How liver venous deprivation is “pushing limits”

Boris Guiu

Both the Andreas Gruentzig Lecture at this year’s Cardiovascular and Interventional Radiological Society of Europe meeting (CIRSE; 10–14 September, Barcelona, Spain) and a presentation of interim data at the ‘New Frontiers’ FIRST@CIRSE session informed delegates of the innovative future liver remnant (FLR) hypertrophy technique, liver venous deprivation (LVD).

As Remon Korenblik (Maastricht University Medical Center, Maastricht, The Netherlands) and Boris Guiu (Hôpital Saint-Eloi, Montpellier, France) explained in the context of the data presentation and lecture respectively, LVD involves combining hepatic and portal vein embolization (HVE/PVE) to cause FLR growth. Guiu referred to the ongoing DRAGON 1 trial on which Korenblik presented as an example of “pushing the limits” and a key takeaway message from these presentations was that there is a “place [for] LVD in the future”, and that further studies will “define” exactly what that is.

Portal and hepatic vein embolization in metastatic colorectal cancer treatment

DRAGON 1, as Korenblik conveyed to attendees, is a multinational, multicentre, prospective and single-arm trial, of which the purpose is to “assess training, implementation, safety and feasibility of combined PVE and HVE to accelerate FLR hypertrophy in patients with borderline resectable colorectal cancer liver metastases [CRLM]”. Korenblik alluded to the importance of the trial—“the cornerstone [of CRLM] treatment is resection” but in cases of “insufficient FLR” this is not an option, hence, investigating whether the FLR can be increased in size, so that resection is possible.
The primary endpoint for the DRAGON 1 trial is “a composite of the safety of combined PVE and HVE, 90-day mortality, and one-year accrual monitoring of each participating centre.” Secondary endpoints feature feasibility of resection, FLR hypertrophy, overall survival and disease-free survival.

The interim results from the trial so far, which Korenblik shared with delegates, seem to demonstrate that combined HVE and PVE “induces fast and extensive FLR hypertrophy and leads to high rates of resectability”. The definitive analyses after the DRAGON 1 trial completion are needed to confirm these assumptions. “We also found this in a recent pooled analysis, which will be published shortly,” Korenblik reported, “in which we saw statistically significant higher resectability rates after PVE/HVE compared to PVE alone.”
Next for the DRAGON Initiative, which is behind a series of trials to determine the safety and efficacy of combined PVE and HVE, is the beginning of recruitment for DRAGON 2, Korenblik asserted. This study “will investigate the efficacy and survival of patients after PVE alone compared to PVE and HVE combined in a multinational, multicentre randomised controlled trial”.

Guiu first acknowledged in his lecture, as did Korenblik, the relative clinical success of PVE alone and how it has been considered “really efficient” for decades—but that appetite to improve this further has led to the development of techniques capable of increasing FLR hypertrophy, and thus resection rates. From 2016, when Guiu and colleagues carried out the first study of combined PVE and HVE, yielding “attractive initial results”, cohort studies have confirmed the technique’s outperformance of any other preparation technique, including ALPPS (associating liver partition and portal vein ligation for staged hepatectomy)—historically regarded as “the most efficient technique in terms of volumetric gain [in the FLR]”—or even hepatectomy, in terms of functional gain. Functional increase, Guiu duly noted, is, in addition to volumetric gain, “very important” in the context of liver preparation for hepatectomy.

“There is probably a place for [liver venous deprivation] but we need definitely more data”

“Now we are five or six years on [from the first study], we have now several [more…] from different teams,” Guiu elaborated for attendees. “All but one is showing that LVD outperforms PVE in terms of volumetric gain”, and the presenter went on to acknowledge that there is evidence that LVD also leads to fewer post-resection complications.
With “enthusiasm sparked” by the aforementioned findings, the next step, Guiu averred, is to go about obtaining multicentre, prospective study data. An example the presenter gave is the French HYPERLIV-01 randomised controlled trial comparing PVE with LVD, using glue in the hepatic veins in addition to proximal plugs. As Guiu noted, the trial “has already completed more than two-thirds of its accrual in 11 centres,” and the DRAGON Initiative will also provide key evidence of the value of performing LVD, through its series of trials, as relayed by Korenblik. “There is probably a place for LVD but we need definitely more data […] the objective is to define more precisely the place of this technique,” was Guiu’s conclusion regarding LVD versus PVE for FLR hypertrophy.

The presenter’s final remarks were on innovation within clinical practice more broadly and how to achieve “wide acceptance” of a new technique, such as LVD within the IR community. “I firmly believe that our role should not be limited to [research and innovation]”, Guiu stated, emphasising the “need to disseminate knowledge as part of our mission—new ideas would certainly be pointless if they were to remain confidential.” The goal, the presenter concluded, is to “ignite interest” in the latest innovations, as this is ultimately for patients’ benefit.


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