The Intention-to-treat Effect of Bridge Therapies in the Setting of Milan-in Patients
Condition: Liver Cancer; Transplant; Failure, Liver
MeSH terms: Liver Neoplasms
Study type: Observational

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.
    

Intervention name(s): Bridging followed by transplant; Direct liver transplant
Intervention type(s): Procedure; Procedure
Intervention description(s): Trans-arterial chemoembolization or percutaneous alcohol injection or radio-frequency ablation during the waiting time followed by liver transplant; Direct liver transplant (no neoadjuvant approaches during the waiting time period)
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