Brief Summary: Some colorectal liver metastases can only be resected after inducing liver regeneration by portal vein embolization (PVE) to increase size function of the future liver remnant (FLR). While PVE is standard, embolization of portal vein and hepatic veins (PVE/HVE) on one side of the liver may faster and more extensive liver size and function growth. PVE/HVE is a novel procedure and requires a safety and feasibility evaluation in a pretrial (DRAGON1) to then be compared in a randomized controlled trial (RCT) to PVE (DRAGON 2).
Detailed Description: Resection of liver metastases from colorectal cancer (CRLM) improves survival compared to chemotherapy alone and may lead to cure in up to 40% of patients. Surgical resectability is limited by location of metastases and by FLR size and function. Commonly, the volume of the future liver remnant (FLR) should be at least 30% of the functional FLR volume. If this volume criterion is not met, the induction of liver regeneration between a two-stage hepatectomy is performed at many centers, with the aim to render patients resectable and reduce the risk of post hepatectomy liver failure. Gold standard to induce regeneration is the embolization of the portal vein branches to the tumor carrying liver (PVE) to induce regeneration of the FLR. Recently, combined embolization of both portal and hepatic veins (PVE/HVE) has been described as an alternative to portal vein embolization because it accelerates and increases growth of the FLR. PVE/HVE combines simultaneous embolization of the portal main branches into the tumor bearing liver and the hepatic vein draining them. The tissue in the part of the liver treated with PVE/HVE stays viable because the hepatic artery continues to supplies the liver deprived of portal and hepatic veins. Preclinical studies in pigs have demonstrated feasibility of this method and human case series show accelerated and increased liver growth. No multi-center evaluation has been performed so far. DRAGON 1 is an international, prospective, multi-center trial to test enrolment capacity of participants and safety of portal and hepatic vein embolization (PVE/HVE). DRAGON 1 will form the basis of the RCT DRAGON 2 to compare PVE with PVE/HV. DRAGON 2 is expected to start in 2021.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
Procedure/Surgery: Combined portal vein embolization and hepatic vein embolization (PVE/HVE) • All techniques of PVE allowed (ipsi-lateral, contra-lateral, trans-splenic, all embolization agents except for ethanol alone) • All modifications of HVE allowed (venous occlusion umbrellas; trans-jugular, trans-hepatic, no use of vein glue to avoid lung embolization; staged approach allowed, but first PVE, then HVE and within 48 hours)
Ability of each center to enroll 3 patients in 12 months without mortality due to the intervention.
Ability of each center to enroll 3 patients for PVE/HVE in 12 months safely and perform the procedure including the liver resection without 90-day mortality after resection due to complications. If this goal is achieved center will be enrolled in DRAGON 2.
Time frame: 1 year/ 90 day mortality
Efficacy assessment: standardized future liver remnant volume
Increased of standardized future liver remnant volume between initial imaging and imaging at 1 week, 3 weeks, 6 weeks, degree of hypertrophy based on standard future liver remnant volume, kinetic growth
Time frame: 6 weeks
Feasibility assessment: resection rate
ion of patients proceeding to complete resection (=resection rate)
Time frame: 1 year follow up
Mortality assessment
90-mortality after resection
Time frame: 90 days
Overall survival after PVE/HVE
Overall survival
Time frame: 1 year follow up
Oncological effectiveness of PVE/HVE
Disease-free survival after 1 year
Time frame: 1 year
General complication assessment
90-day complications, general (Clavien-Dindo)
Time frame: 90 days
Liver specific complication assessment
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TREATMENT
Masking
NONE
Enrollment
111
Yale School of Medicine
New Haven, Connecticut, United States
Rush University Medical Center
Chicago, Illinois, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
Monash Health, Clayton
Clayton, Victoria, Australia
Social Medical Center, South
Vienna, Austria
Hôpital Erasme
Brussels, Brussels Capital, Belgium
CHU-UCL Namur site Godinne
Yvoir, Namen, Belgium
CHU de Liège
Liège, Belgium
The Ottawa Hospital
Ottawa, Ontario, Canada
...and 32 more locations
90-day complications, liver specific (FABIB-classification)
Time frame: 90 days