Lai Quirino, Vitale Alessandro, Halazun Karim, Iesari Samuele, Viveiros André, Bhangui Prashant, Mennini Gianluca, Wong Tiffany, Uemoto Shinji, Lin Chih-Che, Mittler Jens, Ikegami Toru, Zhe Yang, Zheng Shu-Sen, Soejima Yuji, Hoppe-Lotichius Maria, Chen Chao-Long, Kaido Toshimi, Lo Chung Mau, Rossi Massimo, Soin Arvinder Singh, Finkenstedt Armin, Emond Jean C, Cillo Umberto, Lerut Jan
Institut de Recherche Expérimentale et Clinique Université catholique de Louvain, 1200 Brussels, Belgium.
Hepatobiliary and Organ Transplantation Unit, Sapienza University, 00161 Rome, Italy.
Cancers (Basel). 2020 Feb 14;12(2):452. doi: 10.3390/cancers12020452.
Since the introduction of Milan Criteria, all scoring models describing the prognosis of hepatocellular cancer (HCC) after liver transplantation (LT) have been exclusively based on characteristics available at surgery, therefore neglecting the intention-to-treat principles. This study aimed at developing an intention-to-treat model through a competing-risk analysis. Using data available at first referral, an upper limit of tumor burden for downstaging was identified beyond which successful LT becomes an unrealistic goal. Twelve centers in Europe, United States, and Asia (Brussels, Sapienza Rome, Padua, Columbia University New York, Innsbruck, Medanta-The Medicity Dehli, Hong Kong, Kyoto, Kaohsiung Taiwan, Mainz, Fukuoka, Shulan Hospital Hangzhou) created a Derivation (n = 2318) and a Validation Set (n = 773) of HCC patients listed for LT between January2000-March 2017. In the Derivation Set, the competing-risk analysis identified two independent covariables predicting post-transplant HCC-related death: combined HCC number and diameter (SHR = 1.15; < 0.001) and alpha-fetoprotein (AFP) (SHR = 1.80; < 0.001). WE-DS Model showed good diagnostic performances at internal and external validation. The identified upper limit of tumor burden for downstaging was AFP ≤ 20 ng/mL and up-to-twelve as sum of HCC number and diameter; AFP = 21-200 and up-to-ten; AFP = 201-500 and up-to-seven; AFP = 501-1000 and up-to-five. The WE-DS Model proposed here, based on morphologic and biologic data obtained at first referral in a large international cohort of HCC patients listed for LT, allowed identifying an upper limit of tumor burden for downstaging beyond which successful LT, following downstaging, results in a futile transplantation.
自米兰标准推出以来，所有描述肝移植（LT）后肝细胞癌（HCC）预后的评分模型均完全基于手术时可得的特征，因此忽略了意向性治疗原则。本研究旨在通过竞争风险分析建立一个意向性治疗模型。利用首次转诊时可得的数据，确定了降期的肿瘤负荷上限，超过该上限成功进行肝移植将成为不切实际的目标。欧洲、美国和亚洲的12个中心（布鲁塞尔、罗马第一大学、帕多瓦、纽约哥伦比亚大学、因斯布鲁克、印度德里梅丹塔医院、香港、京都、中国台湾高雄、美因茨、福冈、杭州树兰医院）创建了一个2000年1月至2017年3月期间等待肝移植的HCC患者的推导集（n = 2318）和验证集（n = 773）。在推导集中，竞争风险分析确定了两个预测移植后HCC相关死亡的独立协变量：HCC数量与直径之和（SHR = 1.15；P < 0.001）和甲胎蛋白（AFP）（SHR = 1.80；P < 0.001）。WE-DS模型在内部和外部验证中均显示出良好的诊断性能。确定的降期肿瘤负荷上限为：AFP≤20 ng/mL且HCC数量与直径之和最多为12个；AFP = 21 - 200且最多为10个；AFP = 201 - 500且最多为7个；AFP = 501 - 1000且最多为5个。这里提出的WE-DS模型基于在一个大型国际队列中首次转诊时获得的形态学和生物学数据，该队列中的HCC患者等待肝移植，它能够确定降期的肿瘤负荷上限，超过该上限，降期后成功进行肝移植将导致无效移植。
