Efficacy of combined modality therapy with sorafenib following hepatic arterial injection chemotherapy and three‑dimensional conformal radiotherapy for advanced hepatocellular carcinoma with major vascular invasion

Nomura,Takako; Tani,Joji; Deguchi,Akihiro; Nakahara,Mai; Oura,Kyoko; Tadokoro,Tomoko; Fujita,Koji; Mimura,Shima; Sakamoto,Teppei; Morishita,Asahiro; Yoneyama,Hirohito; Kobara,Hideki; Sanomura,Takayuki; Nishiyama,Yoshihiro; Okano,Keiichi; Suzuki,Yasuyuki; Takahashi,Shigeo; Shibata,Toru; Tsutsui,Kunihiko; Himoto,Takashi; Masaki,Tsutomu

doi:10.3892/mco.2019.1920

Efficacy of combined modality therapy with sorafenib following hepatic arterial injection chemotherapy and three‑dimensional conformal radiotherapy for advanced hepatocellular carcinoma with major vascular invasion

Authors:
- Takako Nomura
- Joji Tani
- Akihiro Deguchi
- Mai Nakahara
- Kyoko Oura
- Tomoko Tadokoro
- Koji Fujita
- Shima Mimura
- Teppei Sakamoto
- Asahiro Morishita
- Hirohito Yoneyama
- Hideki Kobara
- Takayuki Sanomura
- Yoshihiro Nishiyama
- Keiichi Okano
- Yasuyuki Suzuki
- Shigeo Takahashi
- Toru Shibata
- Kunihiko Tsutsui
- Takashi Himoto
- Tsutomu Masaki
View Affiliations

Affiliations: Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kita‑gun, Kagawa 761‑0793, Japan, Department of Internal Medicine, Yashima General Hospital, Takamatsu, Kagawa 761‑0113, Japan, Department of Internal Medicine, Kagawa Rosai Hospital, Marugame, Kagawa 763‑8502, Japan, Department of Radiology, Faculty of Medicine, Kagawa University, Kita‑gun, Kagawa 761‑0793, Japan, Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kita‑gun, Kagawa 761‑0793, Japan, Department of Radiation Oncology, Kagawa University Hospital, Kita‑gun, Kagawa 761‑0793, Japan, Department of Clinical Examination, Faculty of Health Sciences, Kagawa Prefectural University of Health Sciences, Takamatsu, Kagawa 761‑0123, Japan
Published online on: September 9, 2019 https://doi.org/10.3892/mco.2019.1920
Pages: 447-454
Copyright: © Nomura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The prognosis of hepatocellular carcinoma (HCC) patients exhibiting macroscopic vascular invasion (MVI) is poor, and the most appropriate treatment approach remains unclear. The current study aimed to investigate the efficacy and safety of sorafenib treatment following chemoradiotherapy for advanced HCC exhibiting MVI. A newly reported regimen, including 5‑fluorouracil and cisplatin therapy (NewFP), plus three‑dimensional conformal radiotherapy (3D‑CRT) for MVI was used as the initial treatment. Additionally, sorafenib, as a secondary treatment, was administered after NewFP plus 3D‑CRT for MVI. The present retrospective study enrolled patients with unresectable advanced HCC that was treated with NewFP plus 3D‑CRT for MVI between January 2009 and December 2017. In total, 32 HCC patients with MVI were registered. Of these 32 patients, 18 were treated with NewFP plus 3D‑CRT for MVI (NewFP + 3D‑CRT group) and 14 were treated with sorafenib following NewFP plus 3D‑CRT for MVI (sorafenib after NewFP + 3D‑CRT group). The study endpoints were overall survival, overall response rate and disease control rate. Clinical factors influencing overall survival were identified using univariate and multivariate analyses. The median survival time in the NewFP + 3D‑CRT group and sorafenib following NewFP + 3D‑CRT group was 6.7 and 49.2 months, respectively (P=0.0003). For patients with advanced HCC exhibiting MVI, the initial treatment with NewFP plus 3D‑CRT for MVI was well tolerated. The administration of sorafenib as the secondary treatment following NewFP plus 3D‑CRT for MVI was associated with a significantly higher overall response rate, disease control rate and increased overall survival as compared with the NewFP plus 3D‑CRT treatment.

View Figures

View References

1	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
2	Llovet JM, Bustamante J, Castells A, Vilana R, Ayuso Mdel C, Sala M, Brú C, Rodés J and Bruix J: Natural history of untreated nonsurgical hepatocellular carcinoma: Rationale for the design and evaluation of therapeutic trials. Hepatology. 29:62–67. 1999. View Article : Google Scholar : PubMed/NCBI
3	Minagawa M and Makuuchi M: Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus. World J Gastroenterol. 12:7561–7567. 2006. View Article : Google Scholar : PubMed/NCBI
4	Cabibbo G, Enea M, Attanasio M, Bruix J, Craxi A and Camma C: A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma. Hepatology. 51:1274–1283. 2010. View Article : Google Scholar : PubMed/NCBI
5	Bruix J, Reig M and Sherman M: Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology. 150:835–853. 2016. View Article : Google Scholar : PubMed/NCBI
6	Bruix J and Sherman M; American Association for the Study of Liver Diseases, : Management of hepatocellular carcinoma: An update. Hepatology. 53:1020–1022. 2011. View Article : Google Scholar : PubMed/NCBI
7	Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008. View Article : Google Scholar : PubMed/NCBI
8	Bruix J, Cheng AL, Meinhardt G, Nakajima K, De Sanctis Y and Llovet J: Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies. J Hepatol. 67:999–1008. 2017. View Article : Google Scholar : PubMed/NCBI
9	Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, 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. 10:25–34. 2009. View Article : Google Scholar : PubMed/NCBI
10	Kudo M and Ueshima K: Positioning of a molecular-targeted agent, sorafenib, in the treatment algorithm for hepatocellular carcinoma and implication of many complete remission cases in Japan. Oncology. 78 (Suppl 1):S154–S166. 2010. View Article : Google Scholar
11	Zhao JD, Liu J, Ren ZG, Gu K, Zhou ZH, Li WT, Chen Z, Xu ZY, Liu LM and Jiang GL: Maintenance of Sorafenib following combined therapy of three-dimensional conformal radiation therapy/intensity-modulated radiation therapy and transcatheter arterial chemoembolization in patients with locally advanced hepatocellular carcinoma: A phase I/II study. Radiat Oncol. 5:122010. View Article : Google Scholar : PubMed/NCBI
12	Citrin DE: Recent developments in radiotherapy. N Engl J Med. 377:1065–1075. 2017. View Article : Google Scholar : PubMed/NCBI
13	Huang YJ, Hsu HC, Wang CY, Wang CJ, Chen HC, Huang EY, Fang FM and Lu SN: The treatment responses in cases of radiation therapy to portal vein thrombosis in advanced hepatocellular carcinoma. Int J Radiat Oncol Biol Phys. 73:1155–1163. 2009. View Article : Google Scholar : PubMed/NCBI
14	Nakazawa T, Hidaka H, Shibuya A, Okuwaki Y, Tanaka Y, Takada J, Minamino T, Watanabe M, Kokubu S and Koizumi W: Overall survival in response to sorafenib versus radiotherapy in unresectable hepatocellular carcinoma with major portal vein tumor thrombosis: Propensity score analysis. BMC Gastroenterol. 14:842014. View Article : Google Scholar : PubMed/NCBI
15	Park HC, Yu JI, Cheng JC, Zeng ZC, Hong JH, Wang ML, Kim MS, Chi KH, Liang PC, Lee RC, et al: Consensus for radiotherapy in hepatocellular carcinoma from the 5th Asia-pacific primary liver cancer expert meeting (APPLE 2014): Current practice and future clinical trials. Liver Cancer. 5:162–174. 2016. View Article : Google Scholar : PubMed/NCBI
16	Wang K, Guo WX, Chen MS, Mao YL, Sun BC, Shi J, Zhang YJ, Meng Y, Yang YF, Cong WM, et al: Multimodality treatment for hepatocellular carcinoma with portal vein tumor thrombus: A large-scale, multicenter, propensity matching score analysis. Medicine (Baltimore). 95:e30152016. View Article : Google Scholar : PubMed/NCBI
17	Ikeda M, Mitsunaga S, Shimizu S, Ohno I, Takahashi H, Okuyama H, Kuwahara A and Okusaka T: Current status of hepatocellular carcinoma in Japan. Chin Clin Oncol. 2:402013.PubMed/NCBI
18	Nagamatsu H, Hiraki M, Mizukami N, Yoshida H, Iwamoto H, Sumie S, Torimura T and Sata M: Intra-arterial therapy with cisplatin suspension in lipiodol and 5-fluorouracil for hepatocellular carcinoma with portal vein tumour thrombosis. Aliment Pharmacol Ther. 32:543–550. 2010. View Article : Google Scholar : PubMed/NCBI
19	Kodama K, Kawaoka T, Aikata H, Uchikawa S, Nishida Y, Inagaki Y, Hatooka M, Morio K, Nakahara T, Murakami E, et al: Comparison of outcome of hepatic arterial infusion chemotherapy combined with radiotherapy and sorafenib for advanced hepatocellular carcinoma patients with major portal vein tumor thrombosis. Oncology. 94:215–222. 2018. View Article : Google Scholar : PubMed/NCBI
20	Inoue Y, Hasegawa K, Ishizawa T, Aoki T, Sano K, Beck Y, Imamura H, Sugawara Y, Kokudo N and Makuuchi M: Is there any difference in survival according to the portal tumor thrombectomy method in patients with hepatocellular carcinoma? Surgery. 145:9–19. 2009. View Article : Google Scholar : PubMed/NCBI
21	Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC and Gwyther SG: New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, national cancer institute of the United States, national cancer institute of Canada. J Natl Cancer Inst. 92:205–216. 2000. View Article : Google Scholar : PubMed/NCBI
22	Lencioni R and Llovet JM: Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 30:52–60. 2010. View Article : Google Scholar : PubMed/NCBI
23	Chan SL, Chong CC, Chan AW, Poon DM and Chok KS: Management of hepatocellular carcinoma with portal vein tumor thrombosis: Review and update at 2016. World J Gastroenterol. 22:7289–7300. 2016. View Article : Google Scholar : PubMed/NCBI
24	Song DS, Song MJ, Bae SH, Chung WJ, Jang JY, Kim YS, Lee SH, Park JY, Yim HJ, Cho SB, et al: A comparative study between sorafenib and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis. J Gastroenterol. 50:445–454. 2015. View Article : Google Scholar : PubMed/NCBI
25	Zhu K, Chen J, Lai L Meng X, Zhou B, Huang W, Cai M and Shan H: Hepatocellular carcinoma with portal vein tumor thrombus: Treatment with transarterial chemoembolization combined with sorafenib-a retrospective controlled study. Radiology. 272:284–293. 2014. View Article : Google Scholar : PubMed/NCBI
26	Yoon SM, Ryoo BY, Lee SJ, Kim JH, Shin JH, An JH, Lee HC and Lim YS: 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. 4:661–669. 2018. View Article : Google Scholar : PubMed/NCBI
27	Bruix J, Qin S, Merle P, Granito A, Huang YH, 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. 389:56–66. 2017. View Article : Google Scholar : PubMed/NCBI
28	Kudo M: Lenvatinib in advanced hepatocellular carcinoma. Liver Cancer. 6:253–263. 2017. View Article : Google Scholar : PubMed/NCBI
29	Kudo M: A new era of systemic therapy for hepatocellular carcinoma with regorafenib and lenvatinib. Liver Cancer. 6:177–184. 2017. View Article : Google Scholar : PubMed/NCBI
30	Iavarone M, Cabibbo G, Piscaglia F, Zavaglia C, Grieco A, Villa E, Cammà C and Colombo M; SOFIA (SOraFenib Italian Assessment) study group, : Field-practice study of sorafenib therapy for hepatocellular carcinoma: A prospective multicenter study in Italy. Hepatology. 54:2055–2063. 2011. View Article : Google Scholar : PubMed/NCBI
31	Hatooka M, Kawaoka T, Aikata H, Inagaki Y, Morio K, Nakahara T, Murakami E, Tsuge M, Hiramatsu A, Imamura M, et al: Hepatic arterial infusion chemotherapy followed by sorafenib in patients with advanced hepatocellular carcinoma (HICS55): An open label, non-comparative phase II trial. BMC Cancer. 18:6332018. View Article : Google Scholar : PubMed/NCBI
32	Ikeda M, Mitsunaga S, Shimizu S, Ohno I, Takahashi H, Okuyama H, Kuwahara A, Kondo S, Morizane C, Ueno H, et al: Efficacy of sorafenib in patients with hepatocellular carcinoma refractory to transcatheter arterial chemoembolization. J Gastroenterol. 49:932–940. 2014. View Article : Google Scholar : PubMed/NCBI
33	Hatooka M, Kawaoka T, Aikata H, Morio K, Kobayashi T, Hiramatsu A, Imamura M, Kawakami Y, Murakami E, Waki K, et al: Comparison of outcome of hepatic arterial infusion chemotherapy and Sorafenib in patients with hepatocellular carcinoma refractory to Transcatheter arterial chemoembolization. Anticancer Res. 36:3523–3529. 2016.PubMed/NCBI
34	Yang Q, Zhang S, Kang M, Dong R and Zhao J: Synergistic growth inhibition by sorafenib and cisplatin in human osteosarcoma cells. Oncol Rep. 33:2537–2544. 2015. View Article : Google Scholar : PubMed/NCBI
35	Ikeda M, Shimizu S, Sato T, Morimoto M, Kojima Y, Inaba Y, Hagihara A, Kudo M, Nakamori S, Kaneko S, et al: Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: Randomized phase II trial. Ann Oncol. 27:2090–2096. 2016. View Article : Google Scholar : PubMed/NCBI