The Hong Kong consensus statements on unresectable hepatocellular carcinoma: narrative review and update for 2021

Background and Objective Hong Kong, like many parts of Asia, faces a high burden of hepatocellular carcinoma (HCC) caused by high endemic rates of hepatitis B virus infection. Hong Kong clinicians have developed a high level of expertise in HCC treatment across surgical, transarterial, ablative, radiotherapeutic and systemic modalities. This publication summarizes the latest evidence-based recommendations on how these modalities should be used. Methods In two meetings held in 2020, a multidisciplinary panel of surgeons, oncologists and interventional radiologists performed a narrative review of evidence on the management of HCC, with an emphasis on treatment of HCC not amenable to surgical resection. Close attention was paid to new evidence published since the previous version of these statements in 2018. Key Content and Findings The expert panel has formulated 60 consensus statements to guide the staging and treatment of unresectable HCC. Since the previous version of these statements, considerable additions have been made to the recommendations on use of targeted therapies and immunotherapies because of the large volume of new evidence. Conclusions Our consensus statements offer guidance on how to select HCC patients for surgical or non-surgical treatment and for choosing among non-surgical modalities for patients who are not candidates for resection. In particular, there is a need for more evidence to aid physicians in the selection of second-line systemic therapies, as currently most data are limited to patients with disease progression on first-line sorafenib.

[1]  M. Makary,et al.  Locoregional Therapies for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis , 2021, Cancers.

[2]  Bixiang Zhang,et al.  Treatment for hepatocellular carcinoma with tumor thrombosis in the hepatic vein or inferior vena cava: A comprehensive review , 2021, World journal of gastrointestinal surgery.

[3]  M. Kudo,et al.  IMbrave150: Updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC). , 2021, Journal of Clinical Oncology.

[4]  M. Kudo,et al.  Nivolumab (NIVO) plus ipilimumab (IPI) combination therapy in patients (Pts) with advanced hepatocellular carcinoma (aHCC): Long-term results from CheckMate 040. , 2021 .

[5]  T. Kimura,et al.  Multicenter prospective study of stereotactic body radiotherapy for previously untreated solitary primary hepatocellular carcinoma: The STRSPH study , 2020, Hepatology research : the official journal of the Japan Society of Hepatology.

[6]  C. Chiang,et al.  Prognostic Factors and Survival in Advanced Large Hepatocellular Carcinomas Treated with Combined Transarterial Chemoembolisation and Hypofractionated Image-guided Radiotherapy , 2020 .

[7]  Yulei N. Wang,et al.  Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. , 2020, The New England journal of medicine.

[8]  M. Kudo,et al.  A Changing Paradigm for the Treatment of Intermediate-Stage Hepatocellular Carcinoma: Asia-Pacific Primary Liver Cancer Expert Consensus Statements , 2020, Liver Cancer.

[9]  K. Stuart,et al.  Efficacy and Toxicity of Stereotactic Body Radiotherapy for Early to Advanced Stage Hepatocellular Carcinoma - Initial Experience From an Australian Liver Cancer Service. , 2020, Clinical oncology (Royal College of Radiologists (Great Britain)).

[10]  R. Sacco,et al.  Comparison between Y90 Radioembolization Plus Sorafenib and Y90 Radioembolization alone in the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis , 2020, Cancers.

[11]  FDA grants accelerated approval to nivolumab and ipilimumab combination for hepatocellular carcinoma , 2020, Case Medical Research.

[12]  Y. Yen,et al.  Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO. , 2020, Annals of oncology : official journal of the European Society for Medical Oncology.

[13]  Jian Sun,et al.  Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy for Unresectable Hepatitis B Virus-related Hepatocellular Carcinoma: A Single Center Study of 45 Patients. , 2020, Annals of surgery.

[14]  C. Mar,et al.  Stereotactic Body Radiotherapy for Large Unresectable Hepatocellular Carcinomas - A Single Institution Phase II Study. , 2020, Clinical oncology (Royal College of Radiologists (Great Britain)).

[15]  R. Lencioni,et al.  mRECIST for HCC: Performance and novel refinements. , 2020, Journal of hepatology.

[16]  M. Kudo,et al.  Baseline liver function and outcomes in the phase III REFLECT study in patients with unresectable hepatocellular carcinoma (uHCC). , 2020 .

[17]  R. Salem,et al.  Toxicity and Survival of Hepatocellular Carcinoma Patients with Hepatitis B Infection Treated with Yttrium-90 Radioembolization: An Updated 15-Year Study. , 2020, Journal of vascular and interventional radiology : JVIR.

[18]  Jun Kato,et al.  Switching to systemic therapy after locoregional treatment failure: Definition and best timing , 2020, Clinical and molecular hepatology.

[19]  D. Klass,et al.  Ablative Transarterial Radioembolization Improves Survival in Patients with HCC and Portal Vein Tumor Thrombus , 2020, CardioVascular and Interventional Radiology.

[20]  M. Kudo,et al.  Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial , 2019, Gut.

[21]  J. Ringash,et al.  Nonsurgical management of advanced hepatocellular carcinoma: a clinical practice guideline. , 2019, Current oncology.

[22]  H. Lang ALPPS - Beneficial or detrimental? , 2019, Surgical oncology.

[23]  G. Abou-Alfa,et al.  Outcomes based on albumin‐bilirubin (ALBI) grade in the phase III CELESTIAL trial of cabozantinib versus placebo in patients with advanced hepatocellular carcinoma (HCC) , 2019, Annals of Oncology.

[24]  N. Syn,et al.  Liver Resection for Nonalcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma. , 2019, Journal of the American College of Surgeons.

[25]  Xin-hui Xie,et al.  Radiofrequency ablation vs. surgical resection for resectable hepatocellular carcinoma: A systematic review and meta-analysis , 2019, Molecular and clinical oncology.

[26]  M. Kudo,et al.  CheckMate 459: A randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC) , 2019, Annals of Oncology.

[27]  M. Kudo,et al.  Nivolumab in Advanced Hepatocellular Carcinoma: Sorafenib-Experienced Asian Cohort Analysis. , 2019, Journal of hepatology.

[28]  F. Piscaglia,et al.  Liver function changes after transarterial chemoembolization in US hepatocellular carcinoma patients: the LiverT study , 2019, BMC Cancer.

[29]  Sudip Ghosh,et al.  Microwave ablation compared with radiofrequency ablation for treatment of hepatocellular carcinoma and liver metastases: a systematic review and meta-analysis , 2019, OncoTargets and therapy.

[30]  M. Kudo,et al.  Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child–Pugh A Liver Function: A Proof-Of-Concept Study , 2019, Cancers.

[31]  R. Poon,et al.  ALPPS Versus Portal Vein Embolization for Hepatitis-related Hepatocellular Carcinoma , 2019, Annals of surgery.

[32]  M. Kudo,et al.  Impact of Baseline ALBI Grade on the Outcomes of Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Multicenter Study , 2019, Cancers.

[33]  G. J. Yoshida,et al.  Sorafenib with Transarterial Chemoembolization Achieves Improved Survival vs. Sorafenib Alone in Advanced Hepatocellular Carcinoma: A Nationwide Population-Based Cohort Study , 2019, Cancers.

[34]  M. Kudo,et al.  Results of KEYNOTE-240: phase 3 study of pembrolizumab (Pembro) vs best supportive care (BSC) for second line therapy in advanced hepatocellular carcinoma (HCC). , 2019, Journal of Clinical Oncology.

[35]  M. Kudo,et al.  Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040. , 2019, Journal of Clinical Oncology.

[36]  Bo Hyun Kim,et al.  Sorafenib with or without concurrent transarterial chemoembolization in patients with advanced hepatocellular carcinoma: The phase III STAH trial. , 2019, Journal of hepatology.

[37]  M. Kudo,et al.  Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. , 2019, The Lancet. Oncology.

[38]  J. Fung,et al.  Long-term survival comparison between primary transplant and upfront curative treatment with salvage transplant for early stage hepatocellular carcinoma. , 2019, Asian journal of surgery.

[39]  M. Kudo,et al.  Checkmate-040: Nivolumab (NIVO) in patients (pts) with advanced hepatocellular carcinoma (aHCC) and Child-Pugh B (CPB) status. , 2019, Journal of Clinical Oncology.

[40]  A. Chan,et al.  Better survival after stereotactic body radiation therapy following transarterial chemoembolization in nonresectable hepatocellular carcinoma: A propensity score matched analysis. , 2019, Surgical oncology.

[41]  T. de Baère,et al.  Updated use of TACE for hepatocellular carcinoma treatment: How and when to use it based on clinical evidence. , 2019, Cancer treatment reviews.

[42]  E. Assenat,et al.  Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor Response, Toxicity, and Survival after Yttrium-90 Resin Microsphere Radioembolization in Hepatocellular Carcinoma. , 2018, Journal of vascular and interventional radiology : JVIR.

[43]  Sidong Wei,et al.  Revisiting Partial Hepatectomy of Large Hepatocellular Carcinoma in Older Patients , 2018, Scientific Reports.

[44]  FDA approves lenvatinib for unresectable hepatocellular carcinoma , 2018, Case Medical Research.

[45]  M. Abecassis,et al.  Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases , 2018, Hepatology.

[46]  Gisela Schwab,et al.  Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma , 2018, The New England journal of medicine.

[47]  C. Spreafico,et al.  Patients with Barcelona Clinic Liver Cancer Stages B and C Hepatocellular Carcinoma: Time for a Subclassification , 2018, Liver Cancer.

[48]  Yao-ting Chen,et al.  Radiofrequency Ablation Combined with Transcatheter Arterial Chemoembolization Therapy Versus Surgical Resection for Hepatocellular Carcinoma within the Milan Criteria: A Meta-Analysis , 2018, Korean journal of radiology.

[49]  J. Shin,et al.  Efficacy and Safety of Transarterial Chemoembolization Plus External Beam Radiotherapy vs Sorafenib in Hepatocellular Carcinoma With Macroscopic Vascular Invasion: A Randomized Clinical Trial , 2018, JAMA oncology.

[50]  K. Rosenzweig,et al.  Stereotactic body radiation therapy following transarterial chemoembolization for unresectable hepatocellular carcinoma. , 2018, Journal of gastrointestinal oncology.

[51]  M. Kudo,et al.  Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial , 2018, The Lancet.

[52]  H. Saitsu,et al.  Prediction of post-progression survival in patients with advanced hepatocellular carcinoma treated with sorafenib by using time-dependent changes in clinical characteristics , 2018 .

[53]  V. Gebski,et al.  SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[54]  M. Kudo,et al.  Deterioration of liver function after transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): An exploratory analysis of OPTIMIS—An international observational study assessing the use of sorafenib after TACE. , 2018 .

[55]  M. Kudo Lenvatinib May Drastically Change the Treatment Landscape of Hepatocellular Carcinoma , 2018, Liver Cancer.

[56]  Chung-Pin Li,et al.  Validation of the albumin‐bilirubin grade‐based integrated model as a predictor for sorafenib‐failed hepatocellular carcinoma , 2018, Liver international : official journal of the International Association for the Study of the Liver.

[57]  T. Yau,et al.  Hong Kong Consensus Statements for the Management of Unresectable Hepatocellular Carcinoma , 2018, Liver Cancer.

[58]  F. Piscaglia,et al.  Patient Selection for Transarterial Chemoembolization in Hepatocellular Carcinoma: Importance of Benefit/Risk Assessment , 2018, Liver Cancer.

[59]  Daniel A. Anaya,et al.  Liver Resection and Surgical Strategies for Management of Primary Liver Cancer , 2018, Cancer control : journal of the Moffitt Cancer Center.

[60]  V. Mazzaferro,et al.  The SIRveNIB and SARAH trials, radioembolization vs. sorafenib in advanced HCC patients: reasons for a failure, and perspectives for the future. , 2018, Hepatobiliary surgery and nutrition.

[61]  W. Yeo,et al.  Ablative Chemoembolization for Hepatocellular Carcinoma: A Prospective Phase I Case-Control Comparison with Conventional Chemoembolization. , 2017, Radiology.

[62]  H. Yasunaga,et al.  Short-Term Outcomes following Hepatectomy in Elderly Patients with Hepatocellular Carcinoma: An Analysis of 10,805 Septuagenarians and 2,381 Octo- and Nonagenarians in Japan , 2017, Liver Cancer.

[63]  S. Fan,et al.  Randomized clinical trial of hepatic resection versus radiofrequency ablation for early‐stage hepatocellular carcinoma , 2017, The British journal of surgery.

[64]  Rachida Lebtahi,et al.  Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. , 2017, The Lancet. Oncology.

[65]  H. S. Kim,et al.  Radiofrequency ablation versus resection for hepatocellular carcinoma in patients with Child-Pugh A liver cirrhosis: a meta-analysis. , 2017, Clinical radiology.

[66]  B. Luo,et al.  Radiofrequency Ablation versus Hepatic Resection for Small Hepatocellular Carcinoma: Systematic Review of Randomized Controlled Trials with Meta-Analysis and Trial Sequential Analysis. , 2017, Radiology.

[67]  M. Kudo,et al.  Hepatic Function during Repeated TACE Procedures and Prognosis after Introducing Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Analysis , 2017, Digestive Diseases.

[68]  T. Gamblin,et al.  Transarterial chemoembolization in hepatocellular carcinoma with portal vein tumor thrombosis: a systematic review and meta-analysis. , 2017, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[69]  D. Stocken,et al.  Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial. , 2017, The lancet. Gastroenterology & hepatology.

[70]  Liwen Liu,et al.  Effects of radiofrequency ablation versus other ablating techniques on hepatocellular carcinomas: a systematic review and meta-analysis , 2017, World Journal of Surgical Oncology.

[71]  Lequn Li,et al.  Surgical resection for hepatocellular carcinoma with portal vein tumor thrombus in the Asia-Pacific region beyond the Barcelona Clinic Liver Cancer treatment algorithms: a review and update , 2017, Oncotarget.

[72]  M. Kudo,et al.  Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial , 2017, The Lancet.

[73]  H. Fukuda,et al.  Treatment of Advanced Hepatocellular Carcinoma after Failure of Sorafenib Treatment: Subsequent or Additional Treatment Interventions Contribute to Prolonged Survival Postprogression , 2017, Gastroenterology research and practice.

[74]  M. Kudo,et al.  Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update , 2017, Hepatology International.

[75]  S. Kwan,et al.  Segmental Yttrium-90 Radioembolization versus Segmental Chemoembolization for Localized Hepatocellular Carcinoma: Results of a Single-Center, Retrospective, Propensity Score-Matched Study. , 2017, Journal of vascular and interventional radiology : JVIR.

[76]  D. Lu,et al.  Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10‐year intention‐to‐treat analysis , 2017, Hepatology.

[77]  Hong Wu,et al.  Radiofrequency ablation using a 10‐mm target margin for small hepatocellular carcinoma in patients with liver cirrhosis: A prospective randomized trial , 2017, Journal of surgical oncology.

[78]  J. Titano,et al.  Radiation Segmentectomy versus TACE Combined with Microwave Ablation for Unresectable Solitary Hepatocellular Carcinoma Up to 3 cm: A Propensity Score Matching Study. , 2017, Radiology.

[79]  M. Rebelatto,et al.  Phase I/II study of durvalumab and tremelimumab in patients with unresectable hepatocellular carcinoma (HCC): Phase I safety and efficacy analyses. , 2017 .

[80]  A. Singal,et al.  Is the Hong Kong Liver Cancer Staging System Ready to Replace the Barcelona Clinic Liver Cancer System? , 2017, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[81]  J. Geschwind,et al.  Validation of the Hong Kong Liver Cancer Staging System in Determining Prognosis of the North American Patients Following Intra‐arterial Therapy , 2017, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[82]  J. Shindoh,et al.  Effect of Background Liver Cirrhosis on Outcomes of Hepatectomy for Hepatocellular Carcinoma , 2017, JAMA surgery.

[83]  C. Lo,et al.  Impact of split completeness on future liver remnant hypertrophy in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in hepatocellular carcinoma: Complete‐ALPPS versus partial‐ALPPS , 2017, Surgery.

[84]  M. Kudo,et al.  The albumin–bilirubin grade improves hepatic reserve estimation post‐sorafenib failure: implications for drug development , 2017, Alimentary pharmacology & therapeutics.

[85]  Masatoshi Kudo,et al.  Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial , 2017, The Lancet.

[86]  A. Rademaker,et al.  Y90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma. , 2016, Gastroenterology.

[87]  P. Liang,et al.  Long-term survival analysis in combined transarterial embolization and stereotactic body radiation therapy versus stereotactic body radiation monotherapy for unresectable hepatocellular carcinoma >5 cm , 2016, BMC Cancer.

[88]  E. Kunieda,et al.  Phase 2 study of stereotactic body radiotherapy and optional transarterial chemoembolization for solitary hepatocellular carcinoma not amenable to resection and radiofrequency ablation , 2016, Cancer.

[89]  A. Facciorusso,et al.  Drug-eluting beads versus conventional chemoembolization for the treatment of unresectable hepatocellular carcinoma: A meta-analysis. , 2016, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[90]  Zhen Chen,et al.  Radiofrequency ablation plus chemoembolization versus radiofrequency ablation alone for hepatocellular carcinoma: A systematic review and meta-analysis. , 2016, Clinics and research in hepatology and gastroenterology.

[91]  Riccardo Lencioni,et al.  Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial. , 2016, Journal of hepatology.

[92]  Ching-Lung Lai,et al.  Epidemiology of Hepatocellular Carcinoma in the Asia-Pacific Region , 2016, Gut and liver.

[93]  W. Lau,et al.  Randomized clinical trial of chemoembolization plus radiofrequency ablation versus partial hepatectomy for hepatocellular carcinoma within the Milan criteria , 2016, The British journal of surgery.

[94]  A. Gasbarrini,et al.  Application of the Intermediate-Stage Subclassification to Patients With Untreated Hepatocellular Carcinoma , 2016, The American Journal of Gastroenterology.

[95]  M. Kudo,et al.  Effectiveness of Sorafenib in Patients with Transcatheter Arterial Chemoembolization (TACE) Refractory and Intermediate-Stage Hepatocellular Carcinoma , 2015, Liver Cancer.

[96]  Xu Fu,et al.  Validation of models in patients with hepatocellular carcinoma: comparison of Hong Kong Liver Cancer with Barcelona Clinic Liver Cancer staging system in a Chinese cohort , 2015, European journal of gastroenterology & hepatology.

[97]  Isabel B. Lokody International Liver Cancer Association Annual Conference. , 2015, The Lancet. Oncology.

[98]  G. Eslick,et al.  Transcatheter Arterial Chemoembolization Plus Radiotherapy Compared With Chemoembolization Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-analysis. , 2015, JAMA oncology.

[99]  M. Colombo,et al.  Predictors of survival in patients with advanced hepatocellular carcinoma who permanently discontinued sorafenib , 2015, Hepatology.

[100]  A. Russo,et al.  Prognostic Relevance of Objective Response According to EASL Criteria and mRECIST Criteria in Hepatocellular Carcinoma Patients Treated with Loco-Regional Therapies: A Literature-Based Meta-Analysis , 2015, PloS one.

[101]  Mohamad Amin Pourhoseingholi,et al.  Hepatocellular carcinoma in Asia: Prevention strategy and planning. , 2015, World journal of hepatology.

[102]  S. Saab,et al.  Management of hepatocellular carcinoma with portal vein thrombosis. , 2015, World journal of gastroenterology.

[103]  T. Yau,et al.  Hong Kong Consensus Recommendations on the Management of Hepatocellular Carcinoma , 2015, Liver Cancer.

[104]  M. Kudo,et al.  Transarterial Chemoembolization Failure/Refractoriness: JSH-LCSGJ Criteria 2014 Update , 2014, Oncology.

[105]  M. Kudo,et al.  Brivanib as adjuvant therapy to transarterial chemoembolization in patients with hepatocellular carcinoma: A randomized phase III trial , 2014, Hepatology.

[106]  M. Yoshikawa,et al.  Efficacy of Sorafenib in Intermediate-Stage Hepatocellular Carcinoma Patients Refractory to Transarterial Chemoembolization , 2014, Oncology.

[107]  S. Fan,et al.  Good longterm survival after primary living donor liver transplantation for solitary hepatocellular carcinomas up to 8 cm in diameter. , 2014, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[108]  M. Abecassis,et al.  Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: Multicenter radiology‐pathology correlation and survival of radiation segmentectomy , 2014, Hepatology.

[109]  S. Fan,et al.  Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. , 2014, Gastroenterology.

[110]  E. Kunieda,et al.  Stereotactic body radiotherapy for small hepatocellular carcinoma: A retrospective outcome analysis in 185 patients , 2014, Acta oncologica.

[111]  K. Gao,et al.  Radiofrequency ablation of hepatocellular carcinoma sized > 3 and ≤ 5 cm: is ablative margin of more than 1 cm justified? , 2013, World journal of gastroenterology.

[112]  T. Mok,et al.  Unresectable hepatocellular carcinoma: randomized controlled trial of transarterial ethanol ablation versus transcatheter arterial chemoembolization. , 2013, Radiology.

[113]  S. Fan,et al.  Survival analysis of high-intensity focused ultrasound ablation in patients with small hepatocellular carcinoma. , 2013, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[114]  F. Lee,et al.  Impact of fractionated stereotactic body radiotherapy on liver function in patients with hepatitis B virus-related hepatocellular carcinoma: Clinical and dosimetric analysis , 2013 .

[115]  Dong Han Lee,et al.  Stereotactic body radiation therapy for inoperable hepatocellular carcinoma as a local salvage treatment after incomplete transarterial chemoembolization , 2012, Cancer.

[116]  Drew M. Pardoll,et al.  The blockade of immune checkpoints in cancer immunotherapy , 2012, Nature Reviews Cancer.

[117]  Cynthia S. Johnson,et al.  Stereotactic body radiotherapy for primary hepatocellular carcinoma. , 2011, International journal of radiation oncology, biology, physics.

[118]  S. Fan,et al.  Survival Analysis of Re-resection Versus Radiofrequency Ablation for Intrahepatic Recurrence After Hepatectomy for Hepatocellular Carcinoma , 2011, World Journal of Surgery.

[119]  J. Bruix,et al.  Management of hepatocellular carcinoma: An update , 2011, Hepatology.

[120]  P. Prasoon,et al.  Surgical vs percutaneous radiofrequency ablation for hepatocellular carcinoma in dangerous locations. , 2011, World journal of gastroenterology.

[121]  H. Jang,et al.  Long-term effect of stereotactic body radiation therapy for primary hepatocellular carcinoma ineligible for local ablation therapy or surgical resection. Stereotactic radiotherapy for liver cancer , 2010, BMC Cancer.

[122]  K. Sung,et al.  Combination of transarterial chemoembolization and three-dimensional conformal radiotherapy for hepatocellular carcinoma with inferior vena cava tumor thrombus. , 2010, International journal of radiation oncology, biology, physics.

[123]  S. Fan,et al.  Combined resection and radiofrequency ablation for multifocal hepatocellular carcinoma: prognosis and outcomes. , 2010, World journal of gastroenterology.

[124]  S. Paggi,et al.  Sorafenib in Advanced Hepatocellular Carcinoma , 2008 .

[125]  S. Paik,et al.  Combined Hepatectomy and Radiofrequency Ablation for Multifocal Hepatocellular Carcinomas: Long-term Follow-up Results and Prognostic Factors , 2007, Annals of Surgical Oncology.

[126]  T. Pawlik,et al.  Is Extended Hepatectomy for Hepatobiliary Malignancy Justified? , 2004, Annals of surgery.

[127]  Steven A Curley,et al.  Extended hepatectomy in patients with hepatobiliary malignancies with and without preoperative portal vein embolization. , 2002, Archives of surgery.

[128]  A. Venook,et al.  Liver transplantation for hepatocellular carcinoma: Expansion of the tumor size limits does not adversely impact survival , 2001, Hepatology.

[129]  H. Bismuth,et al.  Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization. , 2000, Annals of surgery.

[130]  R. Groszmann,et al.  American association for the study of liver diseases , 1992 .

[131]  M. Dumont,et al.  European Association for the Study of the Liver , 1971 .

[132]  J. Titano,et al.  Radiation Segmentectomy versus Selective Chemoembolization in the Treatment of Early-Stage Hepatocellular Carcinoma. , 2018, Journal of vascular and interventional radiology : JVIR.

[133]  M. Kudo,et al.  Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. , 2018, The lancet. Gastroenterology & hepatology.

[134]  A. Askari,et al.  Survival following redo hepatectomy vs radiofrequency ablation for recurrent hepatocellular carcinoma: a systematic review and meta-analysis. , 2017, HPB : the official journal of the International Hepato Pancreato Biliary Association.

[135]  Y 90 Radioembolization Significantly Prolongs Time to Progression Compared With Chemoembolization in Patients With Hepatocellular Carcinoma , 2017 .

[136]  Liang-liang Xu 许亮亮,et al.  Hepatic resection combined with radiofrequency ablation versus hepatic resection alone for multifocal hepatocellular carcinomas: A meta-analysis , 2017, Current Medical Science.

[137]  E. Ntzani,et al.  The role of portal vein embolization in the surgical management of primary hepatobiliary cancers. A systematic review. , 2017, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[138]  L. Mariani,et al.  Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. , 2009, The Lancet. Oncology.

[139]  M. Makuuchi,et al.  Measurement of liver volume and hepatic functional reserve as a guide to decision‐making in resectional surgery for hepatic tumors , 1997, Hepatology.