network meta-analysis of treatment regimens for inoperable advanced hepatocellular carcinoma with portal vein invasion

Purpose: We assessed the efficacy and safety of different modalities using the network meta-analysis for inoperable hepatocellular carcinoma (HCC) with portal vein invasion. The interested modalities included stereotactic body radiotherapy (SBRT) combined with transarterial chemoembolization (TACE), three-dimensional radiotherapy (3D-RT) combined with hepatic arterial infusion chemotherapy (HAIC) or TACE, TACE plus sorafenib, and use of SBRT, HAIC, sorafenib, and TACE alone. Methods: PubMed and Cochrane Library electronic databases were systematically searched for eligible studies published up to June 2017. We used network meta-analysis to compare the disease control rate (DCR) and severe adverse events for the eight interested regimens included in this analysis. Study quality was assessed following the Grading of Recommendations, Assessment, Development and Evaluations method. Results: Fifteen studies published between 2010 and 2016 involving a total of 2,359 patients were enrolled in this network meta-analysis. With indirect comparison of DCR and overall safety, the pooled results showed that RT plus HAIC was the most effective regimen in treating advanced HCC with portal vein tumor thrombosis, followed by RT plus TACE. HAIC alone and sorafenib combined with HAIC appeared least effective intervention regimens. The incidence of treatment-related adverse events of grade 3 or 4 occurred less in the patients who received SBRT alone compared with other interested regimens. Conclusion: 3D-RT combined with HAIC or TACE showed more favorable treatment responses compared with other regimens in advanced HCC patients with portal vein tumor thrombosis.

[1]  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.

[2]  J. Lang,et al.  New Evidence and Perspectives on the Management of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus , 2017, Journal of clinical and translational hepatology.

[3]  Guang-shun Yang,et al.  Transarterial chemoembolization (TACE) combined with sorafenib versus TACE for hepatocellular carcinoma with portal vein tumor thrombus: a systematic review and meta-analysis , 2017, Oncotarget.

[4]  J. Yue,et al.  Comparison of intra-arterial chemoembolization with and without radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a meta-analysis , 2016, Therapeutics and clinical risk management.

[5]  Kang Wang,et al.  Efficacy of the treatment of transarterial chemoembolization combined with radiotherapy for hepatocellular carcinoma with portal vein tumor thrombus: A propensity score analysis , 2016, Hepatology research : the official journal of the Japan Society of Hepatology.

[6]  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.

[7]  M. Imamura,et al.  Comparison of hepatic arterial infusion chemotherapy versus sorafenib monotherapy in patients with advanced hepatocellular carcinoma , 2015, Journal of digestive diseases.

[8]  J. Heo,et al.  New perspectives on the management of hepatocellular carcinoma with portal vein thrombosis , 2015, Clinical and molecular hepatology.

[9]  K. Awai,et al.  Role of 3‐D conformal radiotherapy for major portal vein tumor thrombosis combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma , 2015, Hepatology research : the official journal of the Japan Society of Hepatology.

[10]  Myeong Jun Song,et al.  A comparative study between sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis , 2015, Journal of Gastroenterology.

[11]  Zong-tao Hu,et al.  A comparison between three‐dimensional conformal radiotherapy combined with interventional treatment and interventional treatment alone for hepatocellular carcinoma with portal vein tumour thrombosis , 2015, Journal of medical imaging and radiation oncology.

[12]  P. Bie,et al.  Transarterial Chemoembolization (TACE) plus Sorafenib Versus TACE for Intermediate or Advanced Stage Hepatocellular Carcinoma: A Meta-Analysis , 2014, PloS one.

[13]  Y. Shin,et al.  Sorafenib alone versus sorafenib combined with transarterial chemoembolization for advanced-stage hepatocellular carcinoma: results of propensity score analyses. , 2013, Radiology.

[14]  Kristian Thorlund,et al.  Demystifying trial networks and network meta-analysis , 2013, BMJ.

[15]  Zahra Kassam,et al.  Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  Z. Ren,et al.  Transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a meta-analysis , 2013, BMC Gastroenterology.

[17]  G. Han,et al.  Sorafenib in combination with transarterial chemoembolization improves the survival of patients with unresectable hepatocellular carcinoma: A propensity score matching study , 2013, Journal of digestive diseases.

[18]  A. Gasbarrini,et al.  Cost‐effectiveness of sorafenib treatment in field practice for patients with hepatocellular carcinoma , 2013, Hepatology.

[19]  Sang Gyune Kim,et al.  The efficacy of hepatic arterial infusion chemotherapy as an alternative to sorafenib in advanced hepatocellular carcinoma , 2012, Asia-Pacific journal of clinical oncology.

[20]  R. Stauber,et al.  Advanced-stage hepatocellular carcinoma: transarterial chemoembolization versus sorafenib. , 2012, Radiology.

[21]  H. Won,et al.  Radiotherapy plus transarterial chemoembolization for hepatocellular carcinoma invading the portal vein: long-term patient outcomes. , 2012, International journal of radiation oncology, biology, physics.

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

[23]  H. Shirato,et al.  Efficacy of therapy for advanced hepatocellular carcinoma: Intra‐arterial 5‐fluorouracil and subcutaneous interferon with image‐guided radiation , 2011, Journal of gastroenterology and hepatology.

[24]  Georgia Salanti,et al.  Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. , 2011, Journal of clinical epidemiology.

[25]  S. Bae,et al.  A comparative study of high-dose hepatic arterial infusion chemotherapy and transarterial chemoembolization using doxorubicin for intractable, advanced hepatocellular carcinoma , 2010, The Korean journal of hepatology.

[26]  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.

[27]  Riccardo Lencioni,et al.  Modified RECIST (mRECIST) Assessment for Hepatocellular Carcinoma , 2010, Seminars in liver disease.

[28]  Y. Guan,et al.  Transcatheter arterial chemoembolization in combination with radiotherapy for unresectable hepatocellular carcinoma: a systematic review and meta-analysis. , 2009, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[29]  N. Toyota,et al.  Intra-arterial 5-fluorouracil/interferon combination therapy for advanced hepatocellular carcinoma with or without three-dimensional conformal radiotherapy for portal vein tumor thrombosis , 2009, Journal of Gastroenterology.

[30]  Maria Hawkins,et al.  Phase I study of individualized stereotactic body radiotherapy for hepatocellular carcinoma and intrahepatic cholangiocarcinoma. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  S. Ahn,et al.  Repetitive short‐course hepatic arterial infusion chemotherapy with high‐dose 5‐fluorouracil and cisplatin in patients with advanced hepatocellular carcinoma , 2007, Cancer.

[32]  Tae Hyun Kim,et al.  Three-Dimensional Conformal Radiotherapy of Unresectable Hepatocellular Carcinoma Patients for Whom Transcatheter Arterial Chemoembolization Was Ineffective or Unsuitable , 2006, American journal of clinical oncology.

[33]  Charles R. Thomas,et al.  External beam radiation therapy for hepatocellular carcinoma: potential of intensity-modulated and image-guided radiation therapy. , 2004, Gastroenterology.

[34]  C. Zheng,et al.  Expression of plasma vascular endothelial growth factor in patients with hepatocellular carcinoma and effect of transcatheter arterial chemoembolization therapy on plasma vascular endothelial growth factor level. , 2004, World journal of gastroenterology.

[35]  M. Makuuchi,et al.  Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey , 2004, Cancer.

[36]  C. Suh,et al.  Clinical results of 3-dimensional conformal radiotherapy combined with transarterial chemoembolization for hepatocellular carcinoma in the cirrhotic patients. , 2003, Hepatology research : the official journal of the Japan Society of Hepatology.

[37]  J. Bruix,et al.  Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival , 2003, Hepatology.

[38]  N. Enomoto,et al.  Radiation therapy in combination with transcatheter arterial chemoembolization for hepatocellular carcinoma with extensive portal vein involvement , 2001, Journal of gastroenterology and hepatology.

[39]  M. Makuuchi,et al.  Results of surgical and nonsurgical treatment for small‐sized hepatocellular carcinomas: A retrospective and nationwide survey in Japan , 2000, Hepatology.

[40]  S. H. Cheng,et al.  A pilot study of three‐dimensional conformal radiotherapy in unresectable hepatocellular carcinoma , 1999, Journal of gastroenterology and hepatology.

[41]  J. Bruix,et al.  Natural history of untreated nonsurgical hepatocellular carcinoma: Rationale for the design and evaluation of therapeutic trials , 1999, Hepatology.

[42]  M. Schipper,et al.  Stereotactic Body Radiation Therapy as an Alternative to Transarterial Chemoembolization for Hepatocellular Carcinoma. , 2018, International journal of radiation oncology, biology, physics.

[43]  Jun Zhang,et al.  Stereotactic body radiotherapy combined with transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombosis. , 2014, Molecular and clinical oncology.

[44]  S. Kanazawa,et al.  Efficacy of hepatic arterial infusion chemotherapy in combination with irradiation for advanced hepatocellular carcinoma with portal vein invasion , 2014, Hepatology International.

[45]  Alex J. Sutton,et al.  Evidence Synthesis for Decision Making Inconsistency in Networks of Evidence Based on Randomized Controlled Trials. , 2013 .

[46]  J. Higgins Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration , 2011 .

[47]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. , 2010, International journal of surgery.

[48]  Armando Santoro,et al.  Sorafenib: a review of its use in advanced hepatocellular carcinoma. , 2009, Drugs.

[49]  安東 栄治 Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis : analysis of 48 cases , 2002 .

[50]  J. Higginson,et al.  International Agency for Research on Cancer. , 1968, WHO chronicle.