Abstract
A 36-year-old man had been diagnosed with a solitary hepatocellular carcinoma in the right lobe of the liver by computed tomography, and right hemihepatectomy was performed 16 years previously. Approximately 13 years later, he underwent partial hepatectomy because of intrahepatic recurrence in segment 4. Multinodular intrahepatic recurrences in the remnant liver were identified 19 months after repeat hepatectomy, and he underwent transcatheter arterial chemoembolization therapy. Ultimately, six transcatheter arterial chemoembolization therapies were required because of multiple repeat multinodular intrahepatic recurrences. The patient was refractory to transcatheter arterial chemoembolization, and therefore, he participated in a trial of lenvatinib monotherapy. At lenvatinib initiation, his liver function was Child–Pugh class A. Enhanced abdominal computed tomography detected four tumors in the remnant liver. Enhanced abdominal computed tomography findings at the first evaluation showed no residual contrast uptake on arterial phase images, corresponding to a complete response according to Response Evaluation Criteria in Solid Tumors at 4 months after initiation of lenvatinib. The patient was able to continue long-term lenvatinib therapy with well-controlled general health, and he maintained a complete response for two years and three months. Here, we describe his clinical course and radiological results during lenvatinib monotherapy.
Similar content being viewed by others
References
Bray F, Ferlay J, Soerjomataran I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.
Fan ST, Lo CM, Liu CL, et al. Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths. Ann Surg. 1999;229:322–30.
Bruix J, Sherman M. American association for the study of liver diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–2.
Yamamoto M, Katagiri S, Ariizumi S, et al. Tips for anatomical hepatectomy for hepatocellular carcinoma by the Glissonean pedicle approach (with videos). J Hepatobiliary Pancreat Sci. 2014;21:53–6.
Grieco A, Pompili M, Caminiti MG, et al. Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre. Gut. 2005;54:411–8.
Llovet JM, Di Bisceglie AM, Bruix J, et al. Panel of experts in HCC-design clinical trials. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Institute. 2008;100:698–711.
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Medd. 2008;359:378–90.
Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomized, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.
Marrero JA, Kudo M, Venook AP, et al. Observational registry of sorafenib use in clinical practice across Child-Pugh subgroups: the GIDEON study. J Hepatol. 2016;65:1140–7.
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;391:1163–73.
Mody K, Abou-Alfa GK. Systemic therapy for advanced hepatocellular carcinoma in an evolving landscape. Curr Treat Options Oncol. 2019;20:3.
Tong MJ, Blatt LM, Kao VW. Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America. J Gastroenterol Hepatol. 2001;16:553–9.
Trevisani F, De Notariis S, Rapaccini G, et al. Italian Liver Cancer Group. Italian Liver Cancer Group: Semiannual and annual surveillance of cirrhotic patients for hepatocellular carcinoma: effects on cancer stage and patient survival (Italian experience). Am J Gastroenterol. 2002;97:734–44.
Stravitz RT, Heuman DM, Chand N, et al. Surveillance for hepatocellular carcinoma in patients with cirrhosis improves outcome. Am J Med. 2008;121:119–26.
Kokudo N, Hasegawa K, Akahane M, et al. Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH-HCC Guidelines). Hepatol Res. 2015;45:1109–13.
Kudo M, Matsui O, Izumi N, et al. Transarterial chemoembolization failure/refractoriness: JSH-LCSGJ criteria 2014 update. Oncology. 2014;87:22–31.
Arizumi T, Ueshima K, Minami T, et al. Effectiveness of sorafenib in patients with transcatheter arterial chemoembolization (TACE) refractory and intermediate-stage hepatocellular carcinoma. Liver Cancer. 2015;4:253–62.
Ogasawara S, Chiba T, Ooka Y, et al. Efficacy of sorafenib in intermediate-stage hepatocellular carcinoma patients refractory to transarterial chemoembolization. Oncology. 2014;87:330–41.
Bruix J, Qin S, Merle P, et al. RESORCE Investigators. 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.
Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med. 2018;379:54–63.
Zhu AX, Kang YK, Yen CJ, et al. REACH-2 study investigators. 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;20:282–96.
Zhu AX, Finn RS, Edeline J, 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;19:940–52.
El-Khoueiry AB, Sangro B, Yau T, 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;389:2492–502.
Kudo M. Lenvatinib may drastically change the treatment landscape of hepatocellular carcinoma. Liver Cancer. 2018;7:1–9.
Eso Y, Marusawa H. Novel approaches for molecular targeted therapy against hepatocellular carcinoma. Hepatol Res. 2018;48:597–607.
Shimose S, Kawaguchi T, Tanaka M, et al. Lenvatinib prolongs the progression-free survival time of patients with intermediate-stage hepatocellular carcinoma refractory to transarterial chemoembolization: A multicenter cohort study using data mining analysis. Oncol Lett. 2020;20:2257–65.
Takahashi A, Moriguchi M, Seko Y, et al. Impact of relative dose intensity of early-phase lenvatinib treatment on therapeutic response in hepatocellular carcinoma. Anticancer Res. 2019;39:5149–56.
Fuchigami A, Imai Y, Uchida Y, et al. Therapeutic efficacy of lenvatinib for patients with unresectable hepatocellular carcinoma based on the middle-term outcome. PLoS ONE. 2020;15: e0231427.
Tada T, Kumada T, Hiraoka A, et al. Safety and efficacy of lenvatinib in elderly patients with unresectable hepatocellular carcinoma: A multicenter analysis with propensity score matching. Hepatol Res. 2020;50:75–83.
Hiraoka A, Kumada T, Atsukawa M, et al. Real-life Practice Experts for HCC (RELPEC) Study Group, HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan). Prognostic factor of lenvatinib for unresectable hepatocellular carcinoma in real-world conditions-Multicenter analysis. Cancer Med. 2019;8:3719–28.
Takeda H, Nishijima N, Nasu A, et al. Long-term antitumor effect of lenvatinib on unresectable hepatocellular carcinoma with portal vein invasion. Hepatol Res. 2019;49:594–9.
Cheon J, Chon HJ, Bang Y, et al. Real-world efficacy and safety of lenvatinib in Korean patients with advanced hepatocellular carcinoma: a multicenter retrospective analysis. Liver Cancer. 2020;9:613–24.
Hiraoka A, Kumada T, Tsuji K, et al. Validation of modified ALBI grade for more detailed assessment of hepatic function in hepatocellular carcinoma patients: a multicenter analysis. Liver Cancer. 2019;8:121.
Ogushi K, Chuma M, Uojima H, et al. Safety and efficacy of lenvatinib treatment in Child-Pugh A and B patients with unresectable hepatocellular carcinoma in clinical practice: a multicenter analysis. Clin Exp Gastroenterol. 2020;13:385–96.
Ohki T, Sato K, Kondo M, et al. Relationship between outcomes and relative dose intensity of lenvatinib treatment in patients with advanced hepatocellular carcinoma. Liver Res. 2020;4:199–205.
Park JG. Long-term outcomes of patients with advanced hepatocellular carcinoma who achieved complete remission after sorafenib therapy. Clin Mol Hepatol. 2015;21:287–94.
Hiraoka A, Kumada T, Fukunishi S, et al. On behalf of the Real-Life Practice Experts for HCC (RELPEC) study group and HCC 48 Group: Post-progression treatment eligibility of unresectable hepatocellular carcinoma patients treated with lenvatinib. Liver Cancer. 2020;9:73–83.
Acknowledgements
None.
Funding
All authors revised the manuscript, approved the manuscript to be published, and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Author information
Authors and Affiliations
Contributions
MI designed, performed and edited this study. MK and MS edited the manuscript and supervised. HM, HK and KM worked on data acquisition and interpretation of data.
Corresponding author
Ethics declarations
Conflict of interest
Morihiko Ishizaki, Masaki Kaibori, Hideyuki Matsushima, Hisashi Kosaka, Kosuke Matsui, and Mitsugu Sekimoto, declare that they have no conflict of interest.
Human rights
All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Informed consent
Informed consent was obtained from all patients for being included in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ishizaki, M., Kaibori, M., Matsushima, H. et al. Long-term complete response to lenvatinib in a patient with unresectable hepatocellular carcinoma. Clin J Gastroenterol 14, 1700–1705 (2021). https://doi.org/10.1007/s12328-021-01506-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12328-021-01506-3