The Intention-to-treat Effect of Bridge Therapies in the Setting of Milan-in Patients

Completed

• Conditions: Liver Cancer; Transplant; Failure, Liver
• Interventions: Procedure: Direct liver transplant; Procedure: Bridging followed by transplant

• Registration Number: NCT03723304
• Lead Sponsor: European Hepatocellular Cancer Liver Transplant Group

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.

Study Timeline

• Study Start: 2018-03-01
• Status Verified: 2018-10
• Primary Completion: 2018-10-15
• Study Completion: 2018-10-15
• Study First Submitted: 2018-10-25
• Study First Submitted QC: 2018-10-26
• Last Update Submitted: 2018-10-26
• Study First Posted: 2018-10-29
• Last Update Posted: 2018-10-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1083

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Direct liver transplant	Direct liver transplant	All the cases listed for liver transplantation and then transplanted/dropped-out without undergoing any neo-adjuvant loco-regional treatment
Bridging followed by transplant	Bridging followed by transplant	All the cases listed for liver transplantation and then transplanted/dropped-out after undergoing at least one neo-adjuvant loco-regional treatment

Primary Outcome Measures

Name	Time	Method
Tumour-specific liver transplant failure rate	up to 5 years from first referral	Any case of tumor-related drop-out during the waiting list period or post-transplant recurrence

Trial Locations

Locations (1)

UCL; 🇧🇪 Brussels, Belgium