A Worldwide Score for Hepatocellular Cancer and Liver Transplantation

NCT ID: NCT03595345

Last Updated: 2018-10-29

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 3100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-12-15
• Study Completion Date: 2018-10-15

Brief Summary

The present study has been developed with multiple aims: 1) to refine available models for liver transplantation which would be able to cover the fate of HCC candidates from an ITT point of view; 2) to develop such an approach on cohorts coming from both Eastern and Western countries; 3) to maintain simplicity of use; 4) to provide individual prognostication taking into account different causes of death, through a competing-risk model; 5) to provide an external validation on cohorts coming from both Eastern and Western countries. All these aims converge at providing a comprehensive and useful assessment suitable for both candidates selection and allocation priority.

Detailed Description

For two decades, the Milan Criteria (MC) have represented the cornerstone in the selection of patients with hepatocellular cancer (HCC) as candidates for liver transplantation (LT). Since then, several Western and Eastern centres have tried to overcome MC stringency with the aim to expand the number of potentially transplantable patients without increasing the risk of post-LT tumour recurrence. Recently, variables correlated with HCC biology have been introduced to capture its aggressiveness and suitability for LT. Among the most commonly proposed, we can cite the alpha-fetoprotein (AFP) and the radiological response after neo-adjuvant loco-regional treatments (LRT). The effort to combine HCC morphology and biology is now emerging as the more promising approach for further refining the selection process of HCC candidates. The recently proposed prognostic indexes Metroticket 2.0, Time-Radiological-response-Alpha-fetoprotein-INflammation (TRAIN), Model Of Recurrence After Liver transplant (MORAL) and French AFP-model represent the most promising results of such planned endeavours.

With the intent to be clinically useful, a prognostic system must achieve not only the most common performance metrics, such as discrimination and calibration, but also an adequate coverage of the population in which it would be applied. It can be argued that a prognostic system based only on criteria available at the moment of LT could not satisfy such a pre-requisite when the entire population of HCC patients waiting in the list for LT is taken into account, considering an intention-to-treat (ITT) point of view. In this sense, only the TRAIN system developed an ITT analysis, whereas the remaining were all based on pre-transplant information. The second quality that a clinically useful prognostic system should have is its immediacy. Thus, it should be based on commonly available information, not requiring additional analyses or exams if not justified by a substantial improvement in accuracy. Last but not least, a prognostic system should also provide for an individual prediction in addition to risk-stratification, with the intent to offer personalized prognostication for each different patient. To date, only the Metroticket 2.0 fulfils these two last requisites. A final important quality of the Metroticket 2.0 is that it applied a competing-risk analysis able to clean up the HCC-related cause of death from other non-tumour-related causes.

On this background, we developed the present study with multiple aims: 1) to refine available models which would be able to cover the fate of HCC candidates from an ITT point of view; 2) to develop such an approach on cohorts coming from both Eastern and Western countries; 3) to maintain simplicity of use; 4) to provide individual prognostication taking into account different causes of death, through a competing-risk model; 5) to provide an external validation on cohorts coming from both Eastern and Western countries. All these aims converge at providing a comprehensive and useful assessment suitable for both candidates selection and allocation priority.

Conditions

Liver Cancer; Dropout, Patient; Recurrence

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Training set

2200 HCC cases from East and West centres enlisted for LT and then delisted or transplanted

Liver transplantation

Intervention Type: PROCEDURE

Liver transplantation

West validation set

630 HCC cases from a Western centre enlisted for LT and then delisted or transplanted

Liver transplantation

Intervention Type: PROCEDURE

Liver transplantation

East validation set

300 HCC cases from a Eastern centre enlisted for LT and then delisted or transplanted

Liver transplantation

Intervention Type: PROCEDURE

Liver transplantation

Interventions

Liver transplantation

Liver transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• All the adult ((≥18 years) patients enlisted for liver transplant with the radiological/histological diagnosis of hepatocellular cancer during the period 01/01/2000-31/03/2017

Exclusion Criteria

• Mixed hepatocellular-cholangiocellular
• Cholangiocellular cancer misdiagnosed as HCC
• Post-LT incidental HCC.
• Patients enlisted before 01/01/2000

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Hepatocellular Cancer Liver Transplant Group

OTHER

Sponsor Role: lead

Responsible Party

Quirino Lai

Principal investigator and Data manager of the EurHeCaLT Study Group

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

UCL

Brussels, , Belgium

Countries

Belgium

Other Identifiers

#0001

Identifier Type: -

Identifier Source: org_study_id