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

R Korenblik; B Olij; L A Aldrighetti; M Abu Hilal; M Ahle; B Arslan; L J van Baardewijk; I Baclija; C Bent; C L Bertrand; B Björnsson; M T de Boer; S W de Boer; R P H Bokkers; I H M Borel Rinkes; S Breitenstein; R C G Bruijnen; P Bruners; M W Büchler; J C Camacho; A Cappelli; U Carling; B K Y Chan; D H Chang; J Choi; J Codina Font; M Crawford; D Croagh; E Cugat; R Davis; D W De Boo; F De Cobelli; J F De Wispelaere; O M van Delden; M Delle; O Detry; R Díaz-Nieto; A Dili; J I Erdmann; O Fisher; C Fondevila; Å Fretland; F Garcia Borobia; A Gelabert; L Gérard; F Giuliante; P D Gobardhan; F Gómez; T Grünberger; D J Grünhagen; J Guitart; J Hagendoorn; J Heil; D Heise; E Herrero; G F Hess; M H Hoffmann; R Iezzi; F Imani; J Nguyen; E Jovine; J C Kalff; G Kazemier; T P Kingham; J Kleeff; O Kollmar; W K G Leclercq; S Lopez Ben; V Lucidi; A MacDonald; D C Madoff; S Manekeller; G Martel; A Mehrabi; H Mehrzad; M R Meijerink; K Menon; P Metrakos; C Meyer; A Moelker; S Modi; N Montanari; J Navines; U P Neumann; P Peddu; J N Primrose; X Qu; D Raptis; F Ratti; F Ridouani; C Rogan; U Ronellenfitsch; S Ryan; C Sallemi; J Sampere Moragues; P Sandström; L Sarriá; A Schnitzbauer; M Serenari; A Serrablo; M L J Smits; E Sparrelid; E Spüntrup; G A Stavrou; R P Sutcliffe; I Tancredi; J C Tasse; V Udupa; D Valenti; Y Fundora; T J Vogl; X Wang; S A White; W A Wohlgemuth; D Yu; I A J Zijlstra; C A Binkert; M H A Bemelmans; C van der Leij; E Schadde; R M van Dam

doi:10.1007/s00270-022-03176-1

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

Cardiovasc Intervent Radiol. 2022 Sep;45(9):1391-1398. doi: 10.1007/s00270-022-03176-1. Epub 2022 Jul 5.

Authors

R Korenblik^{1

2}, B Olij^{3

4}, L A Aldrighetti⁵, M Abu Hilal⁶, M Ahle⁷, B Arslan⁸, L J van Baardewijk⁹, I Baclija¹⁰, C Bent¹¹, C L Bertrand¹², B Björnsson¹³, M T de Boer¹⁴, S W de Boer¹⁵, R P H Bokkers¹⁶, I H M Borel Rinkes¹⁷, S Breitenstein¹⁸, R C G Bruijnen¹⁹, P Bruners²⁰, M W Büchler²¹, J C Camacho²², A Cappelli²³, U Carling²⁴, B K Y Chan²⁵, D H Chang²⁶, J Choi²⁷, J Codina Font²⁸, M Crawford²⁹, D Croagh³⁰, E Cugat³¹, R Davis³², D W De Boo³³, F De Cobelli³⁴, J F De Wispelaere³⁵, O M van Delden³⁶, M Delle³⁷, O Detry³⁸, R Díaz-Nieto²⁵, A Dili¹², J I Erdmann³⁹, O Fisher²⁹, C Fondevila⁴⁰, Å Fretland⁴¹, F Garcia Borobia⁴², A Gelabert^{43

44}, L Gérard⁴⁵, F Giuliante⁴⁶, P D Gobardhan⁴⁷, F Gómez⁴⁸, T Grünberger⁴⁹, D J Grünhagen⁵⁰, J Guitart⁴⁴, J Hagendoorn¹⁷, J Heil⁵¹, D Heise⁵², E Herrero⁵³, G F Hess⁵⁴, M H Hoffmann⁵⁵, R Iezzi⁵⁶, F Imani⁵⁷, J Nguyen⁵⁸, E Jovine⁵⁹, J C Kalff⁶⁰, G Kazemier⁶¹, T P Kingham⁶², J Kleeff⁶³, O Kollmar⁵⁴, W K G Leclercq⁶⁴, S Lopez Ben⁶⁵, V Lucidi⁶⁶, A MacDonald⁶⁷, D C Madoff⁶⁸, S Manekeller⁶⁰, G Martel⁶⁹, A Mehrabi²¹, H Mehrzad⁷⁰, M R Meijerink⁷¹, K Menon⁷², P Metrakos⁷³, C Meyer⁷⁴, A Moelker⁷⁵, S Modi⁷⁶, N Montanari⁷⁷, J Navines³¹, U P Neumann^{4

52}, P Peddu⁷⁸, J N Primrose⁷⁹, X Qu⁸⁰, D Raptis⁸¹, F Ratti⁵, F Ridouani²², C Rogan⁸², U Ronellenfitsch⁶³, S Ryan⁸³, C Sallemi⁸⁴, J Sampere Moragues⁸⁵, P Sandström¹³, L Sarriá⁸⁶, A Schnitzbauer⁵¹, M Serenari⁸⁷, A Serrablo⁸⁸, M L J Smits¹⁹, E Sparrelid⁸⁹, E Spüntrup⁹⁰, G A Stavrou⁹¹, R P Sutcliffe⁹², I Tancredi⁹³, J C Tasse⁸, V Udupa⁹⁴, D Valenti⁹⁵, Y Fundora⁴⁰, T J Vogl⁹⁶, X Wang⁹⁷, S A White⁹⁸, W A Wohlgemuth⁹⁹, D Yu¹⁰⁰, I A J Zijlstra⁷¹, C A Binkert¹⁰¹, M H A Bemelmans^{4

52}, C van der Leij¹⁵, E Schadde^#^{18

102}, R M van Dam^#^{103

104

105}

Affiliations

¹ GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht Universiteitssingel 40 room 5.452, 6229 ET, Maastricht, The Netherlands. remon.korenblik@mumc.nl.
² Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands. remon.korenblik@mumc.nl.
³ GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht Universiteitssingel 40 room 5.452, 6229 ET, Maastricht, The Netherlands.
⁴ Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands.
⁵ Department of Surgery, Ospedale San Raffaele, Milan, Italy.
⁶ Department of Surgery, Fondazione Poliambulanza, Brescia, Italy.
⁷ Deparment of Radiology, University Hospital, Linköping, Sweden.
⁸ Department of Radiology, Rush University Medical Center, Chicago, USA.
⁹ Department of Radiology, Maxima Medisch Centrum, Eindhoven, The Netherlands.
¹⁰ Department of Radiology, Clinic Favoriten, Vienna, Austria.
¹¹ Department of Radiology, Bournemouth and Christuchurch, The Royal Bournemouth and Christchurch Hospitals, Bournemouth and Christuchurch, UK.
¹² Department of Surgery, CHU UCLouvain Namur, Namur, Belgium.
¹³ Department of Surgery, Biomedical and Clinical Sciences, Linköping University Hospital, Linköping, Sweden.
¹⁴ Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands.
¹⁵ Deparment of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
¹⁶ Department of Radiology, University Medical Center Groningen, Groningen, The Netherlands.
¹⁷ Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁸ Department of General and Visceral Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland.
¹⁹ Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands.
²⁰ Department of Radiology, University Hospital Aachen, Aachen, Germany.
²¹ Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
²² Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA.
²³ Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
²⁴ Department of Radiology, University Hospital Oslo, Oslo, Norway.
²⁵ Department of Surgery, Aintree University Hospitals NHS, Liverpool, UK.
²⁶ Department of Radiology, University Hospital Heidelberg, Heidelberg, Germany.
²⁷ Department of Surgery, Western Health Footscray, Footscray, Australia.
²⁸ Department of Radiology, University Hospital Dr. Josep Trueta de Girona, Girona, Spain.
²⁹ Department of Surgery, Royal Prince Alfred Hospital, Camperdown, Australia.
³⁰ Department of Surgery, Monash Health, Clayton, Australia.
³¹ Department of Surgery, University Hospital Germans Trias I Pujol, Badalona, Spain.
³² Department of Radiology, Aintree University Hospitals NHS, Liverpool, UK.
³³ Department of Radiology, Monash Health, Clayton, Australia.
³⁴ Department of Radiology, Ospedale San Raffaele, Milan, Italy.
³⁵ Department of Radiology, CHU UCLouvain Namur, Namur, Belgium.
³⁶ Department of Radiology, Amsterdam University Medical Centers Location AMC, Amsterdam, The Netherlands.
³⁷ Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
³⁸ Department of Surgery, CHU de Liège, Liège, Belgium.
³⁹ Department of Surgery, Amsterdam University Medical Centers Location AMC, Amsterdam, The Netherlands.
⁴⁰ Department of Surgery, Hospital Clínic de Barcelona, Barcelona, Spain.
⁴¹ Department of Surgery, University Hospital Oslo, Oslo, Norway.
⁴² Department of Surgery, Hospital Parc Taulí de Sabadell, Sabadell, Spain.
⁴³ Department of Radiology, Hospital Parc Taulí de Sabadell, Sabadell, Spain.
⁴⁴ Department of Radiology, University Hospital Mútua Terassa, Terassa, Spain.
⁴⁵ Department of Radiology, CHU de Liège, Liège, Belgium.
⁴⁶ Department of Surgery, Gemelli University Hospital Rome, Rome, Italy.
⁴⁷ Department of Surgery, Amphia, Breda, The Netherlands.
⁴⁸ Department of Radiology, Hospital Clínic de Barcelona, Barcelona, Spain.
⁴⁹ Department of Surgery, HPB Center Vienna Health Network, Clinic Favoriten, Vienna, Austria.
⁵⁰ Department of Surgery, Erasmus Medisch Centrum, Rotterdam, The Netherlands.
⁵¹ Department of Surgery, University Hospital Frankfurt, Frankfurt, Germany.
⁵² Department of General, Visceral and Transplant Surgery, University Hospital Aachen, Aachen, Germany.
⁵³ Department of Surgery, University Hospital Mútua Terassa, Terassa, Spain.
⁵⁴ Department of Surgery, Clarunis University Hospital, Basel, Switzerland.
⁵⁵ Department of Radiology, St. Clara Spital, Basel, Switzerland.
⁵⁶ Department of Radiology, Gemelli University Hospital, Rome, Italy.
⁵⁷ Department of Radiology, Amphia, Breda, The Netherlands.
⁵⁸ Department of Radiology, Western Health Footscray, Footscray, Australia.
⁵⁹ Department of Surgery, Ospedale Maggiore di Bologna, Bologna, Italy.
⁶⁰ Department of Surgery, University Hospital Bonn, Bonn, Germany.
⁶¹ Department of Surgery, Amsterdam University Medical Centers Location VU, Amsterdam, The Netherlands.
⁶² Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
⁶³ Department of Surgery, University Hospital Halle (Saale), Halle, Germany.
⁶⁴ Department of Surgery, Maxima Medisch Centrum, Eindhoven, The Netherlands.
⁶⁵ Department of Surgery, University Hospital Dr. Josep Trueta de Girona, Girona, Spain.
⁶⁶ Department of Surgery, Hôpital Erasme, Brussels, Belgium.
⁶⁷ Department of Radiology, Oxford University Hospital NHS, Oxford, UK.
⁶⁸ Department of Radiology, Yale School of Medicine, New Haven, USA.
⁶⁹ Department of Surgery, The Ottawa Hospital, Ottawa, Canada.
⁷⁰ Department of Radiology, Queen Elizabeth Hospital Birmingham NHS, Birmingham, UK.
⁷¹ Department of Radiology, Amsterdam University Medical Centers Location VU, Amsterdam, The Netherlands.
⁷² Department of Surgery, King's College Hospital NHS, London, UK.
⁷³ Department of Surgery, McGill University Health Centre, Montréal, Canada.
⁷⁴ Department of Radiology, University Hospital Bonn, Bonn, Germany.
⁷⁵ Department of Radiology and Nuclear Medicine, Erasmus Medisch Centrum, Rotterdam, The Netherlands.
⁷⁶ Department of Radiology, University Hospital Southampton NHS, Southampton, UK.
⁷⁷ Department of Radiology, Ospedale Maggiore Di Bologna, Bologna, Italy.
⁷⁸ Department of Radiology, King's College Hospital NHS, London, UK.
⁷⁹ Department of Surgery, University Hospital Southampton NHS, Southampton, UK.
⁸⁰ Department of Radiology, Zhongshan Hospital, Fundan University, Shanghai, China.
⁸¹ Department of Surgery, Royal Free Hospital NHS, London, UK.
⁸² Department of Radiology, Royal Prince Alfred Hospital, Camperdown, Australia.
⁸³ Department of Radiology, The Ottawa Hospital, Ottawa, Canada.
⁸⁴ Department of Radiology, Fondazione Poliambulanza, Brescia, Italy.
⁸⁵ Department of Radiology, University Hospital Germans Trias I Pujol, Badalona, Spain.
⁸⁶ Department of Radiology, University Hospital Miguel Servet, Saragossa, Spain.
⁸⁷ Department of Surgery, General Surgery and Transplant Unit, IRCCS Azienda Ospedaliero- Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
⁸⁸ Department of Surgery, University Hospital Miguel Servet, Saragossa, Spain.
⁸⁹ Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
⁹⁰ Department of Radiology, Klinikum Saarbrücken gGmbH, Saarbrücken, Germany.
⁹¹ Department of Surgery, Klinikum Saarbrücken gGmbH, Saarbrücken, Germany.
⁹² Department of Surgery, Queen Elizabeth Hospital Birmingham NHS, Birmingham, UK.
⁹³ Department of Radiology, Hôpital Erasme, Brussels, Belgium.
⁹⁴ Department of Surgery, Oxford University Hospital NHS, Oxford, UK.
⁹⁵ Department of Radiology, McGill University Health Centre, Montréal, Canada.
⁹⁶ Department of Radiology, University Hosptital Frankfurt, Frankfurt, Germany.
⁹⁷ Department of Surgery, Zhongshan Hospital, Fundan University, Shanghai, China.
⁹⁸ Department of Surgery, Newcastle Upon Tyne Hospitals NHS, Newcastle upon Tyne, UK.
⁹⁹ Department of Radiology, University Hospital Halle (Saale), Halle, Germany.
¹⁰⁰ Department of Radiology, Royal Free Hospital NHS, London, UK.
¹⁰¹ Department of Radiology, Cantonal Hospital Winterthur, Winterthur, Switzerland.
¹⁰² Department of Surgery, Rush University Medical Center Chicago, Chicago, USA.
¹⁰³ GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht Universiteitssingel 40 room 5.452, 6229 ET, Maastricht, The Netherlands. r.van.dam@mumc.nl.
¹⁰⁴ Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands. r.van.dam@mumc.nl.
¹⁰⁵ Department of General, Visceral and Transplant Surgery, University Hospital Aachen, Aachen, Germany. r.van.dam@mumc.nl.

^# Contributed equally.

Abstract

Study purpose: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases.

Methods: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection.

Results: Not applicable.

Conclusion: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR.

Trial registration: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Keywords: Colorectal cancer liver metastases (CRLM); Combined portal- and hepatic vein embolization (PVE/HVE); Future liver remnant (FLR); Hepatic vein embolization (HVE); Liver hypertrophy; Portal vein embolization (PVE).

MeSH terms

Accreditation
Embolization, Therapeutic* / methods
Hepatectomy / methods
Hepatic Veins / pathology
Hepatomegaly
Humans
Hypertrophy / etiology
Hypertrophy / pathology
Hypertrophy / surgery
Liver / surgery
Liver Neoplasms* / diagnostic imaging
Liver Neoplasms* / pathology
Liver Neoplasms* / therapy
Multicenter Studies as Topic
Portal Vein / pathology
Prospective Studies
Treatment Outcome

Associated data

ClinicalTrials.gov/NCT04272931
NTR/ntr-7153506819

Abstract

MeSH terms

Associated data

Grants and funding