Abstract
Objective: We examined early predictors of the outcome in hepatocellular carcinoma (HCC) patients after transarterial chemoembolization (TACE). Methods: We analyzed 116 patients with unresectable HCC treated with initial TACE. α-Fetoprotein (AFP) or des-γ-carboxy prothrombin (DCP) response was assessed in patients who had baseline AFP levels ≥200 ng/ml or DCP ≥60 mAU/ml; a positive response was defined as a reduction of >50% compared to baseline 1 month after TACE. Results: A baseline AFP level ≥200 ng/ml was associated with a poor overall survival (OS) (29.4 vs. 6.1 months; p <0.0001). AFP response had no significantly prognostic effects on the OS. Conversely, although the baseline DCP did not influence the OS, DCP responders showed a significantly better OS than nonresponders (67.0 vs. 19.8 months, p = 0.020). The baseline AFP (p = 0.004) and initial tumor response evaluated by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) (p = 0.012) were found to be independent predictors of the OS. The combination of the baseline AFP and initial assessment by mRECIST allowed stratification of the OS. Conclusions: The combination of the baseline AFP level and mRECIST is useful for the early prediction of the OS in HCC patients who underwent TACE.
References
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
2.
Llovet JM, Bru C, Bruix J: Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 1999;19:329-338.
3.
Forner A, Reig ME, de Lope CR, Bruix J: Current strategy for staging and treatment: BCLC update and future prospects. Semin Liver Dis 2010;30:61-74.
4.
Llovet JM, Bruix J: Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 2003;37:429-442.
5.
Raoul JL, Sangro B, Forner A, Mazzaferro V, Piscaglia F, Bolondi L, Lencioni R: Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev 2011;37:212-220.
6.
Ebied OM, Federle MP, Carr BI, Pealer KM, Li W, Amesur N, Zajko A: Evaluation of responses to chemoembolization in patients with unresectable hepatocellular carcinoma. Cancer 2003;97:1042-1050.
7.
Vogl TJ, Trapp M, Schroeder H, Mack M, Schuster A, Schmitt J, Neuhaus P, Felix R: Transarterial chemoembolization for hepatocellular carcinoma: volumetric and morphologic CT criteria for assessment of prognosis and therapeutic success-results from a liver transplantation center. Radiology 2000;214:349-357.
8.
Memon K, Kulik L, Lewandowski RJ, Wang E, Ryu RK, Riaz A, Nikolaidis P, Miller FH, Yaghmai V, Baker T, Abecassis M, Benson AB 3rd, Mulcahy MF, Omary RA, Saiem R: Alpha-fetoprotein response correlates with EASL response and survival in solitary hepatocellular carcinoma treated with transarterial therapies: a subgroup analysis. J Hepatol 2012;56:1112-1120.
9.
Bruix J, Sherman M: Management of hepatocellular carcinoma. Hepatology 2005;42:1208-1236.
10.
Lencioni R, Llovet JM: Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010;30:52-60.
11.
Liebman HA, Furie BC, Tong MJ, Blanchard RA, Lo KJ, Lee SD, Coleman MS, Furie B: Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med 1984;310:1427-1431.
12.
Fujiyama S, Izuno K, Gohshi K, Shibata J, Sato T: Clinical usefulness of des-gamma-carboxy prothrombin assay in early diagnosis of hepatocellular carcinoma. Dig Dis Sci 1991;36:1782-1792.
13.
Aoyagi Y, Oguro M, Yanagi M, Mita Y, Suda T, Suzuki Y, Hata K, Ichii K, Asakura H: Clinical significance of simultaneous determinations of alpha-fetoprotein and des-gamma-carboxy prothrombin in monitoring recurrence in patients with hepatocellular carcinoma. Cancer 1996;77:1781-1786.
14.
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A: AJCC Cancer Staging Manual, ed 7. New York, Springer, 2010.
15.
Takai S, Sakaguchi H, Anai H, Tanaka T, Yamamoto K, Morimoto K, Nishiofuku H, Inoue M, Sueyoshi S, Nagata T, Hidaka T, Uchida H, Kichikawa K: Long-term outcome of transcatheter subsegmental and segmental arterial chemoembolization using lipiodol for hepatocellular carcinoma. Cardiovasc Intervent Radiol 2012;35:544-554.
16.
Riaz A, Ryu RK, Kulik LM, Mulcahy MF, Lewandowski RJ, Minocha J, Ibrahim SM, Sato KT, Baker T, Miller FH, Newman S, Omary R, Abecassis M, Benson AB 3rd, Salem R: Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival. J Clin Oncol 2009;27:5734-5742.
17.
Park H, Kim SU, Park JY, Kim do Y, Ahn SH, Chon CY, Han KH, Seong J: Clinical usefulness of double biomarkers AFP and PIVKA-II for subdividing prognostic groups in locally advanced hepatocellular carcinoma. Liver Int 2014;34:313-321.
18.
Sieghart W, Hucke F, Pinter M, Graziadei I, Vogel W, Müller C, Heinzl H, Trauner M, Peck-Radosavljevic M: The ART of decision making: retreatment with transarterial chemoembolization in patients with hepatocellular carcinoma. Hepatology 2013;57:2261-2273.
19.
Hucke F, Sieghart W, Pinter M, Graziadei I, Vogel W, Müller C, Heinzl H, Waneck F, Trauner M, Peck-Radosavljevic M: The ART strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE. J Hepatol 2014;60:118-126.
20.
Wang Y, Chen Y, Ge N, Zhang L, Xie X, Zhang J, Chen R, Wang Y, Zhang B, Xia J, Gan Y, Ren Z, Ye S: Prognostic significance of alpha-fetoprotein status in the outcome of hepatocellular carcinoma after treatment of transcatheter chemoembolization. Ann Surg Oncol 2012;19:3540-3546.
21.
Lee YK, Kim SU, Kim DY, Ahn SH, Lee KH, Lee DY, Han KH, Chon CY, Park JY: Prognostic value of α-fetoprotein and des-γ-carboxy prothrombin responses in patients with hepatocellular carcinoma treated with transarterial chemoembolization. BMC Cancer 2013;13:5.
22.
Huo TI, Hsu CY, Huang YH, Su CW, Lin HC, Lee RC, Chiou YY, Chiang JH, Lee PC, Lee SD: Prognostic prediction across a gradient of total tumor volume in patients with hepatocellular carcinoma undergoing locoregional therapy. BMC Gastroenterol 2010;10:146.
23.
Meguro M, Mizuguchi T, Nishidate T, Okita K, Ishii M, Oda S, Ueki T, Akizuki E, Hirata K: Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients. World J Gastroenterol 2015;21:4933-4945.
24.
Kim HS, Park JW, Jang JS, Kim HJ, Shin WG, Kim KH, Lee JH, Kim HY, Jang MK: Prognostic values of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in hepatitis B virus-related hepatocellular carcinoma: a prospective study. J Clin Gastroenterol 2009;43:482-488.
25.
Park WH, Shim JH, Han SB, Won HJ, Shin YM, Kim YS, Lim YS, Lee HC: Clinical utility of des-γ-carboxyprothrombin kinetics as a component to radiologic response in patients with hepatocellular carcinoma undergoing transarterial chemoembolization. J Vasc Interv Radiol 2012;23:927-936.
26.
Kang K, Kim JH, Kang SH, Lee BJ, Seo YS, Yim HJ, Yeon JE, Park JJ, Kim JS, Bak YT, Byun KS: The influence of alcoholic liver disease on serum PIVKA-II levels in patients without hepatocellular carcinoma. Gut Liver 2015;9:224-230.
27.
Yamasaki N, Sugawara Y, Tamura S, Kaneko J, Yoshida H, Aoki T, Hasegawa K, Akahane M, Ohtomo K, Fukayama M, Koike K, Kokudo N: Diagnostic accuracy of α-fetoprotein and des-γ-carboxy prothrombin in screening for hepatocellular carcinoma in liver transplant candidates. Hepatol Res 2011;41:1199-1207.
28.
Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z: 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.
29.
Llovet JM, Ricci S, Mazzaferro V, Higard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, GretenTF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-390.
30.
Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Latha C, Schwartz B, Tayler I, Moscovici M, Saltz LB: Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2006;24:4293-4300.
31.
Yoo JJ, Lee JH, Lee SH, Lee DH, Cho Y, Lee YB, Yu SJ, Kim HC, Kim YJ, Yoon JH, Kim CY, Lee HS: Comparison of the effects of transarterial chemoembolization for hepatocellular carcinoma between patients with and without extrahepatic metastases. PLoS One 2014;9:e113926.
32.
Llovet JM, Bruix J: Novel advancements in the management of hepatocellular carcinoma in 2008. J Hepatol 2008;48(suppl 1):S20-S37.
33.
Chung JW, Park JH, Han JK, Choi BI, Han MC, Lee HS, Kim CY: Hepatic tumors: predisposing factors for complications of transcatheter oily chemoembolization. Radiology 1996;198:33-40.
34.
Chung GE, Lee JH, Kim HY, Hwang SY, Kim JS, Chung JW, Yoon JH, Lee HS, Kim YJ: Transarterial chemoembolization can be safety performed in patients with hepatocellular carcinoma invading the main portal vein and may improve the overall survival. Radiology 2011;258:627-634.
35.
Lee KM, Kim JS, Choi IJ, Chung JW, Park JH, Kim CY: The safety and efficacy of transcatheter arterial chemoembolization in the treatment of patients with hepatocellular carcinoma and main portal vein obstruction: a prospective controlled study. Cancer 1997;79:2087-2094.
36.
Luo J, Guo RP, Lai EC, Zhang YJ, Lau WY, Chen MS, Shi M: Transarterial chemoembolization for unresectable hepatocellular carcinoma with portal vein tumor thrombosis: a prospective comparative study. Ann Surg Oncol 2011;18:413-420.
37.
Raoul JL, Sangro B, Forner A, Mazzaferro V, Piscaglia F, Bolondi L, Lencioni R: Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization. Cancer Treat Rev 2011;37:212-220.
38.
Pinter M, Hucke F, Graziadei I, Vogel W, Maieron A, Königsberg R, Stauber R, Grünberger B, Müller C, Kölblinger C, Peck- Radosavljevic M, Sieghart W: Advanced-stage hepatocellular carcinoma: transarterial chemoembolization versus sorafenib. Radiology 2012;263:590-599.
39.
Mazzaferro V, Sposito C, Bhoori S, Romito R, Chiesa C, Morosi C, Maccauro M, Machiano A, Bongini M, Lanoctia R, Civelli E, Bobardieri E, Camerini T, Spreafico C: Yttritium- 90 radioembolization for intermediate-advanced hepatocellular carcinoma: a phase 2 study. Hepatology 2013;57:1826-1837.
40.
Cho YY, Lee M, Kim HC, Chung JW, Kim YH, Gwak GY, Bae SH, Kim DY, Heo J, Kim YJ: Radioembolization is a safe and effective treatment for hepatocellular carcinoma with portal vein thrombosis: a propensity score analysis. PLoS One 2016;11:e0154986.
© 2016 S. Karger AG, Basel
2016
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
