Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis

被引：1666

作者：

Mazzaferro, Vincenzo ^{[1
]}

Llovet, Josep M. ^{[2
,8
,49
]}

Miceli, Rosalbo ^{[1
]}

Bhoori, Sherrie ^{[1
]}

Schiavo, Marcello ^{[1
]}

Mariani, Luigi ^{[1
]}

Camerini, Tiziona ^{[1
]}

Roayaie, Sasan ^{[2
,54
]}

Schwartz, Myron E. ^{[2
]}

Grazi, Gian Luca ^{[3
,35
]}

Adam, Rene ^{[4
,28
]}

Neuhaus, Peter ^{[5
,6
,30
]}

Salizzoni, Mauro ^{[7
,44
]}

Bruix, Jordi ^{[8
,49
]}

Forner, Alejandro ^{[8
,49
]}

De Carlis, Luciano ^{[9
,37
]}

Cillo, Umberto ^{[10
,41
]}

Burroughs, Andrew K. ^{[11
,52
]}

Troisi, Roberto ^{[12
,25
]}

Rossi, Massimo ^{[13
,43
]}

Gerunda, Giorgio E. ^{[14
]}

Lerut, Jan ^{[15
,23
]}

Belghiti, Jacques ^{[16
,29
]}

Boin, Ilka ^{[17
,26
]}

Gugenheim, Jean ^{[18
,27
]}

Rochling, Fedja ^{[19
,56
]}

Van Hoek, Bart ^{[20
,46
]}

Majno, Pietro ^{[21
]}

Graziadei, Ivo ^{[22
]}

Vogel, Wolfgang ^{[22
]}

Lerut, Jan ^{[15
,23
]}

Lucidi, Valerio ^{[24
]}

de Hemptinne, Bernard ^{[25
]}

Troisi, Roberto ^{[12
,25
]}

Boin, Ilka ^{[17
,26
]}

Leopardi, Luiz ^{[26
]}

Cotsoglou, Christian ^{[27
]}

Gugenheim, Jean ^{[18
,27
]}

Iannelli, Antonio ^{[27
]}

Staccini, Aline ^{[27
]}

Adam, Rene ^{[4
,28
]}

Belghiti, Jacques ^{[16
,29
]}

Neuhaus, Peter ^{[5
,6
,30
]}

Koenigsrainer, Alfred ^{[31
]}

Steurer, Wolfgang ^{[31
]}

Cautero, Nicola ^{[32
]}

Risaliti, Andrea ^{[32
]}

Lupo, Luigi ^{[33
]}

Colledan, Michele ^{[34
]}

De Giorgio, Massimo ^{[34
]}

机构：

[1] Natl Canc Inst, Via Venezian 1, I-20133 Milan, Italy

[2] Mt Sinai Sch Med, New York, NY USA

[3] St Orsola Marcello Malpighi Hosp, Bologna, Italy

[4] Hop Paul Brousse, Paris, France

[5] Charite, D-13353 Berlin, Germany

[6] Sch Med, Berlin, Germany

[7] Molinette Mauriziano Hosp, Turin, Italy

[8] Hosp Clin Barcelona, Live Canc Grp, Barcelona, Spain

[9] Osped Niguarda Ca Granda, Milan, Italy

[10] Padova Univ Hosp, Sch Med, Padua, Italy

[11] Royal Free Hosp, London NW3 2QG, England

[12] Ghent Univ Hosp, Sch Med, B-9000 Ghent, Belgium

[13] Univ Roma La Sapienza, Umberto I Hosp, Rome, Italy

[14] Univ Hosp Modena, Modena, Italy

[15] St Luc Univ Hosp, Brussels, Belgium

[16] Hop Beaujon, Paris, France

[17] Univ Hosp Campinas, Sao Paulo, Brazil

[18] Hop Archet 2, Nice, France

[19] Nebraska Med Ctr, Omaha, NE USA

[20] Leiden Univ, Med Ctr, Leiden, Netherlands

[21] Hop Cantonal Univ Geneva, Geneva, Switzerland

[22] Univ Hosp Innsbruck, Innsbruck, Austria

[23] Univ Hosp St Luc, Brussels, Belgium

[24] Erasme Univ Hosp, Brussels, Belgium

[25] Univ Hosp & Med Sch Ghent, Ghent, Belgium

[26] Univ Hosp Campinas, Sao Paulo, Brazil

[27] Hop Archet 2, Nice, France

[28] Villejuif Paul Brousse Hosp, Paris, France

[29] Beaujon Hosp, Paris, France

[30] Univ Hosp Berlin, Berlin, Germany

[31] Univ Hosp Tuebingen, Tubingen, Germany

[32] Ospedali Riuniti, Ancona, Italy

[33] Univ Bari, AO Policlin Hosp, Bari, Italy

[34] Ospedali Riuniti Hosp, Bergamo, Italy

[35] SantOrsola Malpighi Hosp, Bologna, Italy

[36] Ist Nazl Tumori, Milan, Italy

[37] Ospedale Niguarda Hosp, Milan, Italy

[38] Ospedale Maggiore Policlin Hospital, Milan, Italy

[39] Univ Hosp Modena, Modena, Italy

[40] Cardarelli Hosp, Naples, Italy

[41] Univ Hosp Padova, Padua, Italy

[42] Tor Vergata Univ Hosp, Rome, Italy

[43] Univ Roma La Sapienza, Policlin Umberto 1, Rome, Italy

[44] Molinette Mauriziano Hosp, Turin, Italy

[45] Policlin Hosp, Udine, Italy

[46] Liver Transplantat Unit, Leiden, Netherlands

[47] Med Univ Warsaw, Warsaw, Poland

[48] Santo Antonio Hosp, Porto, Portugal

[49] BCLC Grp Hosp Clin, Barcelona, Spain

[50] Karolinska Univ Hosp, Stockholm, Sweden

来源：

LANCET ONCOLOGY | 2009年 / 10卷 / 01期

关键词：

REGRESSION; RESECTION; MODELS; CLASSIFICATION; MANAGEMENT; CIRRHOSIS; ACCURACY; DISEASE; SIZE;

D O I：

10.1016/S1470-2045(08)70284-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Patients undergoing liver transplantation for hepatocellular carcinoma within the Milan criteria (single turnour <= 5 cm. in size or <= 3 tumours each <= 3 cm in size, and no macrovascular invasion) have an excellent outcome. However, survival for patients with cancers that exceed these criteria remains unpredictable and access to transplantation is a balance of maximising patients' chances of cure and organ availability. The aim of this study was to explore the survival of patients with tumours that exceed the Milan criteria, to assess whether the criteria could be less restrictive, enabling more patients to qualify as transplant candidates, and to derive a prognostic model based on objective tumour characteristics, to see whether the Milan criteria could be expanded. Methods Data on patients who underwent transplantation for hepatocellular carcinoma despite exceeding Milan criteria at different centres were recorded via a web-based survey completed by specialists from each Centre. The survival of these patients was correlated retrospectively with the size of the largest turnour nodule, number of nodules, and presence or absence of microvascular invasion detected at pathology. Contoured multivariable regression Cox models produced survival estimates by means of different combinations of the covariates. The primary aim of this study was to derive a prognostic model of overall survival based on tumour characteristics, according to the main parameters used in the Tumour Node Metastasis classification. The secondary aim was the identification of a subgroup of patients with hepatocellular carcinoma exceeding the Milan criteria, who achieved a 5-year overall survival of at least 70%-ie, similar to the outcome expected for patients who meet the Milan criteria. Findings Over a 10-month period, between June 25, 2006, and April 3, 2007, data for 1556 patients who underwent transplantation for hepatocellular carcinoma were entered on the database by 36 centres. 1112 patients had hepatocellular carcinoma exceeding Milan criteria and 444 patients had hepatocellular carcinoma shown not to exceed Milan criteria at post-transplant pathology review. In the group of patients with hepatocellular carcinomas exceeding the criteria, the median size of the largest nodule was 40 mm (range 4-200) and the median number of nodules was four (1-20). 454 of 1112 patients (41%) had microvascular invasion and, for those transplanted outside the Milan criteria, 5-year overall survival was 53.6% (95% Cl 50.1-57.0), compared with 73.3% (68.2-77.7) for those that met the criteria. Hazard ratios (HR) associated with increasing values of size and number were 1.34 (.-25-1.44) and 1.51 (1.21-1.88), respectively. The effect was linear for size, whereas for number of tumours, the effect tended to plateau above three tumours. The effect of turnour size and number on survival was mediated by recurrence (b=0.08, SE=0.12, p=0.476). The presence of microvascular invasion doubled HRs in all scenarios. The 283 patients without microvascular invasion, but who fell within the Up-to-seven criteria (hepatocellular carcinomas with seven as the sum of the size of the largest tumour [in cm] and the number of tumours) achieved a 5-year overall survival of 71.2% (64.3-77.0). Interpretation More patients with hepatocellular carcinoma could be candidates for transplantation if the current dual (yes/no) approach to candidacy, based on the strict Milan criteria, were replaced with a more precise estimation of survival contouring individual turnour characteristics and use of the up-to-seven criteria.

引用

页码：35 / 43

页数：9

共 41 条

[41] Genotype-phenotype correlation in hepatocellular adenoma: New classification and relationship with HCC [J].

Zucman-Rossi, J ;

Jeannot, E ;

Van Nhieu, JT ;

Scoazec, JY ;

Guettier, C ;

Rebouissou, S ;

Bacq, Y ;

Leteurtre, E ;

Paradis, V ;

Michalak, S ;

Wendum, D ;

Chiche, L ;

Fabre, M ;

Mellottee, L ;

Laurent, C ;

Partensky, C ;

Castaing, D ;

Zafrani, ES ;

Laurent-Puig, P ;

Balabaud, C ;

Bioulac-Sage, P .

HEPATOLOGY, 2006, 43 (03) :515-524

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