Efficacy of combination therapy with transcatheter arterial chemoembolization and radiofrequency ablation for intermediate-stage hepatocellular carcinoma

Abstract

Objectives: Transcatheter arterial chemoembolization (TACE) is the standard therapy for patients with intermediate-stage hepatocellular carcinoma (HCC). This study aimed to determine whether combination therapy with radiofrequency ablation (RFA) and TACE was superior to TACE monotherapy for intermediate-stage HCC and identify cases in which this technique was the most effective.

Materials and methods: We selected patients with intermediate HCC who met the following eligibility criteria: (1) ≥ 20 years of age, (2) receiving initial therapy, (3) ≤7 tumors, and (4) maximum tumor diameter <5?cm. We performed propensity score matching (PSM) using potential confounding factors. We retrospectively compared the cumulative overall survival rate and recurrence-free survival rate between the TACE?+?RFA and TACE groups. Additionally, a sub-group analysis was performed for preoperative factors.

Results: Among the 103 patients, 92 were selected using PSM. The cumulative overall survival rates at 1, 3, and 5 years for the TACE?+?RFA group were 97.4%, 70.4%, and 60.4%, respectively, which were significantly higher than those for the TACE group (92.7%, 55.7%, and 22.8%, respectively, p?=?.045). The recurrence-free survival rates at 0.5, 1, and 2 years for the TACE?+?RFA group were 80.0%, 58.6%, and 33.3%, respectively, which were significantly higher than those for the TACE group (34.5%, 8.8%, and 2.9%, respectively, p?p?=?.036).

Conclusions: The addition of RFA to TACE improved cumulative overall and recurrence-free survival in patients with intermediate-stage HCC, especially in patients with AFP <100.     

Comparison of therapeutic effectiveness of combined interventional therapy for 1126 cases of primary liver cancer

AIM: To verify the effect of combined interventional therapy for hepatocellular carcinoma (HCC). METHODS: The clinical data of 1126 HCC patients who received combined interventional therapy for transcatheter arterial chemoembolization (TACE) before or after hepatectomy, TACE and radio-frequency ablation (RFA), Chinese medicine treatment and biotherapy after TACE or transcatheter arterial infusion (TAI), were reviewed according to the results of their liver function, alpha-fetoprotein, image data, color-ultrosonography finding and survival rate. RESULTS: A total of 874 patients were followed up for a period of 2 to 63 mo. The overall 1-, 3- and 5-year survival rates were 67.8%, 28.7% and 18.8% respectively. The 1- 3- and 5- year survival rates of patients who received TACE were 74.7%, 41.4%, 36.9% before hepatectomy and 78.9%, 40.4%, 37.5% after hepatectomy. The effective rate (PR NC) after TACE and RFA was 93.4%, the 1- and 3- year survival rates were 74.5% and 36.8% after TACE and RFA. The effective rate of PR NC after TACE was 83.2%. The 1-, 3- and 5- year survival rates were 69.3%, 21.7%, 8.4% after TACE. The effective rate of PR NC after TAI was 27.5%, the 1- and 2- year survival rates were 11.6% and 0% after TAI. The liver function, color-ultrosonography finding and alpha-fetoprotein after TACE RFA, TACE and TAI were compared. There was no significant difference in each index between TACE and RFA or TACE as well as in liver function between TACE and RFA or between TACE and TAI. CONCLUSION: The therapeutic effectiveness of TACE before or after hepatectomy is most significant, while the effect of TACE and RFA is better than that of TACE, and the effect of TAI is minimal.     

Transarterial chemoembolization in hepatocellular carcinoma treatment: Barcelona clinic liver cancer staging system

Hepatocellular carcinoma(HCC),the fifth most common cancer that predominantly occurs in liver cirrhosis patients,requires staging systems to design treatments. The barcelona clinic liver cancer staging system(BCLC) is the most commonly used HCC management guideline. For BCLC stage B(intermediate HCC),transarterial chemoembolization(TACE) is the standard treatment. Many studies support the use of TACE in early and advanced HCC patients. For BCLC stage 0(very early HCC),TACE could be an alternative for patients unsuitable for radiofrequency ablation(RFA) or hepatic resection. In patients with BCLC stage A,TACE plus RFA provides better local tumor control than RFA alone. TACE can serve as bridge therapy for patients awaiting liver transplantation. For patients with BCLC B,TACE provides survival benefits compared with supportive care options. However,because of the substantial heterogeneity in the patient population with this stage,a better patient stratification system is needed to select the best candidates for TACE. Sorafenib represents the first line treatment in patients with BCLC C stage HCC. Sorafenib plus TACE has shown a demonstrable effect in delaying tumor progression. Additionally,TACE plus radiotherapy has yielded better survival in patients with HCC and portal venous thrombosis. Considering these observations together,TACE clearly has a critical role in the treatment of HCC as a stand-alone or combination therapy in each stage of HCC. Diverse treatment modalities should be used for patients with HCC and a better patient stratification system should be developed to select the best candidates for TACE.     

Combined locoregional treatment of patients with hepatocellular carcinoma: state of the art

In recent years, a combination of intervention therapies has been widely applied in the treatment of hepatocellular carcinoma(HCC). One such combined strategy is based on the combination of the percutaneous approach, such as radiofrequency ablation(RFA), and the intra-arterial locoregional approach, such as trans-arterial chemoembolization(TACE). Several types of evidence have supported the feasibility and benefit of combined therapy, despite some studies reporting conflicting results and outcomes. The aim of this review was to explain the technical aspects of different combined treatments and to comprehensively analyze and compare the clinical efficacy and safety of this combined treatment option and monotherapy, either as TACE or RFA alone, in order to provide clinicians with an unbiased opinion and valuable information. Based on a literature review and our experience, combined treatment seems to be a safe and effective option in the treatment of patients with early/intermediate HCC when surgical resection is not feasible; furthermore, this approach provides better results than RFA and TACE alone for the treatment of large HCC, defined as those exceeding 3 cm in size. It can also expand the indication for RFA to previously contraindicated "complex cases", with increased risk of thermal ablation related complications due to tumor location, or to "complex patients" with high bleeding risk.     

Outcome of transarterial chemoembolization monotherapy, and in combination with percutaneous ethanol injection, or radiofrequency ablation therapy for hepatocellular carcinoma

Aim:  Hepatocellular carcinoma (HCC) is one of the most commonly occurring malignances worldwide. Curative therapies such as resection, percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) have been applied to patients with early-stage HCC. Patients with more advanced cancers require local or systemic therapies. We present the results of our retrospective review conducted to evaluate whether transarterial chemoembolization (TACE) alone and combined TACE with percutaneous ablation for HCC exhibited superior efficacy to palliative treatment.
Methods:  The effects of TACE and of the combined therapies (TACE + PEI or TACE + RFA) on the long-term survival rates were evaluated in 268 untreated HCC patients by various statistical analyses.
Results:  The cumulative survival rates in the TACE alone group were significantly superior to those in the palliative treatment group. Further, the cumulative survival rates in the combined TACE + PEI/RFA group were significantly superior to those in the TACE alone group. When the comparison among the groups was restricted to patients with two or three tumors fulfilling the Milan criteria, significantly greater prolongation of survival was observed in the combined TACE + PEI/RFA group than in the PEI/RFA alone group.
Conclusions:  The aforementioned treatment modalities yielded greater improvements of the survival rate and survival duration as compared to palliative treatment in HCC patients. Furthermore, in terms of the effect on the survival period, combined TACE + PEI/RFA therapy was more effective than TACE monotherapy, and also more effective than PEI or RFA monotherapy in cases with multiple tumors fulfilling the Milan criteria.     

Meta-analysis of radiofrequency ablation in combination with transarterial chemoembolization for hepatocellular carcinoma

AIM: To compare radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA monotherapy in hepatocellular carcinoma (HCC). METHODS: We searched PubMed, Medline, Embase and Chinese databases (CBMdisc and Wanfang data) for randomized controlled trails comparing RFA plus TACE and RFA alone for treatment of HCC from January 2000 to December 2012. The overall survival rate, re-currence-free survival rate, tumor progression rate, and safety were analyzed and compared. The analysis was conducted on dichotomous outcomes and the standard meta-analytical techniques were used. Pooled odds ratios (ORs) with 95%CIs were calculated using either the fixed-effects or random-effects model. For each meta-analysis, the χ2 and I2 tests were first calculated to assess the heterogeneity of the included trials. For P<0.05 and I 2>50%, the assumption of homogeneity was deemed invalid, and the random-effects model wasused; otherwise, data were assessed using the fixed-effects model. All statistical analysis was conducted us-ing Review manager (version 4.2.2.) from the Cochrane collaboration. RESULTS: Eight randomized controlled trials were identified as eligible for inclusion in this analysis and included 598 patients with 306 treated with RFA plus TACE and 292 with RFA alone. Our data analysis indicated that RFA plus TACE was associated a sig-nificantly higher overall survival rate (OR 1-year=2.96, 95%CI: 1.84-7.74, P<0.001; OR 2-year=3.72, 95%CI: 1.24-11.16, P=0.02; OR 3-year=2.65, 95%CI: 1.81-3.86, P<0.001) and recurrence-free survival rate (OR 3-year=3.00, 95%CI: 1.75-5.13, P<0.001; OR 5-year=2.26, 95%CI: 1.43-3.57, P=0.0004) vs that of RFA alone. The tumor progression rate in patients treated with RFA alone was higher than that of RFA plus TACE (OR=0.60, 95%CI: 0.42-0.88, P=0.008) and there was no significant difference on major complications between two different kinds of treatment (OR=1.20, 95%CI: 0.31-4.62, P=0.79). Additionally, the meta-analysis data of subgroups revealed that the     

术中射频消融加肝动脉化疗栓塞术治疗肝细胞性肝癌

目的探讨开腹术中射频消融（RFA）后行肝动脉造影（DSA）及肝动脉化疗栓塞术（TACE）治疗肝细胞性肝癌的必要性。方法开腹术中射频消融治疗原发性肝癌50例，术后2周常规行DSA及TACE术，再3周后复查CT及AFP。结果DSA＋TACE术发现肿瘤染色及碘化油聚集9例（18％），CT复查见碘化油异常沉积10例（10％），AFP转阴43例（86％），AFP不升高5例（10％），总有效率96％。结论开腹术中射频消融后行DSA＋TACE治疗肝细胞性肝癌是一种非常必要、有效的方法，有望能提高生存率。     

肝动脉化疗栓塞联合经皮射频治疗老年中晚期肝癌的疗效

目的 分析肝动脉化疗栓塞（TACE）联合经皮射频消融（RFA）治疗老年中晚期原发性肝癌（HCC）的疗效,为HCC的临床治疗提供参考.方法 按照随机数字表法将80例患者分为TACE联合RFA治疗组（观察组）和RFA治疗组（对照组）,比较两组治疗效果.结果 观察组肿瘤瘤体缩小率高于对照组,两组比较,差异具有统计学意义（P＜0.05）;甲胎蛋白下降超过50％者,观察组（85.7％）与对照组（55.6％）比较差异具有统计学意义（P＜0.05）.两组不良反应发生情况差异无统计学意义（P＞0.05）;术后24个月随访,观察组生存率27例（67.5％）,对照组生存率17例（42.5％）,两组比较差异具有统计学意义（P＜0.05）.结论 HCC患者对TACE联合RFA治疗的耐受性较好,联合治疗的安全性和可行性较好.     

The effectiveness of radiofrequency ablation for patients with BCLC B1 stage hepatocellular carcinoma downgraded by transarterial chemoembolization

PurposeTo evaluate the effectiveness of radiofrequency ablation (RFA) as a curative therapy for BCLC B1 stage (beyond Milan criteria but within up-to-seven criteria) hepatocellular carcinoma (HCC) followed by downstageing by using transarterial chemoembolization (TACE).MethodsWe retrospectively recruited patients underwent RFA alone and who underwent RFA following downstaging into BCLC B1 stage using TACE between April 2011 and August 2017. Overall survival (OS) and recurrence-free survival (RFS) were compared using the Kaplan-Meier method. A propensity score analysis was performed to reduce potential bias.ResultsThe downstaging TACE+RFA and RFA alone group comprised 50 and 110 patients, respectively. After propensity score matching, the 1-, 2-, and 3-year OS rates were 100%, 92%, 74%, respectively, the 1-, 2-, and 3-year RFS rates were 40%, 36%, and 20%, respectively, for patients in the downstaging TACE+RFA group. The 1-, 2-, and 3-year OS rates were 96%, 90%, and 82%, respectively, the 1-, 2-, and 3-year RFS rates were 51%, 32%, and 32%, respectively, for patients in the RFA group. No statistical differences were observed between the two groups in terms of OS and RFS before and after matching.ConclusionRFA after downstaging into BCLC B1 stage using TACE offered a safe and effective treatment regime for patients with HCC beyond the up-to-seven criteria. The intermediate-term OS and RFS of RFA following downstaging into BCLC B1 stage using TACE for HCC were similar to that of patients who were initially in BCLC B1stage.     

Combination therapy of radiofrequency ablation and transarterial chemoembolization in recurrent hepatocellular carcinoma after hepatectomy compared with single treatment

Aim:  To assess the efficacy and safety of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) in recurrent hepatocellular carcinoma (HCC) after hepatectomy and to compare its outcome with a single modality.
Method:  We retrospectively studied 103 patients with recurrent HCCs after hepatectomy who were excluded from repeat hepatectomy. Of them, 81 patients were male and 22 were female (mean age 55.8 ± 10.7 years; range, 30–80 years). According to treatment modality, these patients were divided into three groups: RFA was used as the sole first-line anticancer treatment in 37 patients (RFA group); TACE was used as the sole first-line anticancer treatment in 35 patients (TACE group). RFA followed by TACE was performed in 31 patients (combination group). There was no significant difference in clinical material between the three groups. Indices including treatment success rate, intrahepatic recurrence rate and survival were obtained for analysis and comparison.
Results:  The treatment success rate of the combination group was significantly higher than that of the TACE group (93.5 vs. 68.6%, P  = 0.011). The intrahepatic recurrence rate of the combination group was significantly lower than that of the TACE group (20.7 vs 57.1%, P  = 0.002) and the RFA group (20.7 vs 43.2%, P  = 0.036). The overall 1-, 3- and 5-year survival rates were 73.9, 51.1 and 28.0% respectively in the RFA group; 65.8, 38.9 and 19.5% respectively in the TACE group; and 88.5, 64.6 and 44.3% respectively in the combination group. There was a significant difference in survival between the combination group and the TACE group ( P  = 0.028).
Conclusion:  RFA combined with TACE was more effective in treating recurrent HCC after hepatectomy compared to single RFA or TACE treatment. This combination therapy can thus be a valuable choice of treatment for recurrent HCC.     

Molecular targeting agents associated with transarterial chemoembolization or radiofrequency ablation in hepatocarcinoma treatment

Hepatocellular carcinoma(HCC)is the fifth most common cause of cancer in the world.According to Barcelona Clinic Liver Cancer modified criteria,patients with early stage disease are candidate to radiofrequency ablation(RFA),while patients with intermediate stage HCC are usually treated by transarterial chemoembolization(TACE).TACE and RFA induce a transient devascularisation effect followed by strong neoangiogenic stimulus.In fact,after these procedures,it has been demonstrated an up-regulation of pro-angiogenic and growth factors such as vascular endothelial growth factor-A,which might contribute to accelerated progression in patients with incomplete response.Several studies have demonstrated that MAP-kinase and AKT pathways,in addition to neo-angiogenesis,have an important role in the development of HCC.In advanced HCC,anti-angiogenic therapy and tyrosine kinases inhibitors showed potential clinical benefit.Actually,a number of clinical studies are ongoing testing these agents in combination with TACE or RFA.In this paper,we have reviewed the most recent preclinical and clinical results of such trials.     

Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan (2009 Revised Version)

The World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST) are inappropriate to assess the direct effects of treatment on the hepatocellular carcinoma (HCC) by locoreginal therapies such as radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Therefore, establishment of response evaluation criteria solely devoted for HCC is needed urgently in the clinical practice as well as in the clinical trials of HCC treatment, such as molecular targeted therapies, which cause necrosis of the tumor. Response Evaluation Criteria in Cancer of the Liver (RECICL) was revised in 2009 by Liver Cancer Study Group of Japan based on the 2004 version of RECICL, which was commonly used in Japan. Major revised points of the RECICL 2009 is to provide TE4a (Complete response with enough ablative margin) and TE4b (complete response without enough ablative margin) for local ablation therapy. Second revised point is that setting the timing at which the overall treatment effects are assessed. Third point is that emergence of new lesion in the liver is regarded as progressive disease, different from 2004 version. Finally, 3 tumor markers including alpha‐fetoprotein (AFP) and AFP‐L3 and des‐gamma‐carboxy protein (DCP) were also added for the overall treatment response. We hope this new treatment response criteria, RECICL, proposed by Liver Cancer Study Group of Japan will benefit the HCC treatment response evaluation in the setting of the daily clinical practice and clinical trials as well not only in Japan, but also internationally.     

Risk factors for recurrence after transarterial chemoembolization for early-stage hepatocellular carcinoma

Background

Radiofrequency ablation (RFA) is a standard therapy for the treatment of hepatocellular carcinoma (HCC) with 3 or fewer tumors of up to 3?cm (early-stage HCC); when RFA is unsuccessful or unfeasible, transcatheter arterial chemoembolization (TACE) has often been performed. However, little information about the outcome of TACE for early-stage HCC has been reported and it is hard to decide whether to perform additional treatment following TACE in these difficult conditions. The aim of this study was to determine the risk factors for local or intrahepatic distant recurrence after TACE in early-stage HCC.

Methods

Among 1,560 newly diagnosed HCC patients who were admitted to Okayama University Hospital, 43 patients with early-stage HCC who received only TACE in at least one nodule were enrolled in this study. We analyzed the risk factors for local and distant recurrence by the Cox proportional hazard model.

Results

The local recurrence rates and intrahepatic distant recurrence rates at 3 months, 6?months, and 1?year were 18.6, 33.4, and 61.8%, and 2.8, 2.8, and 10.2%, respectively. Among 12 parameters examined as possible risk factors for recurrence, heterogeneous Lipiodol uptake (risk ratio 3.38; 95% confidence interval 1.14–10.60) and high serum des-gamma-carboxy prothrombin (DCP) (2.58; 1.03–7.14) were significantly correlated with local recurrence, and the presence of multiple tumors (10.64; 1.76–93.75) was significantly correlated with intrahepatic distant recurrence.

Conclusions

Heterogeneous Lipiodol uptake, high serum DCP, and multiple tumors are risk factors for recurrence in patients with early-stage HCC who have undergone palliative TACE.     

Survival rates according to the Cancer of the Liver Italian Program scores of 345 hepatocellular carcinoma patients after multimodality treatments during a 10-year period in a retrospective study

Background and Aim: The Cancer of the Liver Italian Program (CLIP) score has been demonstrated to have superior prognostic ability in hepatocellular carcinoma (HCC) patients worldwide, but there has never been sufficient assessment of the efficacy of treatment modalities according to the CLIP score. This retrospective cohort study of HCC patients was conducted to assess the efficacy of treatment modalities according to the CLIP score. Methods: We compared the efficacy of hepatic resection (HR) (n = 101), radiofrequency ablation with prior transcatheter arterial chemoembolization (RFA + TACE) (n = 115), percutaneous ethanol injection with prior TACE (PEI + TACE) (n = 43), and TACE (n = 86) as a primary treatment in terms of survival among 345 patients treated at Mie University Hospital between 1995 and 2004, according to CLIP score. Results: The overall survival rates in the RFA + TACE group were significantly higher in the patients with CLIP scores of 1, 2, and 3 or more (5‐year, 70.9%; 3‐year, 73.7%; and 3‐year, 100%, respectively), but they were not significantly different from the 5‐year survival rates of the HR group with a CLIP score of 0 (83.7%). Among the patients with a CLIP score of 0, a significantly higher disease‐free survival rate (5‐year: 33.7%) was obtained in the HR subgroup (n = 35) than in the RFA + TACE subgroup (n = 35), both of which were followed since 2000, but morbidity (21.8%) was highest in the HR group. Conclusion: RFA + TACE is concluded to be a safe treatment modality with better overall survival (5‐year, > 60%) in HCC patients regardless of their CLIP score.     

Interventional oncology: new options for interstitial treatments and intravascular approaches

Superselective TACE is defined as TACE from the distal portion of the feeding subsegmental hepatic artery to evoke strong ischemic effects on a small area of the liver, thus avoiding damage to liver function. Lipiodol (iodized oil) is semi-fluid, and it can flow into the surrounding portal venules and hepatic sinusoids through peribiliary plexus (PBP) and the drainage route from the hypervascular HCC. Therefore, the reversed flow from the hepatic sinusoids and portal venules to the peripheral portion of the tumor and daughter nodules can be blocked by Lipiodol injected before a particulate embolus (such as gelatin sponge particles). Common complications of superselective TACE are mild local pain and fever and temporary minimal changes of liver function. Reported CR ratio of definitely hypervascular HCC are around 30–60% by superselective TACE with Lipiodol for hypervascular HCC less than 5 cm. According to a nationwide survey by the Liver Cancer Study Group of Japan (LCSGJ), overall 5-year survival rate was 26% in patients with HCCs not indicated for surgery or RFA (PEI), mainly treated by segmental or subsegmental TACE using Lipiodol. Therefore, this TACE technique should be widely introduced as the first line technique for TACE therapy of HCC.     

Transarterial chemoembolization in combination with percutaneous ablation therapy in unresectable hepatocellular carcinoma: a meta‐analysis

Background: Recent evidence suggests that transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) or a percutaneous ethanol injection (PEI) may have a synergistic effect in treating hepatocellular carcinoma (HCC). The aim of the current meta‐analysis was to identify the survival benefits of TACE combined with percutaneous ablation (PA) therapy (RFA or PEI) for unresectable HCC compared with those of TACE or PA alone. Methods: Randomized‐controlled trials (RCTs) published as full papers or abstracts were searched to assess the survival benefit or tumour recurrence for patients with unresectable HCC on electronic databases. The primary outcome was survival. The secondary outcomes were response to therapy and tumour recurrence. Results: Ten RCTs met the criteria to perform a meta‐analysis including 595 participants. TACE combined with PA therapy, respectively improved, 1‐, 2‐, and 3‐year overall survival compared with that of monotherapy [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.14–4.57; P=0.020], (OR=4.53, 95% CI 2.62–7.82, P<0.00001) and (OR=3.50, 95% CI 1.75–7.02, P=0.0004). Sensitivity analysis demonstrated a significant benefit in 1‐, 2‐ and 3‐year overall survival of TACE plus PEI compared with that of TACE alone for patients with large HCC lesions, but not in TACE plus RFA vs RFA for patients with small HCCs. The pooled result of five RCTs showed that combination therapy decreased tumour recurrence compared with that of monotherapy (OR=0.45, 95% CI 0.26–0.78, P=0.004). Conclusion: TACE combined with PA therapy especially PEI improved the overall survival status for large HCCs.     

肝动脉化疗栓塞联合射频消融治疗大肝癌的疗效评价

目的探讨经导管肝动脉化疗栓塞（transcatheter arterial chemoembolization,TACE）联合射频消融（radiofrequency ablation,RFA）治疗大肝癌的临床应用价值。方法回顾性分析我院2006年4月至2008年7月收治的66例肝细胞癌患者的治疗结果,根据治疗方法分为TACE＋RFA组、TACE组及RFA组,其中19例行RFA联合TACE治疗（TACE＋RFA组）,24例单纯TACE治疗（TACE组）,23例单纯RFA治疗（RFA组）。结果 TACE＋RFA组的肿瘤坏死率达73.68%,明显高于单纯TACE组及单纯RFA组（分别为50.00%,52.17%,P〈0.01,P〈0.05）。局部复发率分别为26.32%、37.50%和30.43%,三组间无显著统计学差异（P〉0.05）。TACE＋RFA组的平均生存期为28.3个月,显著高于TACE组的13.6个月（P〈0.01）和单纯RFA组的21.7个月（P〈0.05）。结论 TACE联合RFA治疗大肝癌与单纯TACE和单纯RFA治疗效果相比,可提高肿瘤坏死率,延长患者生存期。     

Comparative study of cisplatin and epirubicin in transcatheter arterial chemoembolization for hepatocellular carcinoma

Aim: Transcatheter arterial chemoembolization (TACE) is an established treatment for unresectable hepatocellular carcinoma (HCC). However, it is unclear which chemotherapeutic agent should be selected for TACE. The aim of this study was to compare the efficacy of cisplatin (CDDP) with that of epirubicin (EPI) in TACE for patients with unresectable or relapsed HCC. Methods: We performed a historical cohort study involving 131 patients treated with a first TACE, defined as either an initial treatment for previously untreated HCC or a first treatment for relapsed HCC after curative resections or ablations. Efficacy was estimated as the response rate (RR) and it was adjusted for the confounding factors that were defined in this study. Results: The RR were 62.5% (20/32) for the first TACE with CDDP and 51.5% (51/99) for that with EPI. In the adjusted analysis for a history of hepatectomy, percutaneous treatment combined with TACE and tumor factors, the odds ratio was 1.72 (95% confidence interval [CI] = 0.70–4.48). However, a test for interaction between the number of tumors and the chemotherapeutic agent was statistically significant (P = 0.016). In multiple HCC, the RR were 66.7% (10/17) for CDDP and 39.6% (30/46) for EPI. The odds ratio was 4.11 (95% CI = 1.14–17.2). Conclusion: CDDP may be more effective than EPI in TACE for multiple HCC. A randomized controlled study is needed to clarify the efficacy of CDDP in TACE in patients with multiple HCC.     

Outcome of transarterial chemoembolization in patients with inoperable hepatocellular carcinoma eligible for radiofrequency ablation

AIM: To evaluate the outcome of transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC)<5 cm in diameter eligible for radiofrequency ablation (RFA). METHODS: The treatment-related mortality, morbidity, long-term survival, and prognostic factors of HCC patients who had TACE and fulfilled the present inclusion criteria for RFA were evaluated. RESULTS: Of the 748 patients treated with TACE between January 1990 and December 2002,114 patients were also eligible for RFA. The treatment-related mortality and morbidity were 1% and 19%, respectively. Survival at 1, 3, and 5 years was 80%, 43%, and 23%, respectively. Older age and a high albumin level were associated with a better survival, whereas a high a-fetoprotein level (AFP) and the size of the largest tumor >3 cm in diameter were adverse prognostic factors in multivariate analysis. CONCLUSION: The morbidity, mortality, and survival data after TACE for small HCCs eligible for RFA are comparable to those reported after RFA in the literature. Our data suggest the need for a randomized comparison of the two treatment modalities for small HCCs.     

Balloon-occluded transcatheter arterial chemoembolization for hepatocellular carcinoma

Transcatheter arterial chemoembolization(TACE) is widely accepted as a treatment for patients with hepatocellular carcinoma(HCC) in the intermediate stage according to the Barcelona Clinic Liver Cancer(BCLC) guidelines. Recently, balloon-occluded TACE(B-TACE) was developed in Japan. Despite the lack of a clear definition, B-TACE is generally defined as the infusion of emulsion of chemotherapeutic agents with lipiodol followed by gelatin particles under the occlusion of feeding arteries by a microballoon catheter, which leads to the dense lipiodol emulsion(LE) accumulation in HCC nodules. This phenomenon cannot be explained only by the prevention of proximal migration and leakage of embolization materials; it further involves causing local changes in the hemodynamics of the surrounding occlusion artery and targeted HCC nodules. Balloon-occluded arterial stump pressure plays an important role in the dense LE accumulation in targeted HCC nodules. Although randomized controlled trials comparing the therapeutic effect and the prognosis of B-TACE to those of the other TACE procedures, such as conventional-TACE and drug-eluting beads TACE, are still lacking, B-TACE is thought to be a promising treatment. The purpose of this review is to summarize the mechanism, therapeutic effect, indication, prognosis and complications of BTACE.