Top

International Journal of Clinical Oncology

Published in:

01-10-2014 | Original Article

Assessment of treatment outcomes based on tumor marker trends in patients with recurrent hepatocellular carcinoma undergoing trans-catheter arterial chemo-embolization

Authors: Takuma Arai, Akira Kobayashi, Ayumi Ohya, Masaaki Takahashi, Takahide Yokoyama, Akira Shimizu, Hiroaki Motoyama, Norihiko Furusawa, Tsuyoshi Notake, Noriyuki Kitagawa, Hiroshi Sakai, Hiroshi Imamura, Masumi Kadoya, Shin-ichi Miyagawa

Published in: International Journal of Clinical Oncology | Issue 5/2014

Abstract

Purpose

The aim of the present study was to evaluate whether serum alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) trends might be correlated with overall survival rates in patients with recurrent hepatocellular carcinoma (HCC) undergoing trans-catheter arterial chemo-embolization (TACE).

Methods

We performed a retrospective cohort study of 142 patients with recurrent HCC who were treated by TACE at our hospital from April 1990 to December 2011. Patients were divided into three groups, as follows, according to the trends of the two tumor markers AFP and DCP: the low group, comprising patients with tumor marker levels below the cutoff values (AFP 100 ng/mL and DCP 100 mAU/mL) both pre- and post-TACE; the decreased group, comprising patients with elevated tumor marker levels pre-TACE in whom the levels decreased post-TACE; and the elevated group, comprising patients with elevated tumor marker levels post-TACE.

Result

Analysis using a Cox proportional hazards model identified the DCP trend (elevated group vs. low group, hazard ratio 8.47, 95 % confidence interval 4.53–15.84, p < 0.0001), but not the AFP trend, as an independent prognostic factor for survival. While the AFP trend was correlated only with the overall response rate assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST; p = 0.041), the DCP trend was strongly associated with both the overall response rate (p = 0.009) and the disease control rate (p = 0.004).

Conclusion

The DCP trend might be useful for assessing treatment outcomes after TACE in patients with recurrent HCC.

Forner A, Llovet JM, Bruix J (2012) Hepatocellular carcinoma. Lancet 379:1245–1255PubMedCrossRef

Adachi E, Maeda T, Matsumata T et al (1995) Risk factors for intrahepatic recurrence in human small hepatocellular carcinoma. Gastroenterology 108:768–775PubMedCrossRef

Llovet JM, Fuster J, Bruix J (1999) Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30:1434–1440PubMedCrossRef

Okada S, Shimada K, Yamamoto J et al (1994) Predictive factors for postoperative recurrence of hepatocellular carcinoma. Gastroenterology 106:1618–1624PubMed

Poon RT, Fan ST, Lo CM et al (1999) Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg 229:216–222PubMedCrossRefPubMedCentral

Poon RT, Fan ST, O’Suilleabhain CB et al (2002) Aggressive management of patients with extrahepatic and intrahepatic recurrences of hepatocellular carcinoma by combined resection and locoregional therapy. J Am Coll Surg 195:311–318PubMedCrossRef

Sasaki Y, Imaoka S, Fujita M et al (1987) Regional therapy in the management of intrahepatic recurrence after surgery for hepatoma. Ann Surg 206:40–47PubMedCrossRefPubMedCentral

Takayasu K, Wakao F, Moriyama N et al (1992) Postresection recurrence of hepatocellular carcinoma treated by arterial embolization: analysis of prognostic factors. Hepatology 16:906–911PubMedCrossRef

Lee PH, Lin WJ, Tsang YM et al (1995) Clinical management of recurrent hepatocellular carcinoma. Ann Surg 222:670–676PubMedCrossRefPubMedCentral

10.

Shim JH, Kim KM, Lee YJ et al (2010) Complete necrosis after transarterial chemoembolization could predict prolonged survival in patients with recurrent intrahepatic hepatocellular carcinoma after curative resection. Ann Surg Oncol 17:869–877PubMedCrossRef

11.

Liebman HA, Furie BC, Tong MJ et al (1984) Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med 310:1427–1431PubMedCrossRef

12.

Lok AS, Sterling RK, Everhart JE et al (2010) Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. Gastroenterology 138:493–502PubMedCrossRefPubMedCentral

13.

Liebman HA (1989) Isolation and characterization of a hepatoma-associated abnormal (des-gamma-carboxy)prothrombin. Cancer Res 49:6493–6497PubMed

14.

Arii S, Sata M, Sakamoto M et al (2010) Management of hepatocellular carcinoma: Report of Consensus Meeting in the 45th Annual Meeting of the Japan Society of Hepatology (2009). Hepatol Res 40:667–685PubMedCrossRef

15.

Collier J, Sherman M (1998) Screening for hepatocellular carcinoma. Hepatology 27:273–278PubMedCrossRef

16.

Sherman M (2001) Alphafetoprotein: an obituary. J Hepatol 34:603–605PubMedCrossRef

17.

Tateishi R, Shiina S, Yoshida H et al (2006) Prediction of recurrence of hepatocellular carcinoma after curative ablation using three tumor markers. Hepatology 44:1518–1527PubMedCrossRef

18.

Chan SL, Mo FK, Johnson PJ et al (2009) New utility of an old marker: serial alpha-fetoprotein measurement in predicting radiologic response and survival of patients with hepatocellular carcinoma undergoing systemic chemotherapy. J Clin Oncol 27:446–452PubMedCrossRef

19.

Riaz A, Ryu RK, Kulik LM et al (2009) Alpha-fetoprotein response after locoregional therapy for hepatocellular carcinoma: oncologic marker of radiologic response, progression, and survival. J Clin Oncol 27:5734–5742PubMedCrossRef

20.

Araki T, Itai Y, Furui S et al (1980) Dynamic CT densitometry of hepatic tumors. AJR Am J Roentgenol 135:1037–1043PubMedCrossRef

21.

Kakazu T, Makuuchi M, Kawasaki S et al (1993) Repeat hepatic resection for recurrent hepatocellular carcinoma. Hepatogastroenterology 40:337–341PubMed

22.

Kawasaki S, Makuuchi M, Miyagawa S et al (1995) Results of hepatic resection for hepatocellular carcinoma. World J Surg 19:31–34PubMedCrossRef

23.

Takayasu K, Arii S, Ikai I et al (2006) Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. Gastroenterology 131:461–469PubMedCrossRef

24.

Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52–60PubMedCrossRef

25.

Llovet JM, Di Bisceglie AM, Bruix J et al (2008) Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 100:698–711PubMedCrossRef

26.

Kobayashi M, Ikeda K, Kawamura Y et al (2009) High serum des-gamma-carboxy prothrombin level predicts poor prognosis after radiofrequency ablation of hepatocellular carcinoma. Cancer 115:571–580PubMedCrossRef

27.

McShane LM, Altman DG, Sauerbrei W et al (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23:9067–9072PubMedCrossRef

28.

Sherman M (2010) The resurrection of alphafetoprotein. J Hepatol 52:939–940PubMedCrossRef

29.

Johnson PJ, Williams R (1980) Serum alpha-fetoprotein estimations and doubling time in hepatocellular carcinoma: influence of therapy and possible value in early detection. J Natl Cancer Inst 64:1329–1332PubMed

30.

McIntire KR, Vogel CL, Primack A et al (1976) Effect of surgical and chemotherapeutic treatment on alpha-fetoprotein levels in patients with hepatocellular carcinoma. Cancer 37:677–683PubMedCrossRef

31.

McIntire KR, Vogel CL, Princler GL et al (1972) Serum alpha-fetoprotein as a biochemical marker for hepatocellular carcinoma. Cancer Res 32:1941–1946PubMed

32.

Bloomer JR, Waldmann TA, McIntire KR et al (1975) Alpha-fetoprotein in noneoplastic hepatic disorders. JAMA 233:38–41PubMedCrossRef

33.

Johnson PJ, Portmann B, Williams R (1978) Alpha-fetoprotein concentrations measured by radioimmunoassay in diagnosing and excluding hepatocellular carcinoma. Br Med J 2:661–663PubMedCrossRefPubMedCentral

34.

Silver HK, Gold P, Shuster J et al (1974) Alpha(1)-fetoprotein in chronic liver disease. N Engl J Med 291:506–508PubMedCrossRef

35.

Trevisani F, D’Intino PE, Morselli-Labate AM et al (2001) Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol 34:570–575PubMedCrossRef

36.

Imamura H, Matsuyama Y, Miyagawa Y et al (1999) Prognostic significance of anatomical resection and des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma. Br J Surg 86:1032–1038PubMedCrossRef

37.

Koike Y, Shiratori Y, Sato S et al (2001) Des-gamma-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer 91:561–569PubMedCrossRef

38.

Yamamoto K, Imamura H, Matsuyama Y et al (2009) Significance of alpha-fetoprotein and des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma undergoing hepatectomy. Ann Surg Oncol 16:2795–2804PubMedCrossRef

39.

Llado L, Virgili J, Figueras J et al (2000) A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization. Cancer 88:50–57PubMedCrossRef

40.

Hagiwara S, Kudo M, Kawasaki T et al (2006) Prognostic factors for portal venous invasion in patients with hepatocellular carcinoma. J Gastroenterol 41:1214–1219PubMedCrossRef

41.

Miyaaki H, Nakashima O, Kurogi M et al (2007) Lens culinaris agglutinin-reactive alpha-fetoprotein and protein induced by vitamin K absence II are potential indicators of a poor prognosis: a histopathological study of surgically resected hepatocellular carcinoma. J Gastroenterol 42:962–968PubMedCrossRef

42.

Shirabe K, Itoh S, Yoshizumi T et al (2007) The predictors of microvascular invasion in candidates for liver transplantation with hepatocellular carcinoma-with special reference to the serum levels of des-gamma-carboxy prothrombin. J Surg Oncol 95:235–240PubMedCrossRef

43.

Miller AB, Hoogstraten B, Staquet M et al (1981) Reporting results of cancer treatment. Cancer 47:207–214PubMedCrossRef

44.

Gillmore R, Stuart S, Kirkwood A et al (2011) EASL and mRECIST responses are independent prognostic factors for survival in hepatocellular cancer patients treated with transarterial embolization. J Hepatol 55:1309–1316PubMedCrossRef

Title: Assessment of treatment outcomes based on tumor marker trends in patients with recurrent hepatocellular carcinoma undergoing trans-catheter arterial chemo-embolization
Authors: Takuma Arai
Akira Kobayashi
Ayumi Ohya
Masaaki Takahashi
Takahide Yokoyama
Akira Shimizu
Hiroaki Motoyama
Norihiko Furusawa
Tsuyoshi Notake
Noriyuki Kitagawa
Hiroshi Sakai
Hiroshi Imamura
Masumi Kadoya
Shin-ichi Miyagawa
Publication date: 01-10-2014
Publisher: Springer Japan
Published in: International Journal of Clinical Oncology / Issue 5/2014
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-013-0634-6

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Result

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2014

Next-generation prostate-specific antigen test: precursor form of prostate-specific antigen

Controversies in managing localized prostate cancer: introduction

Massage interventions and treatment-related side effects of breast cancer: a systematic review and meta-analysis

Questionnaire survey for the development and publication of cancer clinical practice guidelines in Japan

Expression and prognostic value of Ars2 in hepatocellular carcinoma

Prognostic predictors and spread patterns in adult ovarian granulosa cell tumors: a multicenter long-term follow-up study of 108 patients

Keynote webinar | Spotlight on antibody–drug conjugates in cancer