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Local Arterial Therapies in the Management of Unresectable Hepatocellular Carcinoma

  • Upper Gastrointestinal Cancers (L Rajdev, Section Editor)
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Opinion statement

Most patients with hepatocellular carcinoma present with intermediate to advanced disease, where curative therapies are no longer an option. These patients with intermediate to advanced disease represent a heterogeneous population with regard to tumor burden, liver function, and performance status. While the Barcelona Clinic Liver Cancer (BCLC) staging system offers guidelines for the management of these patients, strict adherence to these guidelines may limit treatment options for these patients. Several locoregional therapies exist for these patients, including conventional transarterial chemoembolization (cTACE), transarterial embolization (TAE), drug-eluting embolization (DEE), and radioembolization. Evidence is also emerging for the role of radiation therapy including most notably stereotactic body radiation therapy and proton therapy, although at the current time, clinical trial participation is encouraged. While cTACE is traditionally recommended for BCLC B disease, both cTACE and radioembolization are increasingly used for patients with intermediate disease, as well as in select patients with BCLC A and C disease. TAE and DEE are limited in their use currently, due to lack of clear survival benefits or clinical advantages over cTACE. While several studies have demonstrated similar OS between cTACE and radioembolization, radioembolization provides a longer time to progression and fewer toxicities compared to cTACE. This is particularly relevant in the setting of advanced BCLC B and early BCLC C disease, where patients may have limited reserve. Radioembolization also has additional roles as an alternative to ablation, inducing liver hypertrophy, treating patients with PVT, and downstaging lesions to transplant. Ongoing studies will further define the role of locoregional treatment potentially in combination with and in light of developments in systemic therapy.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118–27.

    Article  CAS  PubMed  Google Scholar 

  2. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.

    Article  CAS  PubMed  Google Scholar 

  3. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379(9822):1245–55.

    Article  PubMed  Google Scholar 

  4. Marrero JA, Fontana RJ, Barrat A, Askari F, Conjeevaram HS, Su GL, et al. Prognosis of hepatocellular carcinoma: comparison of 7 staging systems in an American cohort. Hepatology. 2005;41(4):707–16.

    Article  PubMed  Google Scholar 

  5. Cillo U, Vitale A, Grigoletto F, Farinati F, Brolese A, Zanus G, et al. Prospective validation of the Barcelona Clinic Liver Cancer staging system. J Hepatol. 2006;44(4):723–31.

    Article  PubMed  Google Scholar 

  6. Bruix J, Sherman M. American Association for the Study of Liver D. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53(3):1020–2.

    Article  PubMed  PubMed Central  Google Scholar 

  7. European Association For The Study Of The L, European Organisation For R, Treatment Of C. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2012;56(4):908–43.

    Article  Google Scholar 

  8. Schwartz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma. Nat Clin Pract Oncol. 2007;4(7):424–32.

    Article  CAS  PubMed  Google Scholar 

  9. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362(9399):1907–17.

    Article  PubMed  Google Scholar 

  10. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology. 2003;37(2):429–42.

    Article  CAS  PubMed  Google Scholar 

  11. Bolondi L, Burroughs A, Dufour JF, Galle PR, Mazzaferro V, Piscaglia F, et al. Heterogeneity of patients with intermediate (BCLC B) hepatocellular carcinoma: proposal for a subclassification to facilitate treatment decisions. Semin Liver Dis. 2012;32(4):348–59.

    CAS  PubMed  Google Scholar 

  12. Benson AB 3rd, D'Angelica MI, Abbott DE, Abrams TA, Alberts SR, Saenz DA, et al. NCCN guidelines insights: hepatobiliary cancers, version 1.2017. J Natl Compr Cancer Netw. 2017;15(5):563–73.

    Article  Google Scholar 

  13. Lewandowski RJ, Salem R. Yttrium-90 radioembolization of hepatocellular carcinoma and metastatic disease to the liver. Semin Interv Radiol. 2006;23(1):64–72.

    Article  Google Scholar 

  14. Balogh J, Victor D 3rd, Asham EH, Burroughs SG, Boktour M, Saharia A, et al. Hepatocellular carcinoma: a review. J Hepatocell Carcinoma. 2016;3:41–53.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Mouli SK, Hickey R, Thornburg B, Sato KT, Desai K, Gabr A, et al. Single- versus triple-drug chemoembolization for hepatocellular carcinoma: comparing outcomes by toxicity, imaging response, and survival. J Vasc Interv Radiol. 2016;27(9):1279–87.

    Article  PubMed  Google Scholar 

  16. 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(5):1826–37.

    Article  CAS  PubMed  Google Scholar 

  17. Tawada A, Chiba T, Ooka Y, Kanogawa N, Motoyama T, Saito T, et al. Efficacy of transarterial chemoembolization targeting portal vein tumor thrombus in patients with hepatocellular carcinoma. Anticancer Res. 2014;34(8):4231–7.

    PubMed  Google Scholar 

  18. Chern MC, Chuang VP, Liang CT, Lin ZH, Kuo TM. Transcatheter arterial chemoembolization for advanced hepatocellular carcinoma with portal vein invasion: safety, efficacy, and prognostic factors. J Vasc Interv Radiol. 2014;25(1):32–40.

    Article  PubMed  Google Scholar 

  19. Garin E, Lenoir L, Edeline J, Laffont S, Mesbah H, Poree P, et al. Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for hepatocellular carcinoma patients: a new personalized promising concept. Eur J Nucl Med Mol Imaging. 2013;40(7):1057–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rand T, Loewe C, Schoder M, Schmook MT, Peck-Radosavljevic M, Kettenbach J, et al. Arterial embolization of unresectable hepatocellular carcinoma with use of microspheres, lipiodol, and cyanoacrylate. Cardiovasc Interv Radiol. 2005;28(3):313–8.

    Article  Google Scholar 

  21. Maluccio MA, Covey AM, Porat LB, Schubert J, Brody LA, Sofocleous CT, et al. Transcatheter arterial embolization with only particles for the treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol. 2008;19(6):862–9.

    Article  PubMed  Google Scholar 

  22. Sasaki Y, Imaoka S, Kasugai H, Fujita M, Kawamoto S, Ishiguro S, et al. A new approach to chemoembolization therapy for hepatoma using ethiodized oil, cisplatin, and gelatin sponge. Cancer. 1987;60(6):1194–203.

    Article  CAS  PubMed  Google Scholar 

  23. Kishore S, Friedman T, Madoff DC. Update on embolization therapies for hepatocellular carcinoma. Curr Oncol Rep. 2017;19(6):40.

    Article  PubMed  Google Scholar 

  24. Varela M, Real MI, Burrel M, Forner A, Sala M, Brunet M, et al. Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol. 2007;46(3):474–81.

    Article  CAS  PubMed  Google Scholar 

  25. Sangro B, Salem R, Kennedy A, Coldwell D, Wasan H. Radioembolization for hepatocellular carcinoma: a review of the evidence and treatment recommendations. Am J Clin Oncol. 2011;34(4):422–31.

    Article  PubMed  Google Scholar 

  26. Pauwels X, Azahaf M, Lassailly G, Sergent G, Buob D, Truant S, et al. Drug-eluting beads loaded with doxorubicin (DEBDOX) chemoembolisation before liver transplantation for hepatocellular carcinoma: an imaging/histologic correlation study. Cardiovasc Intervent Radiol. 2015;38(3):685–92.

    Article  PubMed  Google Scholar 

  27. Tohme S, Sukato D, Chen HW, Amesur N, Zajko AB, Humar A, et al. Yttrium-90 radioembolization as a bridge to liver transplantation: a single-institution experience. J Vasc Interv Radiol. 2013;24(11):1632–8.

    Article  PubMed  Google Scholar 

  28. Hodavance MS, Vikingstad EM, Griffin AS, Pabon-Ramos WM, Berg CL, Suhocki PV, et al. Effectiveness of transarterial embolization of hepatocellular carcinoma as a bridge to transplantation. J Vasc Interv Radiol. 2016;27(1):39–45.

    Article  PubMed  Google Scholar 

  29. Agopian VG, Morshedi MM, McWilliams J, Harlander-Locke MP, Markovic D, Zarrinpar A, et al. Complete pathologic response to pretransplant locoregional therapy for hepatocellular carcinoma defines cancer cure after liver transplantation: analysis of 501 consecutively treated patients. Ann Surg. 2015;262(3):536–45. discussion 43-5

    Article  PubMed  Google Scholar 

  30. Oligane HC, Xing M, Kim HS. Effect of bridging local-regional therapy on recurrence of hepatocellular carcinoma and survival after orthotopic liver transplantation. Radiology. 2017;282(3):869–79.

    Article  PubMed  Google Scholar 

  31. Sheth RA, Patel MS, Koottappillil B, Shah JA, Oklu R, Mueller P, et al. Role of locoregional therapy and predictors for dropout in patients with hepatocellular carcinoma listed for liver transplantation. J Vasc Interv Radiol. 2015;26(12):1761–8. quiz 8

    Article  PubMed  Google Scholar 

  32. Pompili M, Francica G, Ponziani FR, Iezzi R, Avolio AW. Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation. World J Gastroenterol. 2013;19(43):7515–30.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Lewandowski RJ, Kulik LM, Riaz A, Senthilnathan S, Mulcahy MF, Ryu RK, et al. A comparative analysis of transarterial downstaging for hepatocellular carcinoma: chemoembolization versus radioembolization. Am J Transplant. 2009;9(8):1920–8.

    Article  CAS  PubMed  Google Scholar 

  34. Seehofer D, Nebrig M, Denecke T, Kroencke T, Weichert W, Stockmann M, et al. Impact of neoadjuvant transarterial chemoembolization on tumor recurrence and patient survival after liver transplantation for hepatocellular carcinoma: a retrospective analysis. Clin Transplant. 2012;26(5):764–74.

    Article  PubMed  Google Scholar 

  35. Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359(9319):1734–9.

    Article  PubMed  Google Scholar 

  36. Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35(5):1164–71.

    Article  CAS  PubMed  Google Scholar 

  37. Lencioni R, de Baere T, Soulen MC, Rilling WS, Geschwind JF. Lipiodol transarterial chemoembolization for hepatocellular carcinoma: a systematic review of efficacy and safety data. Hepatology. 2016;64(1):106–16.

    Article  CAS  PubMed  Google Scholar 

  38. Marelli L, Stigliano R, Triantos C, Senzolo M, Cholongitas E, Davies N, et al. Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Interv Radiol. 2007;30(1):6–25.

    Article  Google Scholar 

  39. Tsochatzis E, Meyer T, Marelli L, Burroughs AK. Which transarterial therapy is best for hepatocellular carcinoma?—the evidence to date. J Hepatol. 2010;53(3):588.

    Article  PubMed  Google Scholar 

  40. Sahara S, Kawai N, Sato M, Tanaka T, Ikoma A, Nakata K, et al. Prospective evaluation of transcatheter arterial chemoembolization (TACE) with multiple anti-cancer drugs (epirubicin, cisplatin, mitomycin c, 5-fluorouracil) compared with TACE with epirubicin for treatment of hepatocellular carcinoma. Cardiovasc Interv Radiol. 2012;35(6):1363–71.

    Article  Google Scholar 

  41. Antoch G, Roelle G, Ladd SC, Kuehl H, Heusner TA, Sotiropoulos GC, et al. Selective and sequential transarterial chemoembolization: survival in patients with hepatocellular carcinoma. Eur J Radiol. 2012;81(9):2290–7.

    Article  PubMed  Google Scholar 

  42. Vogl TJ, Naguib NN, Nour-Eldin NE, Farshid P, Lehnert T, Gruber-Rouh T, et al. Retrospective study on the use of different protocols for repeated transarterial chemoembolization in the treatment of patients with hepatocellular carcinoma. Acad Radiol. 2012;19(4):434–9.

    Article  PubMed  Google Scholar 

  43. Petruzzi NJ, Frangos AJ, Fenkel JM, Herrine SK, Hann HW, Rossi S, et al. Single-center comparison of three chemoembolization regimens for hepatocellular carcinoma. J Vasc Interv Radiol. 2013;24(2):266–73.

    Article  PubMed  Google Scholar 

  44. Liu B, Huang JW, Li Y, Hu BS, He X, Zhao W, et al. Single-agent versus combination doxorubicin-based transarterial chemoembolization in the treatment of hepatocellular carcinoma: a single-blind, randomized, phase II trial. Oncology. 2015;89(1):23–30.

    Article  CAS  PubMed  Google Scholar 

  45. Grieco A, Marcoccia S, Miele L, Marmiroli L, Caminiti G, Ragazzoni E, et al. Transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma in cirrhotics: functional hepatic reserve and survival. Hepatogastroenterology. 2003;50(49):207–12.

    PubMed  Google Scholar 

  46. Saccheri S, Lovaria A, Sangiovanni A, Nicolini A, De Fazio C, Ronchi G, et al. Segmental transcatheter arterial chemoembolization treatment in patients with cirrhosis and inoperable hepatocellular carcinomas. J Vasc Interv Radiol. 2002;13(10):995–9.

    Article  PubMed  Google Scholar 

  47. Lu W, Li Y, He X, Chen Y. Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with cirrhosis: evaluation of two kinds of dosages of anticancer drugs and analysis of prognostic factors. Hepatogastroenterology. 2003;50(54):2079–83.

    PubMed  Google Scholar 

  48. Herber SC, Otto G, Schneider J, Schuchmann M, Duber C, Pitton MB, et al. Transarterial chemoembolization in patients not eligible for liver transplantation: single-center results. AJR Am J Roentgenol. 2008;190(4):1035–42.

    Article  PubMed  Google Scholar 

  49. Georgiades C, Geschwind JF, Harrison N, Hines-Peralta A, Liapi E, Hong K, et al. Lack of response after initial chemoembolization for hepatocellular carcinoma: does it predict failure of subsequent treatment? Radiology. 2012;265(1):115–23.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Terzi E, Golfieri R, Piscaglia F, Galassi M, Dazzi A, Leoni S, et al. Response rate and clinical outcome of HCC after first and repeated cTACE performed “on demand”. J Hepatol. 2012;57(6):1258–67.

    Article  CAS  PubMed  Google Scholar 

  51. Malagari K, Pomoni M, Kelekis A, Pomoni A, Dourakis S, Spyridopoulos T, et al. Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Interv Radiol. 2010;33(3):541–51.

    Article  Google Scholar 

  52. • Brown KT, Do RK, Gonen M, Covey AM, Getrajdman GI, Sofocleous CT, et al. Randomized trial of hepatic artery embolization for hepatocellular carcinoma using doxorubicin-eluting microspheres compared with embolization with microspheres alone. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34(17):2046–53. RCT comparing TAE to TACE demonstrating similar outcomes.

    Article  CAS  Google Scholar 

  53. Namur J, Citron SJ, Sellers MT, Dupuis MH, Wassef M, Manfait M, et al. Embolization of hepatocellular carcinoma with drug-eluting beads: doxorubicin tissue concentration and distribution in patient liver explants. J Hepatol. 2011;55(6):1332–8.

    Article  CAS  PubMed  Google Scholar 

  54. Reyes DK, Vossen JA, Kamel IR, Azad NS, Wahlin TA, Torbenson MS, et al. Single-center phase II trial of transarterial chemoembolization with drug-eluting beads for patients with unresectable hepatocellular carcinoma: initial experience in the United States. Cancer J. 2009;15(6):526–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Burrel M, Reig M, Forner A, Barrufet M, de Lope CR, Tremosini S, et al. Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial design. J Hepatol. 2012;56(6):1330–5.

    Article  PubMed  Google Scholar 

  56. Lammer J, Malagari K, Vogl T, Pilleul F, Denys A, Watkinson A, et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Interv Radiol. 2010;33(1):41–52.

    Article  Google Scholar 

  57. Golfieri R, Giampalma E, Renzulli M, Cioni R, Bargellini I, Bartolozzi C, et al. Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer. 2014;111(2):255–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. 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(6):2188–97.

    Article  CAS  PubMed  Google Scholar 

  59. Salem R, Lewandowski RJ, Mulcahy MF, Riaz A, Ryu RK, Ibrahim S, et al. Radioembolization for hepatocellular carcinoma using Yttrium-90 microspheres: a comprehensive report of long-term outcomes. Gastroenterology. 2010;138(1):52–64.

    Article  CAS  PubMed  Google Scholar 

  60. Hilgard P, Hamami M, Fouly AE, 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(5):1741–9.

    Article  CAS  PubMed  Google Scholar 

  61. 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(3):868–78.

    Article  PubMed  Google Scholar 

  62. Salem R, Lewandowski RJ, Kulik L, Wang E, Riaz A, Ryu RK, et al. Radioembolization results in longer time-to-progression and reduced toxicity compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2011;140(2):497–507. e2

    Article  PubMed  Google Scholar 

  63. Soydal C, Arslan MF, Kucuk ON, Idilman R, Bilgic S. Comparison of survival, safety, and efficacy after transarterial chemoembolization and radioembolization of Barcelona Clinic Liver Cancer stage B-C hepatocellular cancer patients. Nucl Med Commun. 2016;37(6):646–9.

    Article  CAS  PubMed  Google Scholar 

  64. • Zhang Y, Li Y, Ji H, Zhao X, Lu H. Transarterial Y90 radioembolization versus chemoembolization for patients with hepatocellular carcinoma: a meta-analysis. Biosci Trends. 2015;9(5):289–98. Large meta-analysis comparing radioembolization to chemoembolization with suggestion of improved overall survival.

    Article  PubMed  Google Scholar 

  65. Lobo L, Yakoub D, Picado O, Ripat C, Pendola F, Sharma R, et al. Unresectable hepatocellular carcinoma: radioembolization versus chemoembolization: a systematic review and meta-analysis. Cardiovasc Interv Radiol. 2016;39(11):1580–8.

    Article  Google Scholar 

  66. • Salem R, Gordon AC, Mouli S, Hickey R, Kallini J, Gabr A, et al. Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology. 2016;151(6):1155–63 e2. Prospective RCT comparing radioembolization to chemoembolization suggesting improved TTP.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Fujiki M, Aucejo F, Choi M, Kim R. Neo-adjuvant therapy for hepatocellular carcinoma before liver transplantation: where do we stand? World J Gastroenterol. 2014;20(18):5308–19.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;334(11):693–9.

    Article  CAS  PubMed  Google Scholar 

  69. Yao FY, Mehta N, Flemming J, Dodge J, Hameed B, Fix O, et al. Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria. Hepatology. 2015;61(6):1968–77.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Kulik LM, Atassi B, van Holsbeeck L, Souman T, Lewandowski RJ, Mulcahy MF, et al. Yttrium-90 microspheres (TheraSphere) treatment of unresectable hepatocellular carcinoma: downstaging to resection, RFA and bridge to transplantation. J Surg Oncol. 2006;94(7):572–86.

    Article  CAS  PubMed  Google Scholar 

  71. Riaz A, Gates VL, Atassi B, Lewandowski RJ, Mulcahy MF, Ryu RK, et al. Radiation segmentectomy: a novel approach to increase safety and efficacy of radioembolization. Int J Radiat Oncol Biol Phys. 2011;79(1):163–71.

    Article  PubMed  Google Scholar 

  72. Vouche M, Habib A, Ward TJ, Kim E, Kulik L, Ganger D, et al. Unresectable solitary hepatocellular carcinoma not amenable to radiofrequency ablation: multicenter radiology-pathology correlation and survival of radiation segmentectomy. Hepatology. 2014;60(1):192–201.

    Article  PubMed  Google Scholar 

  73. Padia SA, Kwan SW, Roudsari B, Monsky WL, Coveler A, Harris WP. Superselective yttrium-90 radioembolization for hepatocellular carcinoma yields high response rates with minimal toxicity. J Vasc Interv Radiol. 2014;25(7):1067–73.

    Article  PubMed  Google Scholar 

  74. Padia SA, Johnson GE, Horton KJ, Ingraham CR, Kogut MJ, Kwan S, et al. Segmental Yttrium-90 radioembolization versus segmental chemoembolization for localized hepatocellular carcinoma: results of a single-center, retrospective, propensity score-matched study. J Vasc Interv Radiol. 2017;28(6):777–85. e1

    Article  PubMed  Google Scholar 

  75. Memon K, Kulik L, Lewandowski RJ, Gupta R, Ryu RK, Miller FH, et al. Prospective evaluation of patients with early-/intermediate-stage hepatocellular carcinoma with disease progression following arterial locoregional therapy: candidacy for systemic treatment or clinical trials. J Vasc Interv Radiol. 2013;24(8):1189–97. e2

    Article  PubMed  Google Scholar 

  76. Shirabe K, Shimada M, Gion T, Hasegawa H, Takenaka K, Utsunomiya T, et al. Postoperative liver failure after major hepatic resection for hepatocellular carcinoma in the modern era with special reference to remnant liver volume. J Am Coll Surg. 1999;188(3):304–9.

    Article  CAS  PubMed  Google Scholar 

  77. Zorzi D, Laurent A, Pawlik TM, Lauwers GY, Vauthey JN, Abdalla EK. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg. 2007;94(3):274–86.

    Article  CAS  PubMed  Google Scholar 

  78. Kim RD, Kim JS, Watanabe G, Mohuczy D, Behrns KE. Liver regeneration and the atrophy-hypertrophy complex. Semin Interv Radiol. 2008;25(2):92–103.

    Article  Google Scholar 

  79. de Graaf W, van den Esschert JW, van Lienden KP, van Gulik TM. Induction of tumor growth after preoperative portal vein embolization: is it a real problem? Ann Surg Oncol. 2009;16(2):423–30.

    Article  PubMed  Google Scholar 

  80. Hayashi S, Baba Y, Ueno K, Nakajo M, Kubo F, Ueno S, et al. Acceleration of primary liver tumor growth rate in embolized hepatic lobe after portal vein embolization. Acta Radiol. 2007;48(7):721–7.

    Article  CAS  PubMed  Google Scholar 

  81. Gaba RC, Lewandowski RJ, Kulik LM, Riaz A, Ibrahim SM, Mulcahy MF, et al. Radiation lobectomy: preliminary findings of hepatic volumetric response to lobar yttrium-90 radioembolization. Ann Surg Oncol. 2009;16(6):1587–96.

    Article  PubMed  Google Scholar 

  82. Edeline J, Lenoir L, Boudjema K, Rolland Y, Boulic A, Le Du F, et al. Volumetric changes after (90)y radioembolization for hepatocellular carcinoma in cirrhosis: an option to portal vein embolization in a preoperative setting? Ann Surg Oncol. 2013;20(8):2518–25.

    Article  PubMed  Google Scholar 

  83. Ahmadzadehfar H, Meyer C, Ezziddin S, Sabet A, Hoff-Meyer A, Muckle M, et al. Hepatic volume changes induced by radioembolization with 90Y resin microspheres. A single-centre study. Eur J Nucl Med Mol Imaging. 2013;40(1):80–90.

    Article  PubMed  Google Scholar 

  84. Vouche M, Lewandowski RJ, Atassi R, Memon K, Gates VL, Ryu RK, et al. Radiation lobectomy: time-dependent analysis of future liver remnant volume in unresectable liver cancer as a bridge to resection. J Hepatol. 2013;59(5):1029–36.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Pamecha V, Davidson B. Portal vein embolization prior to extensive resection for colorectal liver metastases. Ann Surg Oncol. 2009;16(11):3214.

    Article  PubMed  Google Scholar 

  86. Garlipp B, de Baere T, Damm R, Irmscher R, van Buskirk M, Stubs P, et al. Left-liver hypertrophy after therapeutic right-liver radioembolization is substantial but less than after portal vein embolization. Hepatology. 2014;59(5):1864–73.

    Article  CAS  PubMed  Google Scholar 

  87. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359(4):378–90.

    Article  CAS  PubMed  Google Scholar 

  88. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. 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 Oncol. 2009;10(1):25–34.

    Article  CAS  PubMed  Google Scholar 

  89. Korse CM, Bonfrer JM, Prevoo W, Baas P, Taal BG. Increase of angiogenic growth factors after hepatic artery embolization in patients with neuroendocrine tumours. Tumour Biol. 2011;32(4):647–52.

    Article  CAS  PubMed  Google Scholar 

  90. Li X, Feng GS, Zheng CS, Zhuo CK, Liu X. 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. World J Gastroenterol. 2004;10(19):2878–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Sergio A, Cristofori C, Cardin R, Pivetta G, Ragazzi R, Baldan A, et al. Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness. Am J Gastroenterol. 2008;103(4):914–21.

    Article  PubMed  Google Scholar 

  92. Shim JH, Park JW, Kim JH, An M, Kong SY, Nam BH, et al. Association between increment of serum VEGF level and prognosis after transcatheter arterial chemoembolization in hepatocellular carcinoma patients. Cancer Sci. 2008;99(10):2037–44.

    CAS  PubMed  Google Scholar 

  93. Carpizo DR, Gensure RH, Yu X, Gendel VM, Greene SJ, Moore DF, et al. Pilot study of angiogenic response to yttrium-90 radioembolization with resin microspheres. J Vasc Interv Radiol. 2014;25(2):297–306 e1.

    Article  PubMed  Google Scholar 

  94. Choi GH, Shim JH, Kim MJ, Ryu MH, Ryoo BY, Kang YK, et al. Sorafenib alone versus sorafenib combined with transarterial chemoembolization for advanced-stage hepatocellular carcinoma: results of propensity score analyses. Radiology. 2013;269(2):603–11.

    Article  PubMed  Google Scholar 

  95. Chao Y, Chung YH, Han G, Yoon JH, Yang J, Wang J, et al. The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma: final results of the START trial. Int J Cancer. 2015;136(6):1458–67.

    Article  CAS  PubMed  Google Scholar 

  96. Lencioni R, Llovet JM, Han G, Tak WY, Yang J, Guglielmi A, et al. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: the SPACE trial. J Hepatol. 2016;64(5):1090–8.

    Article  CAS  PubMed  Google Scholar 

  97. Chow PK, Poon DY, Khin MW, Singh H, Han HS, Goh AS, et al. Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma. PLoS One. 2014;9(3):e90909.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Cho YY, Lee M, Kim HC, Chung JW, Kim YH, Gwak GY, et al. Radioembolization is a safe and effective treatment for hepatocellular carcinoma with portal vein thrombosis: a propensity score analysis. PLoS One. 2016;11(5):e0154986.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Calderaro J, Rousseau B, Amaddeo G, Mercey M, Charpy C, Costentin C, et al. Programmed death ligand 1 expression in hepatocellular carcinoma: relationship With clinical and pathological features. Hepatology. 2016;64(6):2038–46.

    Article  CAS  PubMed  Google Scholar 

  100. A El-Khoueiry. Phase I/II safety and antitumor activity of nivolumab (nivo) in patients (pts) with advanced hepatocellular carcinoma (HCC): interim analysis of the CheckMate-040 dose escalation study 2016; Available from: http://meetinglibrary.asco.org/content/167136-176.

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Authors and Affiliations

  1. Department of Radiology and Radiologic Sciences, Vanderbilt University Medical Center, 1161 21st Avenue South, CCC-1118 Medical Center North, Nashville, TN, 37232-2675, USA

    Samdeep K. Mouli MD

  2. Division of Hematology-Oncology, Department of Medicine, Vanderbilt University Medical Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN, 37232-6307, USA

    Laura W. Goff MD, MS

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  1. Samdeep K. Mouli MD
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  2. Laura W. Goff MD, MS
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Correspondence to Laura W. Goff MD, MS.

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Samdeep K. Mouli and Laura W. Goff declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Upper Gastrointestinal Cancers

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Mouli, S.K., Goff, L.W. Local Arterial Therapies in the Management of Unresectable Hepatocellular Carcinoma. Curr. Treat. Options in Oncol. 18, 67 (2017). https://doi.org/10.1007/s11864-017-0509-6

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