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A Worldwide Score for Hepatocellular Cancer and Liver Transplantation (TRAIN-SCORE)

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ClinicalTrials.gov Identifier: NCT03595345
Recruitment Status : Completed
First Posted : July 23, 2018
Last Update Posted : October 29, 2018
Sponsor:
Information provided by (Responsible Party):
Quirino Lai, European Hepatocellular Cancer Liver Transplant Group

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.

Condition or disease Intervention/treatment
Liver Cancer Dropout, Patient Recurrence Procedure: Liver transplantation

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.


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Study Type : Observational
Actual Enrollment : 3100 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: A Worldwide Usable Scoring System for Patients With Hepatocellular Cancer Waiting for Liver Transplantation
Actual Study Start Date : December 15, 2016
Actual Primary Completion Date : October 15, 2018
Actual Study Completion Date : October 15, 2018

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Training set
2200 HCC cases from East and West centres enlisted for LT and then delisted or transplanted
Procedure: Liver transplantation
Liver transplantation

West validation set
630 HCC cases from a Western centre enlisted for LT and then delisted or transplanted
Procedure: Liver transplantation
Liver transplantation

East validation set
300 HCC cases from a Eastern centre enlisted for LT and then delisted or transplanted
Procedure: Liver transplantation
Liver transplantation




Primary Outcome Measures :
  1. Tumour-specific death [ Time Frame: 5 years after transplant ]
    Death for recurrence or other HCC-related causes


Secondary Outcome Measures :
  1. Drop-out [ Time Frame: 1 year after waiting list inscription ]
    Drop-out for death or HCC progression



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The participating centers for the creation of the training set cohort were: Brussels (Belgium; n=355), New York Columbia University/Weill Cornell Medical Center (USA; n=353), Innsbruck (Austria; n=330), New Delhi (India; n=270), Rome Sapienza University (Italy; n=265), Kyoto (Japan; n=230), Taiwan (Republic of China; n=200), Mainz (Germany; n=176), Kyushu (Japan; n=161), and Hangzhou Shulan Health Hospital/First Affiliated Hospital (Popular Republic of China; n=94).

For the testing/external cohort, two additional centres participated to the study, namely the Western center from Padua (Italy; n=630) and the Easter center from Hong Kong (n=330) applying the same inclusion/exclusion criteria as for the training cohort.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03595345


Locations
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Belgium
UCL
Brussels, Belgium
Sponsors and Collaborators
European Hepatocellular Cancer Liver Transplant Group

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Responsible Party: Quirino Lai, Principal investigator and Data manager of the EurHeCaLT Study Group, European Hepatocellular Cancer Liver Transplant Group
ClinicalTrials.gov Identifier: NCT03595345     History of Changes
Other Study ID Numbers: #0001
First Posted: July 23, 2018    Key Record Dates
Last Update Posted: October 29, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Quirino Lai, European Hepatocellular Cancer Liver Transplant Group:
delisting
tumor-specific death
Milan Criteria

Additional relevant MeSH terms:
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Recurrence
Liver Neoplasms
Carcinoma, Hepatocellular
Disease Attributes
Pathologic Processes
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type