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Abstract
Over the past few years, despite improvement in screening and diagnosis of hepatocellular carcinoma (HCC), advanced stage remains the most common presentation at diagnosis, with limited management options, especially options available to patients in limited resource countries. There is currently no effective systemic chemotherapy, targeted, or immunologic therapy for advanced stage HCC. Sorafenib is the only approved front-line molecular-targeted treatment,with slight survival benefit. Regorafenib has recently been approved as second line therapy for HCC after failure of sorafenib. Ongoing research on molecular agents targeting different pathways, combination therapies, and immunotherapy, represent hope for new treatment modalities. This manuscript reviews current treatment, ongoing research, and potential future treatments for advanced HCC.
Keywords
Hepatocellular carcinoma
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advanced stage
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molecular targeted agents
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sorafenib
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immune therapy
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Asmaa Gomaa, Imam Waked.
Management of advanced hepatocellular carcinoma: review of current and potential therapies.
Hepatoma Research, 2017, 3: 112-22 DOI:10.20517/2394-5079.2017.03
| [1] |
Global battle against cancer won't be won with treatment alone--effective prevention measures urgently needed to prevent cancer crisis..Cent Eur J Public Health2014;22:23-28
|
| [2] |
Llovet JM,Mazzaferro V,Gane E,de Oliveira AC,Raoul JL.Sorafenib in advanced hepatocellular carcinoma..N Engl J Med2008;359:378-90
|
| [3] |
Kudo M.A new era of systemic therapy for hepatocellular carcinoma with regorafenib and lenvatinib..Liver Cancer2017;6:177-84
|
| [4] |
Sangro B,Bilbao JI.Radioembolization for hepatocellular carcinoma..J Hepatol2012;56:464-73
|
| [5] |
Aerts M,Van Vlierberghe H,Reynaert H.Current status and perspectives of immune-based therapies for hepatocellular carcinoma..World J Gastroenterol2016;22:253-61 PMCID:PMC4698490
|
| [6] |
Llovet JM,Castells A,Ayuso MDC,Brú C,Bruix J.Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials..Hepatology1999;29:62-7
|
| [7] |
Park JW,Colombo M,Schwartz M,Kudo M,Wagner S.Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study..Liver Int2015;35:2155-66 PMCID:PMC4691343
|
| [8] |
Yang JD,Aziz AO,Hashem MB,Abdelmaksoud AH,Afihene MY.Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa Liver Cancer Consortium..Lancet Gastroenterol Hepatol2017;2:103-11
|
| [9] |
Cervello M,Cusimano A,Azzolina A.Targeted therapy for hepatocellular carcinoma: novel agents on the horizon..Oncotarget2012;3:236-60 PMCID:PMC3359882
|
| [10] |
Nojiri K,Shiraki K,Inagaki Y,Kasai C,Yoneda M.Sorafenib and TRAIL have synergistic effect on hepatocellular carcinoma..Int J Oncol2013;42:101-8
|
| [11] |
Cheng AL,Chen Z,Qin S,Luo R,Ye S.Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial..Lancet Oncol2009;10:25-34
|
| [12] |
Cheng AL,Lin DY,Kudo M,Chung HC,Xu J.Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial..J Clin Oncol2013;31:4067-75
|
| [13] |
Johnson PJ,Park JW,Raoul JL,Hsu CH,Heo J.Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study.J Clin Oncol2013;31:3517-24
|
| [14] |
Zhu AX,Evans TJ,Santoro A,Bruix J,Thuluvath PJ.SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma..J Clin Oncol2015;33:559-66
|
| [15] |
Cainap C,Huang WT,Pan H,Kudo M,Chen PJ.Linifanib versus sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial..J Clin Oncol2015;33:172-9 PMCID:PMC4279237
|
| [16] |
Cheng AL,Lim HY,Yang TS,Chao Y,Kudo M.Randomized, open-label phase 2 study comparing frontline dovitinib versus sorafenib in patients with advanced hepatocellular carcinoma..Hepatology2016;64:774-84
|
| [17] |
Iavarone M,Piscaglia F,Grieco A,Cammà C.Field-practice study of sorafenib therapy for hepatocellular carcinoma: a prospective multicenter study in Italy..Hepatology2011;54:2055-63
|
| [18] |
Lencioni R,Ye SL,Chen XP,Furuse J,Guevara LL.GIDEON (Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and of its treatment with sorafeNib): second interim analysis..Int J Clin Pract2014;68:609-17 PMCID:PMC4265239
|
| [19] |
Llovet JM,Lathia CD,Meinhardt G.Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma..Clin Cancer Res2012;18:2290-300
|
| [20] |
Vincenzi B,Russo A,Giuliani F,Rizzo S,Frezza AM.Early skin toxicity as a predictive factor for tumor control in hepatocellular carcinoma patients treated with sorafenib..Oncologist2010;15:85-92 PMCID:PMC3227883
|
| [21] |
Otsuka T,Kawazoe S,Ario K,Kawasoe H,Mizuta T.Skin toxicities and survival in advanced hepatocellular carcinoma patients treated with sorafenib..Hepatol Res2012;42:879-86
|
| [22] |
Reig M,RodriguezLope C,LLarch N,Darnell A,Ayuso C.Early dermatologic adverse events predict better outcome in HCC patients treated with sorafenib..J Hepatol2014;61:318-24
|
| [23] |
Koschny R,Koehler C,Stremmel W.Diarrhea is a positive outcome predictor for sorafenib treatment of advanced hepatocellular carcinoma..Oncology2013;84:6-13
|
| [24] |
Estfan B,Kim R.Sorafenib in advanced hepatocellular carcinoma: hypertension as a potential surrogate marker for efficacy..Am J Clin Oncol2013;36:319-24
|
| [25] |
Pinter M,Graziadei I,Maieron A,Weissmann A,Plank C.Sorafenib in unresectable hepatocellular carcinoma from mild to advanced stage liver cirrhosis..Oncologist2009;14:70-6
|
| [26] |
Iavarone M,Biolato M,Maida M,Basso M,Craxì A.Predictors of survival in patients with advanced hepatocellular carcinoma who permanently discontinued sorafenib..Hepatology2015;62:784-91
|
| [27] |
Reig M,Torres F,RodriguezLope C,LLarch N,Ayuso C.Postprogression survival of patients with advanced hepatocellular carcinoma: rationale for second-line trial design..Hepatology2013;58:2023-31
|
| [28] |
Finn RS,Ikeda K,Tamai T,Younger S,Qin S.A multicenter, open-label, phase 3 trial to compare the efficacy and safety of lenvatinib (E7080) versus sorafenib in first-line treatment of subjects with unresectable hepatocellular carcinoma..J Clin Oncol2014;32 suppl:tps4153
|
| [29] |
Bruix J,Merle P,Huang YH,Pracht M,Rosmorduc O.Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial..Lancet2017;389:56-66
|
| [30] |
Ikeda K,Kawazoe S,Ikeda M,Tamai T,Hisai T.Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma..J Gastroenterol2017;52:512-9 PMCID:PMC5357473
|
| [31] |
Positive Topline Results of Large Phase 3 Trial Show Eisai's Lenvatinib Meets Primary Endpoint in Unresectable Hepatocellular Carcinoma. Available from: http://eisai.mediaroom.com/2017-01-25-Positive-Topline-Results-of-Large-Phase-3-Trial-Show-Eisais-Lenvatinib-Meets-Primary-Endpoint-in-Unresectable-Hepatocellular-Carcinoma. [Last accessed on June 1, 2017].
|
| [32] |
Zhu AX,Ryoo BY,Poon R,Blanc JF,Baron AD,Okusaka T,Trojan J,Chau I,Abada PB,Schwartz JD.Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial..Lancet Oncol2015;16:859-70
|
| [33] |
Zhu AX,Assenat E,Kang YK,Poon RT,Vogel A.Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial..JAMA2014;312:57-67
|
| [34] |
Llovet JM,Raoul JL,Kudo M,Kang YK,Lim HY.Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study..J Clin Oncol2013;31:3509-16
|
| [35] |
Bruix J.Management of hepatocellular carcinoma: an update..Hepatology2011;53:1020-2 PMCID:PMC3084991
|
| [36] |
Strumberg D.Regorafenib for cancer..Expert Opin Investig Drugs2012;21:879-89
|
| [37] |
Santoro A,Borbath I,Salvagni S,Van Vlierberghe H,Kolligs FT.Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study..Lancet Oncol2013;14:55-63
|
| [38] |
Zhu AX,Yen CJ,Poon RT-P,Blanc JF,Baron AD.Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): analysis of patients with elevated α-fetoprotein (AFP) from the randomized phase III REACH study..Am Soc Clinl Oncol2015;35:abstr4108
|
| [39] |
Zhu AX,Malfertheiner P,Kawazoe S,Weissinger F,Barone CA.Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: analysis of REACH trial results by Child-Pugh score..JAMA Oncol2017;3:235-43
|
| [40] |
Finn RS.Current and future treatment strategies for patients with advanced hepatocellular carcinoma: role of mTOR inhibition..Liver Cancer2012;1:247-56 PMCID:PMC3760459
|
| [41] |
Kang YK,Park JW,Lee TY,Chan S,Kim R.Randomized phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma..Ann Oncol2015;26:2457-63
|
| [42] |
Qin S.Apatinib in Chinese patients with advanced hepatocellular carcinoma: a phase II randomized, open-label trial..Am Soc Clin Oncol2014;32 suppl:abstr4019
|
| [43] |
O'Reilly KE,She Q-B,Mills GB,Lane H,Hicklin DJ.mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt..Cancer Res2006;66:1500-8 PMCID:PMC3193604
|
| [44] |
Koeberle D,Demeter G,Ribi K,Saletti P,Horber D.Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29)..Ann Oncol2016;27:856-61
|
| [45] |
Lim HY,Choi HJ,Yoon JH,Rau KM,Yeo W.A phase II study of the efficacy and safety of the combination therapy of the MEK inhibitor refametinib (BAY 86-9766) plus sorafenib for Asian patients with unresectable hepatocellular carcinoma..Clin Cancer Res2014;20:5976-85
|
| [46] |
Okazaki T.PD-1 and PD-1 ligands: from discovery to clinical application..Int Immunol2007;19:813-24
|
| [47] |
Brahmer JR,Lipson EJ.Nivolumab: targeting PD-1 to bolster antitumor immunity..Future Oncol2015;11:1307-26
|
| [48] |
Melero I,Yau TC,Kudo M,Kim TY,Trojan J,Welling TH,Chopra A,Dela Cruz CM,Jaclyn N,El-Khoueiry A. Nivolumab dose escalation and expansion in patients with advanced hepatocellular carcinoma (HCC): the CheckMate 040 study. Available from: https://www.mdlinx.com/gastroenterology/conference-abstract.cfm/60392/?nonus=0&searchstring=&coverage_day=0&page=2. [Last accessed on June 1, 2017].
|
| [49] |
Sangro B,de la Mata M,Garralda E,Riezu-Boj JI,Alfaro C.A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C..J Hepatol2013;59:81-8
|
| [50] |
Fuchs CS,Ryan DP,Kim H,Vincitore M,Stuart KE.A phase II trial of gemcitabine in patients with advanced hepatocellular carcinoma..Cancer2002;94:3186-91
|
| [51] |
Yeo W,Zee B,Lai PB,Koh J,Yu SC,Hui P,Lam KC,Wong HT,Johnson PJ.A randomized phase III study of doxorubicin versus cisplatin/interferon alpha-2b/doxorubicin/fluorouracil (PIAF) combination chemotherapy for unresectable hepatocellular carcinoma..J Natl Cancer Inst2005;97:1532-8
|
| [52] |
de Verdià A.Reversion of multidrug resistance with polyalkylcyanoacrylate nanoparticles: towards a mechanism of action..Br J Cancer1997;76:198
|
| [53] |
Kudo M,Numata K,Tanaka H,Kawazoe S,Sato Y,Furuse J,Fang X,Takeuchi M.S-1 versus placebo in patients with sorafenib-refractory advanced hepatocellular carcinoma (S-CUBE): a randomised, double-blind, multicentre, phase 3 trial..Lancet Gastroenterol Hepatol2017;2:407-17
|
| [54] |
Qin S,Lim HY,Chao Y,Yang TS,Kang WK.Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia..J Clin Oncol2013;31:3501-8
|
| [55] |
Liu L,Han L.Efficacy and safety of oxaliplatin-based chemotherapy for advanced primary hepatic carcinoma: a systemic review and meta analysis of prospective studies..Linchuang Zhongliuxue Zazhi2015;20:769-79
|
| [56] |
Petrelli F,Borgonovo K,Ghilardi M,Barni S.Oxaliplatin-based chemotherapy: a new option in advanced hepatocellular carcinoma. a systematic review and pooled analysis..Clin Oncol2014;26:488-96
|
| [57] |
Abou-Alfa GK,Knox JJ,Davidenko I,Leung T,Saltz LB.Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial..JAMA2010;304:2154-60
|
| [58] |
Del Prete S,Caraglia M,Cennamo G,Piai G,Tarantino L.Sorafenib plus octreotide is an effective and safe treatment in advanced hepatocellular carcinoma: multicenter phase II So. LAR. study..Cancer Chemother Pharmacol2010;66:837-44
|
| [59] |
Petrini I,Ricasoli M,Orlandini C,Bartolozzi C.Phase II trial of sorafenib in combination with 5-fluorouracil infusion in advanced hepatocellular carcinoma..Cancer Chemother Pharmacol2012;69:773-80
|
| [60] |
Hsu CH,Lin ZZ,Shao YY,Hsu C.Phase II study of combining sorafenib with metronomic tegafur/uracil for advanced hepatocellular carcinoma..J Hepatol2010;53:126-31
|
| [61] |
Giuliani F,Addeo R,Maiello E,Pisconti S.Sorafenib plus cisplatin and gemcitabine in the treatment of advanced hepatocellular carcinoma (HCC): a phase II study by the Gruppo Oncologico dell'Italia Meridionale (prot. GOIM 2705)..J Clin Oncol2011;29:225
|
| [62] |
Liu Y,Xu S,Ma N,Qiao L.First-line gemcitabine and oxaliplatin (GEMOX) plus sorafenib, followed by sorafenib as maintenance therapy, for patients with advanced hepatocellular carcinoma: a preliminary study..Int J Clin Oncol2015;20:952-9
|
| [63] |
Assenat E,Thezenas S,Peron JM,Dahan L,Blanc JF,Ramdani M,Bleuse JP.Sorafenib (S) alone versus S combined with gemcitabine and oxaliplatin (GEMOX) in first-line treatment of advanced hepatocellular carcinoma (HCC): final analysis of the randomized phase II GONEXT trial (UNICANCER/FFCD PRODIGE 10 trial)..J Clin Oncol2013;31 suppl 15:abstr4028
|
| [64] |
Yau T,Lee F,Wong H,Leung A,Yau T.A multicenter phase II study of sorafenib, capecitabine, and oxaliplatin (SECOX) in patients with advanced hepatocellular carcinoma: final results of Hong Kong-Singapore Hepatocellular Carcinoma Research Collaborative Group study..J Clin Oncol2013;31 suppl 15:abstr4117
|
| [65] |
Abou-Alfa GK,Knox JJ,Posey J,Kavan P,Murray JJ.Phase III randomized study of sorafenib plus doxorubicin versus sorafenib in patients with advanced hepatocellular carcinoma (HCC): CALGB80802 (Alliance)..Am Soc Clin Oncol2016;suppl 4:abstr192
|
| [66] |
Kudo M,Yokosuka O,Izumi N,Nagano H,Sasaki Y.Prospective randomized controlled phase III trial comparing the efficacy of sorafenib versus sorafenib in combination with low-dose cisplatin/fluorouracil hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma..J Hepatol2016;64:S209-10
|
| [67] |
EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol2012;56:908-43
|
| [68] |
Bruix J.Management of hepatocellular carcinoma..Hepatology2005;42:1208-36
|
| [69] |
Kokudo N,Akahane M,Izumi N,Uemoto S,Kawasaki S.Evidence-based clinical practice guidelines for hepatocellular carcinoma: the Japan society of hepatology 2013 update (3rd JSH-HCC guidelines)..Hepatol Res2015;45:238-46
|
| [70] |
Kudo M,Kokudo N,Sakamoto M,Kojiro M,HCC Expert Panel of Japan Society of Hepatology..Management of hepatocellular carcinoma in Japan: consensus-based clinical practice guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version..Dig Dis2011;29:339-64
|
| [71] |
Chung GE,Kim HY,Kim JS,Yoon JH,Kim YJ.Transarterial chemoembolization can be safely performed in patients with hepatocellular carcinoma invading the main portal vein and may improve the overall survival..Radiology2011;258:627-34
|
| [72] |
Martin R,Robbins K,Dubel G,Padr R.Evaluation of sorafenib in combination with doxorubicin-loaded DC bead as a combination treatment option for HCC..ASCO Gastrointestinal Cancers Symposium2010;suppl:abstr 216
|
| [73] |
Muhammad A,Vidyarthi G,Boyd W,Kumar A.Comparative effectiveness of traditional chemoembolization with or without sorafenib for hepatocellular carcinoma..World J Hepatol2013;5:364-71 PMCID:PMC3724964
|
| [74] |
Bai W,Zhao Y,Yin ZX,Li RJ,Xia JL,Han GH.Sorafenib in combination with transarterial chemoembolization improves the survival of patients with unresectable hepatocellular carcinoma: a propensity score matching study..J Dig Dis2013;14:181-90
|
| [75] |
Choi GH,Kim MJ,Ryoo BY,Shin YM,Lim YS.Sorafenib alone versus sorafenib combined with transarterial chemoembolization for advanced-stage hepatocellular carcinoma: results of propensity score analyses..Radiology2013;269:603-11
|
| [76] |
Qu XD,Wang JH,Chen JM,Liu QX,Liu LX,Qian S.The efficacy of TACE combined sorafenib in advanced stages hepatocellullar carcinoma..BMC Cancer2012;12:263 PMCID:PMC3411397
|
| [77] |
Ohki T,Yamagami M,Yamada T,Kojima K,Toda N.Efficacy of transcatheter arterial chemoembolization followed by sorafenib for intermediate/advanced hepatocellular carcinoma in patients in Japan: a retrospective analysis..Clin Drug Investig2015;35:751-9
|
| [78] |
Hu H,Long X,Shi H,Yang Z.Sorafenib combined with transarterial chemoembolization versus transarterial chemoembolization alone for advanced-stage hepatocellular carcinoma: a propensity score matching study..PLoS One2014;9:e96620
|
| [79] |
Zhang L,Chen X.Transarterial chemoembolization (TACE) plus sorafenib versus TACE for intermediate or advanced stage hepatocellular carcinoma: a meta-analysis..PLoS One2014;9:e100305
|
| [80] |
Kudo M,Izumi N,Kadoya M,Okusaka T,Tsuchiya K.JSH consensus-based clinical practice guidelines for the management of hepatocellular carcinoma: 2014 update by the Liver Cancer Study Group of Japan..Liver Cancer2014;3:458-68 PMCID:PMC4531423
|
| [81] |
Group KLCS.2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma..Ko J Radiol2015;16:465-522 PMCID:PMC4435981
|
| [82] |
Kasai K,Suzuki K.Combination therapy of intra-arterial 5-fluorouracil and systemic pegylated interferon alpha-2b for advanced hepatocellular carcinoma..Int J Clin Oncol2011;16:221-9
|
| [83] |
Song DS,Bae SH,Jang JY,Lee SH,Yim HJ,Park SY.A comparative study between sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis..J Gastroenterol2015;50:445-54
|
| [84] |
Salem R,Sangro B.Yttrium 90 radioembolization for the treatment of hepatocellular carcinoma: biological lessons, current challenges, and clinical perspectives..Hepatology2013;58:2188-97 PMCID:PMC3732811
|
| [85] |
Salem R,Mulcahy MF,Ryu RK,Atassi B,Gates V,Sato KT,Gupta R,Newman SB,Abecassis M.Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes..Gastroenterology2010;138:52-64
|
| [86] |
Salem R,Kulik L,Riaz A,Sato KT,Nikolaidis P,Yaghmai V,Senthilnathan S,Gates VL,Newman S,Chen R,Nemcek AA,Chrisman HB,Omary RA,Benson AB3rd.Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma..Gastroenterology2011;140:497-507 PMCID:PMC3129335
|
| [87] |
Sangro B,Cianni R,Gasparini D,Paprottka PM,Van Buskirk M,Ettorre GM,Giampalma E,Wilhelm K,Izzo F,Maini CL,Cappelli A,Ahmadzadehfar H,Lastoria S.Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation..Hepatology2011;54:868-78
|
| [88] |
Mazzaferro V,Bhoori S,Chiesa C,Maccauro M,Bongini M.Yttrium-90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study..Hepatology2013;57:1826-37
|
| [89] |
Kulik LM,Mulcahy MF,Atassi B,Sato KT,Nemcek AA.Safety and efficacy of 90Y radiotherapy for hepatocellular carcinoma with and without portal vein thrombosis..Hepatology2008;47:71-81
|
| [90] |
Gramenzi A,Mosconi C,Granito A,Marinelli S,Erroi V.Yttrium-90 radioembolization vs sorafenib for intermediate-locally advanced hepatocellular carcinoma: a cohort study with propensity score analysis..Liver Int2015;35:1036-47
|
| [91] |
Cho YY,Kim HC,Kim YH,Bae SH,Kim YJ.Radioembolization is a safe and effective treatment for hepatocellular carcinoma with portal vein thrombosis: a propensity score analysis..PLoS One2016;11:e0154986
|
| [92] |
Salman A,Hassanain M,Boucher LM,Cabrera T,Metrakos P.Combined sorafenib and yttrium-90 radioembolization for the treatment of advanced hepatocellular carcinoma..Curr Oncol2016;23:e472-80
|