraoperative Ultrasound | Clinical Utility of CE-IOUS in Subgroup of Patients Who Received Preoperative Chemotherapy | 7.31 percentage of patients |
Secondary
Description of Technical Arrangements for the CE-IOUS
Description of technical arrangements for the CE-IOUS duration. The length of time during which contrast injection was useable.
Time frame: At time of contrast-enhanced IOUS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Contrast-enhanced Intraoperative Ultrasound | Description of Technical Arrangements for the CE-IOUS | 225 seconds |
Secondary
Performance Evaluation of Intraoperative Ultrasound Contrast: Detection Rate Per Lesion
Detection of malignant lesions by CE-IOUS in chemotherapy-free patients within 3 post-operative months. The detection rate is defined as the proportion of malignant lesions for which there is concordance between the diagnosis established by CE-IOUS and the reference examination.
Time frame: up to 3 months after surgery
Population: There were 22 (40.7%) out of 54 chemotherapy-free patients within 3 post-operative months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Contrast-enhanced Intraoperative Ultrasound | Performance Evaluation of Intraoperative Ultrasound Contrast: Detection Rate Per Lesion | 0.75 proportion of lesions |
Secondary
Performance Evaluation of Intraoperative Ultrasound Contrast Per Lesion: Characterisation Rate
Characterisation rate for focal liver lesions: the proportion of lesions whose nature on CE-IOUS is identical to the nature of the lesions defined by the reference examinations among all the lesions seen on CE-IOUS (malignant and benign)
Time frame: up to 3 months after surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Contrast-enhanced Intraoperative Ultrasound | Performance Evaluation of Intraoperative Ultrasound Contrast Per Lesion: Characterisation Rate | 0.94 proportion of lesions |