Neoadjuvant hepatic arterial infusion chemotherapy for resectable hepatocellular carcinomas

Abstract

Aim: To evaluate the effect of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) on the survival of patients with resectable hepatocellular carcinoma (HCC).

Methods: Between January 2003 and January 2014, 80 patients underwent hepatic resection for HCC. Of these patients, we evaluated 49 patients who met the following inclusion criteria: (1) preserved liver function (Child-Pugh A); (2) resectable HCC (≤ 3 nodules, regardless of the size); and (3) HCC with high-grade malignant potential. Among them, 13 patients underwent neoadjuvant HAIC and curative hepatectomy (treatment group). The remaining 36 patients underwent curative hepatic resection without neoadjuvant therapy (control group). Survival after hepatic resection was compared retrospectively between the groups.

Results: During follow-up, 2 (15.4%) patients in the treatment group and 25 (69.4%) patients in the control group developed recurrence. The 1-, 3-, and 5-year disease-free rates (100%, 78.6%, and 78.6%, respectively vs. 65.8%, 33.7%, and 26.6%, respectively; P = 0.003) and overall survival rates (100%, 100%, and 100%, respectively vs. 91.7%, 77.8%, and 55.3%, respectively; P = 0.037) were significantly better in the treatment group than in the control group.

Conclusion: Neoadjuvant HAIC decreased the risk of recurrence and improved survival in patients with HCC with high malignant potential.

Keywords

Hepatocellular carcinoma / transcatheter arterial chemoembolization / hepatic arterial infusion chemotherapy

References

[1] EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma..J Hepatol2012;56:908-43

[2] Hasegawa K,Imamura H,Aoki T.Prognostic impact of anatomic resection for hepatocellular carcinoma..Ann Surg2005;242:252-9 PMCID:PMC1357731

[3] Belghiti J,Farges O,Fekete F.Intrahepatic recurrence after resection of hepato- cellular carcinoma complicating cirrhosis..Ann Surg1991;214:114-7 PMCID:PMC1358509

[4] Fan ST,Poon RT,Liu CL.Hepatectomy for hepatocellular carcinoma: the surgeon's role in long-term survival..Arch Surg1999;134:1124-30

[5] Imamura H,Miyagawa Y,Shimada R,Makuuchi M.Prognostic significance of anatomical resection and des-γ-carboxy prothrombin in patients with hepatocellular carcinoma..Br J Surg1999;86:1032-8

[6] Chan KM,Wu TJ,Chen TC,Chen MF.Efficacy of surgical resection in management of isolated extrahepatic metastases of hepatocellular carcinoma..World J Gastroenterol2009;15:5481-8 PMCID:PMC2778106

[7] Taketomi A,Kitagawa D,Takeishi K,Kayashima H,Aishima S,Ikegami T,Uchiyama H,Maeda T,Maehara Y.Predictors of extrahepatic recurrence after curative hepatectomy for hepato- cellular carcinoma..Ann Surg Oncol2010;17:2740-6

[8] Lopez PM,Llovet JM.Systematic review: evidence-based management of hepatocellular carcinoma - an updated analysis of randomized controlled trials..Aliment Pharmacol Ther2006;23:1535-47

[9] Llovet JM,Mazzaferro V.Resection and liver transplantation for hepatocellular carcinoma..Semin Liver Dis2005;25:181-200

[10] Kamiyama T,Yokoo H,Tahara M,Tsuruga Y,Taketomi A.Analysis of the risk factors for early death due to disease recurrence or progression within 1 year after hepatectomy in patients with hepatocellular carcinoma..World J Surg Oncol2012;10:107-11 PMCID:PMC3407774

[11] Imamura H,Tanaka E,Hasegawa K,Sugawara Y,Takayama T,Makuuchi M.Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy..J Hepatol2003;38:200-7

[12] Arii S,Yamazoe Y,Morino T,Maetani S.Predictive factors for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy..Cancer1992;69:913-9

[13] Sumie S,Okuda K,Takata A,Watanabe Y,Sata M.Microvascular invasion in patients with hepatocellular carcinoma and its predictable clinicopathological factors..Ann Surg Oncol2008;15:1375-82

[14] Chen XP,Zhang ZW,Chen YF,Qiu FZ.Role of mesohepatectomy with or without transcatheter arterial chemoembolization for large centrally located hepatocellular carcinoma..Dig Surg2007;24:208-13

[15] Minagawa M,Takayama T.Selection criteria for hepatectomy in patients with hepatocellular carcinoma and portal vein tumor thrombus..Ann Surg2001;233:379-84 PMCID:PMC1421254

[16] Sugo H,Beppu T,Kojima K.Role of preoperative transcatheter arterial chemoembolization for resectable hepatocellular carcinoma: relation between postoperative course and the pattern of tumor recurrence..World J Surg2003;27:1295-9

[17] Kaibori M,Matsui Y,Uchida Y,Tanaka H.Influence of transcatheter arterial chemoembolization on the prognosis after hepatectomy for hepatocellular carcinoma in patients with severe liver dysfunction..Anticancer Res2006;26:3685-92

[18] Wu CC,Ho WL,Liu TJ.Preoperative transcatheter arterial chemoembolization for resectable large hepatocellular carcinoma: a reappraisal..Br J Surg1995;82:122-6

[19] Yamasaki S,Kinoshita H,Imaoka S,Kakumoto Y,Yamada R,Arii S,Monden M,Kusano S,Ikeda K,Saoshiro T.A prospective randomized trial of the preventive effect of pre-operative transcatheter arterial embolization against recurrence of hepatocellular carcinoma..Jpn J Cancer Res1996;87:206-11

[20] Liver Cancer Study Group of Japan..The general rules for the clinical and pathological study of primary liver cancer2008;TokyoKanehara121-2

[21] Llovet JM,Bruix J.Prognosis of hepatocellular carcinoma: the BCLC staging classification..Semin Liver Dis1999;31:133-41

[22] Llovet JM,Bruix J,Lencioni R,Sherman M,Lotze M,Gores GJ.Design and endpoints of clinical trials in hepatocellular carcinoma..J Natl Cancer Inst2008;100:698-711

[23] Nagaoka S,Nagamatsu H,Kurogi J,Kajiwara M.Temporary indwelling catheter system via the left brachial artery: evaluation in 83 patients with hepatic tumors..AJR Am J Roentgenol2007;188:652-8

[24] Horii R.Histological assessment of therapeutic response in breast cancer..Breast Cancer2016;23:540-5

[25] Xue TC,Zhang L,Zhang BH.Transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a meta-analysis..BMC Gastroenterol2013;13:60 PMCID:PMC3626696

[26] Ando E,Yamashita F,Yutani S,Sumie S,Okuda K.Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: analysis of 48 cases..Cancer2002;95:588-95

[27] Miyaki D,Aikata H,Fujino H,Kobayashi T,Honda Y,Hiramatsu A,Hyogo H,Yoshimatsu R,Awai K.Evaluation of early response to hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma using the combination of response evaluation criteria in solid tumors and tumor markers..J Gastroenterol Hepatol2015;30:726-32

[28] Ueda H,Tanaka C.Toxicity and efficacy of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma..Oncol Lett2012;3:259-63 PMCID:PMC3362614

[29] Ishikawa T,Kubota T,Honma T,Kamimura T.Prevention of intrahepatic distant recurrence by transcatheter arterial infusion chemotherapy with platinum agents for stage I/II hepatocellular carcinoma..Cancer2011;117:4018-25

[30] Ishikawa T,Abe S,Sugano T,Iwanaga A,Honma T.Hepatic arterial infusion chemotherapy with cisplatin before radical local treatment of early hepatocellular carcinoma (JIS score 0/1) improves survival..Ann Oncol2014;25:1379-84

[31] Ueshima K,Takita M,Tatsumi C,Kitai S,Yada N,Hagiwara S,Chung H.Hepatic arterial infusion chemotherapy using low-dose 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma..Oncology2010;78:148-53

[32] Nagano H,Marubashi S,Eguchi H,Tomimaru Y,Doki Y.Combined IFN-α and 5-FU treatment as a postoperative adjuvant following surgery for hepatocellular carcinoma with portal venous tumor thrombus..Exp Ther Med2013;5:3-10 PMCID:PMC3524132

[33] Nitta H,Imai K,Chikamoto A.Adjuvant hepatic arterial infusion chemotherapy after hepatic resection of hepatocellular carcinoma with macroscopic vascular invasion..World J Surg2013;37:1034-42

[34] Yamanaka N,Fujihara S,Fujimoto J,Mitsunobu M,Uematsu K.Do the tumor cells of hepatocellular carcinomas dislodge into the portal venous stream during hepatic resection?.Cancer1992;70:2263-7

[35] Wong IH,Leung T,Johnson PJ.Hematogenous dissemination of hepatocytes and tumor cells after surgical resection of hepatocellular carcinoma: a quantitative analysis..Clin Cancer Res1999;5:4021-7