DRAGON 1- Training, Accreditation, Implementation and Safety Evaluation of Combined PVE/HVE

Conditions

Colorectal Cancer Liver Metastases

Keywords

Future Liver Remnant, Portal and Hepatic Vein Embolization, Colorectal Liver Metastases

Brief summary

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

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.

Korenblik R, James S, Smits J, Díaz-Nieto R, Davis R, Chan BKY, Erdmann JI, Zijlstra IAJ, Arntz PJW, Kollmar O, Hoffmann MH, Vass DG, Lindsay R, Serenari M, Cappelli A, Gobardhan PD, Imani F, Suarez YF, Muños FG, Grünhagen DJ, Moelker A, Pieterman KJ, Kleeff J, Wohlgemuth WA, Herrero E, Gelabert A, Breitenstein S, Seeger N, Detry O, Gerard L, Sandström PA, Björnsson B, Aldrighetti LA, De Cobelli F, Leclercq WKG, van Baardewijk LJ, Croagh D, De Boo DW, Kingham TP, Ridouani F, Metrakos P, Valenti D, Kalil J, Fretland ÅA, Carling U, Martel G, Ryan S, Udupa V, Macdonald A, Tasse JC, Stavrou GA, Spuentrup E, Borobia FG, Criado E, Sparrelid E, Delle M, Navinés-López J, Moragues JS, Andorrà EC, Schnitzbauer A, Vogl TJ, Heil J, Primrose JN, Modi S, Fouraschen SMG, Bokkers RPH, de Boer MT, Borel Rinkes IHM, Smits MLJ, Gruenberger T, Baclija I, Billingsley KG, Madoff DC, Serrablo A, Sarriá L, Wang X, Xudong Q, Winkens B, Olde Damink SWL, Bemelmans MHA, Dewulf MJL, Binkert CA, Schadde E, van der Leij C, van Dam RM, DRAGON collaborative study group.

2025-04-103 citations

10.1016/j.lanepe.2025.101284

Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy

Remon Korenblik, Bram Olij, Luca Aldrighetti, Mohammad Abu Hilal, Margareta Ahle et al. (100 authors)

CardioVascular and Interventional Radiology2022-07-0531 citations

10.1007/s00270-022-03176-1

Interventions

PROCEDUREPortal and Hepatic Vein Embolization

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)

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Multicenter, 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 a planned subsequent trial (DRAGON 2) that will compare PVE with PVE/HVE. In DRAGON 1 every center has to demonstrate the ability to enroll 3 patients in 12 months safely

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Patients with primarily unresectable/potentially resectable CRLM after conversion chemotherapy with a FLR \<30% in normal livers, or 40% in livers chemotherapy damaged livers. * 18 years and older * Patients up to ECOG 3 (not more than 50% bedbound) * Patients with non-resected primary colorectal cancer (CRC) may be included if and only if there is an intent to remove the CRC after the liver treatment (liver first approach) * Staging CT chest and (if symptomatic) CT/MRI excludes unresectable extrahepatic disease, while metastatic disease that may be cured in the future, is included. * Patients with resectable lung metastases or lung metastases that and be ablated can be included only after statement about resectability/ablatability by tumor board * Patients have to be to understand the trial and provide informed consent.

Exclusion criteria

* Patients with extrahepatic disease other than lung metastases * Patients with metastatic disease to the lung that cannot be ablated or resected will be excluded * Patients with intrahepatic Cholangiocarcinoma (IHCC) * Patients with Perihilar Cholangiocarcinoma (PHCC) * Patients with Hepatocellular Carcinoma (HCC) * Pregnant or lactating women will not be eligible * Potential to get pregnant has to be excluded (obligatory contraception etc.) * Progression by modified RECIST criteria on cross-sectional imaging after conversion chemotherapy is an exclusion criterion. Complete response in cross-sectional imaging after conversion chemotherapy.

Design outcomes

Primary

Measure	Time frame	Description
Ability of each center to enroll 3 patients in 12 months without mortality due to the intervention.	1 year/ 90 day mortality	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.

Secondary

Measure	Time frame	Description
Feasibility assessment: resection rate	1 year follow up	ion of patients proceeding to complete resection (=resection rate)
Mortality assessment	90 days	90-mortality after resection
Overall survival after PVE/HVE	1 year follow up	Overall survival
Efficacy assessment: standardized future liver remnant volume	6 weeks	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
General complication assessment	90 days	90-day complications, general (Clavien-Dindo)
Liver specific complication assessment	90 days	90-day complications, liver specific (FABIB-classification)
Oncological effectiveness of PVE/HVE	1 year	Disease-free survival after 1 year

Countries

Australia, Austria, Belgium, Canada, Germany, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, United Kingdom, United States

Outcome results

None listed