Top

Cancer Chemotherapy and Pharmacology

Published in:

01-01-2017 | Original Article

Early treatment response to transcatheter arterial chemoembolization is associated with time to the development of extrahepatic metastasis and overall survival in intermediate-stage hepatocellular carcinoma

Authors: Sung Won Lee, Hae Lim Lee, Nam Ik Han, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2017

Abstract

Purpose

Transcatheter arterial chemoembolization (TACE) is the treatment of choice for intermediate-stage hepatocellular carcinoma (HCC). The absence of an early response to TACE might indicate alternative therapeutic strategies early in the course of the disease, thus improving outcomes. Therefore, our purpose was to identify the relationship between treatment response after two sessions of TACE and the time to the development of extrahepatic metastasis and overall survival.

Methods

In total, 108 treatment-naïve intermediate-stage HCC patients who received at least two consecutive sessions of TACE as the first-line treatment were analyzed.

Results

The median follow-up duration was 28.5 months. Extrahepatic metastasis developed in 32 patients (29.6%). Patient age >60 years (P = 0.027), alpha-fetoprotein (AFP) >200 ng/ml (P = 0.039), and objective response after two TACE treatments (P = 0.001) were the predictive factors for time to the development of metastasis. The median survival time for the patients who achieved objective response after two sessions of TACE was 45.9 and 14.4 months for the patients who failed to achieve objective response (P = 0.0001). Objective response after two TACE treatments (P = 0.0001) and the occurrence of extrahepatic metastasis (P = 0.002) were associated with overall survival.

Conclusions

Early objective tumor response after two sessions of TACE was associated with prolonged time to metastasis and improved survival. Therefore, surveillance for metastasis should be performed more frequently when an objective response is not obtained after two sessions of TACE and in younger intermediate-stage HCC patients with high AFP levels.

Waly Raphael S, Yangde Z, Yuxiang C (2012) Hepatocellular carcinoma: focus on different aspects of management. ISRN Oncol 2012:421673PubMedPubMedCentral

Huang J, Yan L, Cheng Z, Wu H, Du L, Wang J et al (2010) A randomized trial comparing radiofrequency ablation and surgical resection for HCC conforming to the Milan criteria. Ann Surg 252(6):903–912CrossRefPubMed

Bhangui P, Vibert E, Majno P, Salloum C, Andreani P, Zocrato J et al (2011) Intention-to-treat analysis of liver transplantation for hepatocellular carcinoma: living versus deceased donor transplantation. Hepatology (Baltimore, MD) 53(5):1570–1579CrossRef

Sala M, Llovet JM, Vilana R, Bianchi L, Sole M, Ayuso C et al (2004) Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma. Hepatology (Baltimore, MD) 40(6):1352–1360CrossRef

Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J et al (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet (London, England) 359(9319):1734–1739CrossRef

Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT et al (2002) Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology (Baltimore, MD) 35(5):1164–1171CrossRef

Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology (Baltimore, MD) 37(2):429–442CrossRef

Park JW, Chen M, Colombo M, Roberts LR, Schwartz M, Chen PJ et al (2015) Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE study. Liver Int 35(9):2155–2166CrossRefPubMedPubMedCentral

Vesselle G, Quirier-Leleu C, Velasco S, Charier F, Silvain C, Boucebci S et al (2015) Predictive factors for complete response of chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma. Eur Radiol 26(6):1640–1648CrossRefPubMed

10.

Barman PM, Sharma P, Krishnamurthy V, Willatt J, McCurdy H, Moseley RH et al (2014) Predictors of mortality in patients with hepatocellular carcinoma undergoing transarterial chemoembolization. Dig Dis Sci 59(11):2821–2825CrossRefPubMedPubMedCentral

11.

Si MS, Amersi F, Golish SR, Ortiz JA, Zaky J, Finklestein D et al (2003) Prevalence of metastases in hepatocellular carcinoma: risk factors and impact on survival. Am Surg 69(10):879–885PubMed

12.

Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30(1):52–60CrossRefPubMed

13.

Kim DY, Ryu HJ, Choi JY, Park JY, Lee DY, Kim BK et al (2012) Radiological response predicts survival following transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma. Aliment Pharmacol Ther 35(11):1343–1350CrossRefPubMed

14.

Gillmore R, Stuart S, Kirkwood A, Hameeduddin A, Woodward N, Burroughs AK et al (2011) EASL and mRECIST responses are independent prognostic factors for survival in hepatocellular cancer patients treated with transarterial embolization. J Hepatol 55(6):1309–1316CrossRefPubMed

15.

Kim BK, Kim SU, Kim KA, Chung YE, Kim MJ, Park MS et al (2015) Complete response at first chemoembolization is still the most robust predictor for favorable outcome in hepatocellular carcinoma. J Hepatol 62(6):1304–1310CrossRefPubMed

16.

Georgiades C, Geschwind JF, Harrison N, Hines-Peralta A, Liapi E, Hong K et al (2012) Lack of response after initial chemoembolization for hepatocellular carcinoma: does it predict failure of subsequent treatment? Radiology 265(1):115–123CrossRefPubMedPubMedCentral

17.

Kim HY, Park JW, Joo J, Jung SJ, An S, Woo SM et al (2012) Severity and timing of progression predict refractoriness to transarterial chemoembolization in hepatocellular carcinoma. J Gastroenterol Hepatol 27(6):1051–1056CrossRefPubMed

18.

Pang RW, Joh JW, Johnson PJ, Monden M, Pawlik TM, Poon RT (2008) Biology of hepatocellular carcinoma. Ann Surg Oncol 15(4):962–971CrossRefPubMed

19.

Shyamala K, Girish HC, Murgod S (2014) Risk of tumor cell seeding through biopsy and aspiration cytology. J Int Soc Prev Community Dent 4(1):5–11CrossRefPubMedPubMedCentral

20.

Senthilnathan S, Memon K, Lewandowski RJ, Kulik L, Mulcahy MF, Riaz A et al (2012) Extrahepatic metastases occur in a minority of hepatocellular carcinoma patients treated with locoregional therapies: analyzing patterns of progression in 285 patients. Hepatology (Baltimore, MD) 55(5):1432–1442CrossRef

21.

Arizumi T, Ueshima K, Minami T, Kono M, Chishina H, Takita M et al (2015) Effectiveness of sorafenib in patients with transcatheter arterial chemoembolization (TACE) refractory and intermediate-stage hepatocellular carcinoma. Liver Cancer 4(4):253–262CrossRefPubMedPubMedCentral

22.

do Song S, Choi JY, Yoo SH, Kim HY, Song MJ, Bae SH et al (2013) DC bead transarterial chemoembolization is effective in hepatocellular carcinoma refractory to conventional transarteral chemoembolization: a pilot study. Gut Liver 7(1):89–95CrossRefPubMedPubMedCentral

23.

Woo HY, Heo J (2015) Transarterial chemoembolization using drug eluting beads for the treatment of hepatocellular carcinoma: now and future. Clin Mol Hepatol 21(4):344–348CrossRefPubMedPubMedCentral

24.

El Fouly A, Ertle J, El Dorry A, Shaker MK, Dechene A, Abdella H et al (2015) In intermediate stage hepatocellular carcinoma: radioembolization with yttrium 90 or chemoembolization? Liver Int 35(2):627–635CrossRefPubMed

25.

Kim Y, do Park BJ, Kim YH, Han KH, Cho SB, Cho KR et al (2015) Radioembolization with yttrium-90 resin microspheres in hepatocellular carcinoma: a multicenter prospective study. Am J Clin Oncol 38(5):495–501CrossRefPubMed

26.

Golfieri R, Bilbao JI, Carpanese L, Cianni R, Gasparini D, Ezziddin S et al (2013) Comparison of the survival and tolerability of radioembolization in elderly vs. younger patients with unresectable hepatocellular carcinoma. J Hepatol 59(4):753–761CrossRefPubMed

27.

Zhang L, Hu P, Chen X, Bie P (2014) Transarterial chemoembolization (TACE) plus sorafenib versus TACE for intermediate or advanced stage hepatocellular carcinoma: a meta-analysis. PLoS ONE 9(6):e100305CrossRefPubMedPubMedCentral

28.

Shim SJ, Seong J, Han KH, Chon CY, Suh CO, Lee JT (2005) Local radiotherapy as a complement to incomplete transcatheter arterial chemoembolization in locally advanced hepatocellular carcinoma. Liver Int 25(6):1189–1196CrossRefPubMed

29.

Rossi S, Garbagnati F, Lencioni R, Allgaier HP, Marchiano A, Fornari F et al (2000) Percutaneous radio-frequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply. Radiology 217(1):119–126CrossRefPubMed

Title: Early treatment response to transcatheter arterial chemoembolization is associated with time to the development of extrahepatic metastasis and overall survival in intermediate-stage hepatocellular carcinoma
Authors: Sung Won Lee
Hae Lim Lee
Nam Ik Han
Jeong Won Jang
Si Hyun Bae
Jong Young Choi
Seung Kew Yoon
Publication date: 01-01-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2017
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-016-3202-8

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 medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2017

Rituximab to treat gemcitabine-induced hemolytic–uremic syndrome (HUS) in pancreatic adenocarcinoma: a case series and literature review

Survival impact of neoadjuvant gemcitabine plus S-1 chemotherapy for patients with borderline resectable pancreatic carcinoma with arterial contact

Long noncoding RNA GAS5 inhibits malignant proliferation and chemotherapy resistance to doxorubicin in bladder transitional cell carcinoma

Phase I trial of daily triapine in combination with cisplatin chemotherapy for advanced-stage malignancies

LJM716 in Japanese patients with head and neck squamous cell carcinoma or HER2-overexpressing breast or gastric cancer

Etirinotecan pegol administration is associated with lower incidences of neutropenia compared to irinotecan administration

Keynote webinar | Spotlight on antibody–drug conjugates in cancer