Integration of Systemic and Liver-Directed Therapies for Locally Advanced Hepatocellular Cancer: Harnessing Potential Synergy for New Therapeutic Horizons

Authors: Eric H. Bent MD, PhD1, Eric Wehrenberg-Klee MD2, Eugene J. Koay MD, PhD3, Lipika Goyal MD4, and Jennifer Y. Wo MD1
View More View Less
  • 1 Department of Radiation Oncology;
  • | 2 Division of Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
  • | 3 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; and
  • | 4 Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
Restricted access

Treatment options in locally advanced hepatocellular carcinoma (HCC) have evolved considerably over the past few years with the recent approval of multiple systemic therapies and significant advances in locoregional therapy. Given the poor prognosis for patients with unresectable HCC, there is significant interest in rationally designed combination therapies. This article reviews the treatment options available to patients with locally advanced HCC and discusses the rationale, ongoing trials, and future prospects for combining locoregional and systemic therapy in both the definitive and neoadjuvant settings.

Submitted December 4, 2020; accepted for publication March 16, 2021.

Disclosures: Dr. Wehrenberg-Klee has disclosed receiving consulting fees from SIRTEX, and grant/research support from Boston Scientific. Dr. Koay has disclosed receiving grant/research support from Philips Healthcare, General Electric, Elekta, and Stand Up 2 Cancer; and receiving personal fees from RenovoRx and Taylor & Francis, LLC. Dr. Goyal has disclosed serving as a scientific advisor for Agios Pharmaceuticals Inc., Alentis Therapeutics AG, Debiopharm Group, H3 Biomedicine, Incyte Corporation, QED Therapeutics, Sirtex Medical Ltd., and Taiho Oncology Inc; receiving consulting fees from Agios Pharmaceuticals Inc., Alentis Therapeutics AG, Incyte Corporation, QED Therapeutics, Sirtex Medical Ltd., and Taiho Oncology Inc.; and serving as a scientific consultant for AstraZeneca Pharmaceuticals LP. Dr. Wo has disclosed receiving grant/research support from Genentech. Dr. Bent has disclosed that he has not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Correspondence: Lipika Goyal, MD, Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Yawkey 7E, 55 Fruit Street, Boston, MA 02114. Email: lgoyal@partners.org; and Jennifer Y. Wo, MD, Department of Radiation Oncology, Massachusetts General Hospital, 100 Blossom Street, Boston, MA 02114. Email: jwo@partners.org

Supplementary Materials

    • Supplemental Materials (PDF 62 KB)
  • 1.

    Villanueva A. Hepatocellular carcinoma. N Engl J Med 2019;380:14501462.

  • 2.

    Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2017. Accessed March 22, 2021. Available at: https://seer.cancer.gov/csr/1975_2017/

    • Search Google Scholar
    • Export Citation
  • 3.

    European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol 2018;69:182236.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Cheng S, Chen M, Cai J, et al. Chinese expert consensus on multidisciplinary diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus (2018 edition). Liver Cancer 2020;9:2840.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67:358380.

  • 6.

    Lencioni R, de Baere T, Soulen MC, et al. Lipiodol transarterial chemoembolization for hepatocellular carcinoma: a systematic review of efficacy and safety data. Hepatology 2016;64:106116.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Llovet JM, Real MI, Montaña X, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 2002;359:17341739.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 2002;35:11641171.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Lammer J, Malagari K, Vogl T, et al. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 2010;33:4152.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Salem R, Gordon AC, Mouli S, et al. Y90 radioembolization significantly prolongs time to progression compared with chemoembolization in patients with hepatocellular carcinoma. Gastroenterology 2016;151:11551163.e2.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    O’Doherty J. A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy. J Diagn Imaging Ther 2015;2:134.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Vilgrain V, Pereira H, Assenat E, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol 2017;18:16241636.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Chow PKH, Gandhi M, Tan SB, et al. SIRveNIB: selective internal radiation therapy versus sorafenib in Asia-Pacific patients with hepatocellular carcinoma. J Clin Oncol 2018;36:19131921.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Bujold A, Massey CA, Kim JJ, et al. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol 2013;31:16311639.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Andolino DL, Johnson CS, Maluccio M, et al. Stereotactic body radiotherapy for primary hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2011;81:e447453.

  • 16.

    Hong TS, Wo JY, Yeap BY, et al. Multi-institutional phase II study of high-dose hypofractionated proton beam therapy in patients with localized, unresectable hepatocellular carcinoma and intrahepatic cholangiocarcinoma. J Clin Oncol 2016;34:460468.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Benson AB III, D’Angelica MI, Abbott DE, et al. NCCN Clinical Practice Guidelines in Oncology: Hepatobiliary Cancers. Version 4.2020. Accessed January 15, 2021. To view the most recent version, visit NCCN.org

  • 18.

    Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999;19:329338.

  • 19.

    Yoon SM, Ryoo BY, Lee SJ, et al. Efficacy and safety of transarterial chemoembolization plus external beam radiotherapy vs sorafenib in hepatocellular carcinoma with macroscopic vascular invasion: a randomized clinical trial. JAMA Oncol 2018;4:661669.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Huo YR, Eslick GD. Transcatheter arterial chemoembolization plus radiotherapy compared with chemoembolization alone for hepatocellular carcinoma: a systematic review and meta-analysis. JAMA Oncol 2015;1:756765.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378390.

  • 22.

    Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018;391:11631173.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Pinter M, Jain RK, Duda DG. The current landscape of immune checkpoint blockade in hepatocellular carcinoma: a review. JAMA Oncol 2021;7:113–123.

  • 24.

    Yau T, Kang YK, Kim TY, et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: the CheckMate 040 randomized clinical trial. JAMA Oncol 2020;6:e204564.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 2020;382:18941905.

  • 26.

    Finn RS, Qin S, Ikeda M, et al. IMbrave150: updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC) [abstract]. J Clin Oncol 2021;39(Suppl):Abstract 267.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005;307:5862.

  • 28.

    Yu W, Gu K, Yu Z, et al. Sorafenib potentiates irradiation effect in hepatocellular carcinoma in vitro and in vivo. Cancer Lett 2013;329:109117.

  • 29.

    Kudo M, Ueshima K, Ikeda M, et al. Randomised, multicentre prospective trial of transarterial chemoembolisation (TACE) plus sorafenib as compared with TACE alone in patients with hepatocellular carcinoma: TACTICS trial. Gut 2020;69:14921501.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    He M, Li Q, Zou R, et al. Sorafenib plus hepatic arterial infusion of oxaliplatin, fluorouracil, and leucovorin vs sorafenib alone for hepatocellular carcinoma with portal vein invasion: a randomized clinical trial. JAMA Oncol 2019;5:953960.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Meyer T, Fox R, Ma YT, et al. Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol 2017;2:565575.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Li L, Zhao W, Wang M, et al. Transarterial chemoembolization plus sorafenib for the management of unresectable hepatocellular carcinoma: a systematic review and meta-analysis. BMC Gastroenterol 2018;18:138.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Teyateeti A, Mahvash A, Long JP, et al. Survival outcomes for yttrium-90 transarterial radioembolization with and without sorafenib for unresectable hepatocellular carcinoma patients. J Hepatocell Carcinoma 2020;7:117131.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Ricke J, Klümpen HJ, Amthauer H, et al. Impact of combined selective internal radiation therapy and sorafenib on survival in advanced hepatocellular carcinoma. J Hepatol 2019;71:11641174.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Kroemer G, Galluzzi L, Kepp O, et al. Immunogenic cell death in cancer therapy. Annu Rev Immunol 2013;31:5172.

  • 36.

    Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 2012;366:925931.

  • 37.

    Beyls C, Haustermans K, Deroose CM, et al. Could autoimmune disease contribute to the abscopal effect in metastatic hepatocellular carcinoma? Hepatology 2020;72:11521154.

  • 38.

    Demaria S, Ng B, Devitt ML, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys 2004;58:862870.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Rodríguez-Ruiz ME, Vanpouille-Box C, Melero I, et al. Immunological mechanisms responsible for radiation-induced abscopal effect. Trends Immunol 2018;39:644655.

  • 40.

    Formenti SC, Rudqvist NP, Golden E, et al. Radiotherapy induces responses of lung cancer to CTLA-4 blockade. Nat Med 2018;24:18451851.

  • 41.

    Chi KH, Liu SJ, Li CP, et al. Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. J Immunother 2005;28:129135.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Grassberger C, Hong TS, Hato T, et al. Differential association between circulating lymphocyte populations with outcome after radiation therapy in subtypes of liver cancer. Int J Radiat Oncol Biol Phys 2018;101:12221225.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Chew V, Lee YH, Pan L, et al. Immune activation underlies a sustained clinical response to yttrium-90 radioembolisation in hepatocellular carcinoma. Gut 2019;68:335346.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Kohles N, Nagel D, Jüngst D, et al. Predictive value of immunogenic cell death biomarkers HMGB1, sRAGE, and DNase in liver cancer patients receiving transarterial chemoembolization therapy. Tumour Biol 2012;33:24012409.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45.

    Singh P, Toom S, Avula A, et al. The immune modulation effect of locoregional therapies and its potential synergy with immunotherapy in hepatocellular carcinoma. J Hepatocell Carcinoma 2020;7:1117.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46.

    Hiroishi K, Eguchi J, Baba T, et al. Strong CD8(+) T-cell responses against tumor-associated antigens prolong the recurrence-free interval after tumor treatment in patients with hepatocellular carcinoma. J Gastroenterol 2010;45:451458.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47.

    Zerbini A, Pilli M, Laccabue D, et al. Radiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response. Gastroenterology 2010;138:19311942.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Hansler J, Wissniowski TT, Schuppan D, et al. Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases. World J Gastroenterol 2006;12:37163721.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49.

    Vanpouille-Box C, Alard A, Aryankalayil MJ, et al. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun 2017;8:15618.

  • 50.

    Weichselbaum RR, Liang H, Deng L, et al. Radiotherapy and immunotherapy: a beneficial liaison? Nat Rev Clin Oncol 2017;14:365379.

  • 51.

    Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 2015;520:373377.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 52.

    Kim KJ, Kim JH, Lee SJ, et al. Radiation improves antitumor effect of immune checkpoint inhibitor in murine hepatocellular carcinoma model. Oncotarget 2017;8:4124241255.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53.

    Friedman D, Baird JR, Young KH, et al. Programmed cell death-1 blockade enhances response to stereotactic radiation in an orthotopic murine model of hepatocellular carcinoma. Hepatol Res 2017;47:702714.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 54.

    Choi C, Yoo GS, Cho WK, et al. Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma. World J Gastroenterol 2019;25:24162429.

  • 55.

    Waitz R, Solomon SB, Petre EN, et al. Potent induction of tumor immunity by combining tumor cryoablation with anti-CTLA-4 therapy. Cancer Res 2012;72:430439.

  • 56.

    Theelen WSME, Chen D, Verma V, et al. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials [published online October 20, 2020]. Lancet Respir Med, https://doi.org/10.1016/S2213-2600(20)30391-X

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57.

    McBride S, Sherman E, Tsai CJ, et al. Randomized phase II trial of nivolumab with stereotactic body radiotherapy versus nivolumab alone in metastatic head and neck squamous cell carcinoma. J Clin Oncol 2021;39:3037.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58.

    Zhu AX, Finn RS, Ikeda M, et al. A phase Ib study of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC) [abstract]. J Clin Oncol 2020;38(Suppl):Abstract 4519.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 59.

    Yau T, Zagonel V, Santoro A, et al. Nivolumab (NIVO) + ipilimumab (IPI) + cabozantinib (CABO) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): results from CheckMate 040 [abstract]. J Clin Oncol 2020;38(Suppl):Abstract 478.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 60.

    Munn LL, Jain RK. Vascular regulation of antitumor immunity. Science 2019;365:544545.

  • 61.

    Liu XD, Hoang A, Zhou L, et al. Resistance to antiangiogenic therapy is associated with an immunosuppressive tumor microenvironment in metastatic renal cell carcinoma. Cancer Immunol Res 2015;3:10171029.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 62.

    Lu LC, Lee YH, Chang CJ, et al. Increased expression of programmed death-ligand 1 in infiltrating immune cells in hepatocellular carcinoma tissues after sorafenib treatment. Liver Cancer 2019;8:110120.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 63.

    Kimura T, Kato Y, Ozawa Y, et al. Immunomodulatory activity of lenvatinib contributes to antitumor activity in the Hepa1-6 hepatocellular carcinoma model. Cancer Sci 2018;109:39934002.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 64.

    Chiang CL, Chan ACY, Chiu KWH, et al. Combined stereotactic body radiotherapy and checkpoint inhibition in unresectable hepatocellular carcinoma: a potential synergistic treatment strategy. Front Oncol 2019;9:1157.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 65.

    Juloori A, Liao CY, Lemons JM, et al. Phase I study of stereotactic body radiotherapy followed by ipilimumab with nivolumab vs nivolumab alone in unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2020;108:S149150.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 66.

    Duffy AG, Ulahannan SV, Makorova-Rusher O, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol 2017;66:545551.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 67.

    Pollom EL, Deng L, Pai RK, et al. Gastrointestinal toxicities with combined antiangiogenic and stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys 2015;92:568576.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 68.

    Chen SW, Lin LC, Kuo YC, et al. Phase 2 study of combined sorafenib and radiation therapy in patients with advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2014;88:10411047.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 69.

    Spigel DR, Hainsworth JD, Yardley DA, et al. Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab. J Clin Oncol 2010;28:4348.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 70.

    Small W Jr, Mulcahy MF, Rademaker A, et al. Phase II trial of full-dose gemcitabine and bevacizumab in combination with attenuated three-dimensional conformal radiotherapy in patients with localized pancreatic cancer. Int J Radiat Oncol Biol Phys 2011;80:476482.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 71.

    Crane CH, Eng C, Feig BW, et al. Phase II trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2010;76:824830.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 72.

    Vitale A, Burra P, Frigo AC, et al. Survival benefit of liver resection for patients with hepatocellular carcinoma across different Barcelona Clinic Liver Cancer stages: a multicentre study. J Hepatol 2015;62:617624.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 73.

    Pompili M, Saviano A, de Matthaeis N, et al. Long-term effectiveness of resection and radiofrequency ablation for single hepatocellular carcinoma ≤3 cm. Results of a multicenter Italian survey. J Hepatol 2013;59:8997.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 74.

    Samuel M, Chow PK, Chan Shih-Yen E, et al. Neoadjuvant and adjuvant therapy for surgical resection of hepatocellular carcinoma. Cochrane Database Syst Rev 2009;2009:CD001199.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 75.

    Bruix J, Takayama T, Mazzaferro V, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol 2015;16:13441354.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 76.

    Wang J, He XD, Yao N, et al. A meta-analysis of adjuvant therapy after potentially curative treatment for hepatocellular carcinoma. Can J Gastroenterol 2013;27:351363.

  • 77.

    Wang Z, Ren Z, Chen Y, et al. Adjuvant transarterial chemoembolization for HBV-related hepatocellular carcinoma after resection: a randomized controlled study. Clin Cancer Res 2018;24:20742081.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 78.

    Kaseb A, Pestana RC, Vence LM, et al. Randomized, open-label, perioperative phase II study evaluating nivolumab alone versus nivolumab plus ipilimumab in patients with resectable HCC [abstract]. J Clin Oncol 2019;37(Suppl):Abstract 185.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 79.

    Chen X, Zhang Y, Zhang N, et al. Lenvatinib combined nivolumab injection followed by extended right hepatectomy is a feasible treatment for patients with massive hepatocellular carcinoma: a case report. OncoTargets Ther 2019;12:73557359.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 80.

    Wei X, Jiang Y, Zhang X, et al. Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a randomized, open-label, multicenter controlled study. J Clin Oncol 2019;37:21412151.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 1543 1543 1543
PDF Downloads 202 202 202
EPUB Downloads 0 0 0