DRAGON Investigates Double Venous Embolization

Results from the DRAGON 1 trial were discussed on Tuesday, June 7, by Bernhard Gebauer, MD, an interventional radiologist at the Charité University Hospital in Berlin, Germany.

Dr. Gebauer’s talk covered the growing number of papers looking at the best techniques to improve the functional reserve of the future liver remnant (FLR) ahead of hepatectomy. “Technically, large-volume hepatic resections are possible today, but remaining liver after resection could not large enough to fulfill the function of the liver,” he said. Typically, hypertrophy may be induced by portal vein embolization (PVE), the standard treatment, which takes 3 to 6 weeks or longer for growth. “In these cases, PVE of the resected liver volume introduces an increase of the FLR to fulfill the function of the liver afterwards,” he said.

The new technique investigated in the DRAGON 1 trial takes that one step further. It combines PVE with hepatic vein embolisation (HVE). “On the one hand, this increases the growth of the FLR, and on the other it speeds up the increase, so that we have a shorter interval between PVE and resection,” Dr. Gebauer explained.

DRAGON 1 is a multicenter retrospective trial conducted predominantly in the Netherlands. The first results showed that 160 patients received PVE and 39 PVE/HVE. “They could nicely show that the increase of the FLR was faster and stronger in PVE/HVE patients,” noted Dr. Gebauer. In addition, The PVE/HVE group had better hypertrophy than the PVE group (59% versus 48% respectively) and resectability (90% versus 68%). The rate of hypertrophy—defined as the percentage hypertrophy increase per week—was 21% for those receiving PVE/HVE, and 13% for PVE alone. Additionally, the proportion of patients that had liver failure after the major hepatic resection showed the rate could be reduced from 24.8% (PVE) to 11% (PVE/HVE). “That’s significant, and a major result of the study because that is the clinical goal you're looking for,” he said.

The results of DRAGON 1, therefore, underline the importance of PVE/HVE said Dr. Gebauer. However, there is a need for much further investigation, especially prospective studies, to answer several persistent research questions. “What is the best technique for the embolization of the hepatic vein? Is it plug only, or is it plug and glue?” he said. A second trial, DRAGON II, might just answer this question.

Another question is which of the 3 hepatic veins—right, middle, left or a combination of two—to target during hepatic embolization. In the DRAGON 1 trial, it was open to the investigators and not defined, explained Dr. Gebauer.

Interestingly, a new trial, HYPER-LIV01 is currently recruiting that will not only test the glue and plug technique; it is a prospective trial and is investigating the importance of liver venous deprivation (LVD) – a combination therapy that involves simultaneous PVE and, importantly, right HVE. “It's a more aggressive embolization technique than that seen in the DRAGON trial,” said Dr. Gebauer.

Dr. Gebauer’s own study was inconclusive. “Interestingly, we couldn't show superiority of combination therapy versus PVE,” he said. “And we had an aggressive approach.”

His group studied both plug and glue, and completed a matched-pair analysis of patients with the same tumour disease, antitumour entity and liver volume in order to compare LVD and PVE. “We saw an increase in combination therapy, but it was not significant,” he added.

The problem is that studies comparing the combination therapy versus the PVE only are still rather small. “At the moment the databases are not large enough to really give a clue as to which technique is better,” noted Dr. Gebauer.

Looking at the papers published on different techniques, he added that the hypertrophy rate of the combination therapy with LVD was substantially increased when compared with PVE in some studies. In others, it remained broadly the same. “At the moment, we really can't tell for certain which procedures are better, but I'm sure that, because so many studies are investigating this, very soon we will have an answer,” he said.

Dr. Gebauer is optimistic that techniques will overcome current limitations. “It's a rich field. In 10 years, we will know much more, and will probably be much more aggressive in preparing patients for surgery.” Until then, he advises pragmatic approaches. “We can see a relatively good FLR with PVE alone,” he said. “But in patients where you need a very rapid increase of the FLR, or in patients where FLR is very borderline, you should think about HVE also.”