Identification of an upper limit of tumor burden for downstaging in candidates with hepatocellular cancer waiting for liver transplantation: A west–east collaborative effort

Quirino Lai, Alessandro Vitale, Karim Halazun, Samuele Iesari, André Viveiros, Prashant Bhangui, Gianluca Mennini, Tiffany Wong, Shinji Uemoto, Chih Che Lin, Jens Mittler, Toru Ikegami, Yang Zhe, Shu Sen Zheng, Yuji Soejima, Maria Hoppe-Lotichius, Chao Long Chen, Toshimi Kaido, Chung Mau Lo, Massimo RossiArvinder Singh Soin, Armin Finkenstedt, Jean C. Emond, Umberto Cillo, Jan Lerut

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Abstract

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; p < 0.001) and alpha-fetoprotein (AFP) (SHR = 1.80; p < 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.

Original languageEnglish
Article number452
JournalCancers
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2020

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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