Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection
Author(s): ,
Philip J. Johnson
Affiliations:
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
Corresponding author. Address: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, 2nd floor Sherrington Building, Ashton Street, Liverpool L69 3GE, UK; Tel.: +44 0151 795 8410.
,
Sasan Roayaie
Affiliations:
Liver Cancer Program, White Plains Hospital – Montefiore Health System, White Plains, NY, United States
,
Takashi Kumada
Affiliations:
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki, Gifu 503-8052, Japan
,
Masatoshi Kudo
Affiliations:
Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Osaka, Japan
,
Marta García-Fiñana
Affiliations:
Department of Biostatistics, University of Liverpool, Liverpool, UK
,
Vincenzo Mazzaferro
Affiliations:
University of Milan and Gastrointestinal Surgery and Liver Transplantation Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
,
Paul B.S. Lai
Affiliations:
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
,
Le-Qun Li
Affiliations:
Department of Hepatobiliary Surgery, Affiliated Tumour Hospital of Guangxi Medical University, Nanning, China
,
Bang-De Xiang
Affiliations:
Department of Hepatobiliary Surgery, Affiliated Tumour Hospital of Guangxi Medical University, Nanning, China
,
Charing C.N. Chong
Affiliations:
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
,
Toshifumi Tada
Affiliations:
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki, Gifu 503-8052, Japan
,
KeQing Shi
Affiliations:
Department of Infection and Liver Diseases, Liver Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
,
Alessandro Cucchetti
Affiliations:
Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy
,
Hidenori Toyoda
Affiliations:
Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki, Gifu 503-8052, Japan
,
Sarah Berhane
Affiliations:
Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
,
Jianhong Zhong
Affiliations:
Department of Hepatobiliary Surgery, Affiliated Tumour Hospital of Guangxi Medical University, Nanning, China
Anthony W.H. Chan
Affiliations:
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
EASL LiverTree™. JOHNSON P. Dec 1, 2018; 256738
Prof. Philip JOHNSON
Prof. Philip JOHNSON
Contributions
Journal Abstract
References
Graphical abstract

Graphical abstract

Recurrence is frequent within 2 years of surgical resection of hepatocellular carcinoma. In this large collaboration, we identify readily available, clinical parameters which influence early recurrence. A simple and extensively validated statistical model for estimating early recurrence risk using an online calculator. This facility will enhance patient counselling and will help in design of adjuvant clinical trials.

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.

Keyword(s)
Hepatocellular carcinoma, Recurrence, Resection, ERASL, modelling, prognosis
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