Anthony W H Chan1, Jianhong Zhong2, Sarah Berhane3, Hidenori Toyoda4, Alessandro Cucchetti5, KeQing Shi6, Toshifumi Tada4, Charing C N Chong1, Bang-De Xiang2, Le-Qun Li2, Paul B S Lai1, Vincenzo Mazzaferro7, Marta García-Fiñana8, Masatoshi Kudo9, Takashi Kumada4, Sasan Roayaie10, Philip J Johnson11. 1. State Key Laboratory in Oncology in South China, Sir Y. K. Pao Centre for Cancer, Department of Anatomical & Cellular Pathology, and Department of Surgery, The Chinese University of Hong Kong, Hong Kong. 2. Department of Hepatobiliary Surgery, Affiliated Tumour Hospital of Guangxi Medical University, Nanning, China. 3. Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. 4. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki, Gifu 503-8052, Japan. 5. Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy. 6. Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 7. University of Milan and Gastrointestinal Surgery and Liver Transplantation Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy. 8. Department of Biostatistics, University of Liverpool, Liverpool, UK. 9. Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan. 10. Liver Cancer Program, White Plains Hospital - Montefiore Health System, White Plains, NY, United States. 11. Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. Electronic address: Philip.Johnson@liverpool.ac.uk.
Abstract
BACKGROUND & AIMS: Resection is the most widely used potentially curative treatment for patients with early hepatocellular carcinoma (HCC). However, recurrence within 2 years occurs in 30-50% of patients, being the major cause of mortality. Herein, we describe 2 models, both based on widely available clinical data, which permit risk of early recurrence to be assessed before and after resection. METHODS: A total of 3,903 patients undergoing surgical resection with curative intent were recruited from 6 different centres. We built 2 models for early recurrence, 1 using preoperative and 1 using pre and post-operative data, which were internally validated in the Hong Kong cohort. The models were then externally validated in European, Chinese and US cohorts. We developed 2 online calculators to permit easy clinical application. RESULTS: Multivariable analysis identified male gender, large tumour size, multinodular tumour, high albumin-bilirubin (ALBI) grade and high serum alpha-fetoprotein as the key parameters related to early recurrence. Using these variables, a preoperative model (ERASL-pre) gave 3 risk strata for recurrence-free survival (RFS) in the entire cohort - low risk: 2-year RFS 64.8%, intermediate risk: 2-year RFS 42.5% and high risk: 2-year RFS 20.7%. Median survival in each stratum was similar between centres and the discrimination between the 3 strata was enhanced in the post-operative model (ERASL-post) which included 'microvascular invasion'. CONCLUSIONS: Statistical models that can predict the risk of early HCC recurrence after resection have been developed, extensively validated and shown to be applicable in the international setting. Such models will be valuable in guiding surveillance follow-up and in the design of post-resection adjuvant therapy trials. LAY SUMMARY: The most effective treatment of hepatocellular carcinoma is surgical removal of the tumour but there is often recurrence. In this large international study, we develop a statistical method that allows clinicians to estimate the risk of recurrence in an individual patient. This facility enhances communication with the patient about the likely success of the treatment and will help in designing clinical trials that aim to find drugs that decrease the risk of recurrence.
BACKGROUND & AIMS: Resection is the most widely used potentially curative treatment for patients with early hepatocellular carcinoma (HCC). However, recurrence within 2 years occurs in 30-50% of patients, being the major cause of mortality. Herein, we describe 2 models, both based on widely available clinical data, which permit risk of early recurrence to be assessed before and after resection. METHODS: A total of 3,903 patients undergoing surgical resection with curative intent were recruited from 6 different centres. We built 2 models for early recurrence, 1 using preoperative and 1 using pre and post-operative data, which were internally validated in the Hong Kong cohort. The models were then externally validated in European, Chinese and US cohorts. We developed 2 online calculators to permit easy clinical application. RESULTS: Multivariable analysis identified male gender, large tumour size, multinodular tumour, high albumin-bilirubin (ALBI) grade and high serum alpha-fetoprotein as the key parameters related to early recurrence. Using these variables, a preoperative model (ERASL-pre) gave 3 risk strata for recurrence-free survival (RFS) in the entire cohort - low risk: 2-year RFS 64.8%, intermediate risk: 2-year RFS 42.5% and high risk: 2-year RFS 20.7%. Median survival in each stratum was similar between centres and the discrimination between the 3 strata was enhanced in the post-operative model (ERASL-post) which included 'microvascular invasion'. CONCLUSIONS: Statistical models that can predict the risk of early HCC recurrence after resection have been developed, extensively validated and shown to be applicable in the international setting. Such models will be valuable in guiding surveillance follow-up and in the design of post-resection adjuvant therapy trials. LAY SUMMARY: The most effective treatment of hepatocellular carcinoma is surgical removal of the tumour but there is often recurrence. In this large international study, we develop a statistical method that allows clinicians to estimate the risk of recurrence in an individual patient. This facility enhances communication with the patient about the likely success of the treatment and will help in designing clinical trials that aim to find drugs that decrease the risk of recurrence.
Authors: Diamantis I Tsilimigras; Kota Sahara; Lu Wu; Dimitrios Moris; Fabio Bagante; Alfredo Guglielmi; Luca Aldrighetti; Matthew Weiss; Todd W Bauer; Sorin Alexandrescu; George A Poultsides; Shishir K Maithel; Hugo P Marques; Guillaume Martel; Carlo Pulitano; Feng Shen; Olivier Soubrane; B Groot Koerkamp; Amika Moro; Kazunari Sasaki; Federico Aucejo; Xu-Feng Zhang; Ryusei Matsuyama; Itaru Endo; Timothy M Pawlik Journal: JAMA Surg Date: 2020-09-01 Impact factor: 14.766
Authors: Tiancheng He; Joy Nolte Fong; Linda W Moore; Chika F Ezeana; David Victor; Mukul Divatia; Matthew Vasquez; R Mark Ghobrial; Stephen T C Wong Journal: Comput Med Imaging Graph Date: 2021-03-11 Impact factor: 4.790