Multidisciplinary Management of Patients with Unresectable Hepatocellular Carcinoma: A Critical Appraisal of Current Evidence

Pierre M Gholam, Renuka Iyer, Matthew S Johnson, Pierre M Gholam, Renuka Iyer, Matthew S Johnson

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of new cancer diagnoses in the United States, with an incidence that is expected to rise. The etiology of HCC is varied and can lead to differences between patients in terms of presentation and natural history. Subsequently, physicians treating these patients need to consider a variety of disease and patient characteristics when they select from the many different treatment options that are available for these patients. At the same time, the treatment landscape for patients with HCC, particularly those with unresectable HCC, has been rapidly evolving as new, evidence-based options become available. The treatment plan for patients with HCC can include surgery, transplant, ablation, transarterial chemoembolization, transarterial radioembolization, radiation therapy, and/or systemic therapies. Implementing these different modalities, where the optimal sequence and/or combination has not been defined, requires coordination between physicians with different specialties, including interventional radiologists, hepatologists, and surgical and medical oncologists. As such, the implementation of a multidisciplinary team is necessary to develop a comprehensive care plan for patients, especially those with unresectable HCC.

Keywords: TACE; TARE; hepatocellular carcinoma; locoregional treatment; systemic treatment.

Conflict of interest statement

P.M.G. has received honoraria from Bayer/Onyx for speaking, consulting, and being on advisory boards. He has also received research support from Bayer/Onyx; R.I. has received honoraria from Bayer, Bristol-Myers Squibb, and Eisai for consulting, and grant support from Sirtex and Merck. She is on the NCCN Hepatobiliary Guidelines Panel; M.S.J. received honoraria for consulting from Bayer, Bristol-Myers Squibb, BTG, Boston Scientific, Johnson and Johnson/Ethicon, and Surefire Medical.

References

    1. Cancer Stat Facts: Liver and Intrahepatic Bile Duct Cancer. NCI Surveillance, Epidemiology, and End Results Program. [(accessed on 29 January 2019)]; Available online: .
    1. Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2019. CA Cancer J. Clin. 2019;69:7–34. doi: 10.3322/caac.21551.
    1. Llovet J.M., Burroughs A., Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–1917. doi: 10.1016/S0140-6736(03)14964-1.
    1. Bruix J., Reig M., Sherman M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology. 2016;150:835–853. doi: 10.1053/j.gastro.2015.12.041.
    1. European Association For The Study of The Liver. European Organisation for Research and Treatment of Cancer Treatment Of, EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J. Hepatol. 2012;56:908–943. doi: 10.1016/j.jhep.2011.12.001.
    1. National Comprehensive Cancer Network . NCCN Clinical Practice Guidelines in Oncology, NCCN Guidelines: Hepatobilliary Cancers v1.2019. National Comprehensive Cancer Network; Plymouth Meeting, PA, USA: 2019.
    1. Verslype C., Rosmorduc O., Rougier P. Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2012;23:vii41–vii48. doi: 10.1093/annonc/mds225.
    1. Yau T., Tang Y.F.T., Yao T.-J., Fan S.-T., Lo C.-M., Poon R.T.P. Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology. 2014;146:1691–1700. doi: 10.1053/j.gastro.2014.02.032.
    1. Llovet J.M., Real M.I., Montaña X., Planas R., Coll S., Aponte J., Ayusa C., Sala M., Muchart J., Sola R., et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359:1734–1739. doi: 10.1016/S0140-6736(02)08649-X.
    1. Lo C.M., Ngan H., Tso W.-K., Liu C.-L., Lam C.-M., Poon R.T.-P., Fan S.T., Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35:1164–1171. doi: 10.1053/jhep.2002.33156.
    1. Chow P.K.H., Gandhi M., Tan S.B., Khin M.W., Khasbazar A., Ong J., Choo S.P., Cheow P.C., Chotipanich C., Lim K., et al. SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma. J. Clin. Oncol. 2018:JCO2017760892. doi: 10.1200/JCO.2017.76.0892.
    1. Vilgrain V., Pereira H., Assenat E., Guiu E., Ilonca A.D., Pageaux G.-P., Silbert A., Bouattour M., Lebtahi R., Allham W., 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;18:1624–1636. doi: 10.1016/S1470-2045(17)30683-6.
    1. Llovet J.M., Ricci S., Mazzaferro V., Hilgard P., Gane E., Blanc J.-F., de Oliviera A.C., Santoro A., Raoul J.-L., Forner A., et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 2008;359:378–390. doi: 10.1056/NEJMoa0708857.
    1. Kudo M., Finn R.S., Qin S., Han K.-H., Ikeda K., Piscaglia F., Baron A., Park J.W., Han G., Jassem J., et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial. Lancet. 2018;391:1163–1173. doi: 10.1016/S0140-6736(18)30207-1.
    1. Wilhelm S.M., Dumas J., Adnane L., Lynch M., Carter C.A., Schütz G., Thierauch K.H., Zopf D. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int. J. Cancer. 2011;129:245–255. doi: 10.1002/ijc.25864.
    1. Bruix J., Qin S., Merle P., Granito A., Huang Y.-H., Bodoky G., Pracht M., Yokosuka O., Rosmorduc O., Breder V., et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;389:56–66. doi: 10.1016/S0140-6736(16)32453-9.
    1. Finn R.S., Merle P., Granito A., Huang Y.-H., Bodoky G., Pracht M., Yokosuka O., Rosmorduc O., Gerolami R., Caparello C., et al. Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: Additional analyses from the phase III RESORCE trial. J. Hepatol. 2018;69:353–358. doi: 10.1016/j.jhep.2018.04.010.
    1. Xiang Q., Chen W., Ren W., Wang J., Deng D.Y., Zhang L., Shang C., Chen Y. Cabozantinib suppresses tumor growth and metastasis in hepatocellular carcinoma by a dual blockade of VEGFR2 and MET. Clin. Cancer Res. 2014;20:2959–2970. doi: 10.1158/1078-0432.CCR-13-2620.
    1. Yakes F.M., Chen J., Tan J., Yamaguchi K., Shi Y., Yu P., Qian F., Chu F., Bentzien F., Cancilla B., et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol. Cancer Ther. 2011;10:2298–2308. doi: 10.1158/1535-7163.MCT-11-0264.
    1. Abou-Alfa G.K., Meyer T., Cheng A.L., El-Khoueiry A.B., Rimassa L., Ryoo B.Y., Cicin I., Merle P., Chen Y., Park J.W., et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N. Engl. J. Med. 2018;379:54–63. doi: 10.1056/NEJMoa1717002.
    1. El-Khoueiry A.B., Sangro B., Yau T., Crocenzi T.S., Kudo M., Hsu C., Kim T.Y., Choo S.P., Trojan J., Willing T.H., et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389:2492–2502. doi: 10.1016/S0140-6736(17)31046-2.
    1. Zhu A.X., Finn R.S., Edeline J., Cattan S., Ogasawara S., Palmer D., Verslype C., Zagonel V., Fartoux L., Vogel A., et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): A non-randomised, open-label phase 2 trial. Lancet Oncol. 2018;19:940–952. doi: 10.1016/S1470-2045(18)30351-6.
    1. Zhu A.X., Kang Y.K., Yen C.J., Finn R.S., Galle P.R., Llovet J.M., Assenat E., Brandi G., Pracht M., Lim H.Y., et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20:282–296. doi: 10.1016/S1470-2045(18)30937-9.
    1. Chang T.T., Sahwney R., Monto A., Davoren J.B., Kirkland J.G., Stewart L., Corvera C.U. Implementation of a multidisciplinary treatment team for hepatocellular cancer at a Veterans Affairs Medical Center improves survival. HPB (Oxford) 2008;10:405–411. doi: 10.1080/13651820802356572.
    1. Yopp A.C., Monsour J.C., Beg M.S., Arenas J., Trimmer C., Reddick M., Pedrosa I., Khatri G., Yakoo T., Meyer J.J., et al. Establishment of a multidisciplinary hepatocellular carcinoma clinic is associated with improved clinical outcome. Ann. Surg. Oncol. 2014;21:1287–1295. doi: 10.1245/s10434-013-3413-8.
    1. Serper M., Taddei T., Mehta R., D’Addeo K., Dai F., Aytaman A., Baytarian M., Fox R., Hunt K., Goldberg D.S., et al. Association of provider specialty and multidisciplinary care with hepatocellular carcinoma treatment and mortality. Gastroenterology. 2017;152:1954–1964. doi: 10.1053/j.gastro.2017.02.040.
    1. Charriere B., Muscari F., Maulat C., Bournet B., Bonnet D., Bureau C., Otal P., Peron J.M., Suc B. Outcomes of patients with hepatocellular carcinoma are determined in multidisciplinary team meetings. J. Surg. Oncol. 2017;115:330–336. doi: 10.1002/jso.24500.
    1. Forner A., Reig M., Bruix J. Hepatocellular carcinoma. Lancet. 2018;391:1301–1314. doi: 10.1016/S0140-6736(18)30010-2.

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