Advertisement

Comparison of radiation therapy modalities for hepatocellular carcinoma with portal vein thrombosis: A meta-analysis and systematic review

Published:December 09, 2017DOI:https://doi.org/10.1016/j.radonc.2017.11.013

      Abstract

      Purpose

      We performed a meta-analysis and systematic review to compare the radiotherapy (RT) modalities for hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT).

      Materials and methods

      We searched the PubMed, EMBASE, Medline, and Cochrane library databases. The primary endpoint was the 1-year overall survival (OS), and response rate (RR), local control (LC), 2-year OS, and grade ≥3 toxicity incidence were evaluated as secondary endpoints.

      Results

      Thirty-seven studies comprising 2513 patients were included. The pooled 1-year OS rates for the 3-dimensional conformal RT (3DCRT), selective internal RT (SIRT), and stereotactic body RT (SBRT) groups were 43.8% [95% confidence interval (CI): 37.6–50.2], 46.5% (95% CI: 37.7–55.6), and 48.5% (95% CI: 39.4–57.8). These inter-group differences were not statistically significant (p = 0.635). The pooled response rates were 51.3% (95% CI: 45.7–57.0), 33.3% (95% CI: 18.0–53.2), and 70.7 (95% CI: 63.7–76.8) for 3DCRT, SIRT, and SBRT groups, respectively; p = 0.001 and 0.031 for 3DCRT vs. SBRT and SIRT, respectively. The most common grade ≥ 3 complications were lymphocytopenia and bilirubin abnormalities in the 3DCRT and SIRT groups, respectively. Grade ≥ 3 complication was rare in SBRT group.

      Conclusions

      OS did not differ among the modalities, although the response rates vary among modalities.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Radiotherapy and Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Llovet J.M.
        • Bustamante J.
        • Castells A.
        • Vilana R.
        • Ayuso Mdel C.
        • Sala M.
        • et al.
        Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials.
        Hepatology. 1999; 29: 62-67
        • Minagawa M.
        • Makuuchi M.
        Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus.
        World J Gastroenterol. 2006; 12: 7561-7567
        • Chan S.L.
        • Chong C.C.N.
        • Chan A.W.H.
        • Poon D.M.C.
        • Chok K.S.H.
        Management of hepatocellular carcinoma with portal vein tumor thrombosis: Review and update at 2016.
        World J Gastroenterol. 2016; 22: 7289-7300
        • Liver E.A.S.
        • Liver E.A.S.
        • Canc E.O.R.T.
        EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma.
        Eur J Cancer. 2012; 48: 599-641
        • Llovet J.M.
        • Bru C.
        • Bruix J.
        Prognosis of hepatocellular carcinoma: The BCLC staging classification.
        Semin Liver Dis. 1999; 19: 329-338
        • Llovet J.M.
        • Ricci S.
        • Mazzaferro V.
        • Hilgard P.
        • Gane E.
        • Blanc J.F.
        • et al.
        Sorafenib in advanced hepatocellular carcinoma.
        New Engl J Med. 2008; 359: 378-390
        • Bruix J.
        • Raoul J.L.
        • Sherman M.
        • Mazzaferro V.
        • Bolondi L.
        • Craxi A.
        • et al.
        Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial.
        J Hepatol. 2012; 57: 821-829
        • Chung G.E.
        • Lee J.H.
        • Kim H.Y.
        • Hwang S.Y.
        • Kim J.S.
        • Chung J.W.
        • et al.
        Transarterial chemoembolization can be safely performed in patients with hepatocellular carcinoma invading the main portal vein and may improve the overall survival.
        Radiology. 2011; 258: 627-634
        • Luo J.
        • Guo R.P.
        • Lai E.C.H.
        • Zhang Y.J.
        • Lau W.Y.
        • Chen M.S.
        • et al.
        Transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a prospective comparative study.
        Ann Surg Oncol. 2011; 18: 413-420
        • Kokudo N.
        • Hasegawa K.
        • Akahane M.
        • Igaki H.
        • Izumi N.
        • Ichida T.
        • et al.
        Evidence-based clinical practice guidelines for hepatocellular carcinoma: the japan society of hepatology 2013 update (3rd JSH-HCC Guidelines).
        Hepatol Res. 2015; 45
        • Chok K.S.H.
        • Cheung T.T.
        • Chan S.C.
        • Poon R.T.P.
        • Fan S.T.
        • Lo C.M.
        Surgical outcomes in hepatocellular carcinoma patients with portal vein tumor thrombosis.
        World J Surg. 2014; 38: 490-496
        • Dawson L.A.
        • Ten Haken R.K.
        Partial volume tolerance of the liver to radiation.
        Semin Radiat Oncol. 2005; 15: 279-283
        • Rim C.H.
        • Seong J.
        Application of radiotherapy for hepatocellular carcinoma in current clinical practice guidelines.
        Radiat Oncol J. 2016; 34: 160-167
        • Sanuki N.
        • Takeda A.
        • Kunieda E.
        Role of stereotactic body radiation therapy for hepatocellular carcinoma.
        World J Gastroenterol. 2014; 20: 3100-3111
        • Park H.C.
        • Yu J.I.
        • Cheng J.C.H.
        • Zeng Z.C.
        • Hong J.H.
        • Wang M.L.C.
        • et al.
        Consensus for radiotherapy in hepatocellular carcinoma from the 5th Asia-Pacific primary liver cancer expert meeting (APPLE 2014): current practice and future clinical trials.
        Liver Cancer. 2016; 5: 162-174
        • Salem R.
        • Mazzaferro V.
        • Sangro B.
        Yttrium 90 radioembolization for the treatment of hepatocellular carcinoma: biological lessons, current challenges, and clinical perspectives.
        Hepatology. 2013; 58: 2188-2197
        • Sato K.
        • Lewandowski R.J.
        • Bui J.T.
        • Omary R.
        • Hunter R.D.
        • Kulik L.
        • et al.
        Treatment of unresectable primary and metastatic liver cancer with yttrium-90 microspheres (TheraSphere (R)): Assessment of hepatic arterial embolization.
        Cardiovasc Intervent Radiol. 2006; 29: 522-529
        • Kennedy A.S.
        • Nutting C.
        • Coldwell D.
        • Gaiser J.
        • Drachenberg C.
        Pathologic response and microdosimetry of Y-90 microspheres in man: Review of four explanted whole livers.
        Int J Radiat Oncol Biol Phys. 2004; 60: 1552-1563
        • Kulik L.M.
        • Carr B.I.
        • Mulcahy M.F.
        • Lewandowski R.J.
        • Atassi B.
        • Ryu R.
        • et al.
        Safety and efficacy of Y-90 radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis.
        Hepatology. 2008; 47: 71-81
        • Ozkan Z.G.
        • Poyanli A.
        • Ucar A.
        • Kuyumcu S.
        • Akyuz F.
        • Keskin S.
        • et al.
        Favorable survival time provided with radioembolization in hepatocellular carcinoma patients with and without portal vein thrombosis.
        Cancer Biother Radiopharm. 2015; 30: 132-138
        • Edeline J.
        • Crouzet L.
        • Campillo-Gimenez B.
        • Rolland Y.
        • Pracht M.
        • Guillygomarc'h A.
        • et al.
        Selective internal radiation therapy compared with sorafenib for hepatocellular carcinoma with portal vein thrombosis.
        Eur J Nucl Med Mol Imaging. 2016; 43: 635-643
        • Kudo M.
        • Kitano M.
        • Sakurai T.
        • Nishida N.
        General rules for the clinical and pathological study of primary liver cancer, nationwide follow-up survey and clinical practice guidelines: the outstanding achievements of the liver cancer study group of Japan.
        Dig Dis. 2015; 33: 765-770
      1. Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses; 2011.

        • DerSimonian R.
        • Kacker R.
        Random-effects model for meta-analysis of clinical trials: an update.
        Contemp Clin Trials. 2007; 28: 105-114
        • Cochran W.G.
        The combination of estimates from different experiments.
        Biometrics. 1954; 10: 101-129
        • Higgins J.P.T.
        • Thompson S.G.
        Quantifying heterogeneity in a meta-analysis.
        Stat Med. 2002; 21: 1539-1558
        • Egger M.
        • Smith G.D.
        • Schneider M.
        • Minder C.
        Bias in meta-analysis detected by a simple, graphical test.
        Br Med J. 1997; 315: 629-634
        • Duval S.
        • Tweedie R.
        Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis.
        Biometrics. 2000; 56: 455-463
        • Lau W.Y.
        • Sangro B.
        • Chen P.J.
        • Cheng S.Q.
        • Chow P.
        • Lee R.C.
        • et al.
        Treatment for hepatocellular carcinoma with portal vein tumor thrombosis: the emerging role for radioembolization using Yttrium-90.
        Oncology. 2013; 84: 311-318
        • Yoon S.
        • Lim Y.S.
        • Won H.J.
        • Kim J.H.
        • Kim K.M.
        • Lee H.C.
        • et al.
        Radiotherapy plus transarterial chemoembolization for hepatocellular carcinoma invading the portal vein: long-term patient outcomes.
        Int J Radiat Oncol Biol Phys. 2012; 82: 2004-2011
        • Im J.H.
        • Yoon S.M.
        • Park H.C.
        • Kim J.H.
        • Yu J.I.
        • Kim T.H.
        • et al.
        Radiotherapeutic strategies for hepatocellular carcinoma with portal vein tumour thrombosis in a hepatitis B endemic area.
        Liver Int. 2017; 37: 90-100
        • Hozo S.P.
        • Djulbegovic B.
        • Hozo I.
        Estimating the mean and variance from the median, range, and the size of a sample.
        BMC Med Res Methodol. 2005; 5: 13
        • Lu D.H.
        • Fei Z.L.
        • Zhou J.P.
        • Hu Z.T.
        • Hao W.S.
        A comparison between three-dimensional conformal radiotherapy combined with interventional treatment and interventional treatment alone for hepatocellular carcinoma with portal vein tumour thrombosis.
        J Med Imag Radiat Oncol. 2015; 59: 109-114
        • Choi Y.
        • Kim J.W.
        • Cha H.
        • Han K.H.
        • Seong J.
        Overall response of both intrahepatic tumor and portal vein tumor thrombosis is a good prognostic factor for hepatocellular carcinoma patients receiving concurrent chemoradiotherapy.
        J Radiat Res. 2014; 55: 113-120
        • Chuma M.
        • Taguchi H.
        • Yamamoto Y.
        • Shimizu S.
        • Nakanishi M.
        • Ogawa K.
        • et al.
        Efficacy of therapy for advanced hepatocellular carcinoma: intra-arterial 5-fluorouracil and subcutaneous interferon with image-guided radiation.
        J Gastroenterol Hepatol. 2011; 26: 1123-1132
        • Fujino H.
        • Kimura T.
        • Aikata H.
        • Miyaki D.
        • Kawaoka T.
        • Kan H.
        • et al.
        Role of 3-D conformal radiotherapy for major portal vein tumor thrombosis combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma.
        Hepatol Res. 2015; 45: 607-617
        • Hsu W.C.
        • Wang P.M.
        • Ying K.S.
        • Chao C.J.
        • Huang J.C.
        • Lin G.D.
        Preliminary results of three-dimensional conformal radiotherapy for hepatocellular carcinoma with portal vein thrombosis.
        Chin J Radiol-Taipei. 2002; 27: 59-66
        • Huang Y.J.
        • Hsu H.C.
        • Wang C.Y.
        • Wang C.J.
        • Chen H.C.
        • Huang E.Y.
        • et al.
        The treatment responses in cases of radiation therapy to portal vein thrombosis in advanced hepatocellular carcinoma.
        Int J Radiat Oncol Biol Phys. 2009; 73: 1155-1163
        • Ishikura S.
        • Ogino T.
        • Furuse J.
        • Satake M.
        • Baba S.
        • Kawashima M.
        • et al.
        Radiotherapy after transcatheter arterial chemoembolization for patients with hepatocellular carcinoma and portal vein tumor thrombus.
        Am J Clin Oncol. 2002; 25: 189-193
        • Kim T.H.
        • Kim D.Y.
        • Park J.W.
        • Il Kim Y.
        • Kim S.H.
        • Park H.S.
        • et al.
        Three-dimensional conformal radiotherapy of unresectable hepatocellular carcinoma patients for whom transcatheter arterial chemoembolization was ineffective or unsuitable.
        Am J Clin Oncol-Cancer Clinical Trials. 2006; 29: 568-575
        • Lee J.H.
        • Kim D.H.
        • Ki Y.K.
        • Nam J.H.
        • Heo J.
        • Woo H.Y.
        • et al.
        Three-dimensional conformal radiotherapy for portal vein tumor thrombosis alone in advanced hepatocellular carcinoma.
        Radiat Oncol J. 2014; 32: 170-178
        • Li B.
        • Yu J.
        • Wang L.
        • Li C.
        • Zhou T.
        • Zhai L.
        • et al.
        Study of local three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for patients with stage III hepatocellular carcinoma.
        Am J Clin Oncol. 2003; 26: e92-e99
        • Matsuo Y.
        • Yoshida K.
        • Nishimura H.
        • Ejima Y.
        • Miyawaki D.
        • Uezono H.
        • et al.
        Efficacy of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis/inferior vena cava tumor thrombosis: evaluation by comparison with conventional three-dimensional conformal radiotherapy.
        J Radiat Res. 2016; 57: 512-523
        • Nakazawa T.
        • Hidaka H.
        • Shibuya A.
        • Okuwaki Y.
        • Tanaka Y.
        • Takada J.
        • et al.
        Overall survival in response to sorafenib versus radiotherapy in unresectable hepatocellular carcinoma with major portal vein tumor thrombosis: propensity score analysis.
        Bmc Gastroenterol. 2014; 3: 14
        • Onishi H.
        • Nouso K.
        • Nakamura S.
        • Katsui K.
        • Wada N.
        • Morimoto Y.
        • et al.
        Efficacy of hepatic arterial infusion chemotherapy in combination with irradiation for advanced hepatocellular carcinoma with portal vein invasion.
        Hepatol Int. 2015; 9: 105-112
        • Rim C.H.
        • Yang D.S.
        • Park Y.J.
        • Yoon W.S.
        • Lee J.A.
        • Kim C.Y.
        Effectiveness of high-dose three-dimensional conformal radiotherapy in hepatocellular carcinoma with portal vein thrombosis.
        Jpn J Clin Oncol. 2012; 42: 721-729
        • Shirai S.
        • Kumayama Y.
        • Sato M.
        • Noda Y.
        • Chiba T.
        • Kawaguchi M.
        Cutoff Values for Dose-liver Function Parameters to Prevent Radiation-induced Liver Disease in Advanced Hepatoma.
        J Gastroenterol Hepatol Res. 2015; 4: 1425-1433
        • Tang Q.H.
        • Li A.J.
        • Yang G.M.
        • Lai E.C.
        • Zhou W.P.
        • Jiang Z.H.
        • et al.
        Surgical resection versus conformal radiotherapy combined with TACE for resectable hepatocellular carcinoma with portal vein tumor thrombus: a comparative study.
        World J Surg. 2013; 37: 1362-1370
        • Tazawa J.
        • Maeda M.
        • Sakai Y.
        • Yamane M.
        • Ohbayashi H.
        • Kakinuma S.
        • et al.
        Radiation therapy in combination with transcatheter arterial chemoembolization for hepatocellular carcinoma with extensive portal vein involvement.
        J Gastroenterol Hepatol. 2001; 16: 660-665
        • Toya R.
        • Murakami R.
        • Baba Y.
        • Nishimura R.
        • Morishita S.
        • Ikeda O.
        • et al.
        Conformal radiation therapy for portal vein tumor thrombosis of hepatocellular carcinoma.
        Radiother Oncol. 2007; 84: 266-271
        • Yamada K.
        • Izaki K.
        • Sugimoto K.
        • Mayahara H.
        • Morita Y.
        • Yoden E.
        • et al.
        Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma.
        Int J Radiat Oncol Biol Phys. 2003; 57: 113-119
        • Yu J.I.
        • Park H.C.
        • Lim D.H.
        • Park W.
        • Yoo B.C.
        • Paik S.W.
        • et al.
        Prognostic index for portal vein tumor thrombosis in patients with hepatocellular carcinoma treated with radiation therapy.
        J Korean Med Sci. 2011; 26: 1014-1022
        • Zhang X.B.
        • Wang J.H.
        • Yan Z.P.
        • Qian S.
        • Du S.S.
        • Zeng Z.C.
        Hepatocellular carcinoma with main portal vein tumor thrombus: treatment with 3-dimensional conformal radiotherapy after portal vein stenting and transarterial chemoembolization.
        Cancer. 2009; 115: 1245-1252
        • Akinwande O.
        • Kim D.
        • Edwards J.
        • Brown R.
        • Philips P.
        • Scoggins C.
        • et al.
        Is radioembolization (Y-90) better than doxorubicin drug eluting beads (DEBDOX) for hepatocellular carcinoma with portal vein thrombosis? A retrospective analysis.
        Surg Oncol-Oxford. 2015; 24: 270-275
        • Biederman D.M.
        • Titano J.J.
        • Tabori N.E.
        • Pierobon E.S.
        • Alshebeeb K.
        • Schwartz M.
        • et al.
        Outcomes of radioembolization in the treatment of hepatocellular carcinoma with portal vein invasion: resin versus glass microspheres.
        J Vasc Interv Radiol. 2016; 27: 812-821
        • Golfieri R.
        • Mosconi C.
        • Cappelli A.
        • Giampalma E.
        • Galaverni M.C.
        • Pettinato C.
        • et al.
        Efficacy of radioembolization according to tumor morphology and portal vein thrombosis in intermediate-advanced hepatocellular carcinoma.
        Fut Oncol. 2015; 11: 3133-3142
        • Hilgard P.
        • Hamami M.
        • El Fouly A.
        • Scherag A.
        • Muller S.
        • Ertle J.
        • et al.
        Radioembolization with Yttrium-90 glass microspheres in hepatocellular carcinoma: european experience on safety and long-term survival.
        Hepatology. 2010; 52: 1741-1749
        • Inarrairaegui M.
        • Thurston K.G.
        • Bilbao J.I.
        • D'Avola D.
        • Rodriguez M.
        • Arbizu J.
        • et al.
        Radioembolization with use of Yttrium-90 resin microspheres in patients with hepatocellular carcinoma and portal vein thrombosis.
        J Vasc Interv Radiol. 2010; 21: 1205-1212
        • Kokabi N.
        • Camacho J.C.
        • Xing M.Z.
        • El-Rayes B.F.
        • Spivey J.R.
        • Knechtle S.J.
        • et al.
        Open-label prospective study of the safety and efficacy of glass-based yttrium 90 radioembolization for infiltrative hepatocellular carcinoma with portal vein thrombosis.
        Cancer. 2015; 121: 2164-2174
        • Lee V.H.F.
        • Leung D.K.C.
        • Luk M.Y.
        • Tong C.C.
        • Law M.W.M.
        • Ng S.C.Y.
        • et al.
        Yttrium-90 radioembolization for advanced inoperable hepatocellular carcinoma.
        Oncotarg Ther. 2015; 8: 3457-3464
        • Mazzaferro V.
        • Sposito C.
        • Bhoori S.
        • Romito R.
        • Chiesa C.
        • Morosi C.
        • et al.
        Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study.
        Hepatology. 2013; 57: 1826-1837
        • Tsai A.L.
        • Burke C.T.
        • Kennedy A.S.
        • Moore D.T.
        • Mauro M.A.
        • Dixon R.D.
        • et al.
        Use of Yttrium-90 microspheres in patients with advanced hepatocellular carcinoma and portal vein thrombosis.
        J Vasc Interv Radiol. 2010; 21: 1377-1384
        • Xi M.
        • Zhang L.
        • Zhao L.
        • Li Q.Q.
        • Guo S.P.
        • Feng Z.Z.
        • et al.
        Effectiveness of stereotactic body radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombosis.
        PLoS One. 2013; 8: e63864
        • Lo C.H.
        • Yang J.F.
        • Liu M.Y.
        • Jen Y.M.
        • Lin C.S.
        • Chao H.L.
        • et al.
        Survival and prognostic factors for patients with advanced hepatocellular carcinoma after stereotactic ablative radiotherapy.
        PLoS One. 2017; 12: e0177793
        • Kang J.
        • Nie Q.
        • Du R.
        • Zhang L.
        • Zhang J.
        • Li Q.
        • et al.
        Stereotactic body radiotherapy combined with transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombosis.
        Mol Clin Oncol. 2014; 2: 43-50
        • Choi B.O.
        • Choi I.B.
        • Jang H.S.
        • Kang Y.N.
        • Jang J.S.
        • Bae S.H.
        • et al.
        Stereotactic body radiation therapy with or without transarterial chemoembolization for patients with primary hepatocellular carcinoma: preliminary analysis.
        Bmc Cancer. 2008; 27: 8
        • Therasse P.
        • Arbuck S.G.
        • Eisenhauer E.A.
        • Wanders J.
        • Kaplan R.S.
        • Rubinstein L.
        • et al.
        New guidelines to evaluate the response to treatment in solid Tumors.
        J Natl Cancer Inst. 2000; 92: 205-216
        • Lencioni R.
        • Llovet J.M.
        Modified RECIST (mRECIST) assessment for hepatocellular carcinoma.
        Semin Liver Dis. 2010; 30: 52-60
        • Bruix J.
        • Sherman M.
        • Llovet J.M.
        • Beaugrand M.
        • Lencioni R.
        • Burroughs A.K.
        • et al.
        Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver.
        J Hepatol. 2001; 35: 421-430
      2. Institute NC. Common Terminology Criteria for Adverse Events v4.0. NCI, NIH, DHHS; May 29, 2009. NIH publication # 09-7473.

        • Cox J.D.
        • Stetz J.
        • Pajak T.F.
        Toxicity criteria of the Radiation-Therapy Oncology Group (Rtog) and the European-Organization-for-Research-and-Treatment-of-Cancer (Eortc).
        Int J Radiat Oncol Biol Phys. 1995; 31: 1341-1346
        • Dawson L.A.
        • McGinn C.J.
        • Normolle D.
        • Ten Haken R.K.
        • Walker S.
        • Ensminger W.
        • et al.
        Escalated focal liver radiation and concurrent hepatic artery fluorodeoxyuridine for unresectable intrahepatic malignancies.
        J Clin Oncol. 2000; 18: 2210-2218
        • Seong J.
        • Park H.C.
        • Han K.H.
        • Chon C.Y.
        Clinical results and prognostic factors in radiotherapy for unresectable hepatocellular carcinoma: a retrospective study of 158 patients.
        Int J Radiat Oncol Biol Phys. 2003; 55: 329-336
        • Qi W.X.
        • Fu S.
        • Zhang Q.
        • Guo X.M.
        Charged particle therapy versus photon therapy for patients with hepatocellular carcinoma: a systematic review and meta-analysis.
        Radiother Oncol. 2015; 114: 289-295
        • Gates V.L.
        • Atassi B.
        • Lewandowski R.J.
        • Ryu R.K.
        • Sato K.T.
        • Nemcek A.A.
        • et al.
        Radioembolization with Yttrium-90 microspheres: review of an emerging treatment for liver tumors.
        Future Oncol. 2007; 3: 73-81
        • Sangro B.
        • Carpanese L.
        • Cianni R.
        • Golfieri R.
        • Gasparini D.
        • Ezziddin S.
        • et al.
        Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across barcelona clinic liver cancer stages: a European evaluation.
        Hepatology. 2011; 54: 868-878
      3. Study to Compare Selective Internal Radiation Therapy (SIRT) Versus Sorafenib in Locally Advanced Hepatocellular Carcinoma (HCC) (SIRveNIB), last updated 2016. retrieved from https://clinicaltrials.gov/ct2/show/NCT01135056.

      4. SorAfenib Versus RADIOEMBOLIZATION in Advanced Hepatocellular Carcinoma (SARAH), last updated 2017. retrieved from https://clinicaltrials.gov/ct2/show/NCT01482442.

        • Connolly G.C.
        • Chen R.
        • Hyrien O.
        • Mantry P.
        • Bozorgzadeh A.
        • Abt P.
        • et al.
        Incidence, risk factors and consequences of portal vein and systemic thromboses in hepatocellular carcinoma.
        Thromb Res. 2008; 122: 299-306
        • Truty M.J.
        • Vauthey J.N.
        Surgical resection of high-risk hepatocellular carcinoma: patient selection, preoperative considerations, and operative technique.
        Ann Surg Oncol. 2010; 17: 1219-1225
        • Kothary N.
        • Weintraub J.L.
        • Susman J.
        • Rundback J.H.
        Transarterial chemoembolization for primary hepatocellular carcinoma in patients at high risk.
        J Vasc Interv Radiol. 2007; 18: 1517-1526
      5. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Hepatobiliary cancer Version 2.2017. 2017 May 25; National Comprehensive Cancer Network. Abstract available at <http://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf>

        • Kallini J.R.
        • Gabr A.
        • Salem R.
        • Lewandowski R.J.
        Transarterial radioembolization with Yttrium-90 for the treatment of hepatocellular carcinoma.
        Adv Ther. 2016; 33: 699-714
        • Oladeru O.T.J.A.
        • Miccio J.
        • Yang Y.
        • Xue S.
        • Ryu A.M.
        Stessin Conformal external beam radiation or selective internal radiation therapy-a comparison of treatment outcomes for hepatocellular carcinoma.
        J Gastrointest Oncol. 2016; 7: 433-440
        • Mahnken A.H.
        Current status of transarterial radioembolization.
        World J Radiol. 2016; 8: 449-459
        • Murray L.J.
        • Dawson L.A.
        Advances in stereotactic body radiation therapy for hepatocellular carcinoma.
        Semin Radiat Oncol. 2017; 27: 247-255
        • Weng Z.
        • Ertle J.
        • Zheng S.
        • Lauenstein T.
        • Mueller S.
        • Bockisch A.
        • et al.
        Choi criteria are superior in evluating tumor response in patients treated with transarterial radioembolization for hepatocellular carcinoma.
        Oncol Lett. 2013; 6: 1701-1712
        • Yoon H.
        • Oh D.
        • Park H.C.
        • Kang S.W.
        • Han Y.
        • Lim D.H.
        • et al.
        Predictive factors for gastroduodenal toxicity based on endoscopy following radiotherapy in patients with hepatocellular carcinoma.
        Strahlenther Onkol. 2013; 189: 541-546
        • Qamar A.A.
        • Grace N.D.
        Abnormal hematological indices in cirrhosis.
        Can J Gastroenterol Hepatol. 2009; 23: 441-445
        • Hui Y.
        • Ruihua T.
        • Jing L.
        • Yaxiong L.
        • Ji L.
        • Linjie Y.
        • et al.
        Meta-analysis of doxorubicin-eluting beads via transcatheter arterial chemoembolization in the treatment of unresectable hepatocellular carcinoma.
        Hepatogastroenterology. 2015;
        • Civalleri D.
        • Pellicci R.
        • Decaro G.
        • Giangaspero A.
        • Ettorre G.
        • Decian F.
        • et al.
        Palliative chemoembolization of hepatocellular carcinoma with mitoxantrone, Lipiodol, and Gelfoam. A phase II study.
        Anticancer Res. 1996; 16: 937-941
        • Ueshima K.
        • Kudo M.
        • Takita M.
        • Nagai T.
        • Tatsumi C.
        • Ueda T.
        • et al.
        Hepatic arterial infusion chemotherapy using low-dose 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma.
        Oncology. 2010; 78: 148-153
        • Lee E.W.
        • Alanis L.
        • Cho S.K.
        • Saab S.
        Yttrium-90 selective internal radiation therapy with glass microspheres for hepatocellular carcinoma: current and updated literature review.
        Korean J Radiol. 2016; 17: 472-488
        • Blettner M.
        • Sauerbrei W.
        • Schlehofer B.
        • Scheuchenpflug T.
        • Friedenreich C.
        Traditional reviews, meta-analyses and pooled analyses in epidemiology.
        Int J Epidemiol. 1999; 28: 1-9
        • Stroup D.F.
        • Berlin J.A.
        • Morton S.C.
        • Olkin I.
        • Williamson G.D.
        • Rennie D.
        • et al.
        Meta-analysis of observational studies in epidemiology - A proposal for reporting.
        Jama. 2000; 283: 2008-2012
      6. National Comprehensive Cancer Network (NCCN). NCCN Levels of Evidence and Consensus for Recommendations. accessed Aug 21th, 2017. available at: https://www.nccn.org/professionals/development.aspx.