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01-01-2015 | Original Article

Efficacy of hepatic arterial infusion chemotherapy in combination with irradiation for advanced hepatocellular carcinoma with portal vein invasion

Authors: Hideki Onishi, Kazuhiro Nouso, Shinichiro Nakamura, Kuniaki Katsui, Nozomu Wada, Yuki Morimoto, Koji Miyahara, Yasuto Takeuchi, Kenji Kuwaki, Tetsuya Yasunaka, Yasuhiro Miyake, Hidenori Shiraha, Akinobu Takaki, Yoshiyuki Kobayashi, Kohsaku Sakaguchi, Susumu Kanazawa, Kazuhide Yamamoto

Published in: Hepatology International | Issue 1/2015

Abstract

Background

The presence of portal vein tumor thrombosis (PVTT) is a poor prognostic factor for patients with hepatocellular carcinomas (HCC). The purpose of this study was to determine the treatment effect of irradiation in combination with hepatic arterial infusion chemotherapy (HAIC) for these patients.

Methods

We retrospectively examined the outcome of 67 HCC patients with PVTT of the main trunk or first branch who received HAIC alone or with concurrent irradiation for PVTT (CCRT).

Results

Thirty-four patients received HAIC, and 33 patients received CCRT. The time to progression (TTP) of PVTT in the CCRT group was significantly longer than in the HAIC group (p < 0.01), and the TTP of intrahepatic nodules in the CCRT group tended to be longer than in the HAIC group (p = 0.06). The objective response rates of intrahepatic nodules (52 vs. 18 %, p < 0.01) and PVTT (45 vs. 18 %, p = 0.01) were both significantly higher in the CCRT group than in the HAIC group, respectively. No significant difference in overall survival was found between the two groups (p = 0.14); however, the median survival time in the CCRT group was longer than that in the HAIC group (12.4 vs. 5.7 months, respectively).

Conclusions

CCRT might be a promising treatment for advanced-stage HCC with PVTT. CCRT prolonged the TTP of intrahepatic nodules and PVTT, and it improved the objective response rate of intrahepatic nodules and PVTT.

Adachi E, Maeda T, Kajiyama K, Kinukawa N, Matsumata T, Sugimachi K, et al. Factors correlated with portal venous invasion by hepatocellular carcinoma: univariate and multivariate analyses of 232 resected cases without preoperative treatments. Cancer 1996;77:2022–2031

Stuart KE, Anand AJ, Jenkins RL. Hepatocellular carcinoma in the United States. Prognostic features, treatment outcome, and survival. Cancer 1996;77:2217–2222

Ikai I, Arii S, Kojiro M, Ichida T, Makuuchi M, Matsuyama Y, et al. Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey. Cancer 2004;101:796–802

Portolani N, Coniglio A, Ghidoni S, Giovanelli M, Benetti A, Tiberio GA, et al. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg 2006;243:229–235

Llovet JM, Bustamante J, Castells A, Vilana R, Ayuso Mdel C, Sala M, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology 1999;29:62–67

Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005;42:1208–1236

Arii S, Tanaka J, Yamazoe Y, Minematsu S, Morino T, Fujita K, et al. Predictive factors for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy. Cancer 1992;69:913–919

Yamada R, Sato M, Kawabata M, Nakatsuka H, Nakamura K, Takashima S. Hepatic artery embolization in 120 patients with unresectable hepatoma. Radiology 1983;148:397–401

Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378–390

10.

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

11.

Bruix J, Raoul JL, Sherman M, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol 2012;57:821–829

12.

Ando E, Tanaka M, Yamashita F, Kuromatsu R, Yutani S, Fukumori K, et al. Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases. Cancer 2002;95:588–595

13.

Ueshima K, Kudo M, Takita M, et al. Hepatic arterial infusion chemotherapy using low-dose 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma. Oncology 2010;78(Suppl 1):148–153

14.

Sakon M, Nagano H, Dono K, Nakamori S, Umeshita K, Yamada A, et al. Combined intraarterial 5-fluorouracil and subcutaneous interferon-alpha therapy for advanced hepatocellular carcinoma with tumor thrombi in the major portal branches. Cancer 2002;94:435–442

15.

Obi S, Yoshida H, Toune R, Unuma T, Kanda M, Sato S, et al. Combination therapy of intraarterial 5-fluorouracil and systemic interferon-alpha for advanced hepatocellular carcinoma with portal venous invasion. Cancer 2006;106:1990–1997

16.

Yoshikawa M, Ono N, Yodono H, Ichida T, Nakamura H. Phase II study of hepatic arterial infusion of a fine-powder formulation of cisplatin for advanced hepatocellular carcinoma. Hepatol Res 2008;38:474–483

17.

Kondo M, Morimoto M, Numata K, Nozaki A, Tanaka K. Hepatic arterial infusion therapy with a fine powder formulation of cisplatin for advanced hepatocellular carcinoma with portal vein tumor thrombosis. Jpn J Clin Oncol 2011;41:69–75

18.

Nouso K, Miyahara K, Uchida D, et al. Effect of hepatic arterial infusion chemotherapy of 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma in the Nationwide Survey of Primary Liver Cancer in Japan. Br J Cancer 2013;109:1904–1907

19.

Ingold JA, Reed GB, Kaplan HS, Bagshaw MA. Radiation hepatitis. Am J Roentgenol Radium Ther Nucl Med 1965;93:200–208

20.

Lewin K, Millis RR. Human radiation hepatitis. A morphologic study with emphasis on the late changes. Arch Pathol 1973;96:21–26

21.

Lawrence TS, Robertson JM, Anscher MS, Jirtle RL, Ensminger WD, Fajardo LF. Hepatic toxicity resulting from cancer treatment. Int J Radiat Oncol Biol Phys 1995;31:1237–1248

22.

Liang SX, Zhu XD, Xu ZY, Zhu J, Zhao JD, Lu HJ, et al. Radiation-induced liver disease in three-dimensional conformal radiation therapy for primary liver carcinoma: the risk factors and hepatic radiation tolerance. Int J Radiat Oncol Biol Phys 2006;65:426–434

23.

Nakagawa K, Yamashita H, Shiraishi K, Nakamura N, Tago M, Igaki H, et al. Radiation therapy for portal venous invasion by hepatocellular carcinoma. World J Gastroenterol 2005;11:7237–7241

24.

Kim DY, Park W, Lim DH, Lee JH, Yoo BC, Paik SW, et al. Three-dimensional conformal radiotherapy for portal vein thrombosis of hepatocellular carcinoma. Cancer 2005;103:2419–2426

25.

Lin CS, Jen YM, Chiu SY, Hwang JM, Chao HL, Lin HY, et al. Treatment of portal vein tumor thrombosis of hepatoma patients with either stereotactic radiotherapy or three-dimensional conformal radiotherapy. Jpn J Clin Oncol 2006;36:212–217

26.

Yamada K, Soejima T, Sugimoto K, Mayahara H, Izaki K, Sasaki R, et al. Pilot study of local radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma. Jpn J Clin Oncol 2001;31:147–152

27.

Yamada K, Izaki K, Sugimoto K, Mayahara H, Morita Y, Yoden E, et al. Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 2003;57:113–119

28.

Ishikura S, Ogino T, Furuse J, Satake M, Baba S, Kawashima M, et al. Radiotherapy after transcatheter arterial chemoembolization for patients with hepatocellular carcinoma and portal vein tumor thrombus. Am J Clin Oncol 2002;25:189–193

29.

Zeng ZC, Fan J, Tang ZY, Zhou J, Qin LX, Wang JH, et al. A comparison of treatment combinations with and without radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombus. Int J Radiat Oncol Biol Phys 2005;61:432–443

30.

Lee DS, Seong J. Radiotherapeutic options for hepatocellular carcinoma with portal vein tumor thrombosis. Liver Cancer 2014;3:18–30

31.

Choi C, Choi GH, Kim TH, Tanaka M, Meng MB, Seong J. Multimodality management for Barcelona Clinic Liver Cancer Stage C hepatocellular carcinoma. Liver Cancer 2014;3:405–416

32.

Toyoda H, Nakano S, Kumada T, Takeda I, Sugiyama K, Osada T, et al. The efficacy of continuous local arterial infusion of 5-fluorouracil and cisplatin through an implanted reservoir for severe advanced hepatocellular carcinoma. Oncology 1995;52:295–299

33.

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92:205–216

34.

Fujino H, Kimura T, Aikata H, et al. Role of 3-D conformal radiotherapy for major portal vein tumor thrombosis combined with hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma. Hepatol Res 2014. doi:10.1111/hepr.12392

35.

Han KH, Seong J, Kim JK, Ahn SH, Lee do Y, Chon CY. Pilot clinical trial of localized concurrent chemoradiation therapy for locally advanced hepatocellular carcinoma with portal vein thrombosis. Cancer 2008;113:995–1003

36.

Katamura Y, Aikata H, Takaki S, Azakami T, Kawaoka T, Waki K, et al. Intra-arterial 5-fluorouracil/interferon combination therapy for advanced hepatocellular carcinoma with or without three-dimensional conformal radiotherapy for portal vein tumor thrombosis. J Gastroenterol 2009;44:492–502

Title: Efficacy of hepatic arterial infusion chemotherapy in combination with irradiation for advanced hepatocellular carcinoma with portal vein invasion
Authors: Hideki Onishi
Kazuhiro Nouso
Shinichiro Nakamura
Kuniaki Katsui
Nozomu Wada
Yuki Morimoto
Koji Miyahara
Yasuto Takeuchi
Kenji Kuwaki
Tetsuya Yasunaka
Yasuhiro Miyake
Hidenori Shiraha
Akinobu Takaki
Yoshiyuki Kobayashi
Kohsaku Sakaguchi
Susumu Kanazawa
Kazuhide Yamamoto
Publication date: 01-01-2015
Publisher: Springer India
Published in: Hepatology International / Issue 1/2015
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI: https://doi.org/10.1007/s12072-014-9592-y

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Conclusions

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