Clinical trial NCT03723304: The Intention-to-treat Effect of Bridge Therapies in the Setting of Milan-in Patients
Official title: The Intention-to-treat Effect of Bridging Therapies in the Setting of Milan-in Patients Waiting for Liver Transplantation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Liver Cancer
Transplant; Failure, Liver
Lead sponsor: European Hepatocellular Cancer Liver Transplant Group
Sponsor class: OTHER
First posted: 2018-10-29
Enrollment: 1083
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with radiological/post-bioptic diagnosis of hepatocellular cancer listed for liver transplantation receiving or not receiving any neo-adjuvant treatment before transplant/drop-out

Brief summary: In patients with hepatocellular cancer (HCC) meeting the Milan Criteria (MC), the usefulness of loco-regional therapies (LRT) in the context of liver transplantation (LT) is still debated. The inconsistent literature data are the result of initial selection biases among treated and untreated patients. In order to overcome these shortcomings, an inverse probability of treatment weighting (IPTW) analysis was done in a large patient cohort. After using a competing-risk analysis, the primary end-point of the study aims at identifying the risk factors of HCC-specific LT failure, defined as pre-LT tumour-related drop-out or post-LT recurrence.

Detailed description: Liver transplantation (LT) is the best curative treatment of hepatocellular cancer (HCC) developed in an underlying liver disease. LT is considered as an oncologic successful procedure when a long-term post-transplant tumour-free survival is obtained. Conversely, a failure is equal to pre-transplant drop-out, post-transplant tumour recurrence or death. Due to the allograft scarcity, a HCC patient waiting for a LT is most often treated using neo-adjuvant loco-regional therapies (LRT) in order to minimise the risk of drop-out. When the tumour burden meets the Milan Criteria (MC) at moment of diagnosis, such an approach is called "bridging towards LT".

Two recent international guidelines underlined the importance of the bridging strategy, due to its potential to reduce the risk of pre-LT drop-out and post-LT recurrence. This is especially valid in the case in which a partial/complete tumour response is achieved before LT. Unfortunately, the quality of the evidence obtained from the currently available literature is low due to the lack of randomized controlled trials (RCT). Actually, it is inconceivable to realize RCT in this setting because of logistical and, even more, ethical reasons. Consequently, the majority of reported studies just compare post-LT outcome of treated and untreated patients, failing thereby to analyse the clinical course from an intention-to-treat (ITT) point of view.

Even when looking at studies including the waiting list period, one should keep in mind that substantial differences may exist among initially bridged vs untreated HCC patients regarding tumour burden. In order to overcome these limits, a retrospective analysis of a large European population of MC-IN HCC patients listed for LT was done. After "balancing" this cohort with an inverse probability of treatment weighting (IPTW), we investigated the risk factors for tumour-specific LT failure, especially focusing at the role of LRT.

Eligibility criteria: Inclusion Criteria:

* adults (≥18-year old) listed for liver transplant with a morphologic and/or histologic confirmed hepatocellular cancer

Exclusion Criteria:

* Milan Criteria-out status at first referral
* transplantation or de-listing before January 1, 2001
* other means of loco-regional treatments such as partial hepatectomy, trans-arterial radio-embolization or external radiotherapy
* misdiagnosed mixed hepatocellular-cholangiocellular cancer or cholangiocellular cancer

Primary outcomes:
measure: Tumour-specific liver transplant failure rate
timeFrame: up to 5 years from first referral
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: UCL
Study officials:
affiliation: UCL Brussels
name: Quirino Lai, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lai Q, Vitale A, Iesari S, Finkenstedt A, Mennini G, Onali S, Hoppe-Lotichius M, Manzia TM, Nicolini D, Avolio AW, Mrzljak A, Kocman B, Agnes S, Vivarelli M, Tisone G, Otto G, Tsochatzis E, Rossi M, Viveiros A, Ciccarelli O, Cillo U, Lerut J; European Hepatocellular Cancer Liver Transplant Study Group. The Intention-to-Treat Effect of Bridging Treatments in the Setting of Milan Criteria-In Patients Waiting for Liver Transplantation. Liver Transpl. 2019 Jul;25(7):1023-1033. doi: 10.1002/lt.25492.