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      Transcatheter arterial chemoembolization combined with radiofrequency ablation delays tumor progression and prolongs overall survival in patients with intermediate (BCLC B) hepatocellular carcinoma

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          Abstract

          Background

          This study was designed to evaluate the effectiveness of radiofrequency ablation in patients with intermediate (BCLC B) stage hepatocellular carcinoma who underwent transcatheter arterial chemoembolization.

          Methods

          Included in this study were 211 patients with intermediate stage HCC who underwent initial transcatheter arterial chemoembolization and were potentially amendable for radiofrequency ablation (single tumor with diameter 5-8 cm, median 6.0 cm; 2–5 multiple nodules with diameter less than 5 cm) between January 2005 and December 2011. According to the inclusion and exclusion criteria, 55 patients were treated with following radiofrequency ablation, and the remaining 156 patients were treated with transcatheter arterial chemoembolization alone. The treatment effectiveness, local tumor control and survival outcome between the two groups were compared.

          Results

          The complete tumor necrosis rate after treatment was 76.9% in combination group vs. 46.5% in transcatheter arterial chemoembolization alone group (P = 0.02). The major complication rate was 1.8% in combination group vs. 2.6% in transcatheter arterial chemoembolization alone group. Follow-up observation showed that the total tumor control rate was 74.5% in combination group versus 54.5% in transcatheter arterial chemoembolization alone group (P < 0.001). The 1-, 3- and 5-year survival rates in combination group were significantly higher than those in TACE alone group (P = 0.01).

          Conclusions

          Radiofrequency ablation following initial transcatheter arterial chemoembolization delays tumor progression and prolongs overall survival of patients with intermediate stage HCC tumors.

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          Most cited references19

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          Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma.

          Masao Omata, Laurentius Lesmana, Ryosuke Tateishi … (2010)
          The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations. The working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements. Participants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.
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            Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial.

            Shan Chen, Jun Zhang, Zhen Peng … (2013)
            To compare radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). A randomized controlled trial was conducted on 189 patients with HCC less than 7 cm at a single tertiary referral center between October 2006 and June 2009. Patients were randomly asssigned to receive TACE combined with RFA (TACE-RFA; n = 94) or RFA alone (n = 95). The primary end point was overall survival. The secondary end point was recurrence-free survival, and the tertiary end point was adverse effects. At a follow-up of 7 to 62 months, 34 patients in the TACE-RFA group and 48 patients in the RFA group had died. Thirty-three patients and 52 patients had developed recurrence in the TACE-RFA group and RFA group, respectively. The 1-, 3-, and 4-year overall survivals for the TACE-RFA group and the RFA group were 92.6%, 66.6%, and 61.8% and 85.3%, 59%, and 45.0%, respectively. The corresponding recurrence-free survivals were 79.4%, 60.6%, and 54.8% and 66.7%, 44.2%, and 38.9%, respectively. Patients in the TACE-RFA group had better overall survival and recurrence-free survival than patients in the RFA group (hazard ratio, 0.525; 95% CI, 0.335 to 0.822; P = .002; hazard ratio, 0.575; 95% CI, 0.374 to 0.897; P = .009, respectively). There were no treatment-related deaths. On logistic regression analyses, treatment allocation, tumor size, and tumor number were significant prognostic factors for overall survival, whereas treatment allocation and tumor number were significant prognostic factors for recurrence-free survival. TACE-RFA was superior to RFA alone in improving survival for patients with HCC less than 7 cm.
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              Early-stage hepatocellular carcinoma in patients with cirrhosis: long-term results of percutaneous image-guided radiofrequency ablation.

              Riccardo Lencioni, Dania Cioni, Laura Crocetti … (2005)
              To perform a prospective, intention-to-treat clinical trial to determine the long-term survival rates of patients with hepatic cirrhosis and early-stage hepatocellular carcinoma (HCC) in whom percutaneous image-guided radiofrequency (RF) ablation was used as the sole first-line anticancer treatment. The study was performed with approval of the ethics committee, and written informed consent was obtained for all patients. From June 1, 1996, to January 1, 2003, 206 patients (143 men, 63 women; age range, 51-81 years; mean age, 67 years +/- 7) who were excluded from surgery and who had Child class A or B cirrhosis with either a single HCC less than or equal to 5 cm in diameter or multiple (as many as three) HCCs less than or equal to 3 cm in diameter each were enrolled. RF ablation was performed in 187 (91%) of 206 patients; 19 (9%) were excluded from RF treatment because of unfavorable tumor location. Follow-up ranged from 3 to 78 months (mean, 24 months +/- 21) and included measurement of alpha-fetoprotein level, ultrasonography at 3-month intervals, and spiral computed tomography at 6-month intervals. Patients were observed for recurrence of the treated tumor and for the emergence of new HCC tumors. Survival probabilities were estimated with the Kaplan-Meier method, and differences between survival curves were evaluated with the log-rank test. At the end of the study, 145 patients were alive, and 61 were dead. In the intention-to-treat analysis, overall survival rates were 97% at 1 year, 67% at 3 years, and 41% at 5 years. Median survival was 49 months. In the 187 patients treated with RF ablation, overall survival rates were 97% at 1 year, 71% at 3 years, and 48% at 5 years. Median survival was 57 months. The difference between the two survival curves was not statistically significant (P=.5094). Survival of patients treated with RF ablation was dependent on Child class (P=.0006) and tumor multiplicity (P=.0133). Patients who had Child class A cirrhosis with solitary HCC (n=116) had 1-, 3-, and 5-year survival rates of 100%, 89% and 61%; median survival was 65 months. The 1-, 3-, and 5-year recurrence rates were 14%, 49%, and 81% for the emergence of new tumors and 4%, 10%, and 10% for local tumor progression. RF ablation is an effective first-line treatment for cirrhotic patients with early-stage HCC who were excluded from surgery.
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                Author and article information

                Contributors
                Xin Yin: yin.xin@zs-hospital.sh.cn
                Lan Zhang: zhang.lan@zs-hospital.sh.cn
                Yan-Hong Wang: wang.yanhong@zs-hospital.sh.cn
                Bo-Heng Zhang: zhang.boheng@zs-hospital.sh.cn
                Yu-Hong Gan: gan.yuhong@zs-hospital.sh.cn
                Ning-Lin Ge: ge.ninglin@zs-hospital.sh.cn
                Yi Chen: chen.yi@zs-hospital.sh.cn
                Li-Xin Li: li.lixin@zs-hospital.sh.cn
                Zheng-Gang Ren: ren.zhenggang@zs-hospital.sh.cn
                Journal
                Journal ID (nlm-ta): BMC Cancer
                Journal ID (iso-abbrev): BMC Cancer
                Title: BMC Cancer
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2407
                Publication date (Electronic): 19 November 2014
                Publication date PMC-release: 19 November 2014
                Publication date Collection: 2014
                Volume: 14
                Issue: 1
                Electronic Location Identifier: 849
                Affiliations
                [ ]Liver Cancer Institute & Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032 China
                [ ]Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
                Article
                Publisher ID: 5031
                DOI: 10.1186/1471-2407-14-849
                PMC ID: 4256894
                PubMed ID: 25409554
                SO-VID: cf57c262-c3bd-4323-a94d-a09b4eade2f6
                Copyright © © Yin et al.; licensee BioMed Central Ltd. 2014
                License:

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 27 June 2013
                Date accepted : 6 November 2014
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2014

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: hepatocellular carcinoma,transcatheter arterial chemoembolization,radiofrequency ablation,combination therapy,survival
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: hepatocellular carcinoma, transcatheter arterial chemoembolization, radiofrequency ablation, combination therapy, survival

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