[en] 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).
Disciplines :
Radiology, nuclear medicine & imaging Surgery
Author, co-author :
Korenblik, R ; GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht Universiteitssingel 40 room 5.452, 6229 ET, Maastricht, The Netherlands. remon.korenblik@mumc.nl ; Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands. remon.korenblik@mumc.nl
Olij, B; GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht Universiteitssingel 40 room 5.452, 6229 ET, Maastricht, The Netherlands ; Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
Aldrighetti, L A; Department of Surgery, Ospedale San Raffaele, Milan, Italy
Hilal, M Abu; Department of Surgery, Fondazione Poliambulanza, Brescia, Italy
Ahle, M; Deparment of Radiology, University Hospital, Linköping, Sweden
Arslan, B; Department of Radiology, Rush University Medical Center, Chicago, USA
van Baardewijk, L J; Department of Radiology, Maxima Medisch Centrum, Eindhoven, The Netherlands
Baclija, I; Department of Radiology, Clinic Favoriten, Vienna, Austria
Bent, C; Department of Radiology, Bournemouth and Christuchurch, The Royal Bournemouth and Christchurch Hospitals, Bournemouth and Christuchurch, UK
Bertrand, C L; Department of Surgery, CHU UCLouvain Namur, Namur, Belgium
Björnsson, B; Department of Surgery, Biomedical and Clinical Sciences, Linköping University Hospital, Linköping, Sweden
de Boer, M T; Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
de Boer, S W; Deparment of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
Bokkers, R P H; Department of Radiology, University Medical Center Groningen, Groningen, The Netherlands
Rinkes, I H M Borel; Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
Breitenstein, S; Department of General and Visceral Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
Bruijnen, R C G; Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands
Bruners, P; Department of Radiology, University Hospital Aachen, Aachen, Germany
Büchler, M W; Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany
Camacho, J C; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA
Cappelli, A; Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy
Carling, U; Department of Radiology, University Hospital Oslo, Oslo, Norway
Chan, B K Y; Department of Surgery, Aintree University Hospitals NHS, Liverpool, UK
Chang, D H; Department of Radiology, University Hospital Heidelberg, Heidelberg, Germany
Choi, J; Department of Surgery, Western Health Footscray, Footscray, Australia
Font, J Codina; Department of Radiology, University Hospital Dr. Josep Trueta de Girona, Girona, Spain
Crawford, M; Department of Surgery, Royal Prince Alfred Hospital, Camperdown, Australia
Croagh, D; Department of Surgery, Monash Health, Clayton, Australia
Cugat, E; Department of Surgery, University Hospital Germans Trias I Pujol, Badalona, Spain
Davis, R; Department of Radiology, Aintree University Hospitals NHS, Liverpool, UK
De Boo, D W; Department of Radiology, Monash Health, Clayton, Australia
De Cobelli, F; Department of Radiology, Ospedale San Raffaele, Milan, Italy
De Wispelaere, J F; Department of Radiology, CHU UCLouvain Namur, Namur, Belgium
van Delden, O M; Department of Radiology, Amsterdam University Medical Centers Location AMC, Amsterdam, The Netherlands
Delle, M; Department of Radiology, Karolinska University Hospital, Stockholm, Sweden
DETRY, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie abdo, sénologique, endocrine et de transplantation
Díaz-Nieto, R; Department of Surgery, Aintree University Hospitals NHS, Liverpool, UK
Dili, A; Department of Surgery, CHU UCLouvain Namur, Namur, Belgium
Erdmann, J I; Department of Surgery, Amsterdam University Medical Centers Location AMC, Amsterdam, The Netherlands
Fisher, O; Department of Surgery, Royal Prince Alfred Hospital, Camperdown, Australia
Fondevila, C; Department of Surgery, Hospital Clínic de Barcelona, Barcelona, Spain
Fretland, Å; Department of Surgery, University Hospital Oslo, Oslo, Norway
Borobia, F Garcia; Department of Surgery, Hospital Parc Taulí de Sabadell, Sabadell, Spain
Gelabert, A; Department of Radiology, Hospital Parc Taulí de Sabadell, Sabadell, Spain ; Department of Radiology, University Hospital Mútua Terassa, Terassa, Spain
GERARD, Laurent ; Centre Hospitalier Universitaire de Liège - CHU > > Service médical de radiodiagnostic
Giuliante, F; Department of Surgery, Gemelli University Hospital Rome, Rome, Italy
Gobardhan, P D; Department of Surgery, Amphia, Breda, The Netherlands
Gómez, F; Department of Radiology, Hospital Clínic de Barcelona, Barcelona, Spain
Grünberger, T; Department of Surgery, HPB Center Vienna Health Network, Clinic Favoriten, Vienna, Austria
Grünhagen, D J; Department of Surgery, Erasmus Medisch Centrum, Rotterdam, The Netherlands
Guitart, J; Department of Radiology, University Hospital Mútua Terassa, Terassa, Spain
Hagendoorn, J; Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
Heil, J; Department of Surgery, University Hospital Frankfurt, Frankfurt, Germany
Heise, D; Department of General, Visceral and Transplant Surgery, University Hospital Aachen, Aachen, Germany
Herrero, E; Department of Surgery, University Hospital Mútua Terassa, Terassa, Spain
Hess, G F; Department of Surgery, Clarunis University Hospital, Basel, Switzerland
Hoffmann, M H; Department of Radiology, St. Clara Spital, Basel, Switzerland
Iezzi, R; Department of Radiology, Gemelli University Hospital, Rome, Italy
Imani, F; Department of Radiology, Amphia, Breda, The Netherlands
Nguyen, J; Department of Radiology, Western Health Footscray, Footscray, Australia
Jovine, E; Department of Surgery, Ospedale Maggiore di Bologna, Bologna, Italy
Kalff, J C; Department of Surgery, University Hospital Bonn, Bonn, Germany
Kazemier, G; Department of Surgery, Amsterdam University Medical Centers Location VU, Amsterdam, The Netherlands
Kingham, T P; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
Kleeff, J; Department of Surgery, University Hospital Halle (Saale), Halle, Germany
Kollmar, O; Department of Surgery, Clarunis University Hospital, Basel, Switzerland
Leclercq, W K G; Department of Surgery, Maxima Medisch Centrum, Eindhoven, The Netherlands
Ben, S Lopez; Department of Surgery, University Hospital Dr. Josep Trueta de Girona, Girona, Spain
Lucidi, V; Department of Surgery, Hôpital Erasme, Brussels, Belgium
MacDonald, A; Department of Radiology, Oxford University Hospital NHS, Oxford, UK
Madoff, D C; Department of Radiology, Yale School of Medicine, New Haven, USA
Manekeller, S; Department of Surgery, University Hospital Bonn, Bonn, Germany
Martel, G; Department of Surgery, The Ottawa Hospital, Ottawa, Canada
Mehrabi, A; Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany
Mehrzad, H; Department of Radiology, Queen Elizabeth Hospital Birmingham NHS, Birmingham, UK
Meijerink, M R; Department of Radiology, Amsterdam University Medical Centers Location VU, Amsterdam, The Netherlands
Menon, K; Department of Surgery, King's College Hospital NHS, London, UK
Metrakos, P; Department of Surgery, McGill University Health Centre, Montréal, Canada
Meyer, C; Department of Radiology, University Hospital Bonn, Bonn, Germany
Moelker, A; Department of Radiology and Nuclear Medicine, Erasmus Medisch Centrum, Rotterdam, The Netherlands
Modi, S; Department of Radiology, University Hospital Southampton NHS, Southampton, UK
Montanari, N; Department of Radiology, Ospedale Maggiore Di Bologna, Bologna, Italy
Navines, J; Department of Surgery, University Hospital Germans Trias I Pujol, Badalona, Spain
Neumann, U P; Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands ; Department of General, Visceral and Transplant Surgery, University Hospital Aachen, Aachen, Germany
Peddu, P; Department of Radiology, King's College Hospital NHS, London, UK
Primrose, J N; Department of Surgery, University Hospital Southampton NHS, Southampton, UK
Qu, X; Department of Radiology, Zhongshan Hospital, Fundan University, Shanghai, China
Raptis, D; Department of Surgery, Royal Free Hospital NHS, London, UK
Ratti, F; Department of Surgery, Ospedale San Raffaele, Milan, Italy
Ridouani, F; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA
Rogan, C; Department of Radiology, Royal Prince Alfred Hospital, Camperdown, Australia
Ronellenfitsch, U; Department of Surgery, University Hospital Halle (Saale), Halle, Germany
Ryan, S; Department of Radiology, The Ottawa Hospital, Ottawa, Canada
Sallemi, C; Department of Radiology, Fondazione Poliambulanza, Brescia, Italy
Moragues, J Sampere; Department of Radiology, University Hospital Germans Trias I Pujol, Badalona, Spain
Sandström, P; Department of Surgery, Biomedical and Clinical Sciences, Linköping University Hospital, Linköping, Sweden
Sarriá, L; Department of Radiology, University Hospital Miguel Servet, Saragossa, Spain
Schnitzbauer, A; Department of Surgery, University Hospital Frankfurt, Frankfurt, Germany
Serenari, M; Department of Surgery, General Surgery and Transplant Unit, IRCCS Azienda Ospedaliero- Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy
Serrablo, A; Department of Surgery, University Hospital Miguel Servet, Saragossa, Spain
Smits, M L J; Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands
Sparrelid, E; Department of Surgery, Karolinska University Hospital, Stockholm, Sweden
Spüntrup, E; Department of Radiology, Klinikum Saarbrücken gGmbH, Saarbrücken, Germany
Stavrou, G A; Department of Surgery, Klinikum Saarbrücken gGmbH, Saarbrücken, Germany
Sutcliffe, R P; Department of Surgery, Queen Elizabeth Hospital Birmingham NHS, Birmingham, UK
Tancredi, I; Department of Radiology, Hôpital Erasme, Brussels, Belgium
Tasse, J C; Department of Radiology, Rush University Medical Center, Chicago, USA
Udupa, V; Department of Surgery, Oxford University Hospital NHS, Oxford, UK
Valenti, D; Department of Radiology, McGill University Health Centre, Montréal, Canada
Fundora, Y; Department of Surgery, Hospital Clínic de Barcelona, Barcelona, Spain
Vogl, T J; Department of Radiology, University Hosptital Frankfurt, Frankfurt, Germany
Wang, X; Department of Surgery, Zhongshan Hospital, Fundan University, Shanghai, China
White, S A; Department of Surgery, Newcastle Upon Tyne Hospitals NHS, Newcastle upon Tyne, UK
Wohlgemuth, W A; Department of Radiology, University Hospital Halle (Saale), Halle, Germany
Yu, D; Department of Radiology, Royal Free Hospital NHS, London, UK
Zijlstra, I A J; Department of Radiology, Amsterdam University Medical Centers Location VU, Amsterdam, The Netherlands
Binkert, C A; Department of Radiology, Cantonal Hospital Winterthur, Winterthur, Switzerland
Bemelmans, M H A; Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands ; Department of General, Visceral and Transplant Surgery, University Hospital Aachen, Aachen, Germany
van der Leij, C; Deparment of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
Schadde, E; Department of General and Visceral Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland ; Department of Surgery, Rush University Medical Center Chicago, Chicago, USA
van Dam, R M; 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 ; Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands. r.van.dam@mumc.nl ; Department of General, Visceral and Transplant Surgery, University Hospital Aachen, Aachen, Germany. r.van.dam@mumc.nl
Benoist S, Brouquet A, Penna C, et al. Complete response of colorectal liver metastases after chemotherapy: does it mean cure? J Clin Oncol. 2006;24:3939–45. DOI: 10.1200/JCO.2006.05.8727
Kishi Y, Abdalla EK, Chun YS, et al. Three hundred and one consecutive extended right hepatectomies: evaluation of outcome based on systematic liver volumetry. Ann Surg. 2009;250:540–8. DOI: 10.1097/SLA.0b013e3181b674df
van Gulik TM, van den Esschert JW, de Graaf W, et al. Controversies in the use of portal vein embolization. Dig Surg. 2008;25:436–44. DOI: 10.1159/000184735
van Lienden KP, van den Esschert JW, de Graaf W, et al. Portal vein embolization before liver resection: a systematic review. Cardiovasc Intervent Radiol. 2013;36:25–34. DOI: 10.1007/s00270-012-0440-y
Shindoh J, Tzeng CW, Aloia TA, et al. Safety and efficacy of portal vein embolization before planned major or extended hepatectomy: an institutional experience of 358 patients. J Gastrointest Surg. 2014;18:45–51. DOI: 10.1007/s11605-013-2369-0
Kianmanesh R, Farges O, Abdalla EK, Sauvanet A, Ruszniewski P, Belghiti J. Right portal vein ligation: a new planned two-step all-surgical approach for complete resection of primary gastrointestinal tumors with multiple bilateral liver metastases. J Am Coll Surg. 2003;197:164–70. DOI: 10.1016/S1072-7515(03)00334-X
Jaeck D, Oussoultzoglou E, Rosso E, Greget M, Weber JC, Bachellier P. A two-stage hepatectomy procedure combined with portal vein embolization to achieve curative resection for initially unresectable multiple and bilobar colorectal liver metastases. Ann Surg 2004;240:1037–49; discussion 49–51.
Wicherts DA, Miller R, de Haas RJ, et al. Long-term results of two-stage hepatectomy for irresectable colorectal cancer liver metastases. Ann Surg. 2008;248:994–1005. DOI: 10.1097/SLA.0b013e3181907fd9
Brouquet A, Abdalla EK, Kopetz S, et al. High survival rate after two-stage resection of advanced colorectal liver metastases: response-based selection and complete resection define outcome. J Clin Oncol. 2011;29:1083–90. DOI: 10.1200/JCO.2010.32.6132
Tsai S, Marques HP, de Jong MC, et al. Two-stage strategy for patients with extensive bilateral colorectal liver metastases. HPB (Oxford). 2010;12:262–9. DOI: 10.1111/j.1477-2574.2010.00161.x
Schadde E, Schnitzbauer AA, Tschuor C, Raptis DA, Bechstein WO, Clavien PA. Systematic review and meta-analysis of feasibility, safety, and efficacy of a novel procedure: associating liver partition and portal vein ligation for staged hepatectomy. Ann Surg Oncol. 2015;22:3109–20. DOI: 10.1245/s10434-014-4213-5
Schadde E, Hernandez-Alejandro R, Lang H, de Santibanes E, Clavien PA. ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors. Results of a multicentre analysis: reply. World J Surg. 2015;39:1850–1. DOI: 10.1007/s00268-015-2964-1
Sandstrom P, Rosok BI, Sparrelid E, et al. ALPPS improves resectability compared with conventional two-stage hepatectomy in patients with advanced colorectal liver metastasis: results from a scandinavian multicenter randomized controlled trial (LIGRO Trial). Ann Surg. 2018;267:833–40. DOI: 10.1097/SLA.0000000000002511
Schadde E, Ardiles V, Robles-Campos R, et al. Early survival and safety of ALPPS: first report of the International ALPPS Registry. Ann Surg 2014;260:829–36; discussion 36–8.
Schadde E, Tsatsaris C, Swiderska-Syn M, et al. Hypoxia of the growing liver accelerates regeneration. Surgery. 2017;161:666–79. DOI: 10.1016/j.surg.2016.05.018
Nagino M, Yamada T, Kamiya J, Uesaka K, Arai T, Nimura Y. Left hepatic trisegmentectomy with right hepatic vein resection after right hepatic vein embolization. Surgery. 2003;133:580–2. DOI: 10.1067/msy.2003.105
Hocquelet A, Sotiriadis C, Duran R, Guiu B, Yamaguchi T, Halkic N, Melloul E, Demartines N, Denys A. Preoperative portal vein embolization alone with biliary drainage compared to a combination of simultaneous portal vein, right hepatic vein embolization and biliary drainage in klatskin tumor. Cardiovasc Intervent Radiol. 2018;1885–1891
Schadde E, Guiu B, Deal R, et al. Simultaneous hepatic and portal vein ligation induces rapid liver hypertrophy: a study in pigs. Surgery. 2019;165:525–33. DOI: 10.1016/j.surg.2018.09.001
Guiu B, Chevallier P, Denys A, et al. Simultaneous trans-hepatic portal and hepatic vein embolization before major hepatectomy: the liver venous deprivation technique. Eur Radiol. 2016;26:4259–67. DOI: 10.1007/s00330-016-4291-9
Guiu B, Quenet F, Escal L, et al. Extended liver venous deprivation before major hepatectomy induces marked and very rapid increase in future liver remnant function. Eur Radiol. 2017;27:3343–52. DOI: 10.1007/s00330-017-4744-9
Heil J, Korenblik R, Heid F, et al. Preoperative portal vein or portal and hepatic vein embolization: DRAGON collaborative group analysis. Br J Surg. 2021;108:834–42. DOI: 10.1093/bjs/znaa149
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13. DOI: 10.1097/01.sla.0000133083.54934.ae
Rassam F, Olthof PB, Richardson H, van Gulik TM, Bennink RJ. Practical guidelines for the use of technetium-99m mebrofenin hepatobiliary scintigraphy in the quantitative assessment of liver function. Nucl Med Commun. 2019;40:297–307. DOI: 10.1097/MNM.0000000000000973
de Graaf W, van Lienden KP, Dinant S, et al. Assessment of future remnant liver function using hepatobiliary scintigraphy in patients undergoing major liver resection. J Gastrointest Surg. 2010;14:369–78. DOI: 10.1007/s11605-009-1085-2
Dinant S, de Graaf W, Verwer BJ, et al. Risk assessment of posthepatectomy liver failure using hepatobiliary scintigraphy and CT volumetry. J Nucl Med. 2007;48:685–92. DOI: 10.2967/jnumed.106.038430
