Fast track — ArticlesPredicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis
Introduction
Early-stage hepatocellular carcinoma is recognised as an excellent indication for liver transplantation. The size of the tumour, the number of tumours, and the presence of vascular invasion have been incorporated into the so-called Milan criteria, which predicts a low incidence of recurrence (about 10%) for transplant patients with a single tumour of 5 cm or less in size or with many tumours (up to a maximum of three, each 3 cm or less in size), and no macroscopic vascular invasion. Since the first prospective series done more than 10 years ago,1, 2 these criteria have been validated in several centres around the world, adopted as a prioritisation tool in the United Network of Organ Sharing (UNOS), and incorporated in the Tumour Node Metastasis (TNM) and Barcelona Clinic Liver Cancer (BCLC) staging systems for hepatocellular carcinoma.3, 4, 5, 6
In recent years, several studies have reported a good outcome for some patients transplanted outside these conventional criteria and the dichotomous yes/no nature of these criteria has been challenged for being too strict, because they exclude specific subgroups with meaningful, albeit lower, chances to benefit from transplantation. Furthermore, some patients might be excluded from transplantation as a result of the improvement in the accuracy of imaging techniques that enable the identification of very small lesions (<1 cm), which were undetectable a decade ago. Most of the studies on patients exceeding Milan criteria, however, are retrospective, with only a small number of patients, disease of variable severity, and short follow-up.7, 8, 9, 10, 11, 12 Overall, no precise information can be extracted from these studies, other than the further the distance from conventional limits, the higher the price in terms of malignant recurrences.7
The aim of the current study was to explore the area outside the conventional criteria for liver transplantation in hepatocellular carcinoma, by use of morphological (size of the largest tumour and number of tumours) and histological (microscopic vascular invasion) parameters in a large cohort of patients with adequate follow-up. The working postulation was that beyond the conventional eligibility criteria for transplantation for patients with hepatocellular carcinoma, a continuum in outcome probabilities could be identified linked to characteristics assessed in the TNM classification.5
Section snippets
Study background and data collection
The study design was presented during the International Liver Transplantation Society meeting held in Milan, Italy, in 2006 and a web-based survey of patients who received liver transplantation for hepatocellular carcinoma exceeding the Milan criteria was proposed. The website on which the survey can be completed (www.hcc-olt-metroticket.org) was built at the Clinical Trial Office of the National Cancer Institute of Milan, supported only by grants for investigator-initiated studies. The website
Results
During the 10-month recruitment period, between June 25, 2006, and April 3, 2007, 36 liver-transplantation centres entered data on the website, with an overall data collection of 1556 patients who underwent liver transplantation for hepatocellular carcinoma: 1274 patients (81·9%) from 31 centres in Europe, 269 patients (17·3%) from four centres in America, and 13 patients (0·8%) from one centre in Asia. The study population included 1112 patients (71·5%) with hepatocellular carcinoma exceeding
Discussion
This study, based on an unprecedented sample size of 1112 patients with hepatocellular carcinomas that fell outside the conventional transplantation criteria, aimed to establish a model that is able to predict survival probabilities on the basis of objective tumour parameters—ie, size of the tumour, number of tumours, and microscopic vascular invasion. The model presented here represents the first large-scale attempt to stratify patients with hepatocellular carcinoma in a continuum of outcome
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Investigators are listed at the end of the Article