Long-term prognosis of patients undergoing transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: comparison of cisplatin lipiodol suspension and doxorubicin hydrochloride emulsion.

PURPOSE: To evaluate long-term prognosis of transcatheter arterial chemoembolization (TACE) with use of cisplatin (CDDP) lipiodol (LPD) suspension (CDDP/LPD) compared with that with use of doxorubicin hydrochloride (ADM) LPD emulsion (ADM/LPD) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: One hundred eight patients were treated with use of CDDP/LPD and 26 were treated with use of ADM/LPD. Survival rates and frequency of side effects and complications in the CDDP/LPD group were compared with those in the ADM/LPD group. RESULTS: CDDP/LPD was given at a dose of 15-70 mg (mean dose, 41 mg), whereas ADM/LPD was given at a dose of 20-100 mg (mean dose, 57 mg) throughout the study period. The survival rates in the CDDP/LPD group were 81% at 1 year, 41% at 3 years, 19% at 5 years, and 13% at 7 years, whereas those in the ADM/LPD group were 67% at 1 year, 18% at 3 years, and 0% at 5 years. The CDDP/LPD group showed significantly better survival than the ADM/LPD group (P <.05). In the CDDP/LPD group, there was a significant prolongation of survival in patients with monofocal HCC (P <.05) and patients with HCC assessed as an almost complete LPD accumulation (P <.05). There were no significant differences in survival rates in the ADM/LPD group according to tumor size and number of tumors. Hepatic failure was observed in 8% of all procedures and was not different between the two therapeutic groups. Renal dysfunction was observed in 2% of all treatments involving CDDP/LPD, and it resolved spontaneously with appropriate medications. CONCLUSIONS: TACE with use of low-dose CDDP was efficacious for unresectable HCC and had few complications. TACE with use of CDDP may contribute to prolongation of the life span of patients with HCC versus TACE with use of ADM.     

Intraarterial infusion chemotherapy with lipioclol-CDDP suspension for hepatocellular carcinoma

Purpose: To quantitatively evaluate the usefulness of lipiodol-CDDP suspension (LCS) chemotherapy in hepatocellular carcinoma (HCC). Methods: CDDP (cis-diamminedichloroplatinum) powder was prepared by removing the water and NaCl from aqueous CDDP. Two quantities of prepared CDDP powder, 10 mg and 20 mg, were mixed with 1 ml each of iopamidol 300 mgI/ml (IP300) and lipiodol (LPD) using a high pressure pumping method, thus producing LCS. Thirty-two patients with HCC, who had good renal function [creatinine clearance (Ccr) 50 ml/min or more], received additional intraarterial infusion chemotherapy with LCS or LCS alone. Results: The most frequently observed CDDP powder sizes were 5.95–10.90 μm (average: 11.59 μm). The LCS obtained demonstrated a suspension of 2–12 μm (average 3.69 μm) immediately after mixing, and no significant changes were observed in LCS particle sizes 3 hr after mixing. Moreover, the sustained release with LCS was observed for up to 3 hr. Meanwhile, the peripheral free platinum concentration between intraarterial infusion chemotherapy with LCS and intraarterial infusion with the aqueous solution of CDDP, with respect to variance residence time (VRT), showed a significant difference, with a p value of 0.0382. The survival rate was 89.84% at 1 year, 73.78% at 2 years, and 68.51% at 3 years. Furthermore, the platinum concentration in the tumor was 25–95 times the concentration in the surrounding liver parenchyma. Conclusion: Good clinical results can be expected by applying LCS to HCC.     

不同治疗方案对晚期肝细胞性肝癌预后的影响及因素分析

目的：研究单纯和联合治疗方案对晚期肝细胞肝癌（HCC）预后的影响,分析影响预后的主要因素。 方法：回顾性分析2014年我院收治的133例晚期HCC患者,统计24项预后相关数据,采用Cox单因素和多因素回归模型分析预后影响因素。统计患者接受的所有治疗方式,并分为3种治疗方案：（1）保守治疗58例;（2）单纯肝动脉化疗栓塞术（TACE）治疗58例;（3）联合治疗17例：TACE联合索拉菲尼或者TACE联合立体定向放疗（SBRT）。Kaplan-Meier法绘制生存曲线,并使用Log-rank检验比较患者生存期差异。 结果：133例患者总体中位生存期为7.6个月,其中6个月、1年、2年的生存率分别为57%、30%、12%。多因素分析证明Child-Pugh分级、门静脉癌栓类型、肝外转移类型以及甲胎蛋白水平为影响预后的独立因素。治疗方案上,TACE联合索拉菲尼与TACE联合SBRT之间无明显差异,但均明显优于单纯TACE治疗,且单纯TACE治疗明显优于保守治疗。 结论：Child-Pugh分级、门静脉癌栓类型、肝外转移类型和甲胎蛋白水平是影响晚期HCC预后的独立因素。TACE联合索拉菲尼或TACE联合SBRT的预后均优于单纯TACE治疗,单纯TACE治疗优于保守治疗。     

Transjugular Intrahepatic Portosystemic Shunt for Portal Hypertension in Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

Purpose

In patients with hepatocellular carcinoma (HCC), limited therapeutic options are available for portal hypertension resulted from portal vein tumor thrombus (PVTT). We aimed to determine safety and efficacy of TIPS for treatment of symptomatic portal hypertension in HCC with PVTT.

Methods

We evaluated clinical characteristics of 95 patients with HCC and PVTT out of 992 patients who underwent TIPS. The primary endpoints included success rate, procedural mortality, serious complications, decrease in portosystemic pressure gradient, and symptom relief. The secondary endpoints included recurrence of portal hypertension, overall survival, adverse events related to treatments for HCC, and quality of life measured by Karnofsky Performance Status Scale (KPS).

Results

Success rate of TIPS was 95.8% (91/95), with procedural mortality of 1.1%. Serious complications related to TIPS procedure occurred in 2.1% (2/95) of patients. The symptoms of portal hypertension were well relieved. Variceal bleeding was successfully controlled and terminated in 100% of patients, with a recurrence rate of 39.2% in 12 months. Refractory ascites/hydrothorax was controlled partially or completely in 92.9% of patients during 1 month after TIPS, with a recurrence rate of 17.9% in 12 months. Survival rate at 6, 12, 24, and 36 months was 75.8, 52.7, 26.4, and 3.3%, respectively. No unexpected adverse event related to treatments for HCC was observed. The KPS score was 49 ± 4.5 and 63 ± 4.7 before and 1 month after TIPS, respectively (p < 0.001).

Conclusions

TIPS is a safe and efficacious treatment for symptomatic portal hypertension in HCC with PVTT.

     

Contrast-Enhanced Ultrasonography of Hepatocellular Carcinoma After Chemoembolisation Using Drug-Eluting Beads: A Pilot Study Focused on Sustained Tumor Necrosis

The purpose of this study was to assess the use of contrast-enhanced ultrasonography (CEUS) and the sustained antitumor effect of drug-eluting beads used for transarterial chemoembolisation (TACE) of unresectable hepatocellular carcinoma (HCC). Ten patients with solitary, unresectable HCC underwent CEUS before, 2 days after, and 35 to 40 days after TACE using a standard dose (4 ml) of drug-eluting beads (DC Beads; Biocompatibles, Surrey, UK) preloaded with doxorubicin (25 mg doxorubicin/ml hydrated beads). For CEUS, a second-generation contrast agent (SonoVue, Bracco, Milan, Italy) and a low mechanical–index technique were used. A part of the tumor was characterized as necrotic if it showed complete lack of enhancement. The percentage of necrosis was calculated at the sonographic section that depicted the largest diameter of the tumor. Differences in the extent of early (2 days after TACE) and delayed (35 to 40 days after TACE) necrosis were quantitatively and subjectively assessed. Early post-TACE tumor necrosis ranged from 21% to 70% (mean 43.5% ± 19%). There was a statistically significant (p = 0.0012, paired Student t test) higher percentage of delayed tumor necrosis, which ranged from 24% to 88% (mean 52.3% ± 20.3%). Subjective evaluation showed a delayed obvious increase of the necrotic areas in 5 patients. In 2 patients, tumor vessels that initially remained patent disappeared on the delayed follow-up. A part of tumor necrosis after chemoembolisation of HCC with DEB seems to take place later than 2 days after TACE. CEUS may provide evidence for the sustained antitumor effect of DEB-TACE. Nevertheless, the ideal time for the imaging evaluation of tumor response remains to be defined.     

Phase I Dose-Escalation Study of Tirapazamine Chemoembolization for Unresectable Early- and Intermediate-Stage Hepatocellular Carcinoma

PurposeTo investigate the safety of replacing doxorubicin with tirapazamine in conventional transarterial chemoembolization (TACE) in an Asian population with hepatocellular carcinoma (HCC), and to determine the optimal tirapazamine dose for phase II studies.Materials and MethodsThis was a phase I, 3 + 3 dose-escalation study for patients with unresectable early- and intermediate-stage HCC who received 5, 10, or 20 mg/m² of intra-arterial (IA) tirapazamine followed by ethiodized oil/gelatin sponge-based embolization. Key eligibilities included HCCs no more than 10 cm in diameter, prior embolization allowed, Eastern Cooperative Oncology Group performance status of 0 or 1, Child-Pugh score of 5–7, and platelet count of ≥60,000 μL. Dose-limiting toxicity (DLT) was defined as any grade 3 nonhematological or grade 4 hematological toxicity, with the exception of transient elevation of aminotransferase levels after the procedure.ResultsSeventeen patients were enrolled, 59% of whom had progression from a prior HCC therapy and 35% of whom had progression or recurrence after TACE. All patients tolerated the tirapazamine TACE well without any DLT or serious adverse event. Using the modified Response Evaluation Criteria in Solid Tumors, the complete response (CR) rate was 47%, and the CR + partial response rate was 65%. The median duration of response was not reached. The median time to progression was 12.6 months (95% confidence interval, 5.1–not reached). The median overall survival was 29.3 months. The selected phase II dose was set at a fixed dose of 35 mg of IA tirapazamine.ConclusionsIA tirapazamine with transarterial embolization was well tolerated and showed promising efficacy signals in intermediate-stage HCC, justifying pursuit of a phase II study.     

Hepatic Arterial Infusion Chemotherapy Using Fluorouracil Followed by Systemic Therapy Using Oxaliplatin Plus Fluorouracil and Leucovorin for Patients with Unresectable Liver Metastases from Colorectal Cancer

The purpose of this study was to assess retrospectively the sequential treatment of hepatic arterial infusion (HAI) chemotherapy followed by systemic therapy using oxaliplatin plus 5-flourouracil (5-FU) and leucovorin, namely, FOLFOX, for patients with liver metastases from colorectal cancer. We reviewed 20 patients with unresectable liver metastases from colorectal cancer. Patients were initially treated with HAI chemotherapy until disease progression (5-fluorouracil, 1000 mg/m² intra-arterial infusion, weekly) and then with FOLFOX thereafter (FOLFOX4, n = 13; modified FOLFOX6, n = 7). Adverse events, tumor response, and time to progression for each therapy were evaluated retrospectively, and overall survival was estimated. Toxicity of HAI chemotherapy was generally mild. Of 20 patients, adverse events leading to treatment discontinuation occurred in only 1 patient (5%) during initial therapy using HAI chemotherapy, while 9 patients (45%) exhibited adverse events during subsequent FOLFOX therapy. For HAI chemotherapy and FOLFOX, objective response rates were 85.0% and 35.0%, respectively, and median time to progression was 11.6 and 5.1 months, respectively. Median overall survival was 30.1 months. In conclusion, the sequence of HAI chemotherapy followed by FOLFOX is a promising treatment strategy for the long-term use of active chemotherapeutic agents, leading to a superior tumor response and fewer toxic effects in patients with unresectable liver metastases from colorectal cancer.     

Long-term results of percutaneous ethanol injection therapy for hepatocellular carcinoma in cirrhosis: a European experience

The objective of our work was to evaluate the long-term results of percutaneous ethanol injection (PEI) for the treatment of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. A total of 184 cirrhotic patients with HCC underwent PEI as the only anticancer treatment over an 8-year period. Patients were followed after therapy by means of clinical examinations, laboratory tests, and US and CT studies performed at regular time intervals. Survival rates were determined according to the Kaplan-Meier method. The overall survival was 67 % at 3 years, 41 % at 5 years, and 19 % at 7 years. The 3-, 5-, and 7-year survival rates of patients with single HCC ≤ 3 cm (78, 54, and 28 %, respectively) were significantly higher (p < 0.01) than those of patients with single HCC of 3.1–5 cm (61, 32, and 16, respectively) or multiple HCCs (51, 21, and 0 %, respectively). Survival of Child-Pugh A patients (79 % at 3 years, 53 % at 5 years, and 32 % at 7 years) was significantly longer (p < 0.01) than that of Child-Pugh B patients (50 % at 3 years, 28 % at 5 years, and 8 % at 7 years). A selected group of 70 patients with Child-Pugh A cirrhosis and single HCC ≤ 3 cm had a 7-year survival of 42 %. Long-term survival of cirrhotic patients with HCC treated with PEI is comparable to that reported in published series of matched patients submitted to surgical resection. Received 12 March 1996; Revision received 24 June 1996; Accepted 23 August 1996     

Survival Outcomes of Very Small Drug-Eluting Beads Used in Chemoembolization of Unresectable Hepatocellular Carcinoma

PurposeTo assess the safety and efficacy of transarterial chemoembolization using a 75-μm drug-eluting embolic (DEE) in patients with unresectable hepatocellular carcinoma (HCC).Materials and MethodsThe medical records of 109 patients with a mean age of 64.1 years (range 85–49) treated for unresectable HCC between November 2013 and August 2016 with transarterial chemoembolization using a 75-μm DEE were retrospectively reviewed. Patients who had prior therapy for HCC were excluded. Child-Pugh A patients and Barcelona Clinic Liver Cancer stages A/B patients constituted 68.8% and 65.1% of the patients, respectively. The mean size of the index tumors was 5.8 cm (range 18.5–1.2) with 42 (39%) patients with central tumors around the porta-hepatis region. Portal vein invasion was seen in 10 (9.2%) patients. Tumor response was categorized according to the modified Response Evaluation Criteria in Solid Tumors 1.1, and the toxicity profile was assessed using Common Terminology Criteria for Adverse Events, version 4.03.ResultsAt 1-month follow-up, complete response, objective response, and disease control was seen in 23%, 66%, and 90%, respectively. The median progression-free survival was 11.2 months. The median overall survival was 25.1 months (33.4 months for Child-Pugh A and 28.2 months for Barcelona Clinic Liver Cancer stages A/B), and transplant-free survival was 21.3 months. The 6-, 12-, and 24-month survivals were 91.7%, 75.5%, and 50.5%, respectively. Grade 3 toxicity was seen in 1.8% of the patients; no grade 4 or 5 toxicity was reported.ConclusionsTransarterial chemoembolization using 75-μm DEE is safe and efficacious in the treatment of HCC.     

Hepatic Artery Infusion Chemotherapy Using Fluorouracil,Leucovorin, and Oxaliplatin versus Transarterial Chemoembolization as Initial Treatment for Locally Advanced Hepatocellular Carcinoma: A Propensity Score–Matching Analysis

PurposeTo compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with a modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) regimen with that of transarterial chemoembolization as a locoregional treatment for patients with locally advanced hepatocellular carcinoma (HCC).MethodsThis retrospective study included adult patients with locally advanced HCC who received first-line treatment with either HAIC-mFOLFOX or conventional transarterial chemoembolization monotherapy from January 2015 to December 2016. The outcomes, including tumor response rates, evaluated via imaging assessment using the modified response evaluation criteria in solid tumors; overall survival; progression-free survival; and safety, were compared. The propensity score–matching methodology was used to reduce the influence of confounding factors on the outcomes.ResultsThe study included 131 patients with locally advanced HCC who underwent transarterial chemoembolization and 101 who received HAIC-mFOLFOX as initial treatment. After propensity score matching (n = 67 in each group), patients who received HAIC-mFOLFOX had a higher objective response rate (43.3% vs 13.4%, P = .001), longer median overall survival (13.9 vs 6.0 months, P < .001), and longer median progression-free survival (6.4 vs 2.8 months, P = .001) than those who underwent transarterial chemoembolization. The survival benefit with HAIC-mFOLFOX was strengthened in patients with HCC with vascular invasion (hazard ratio: 0.379; 95% confidence interval: 0.237–0.607). HAIC-mFOLFOX was associated with lower incidences of severe adverse events (8.9% vs 22.9%) and liver toxicity than transarterial chemoembolization.ConclusionsCompared with transarterial chemoembolization, HAIC-mFOLFOX is a potentially safer and more effective locoregional therapy for patients with locally advanced HCC.     

Comparison of Drug-Eluting Embolics versus Conventional Transarterial Chemoembolization for the Treatment of Patients with Unresectable Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

PurposeTo compare the cost-effectiveness of using doxorubicin-loaded drug-eluting embolic (DEE) transarterial chemoembolization versus that of using conventional transarterial chemoembolization for patients with unresectable hepatocellular carcinoma (HCC).Materials and MethodsA decision-analysis model was constructed over the lifespan of a payer’s perspective. The model simulated the clinical course, including periprocedural complications, additional transarterial chemoembolization or other treatments (ablation, radioembolization, or systemic treatment), palliative care, and death, of patients with unresectable HCC. All clinical parameters were derived from the literature. Base case calculations, probabilistic sensitivity analyses, and multiple two-way sensitivity analyses were performed.ResultsIn the base case calculations for patients with a median age of 67 years (range for conventional transarterial chemoembolization: 28–88 years, range for DEE-transarterial chemoembolization: 16–93 years), conventional transarterial chemoembolization yielded a health benefit of 2.11 quality-adjusted life years (QALY) at a cost of $125,324, whereas DEE-transarterial chemoembolization yielded 1.71 QALY for $144,816. In 10,000 Monte Carlo simulations, conventional transarterial chemoembolization continued to be a more cost-effective strategy. conventional transarterial chemoembolization was cost-effective when the complication risks for both the procedures were simultaneously varied from 0% to 30%. DEE-transarterial chemoembolization became cost-effective if the conventional transarterial chemoembolization mortality exceeded that of DEE-transarterial chemoembolization by 17% in absolute values. The two-way sensitivity analyses demonstrated that conventional transarterial chemoembolization was cost-effective until the risk of disease progression was >0.4% of that for DEE-transarterial chemoembolization in absolute values. Our analysis showed that DEE-transarterial chemoembolization would be more cost-effective if it offered >2.5% higher overall survival benefit than conventional transarterial chemoembolization in absolute values.ConclusionsCompared with DEE-transarterial chemoembolization, conventional transarterial chemoembolization yielded a higher number of QALY at a lower cost, making it the more cost-effective of the 2 modalities.     

Transarterial Chemoembolization with Additional Cisplatin Infusion for Hepatocellular Carcinoma Invading the Hepatic Vein

PurposeTo evaluate retrospectively the efficacy of transarterial chemoembolization in patients with hepatocellular carcinoma (HCC) with hepatic vein invasion by comparing the results of conventional transarterial chemoembolization and modified transarterial chemoembolization.Materials and MethodsFrom January 2000 to December 2009, 107 patients with HCC and hepatic vein invasion and Child-Pugh class A were treated by transarterial chemoembolization. Modified transarterial chemoembolization (conventional transarterial chemoembolization followed by additional infusion of 50–100 mg of cisplatin) has been undertaken since 2005. Clinical and radiologic data were reviewed and analyzed retrospectively. The overall survival rates were obtained by the Kaplan-Meier method and compared by the log-rank test.ResultsConventional transarterial chemoembolization was performed in 60 patients, and modified transarterial chemoembolization was performed in 47 patients. No significant differences were observed in major complications between the groups. The median survival was longer in the modified group compared with the conventional group (9.7 mo, 95% confidence interval [CI], 4.3–15.1, vs 6.7 mo, 95% CI, 4.8–8.5; P = .047). By subgroup analysis, modified transarterial chemoembolization increased survival of patients with a diffuse tumor type (8.9 mo, 95% CI, 5.9–11.9, vs 3.8 mo, 95% CI, 2.5–5.0; P = .000) and patients without metastasis (20.9 mo, 95% CI, 12.2–29.5, vs 7.3 mo, 95% CI, 4.1–10.5; P = .005). Multivariate analysis identified three independent predictive factors for mortality: diffuse tumor type (P = .001), metastasis (P = .009), and modified transarterial chemoembolization protocol (P = .003).ConclusionsA survival benefit was suggested with transarterial chemoembolization with additional cisplatin infusion over conventional transarterial chemoembolization in patients with HCC invading the hepatic vein.     

Combined transcatheter arterial chemoembolization and percutaneous ethanol injection for the treatment of large hepatocellular carcinoma: local therapeutic effect and long-term survival rate

The aim of our study was to investigate local therapeutic effects and long-term results of combined transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) in the treatment of large hepatocellular carcinoma (HCC). Eight-six patients (67 males and 19 females, age range 48–75 years, mean age 65.1 years) with Child-Pugh class A (n = 48) or B (n = 38) liver cirrhosis and a large HCC (main tumor 3.1–8 cm in diameter with no more than two daughter nodules) were enrolled in a prospective study. All patients underwent a single TACE session followed by PEI. Follow-up ranged from 4 to 65 months (mean 27.8 months, median 26 months). No major complication occurred. The local therapeutic effect, as assessed on the basis of findings at CT and MR imaging, was complete response in 71 of 86 patients (82 %) and partial response in 15 of 86. Overall survival rates by the Kaplan-Meier method were 92 % at 1 year, 83 % at 2 years, 69 % at 3 years, 58 % at 4 years, and 47 % at 5 years. Survival of Child-Pugh A patients (75 % at 3 years and 59 % at 5 years) was significantly longer (p < 0.01) than that of Child-Pugh B patients (61 % at 3 years and 35 % at 5 years). Combined TACE and PEI is an effective treatment for large HCC. Received 10 June 1997; Revision received 28 August 1997; Accepted 2 September 1997     

A Transarterial Chemoembolization of Balloon-Occluded Alternate Infusions of Cisplatin and Gelatin Particles for Hepatocellular Carcinoma: A Phase I/II Multicenter Prospective Study of Safety and Efficacy

PurposeTo evaluate the safety and efficacy of a newly developed technique of balloon-occluded alternate infusions of cisplatin and gelatin particles in transarterial chemoembolization in hepatocellular carcinoma (HCC) and to evaluate the liver damage following the procedure.Materials and MethodsForty-three patients with HCC from 4 medical centers were enrolled in this multicenter prospective study. Of these, 41 patients were observed for 6 months following balloon-occluded alternate infusion transarterial chemoembolization. The primary endpoint was the safety of the procedure, and the secondary endpoint was the objective response rate (ORR) of the HCCs at 2 months following treatment.ResultsThree patients experienced adverse events, including 1 patient with facial swelling and skin rash, dissection of the celiac artery, and bland portal vein thrombus. No major adverse events were identified. Two (5.3%) patients regressed from a Child-Pugh classification of A to B. The balloon-occluded alternate infusion transarterial chemoembolization treatment achieved a 22.0% complete response (CR) rate and a 73.2% ORR (95% confidence interval [CI], 57.9%–84.4%). In a retrospective analysis of 23 patients with HCCs above the up-to-7 criteria, the CR rate and ORR of the balloon-occluded alternate infusion transarterial chemoembolization were 21.7% and 82.6% (95% CI, 62.3%–93.6%), respectively.ConclusionsBalloon-occluded alternate infusion transarterial chemoembolization is safe and effective for achieving a high ORR while preserving liver function.     

Clinical Significance of the Initial and Best Responses after Chemoembolization in the Treatment of Intermediate-Stage Hepatocellular Carcinoma with Preserved Liver Function

PurposeTo evaluate the clinical implications of initial and best responses during repeated transarterial chemoembolization procedures for hepatocellular carcinoma (HCC).Materials and MethodsThis study included 726 patients who received a diagnosis of intermediate-stage HCC with Child-Pugh class A liver function between 2007 and 2016, and who were treated with transarterial chemoembolization as the first-line treatment. Evaluation of treatment response was based on the modified response evaluation criteria in solid tumors. Overall survival (OS) was compared between response categories after implementation of landmark analysis.ResultsOf the 726 patients, an objective response (complete response [CR] or partial response [PR]) was observed as the initial response in 78.1% of patients. Regarding the best response during the transarterial chemoembolization series, 87.2% of patients were overall responders. The median OS of initial responders (n = 483) was not significantly different from that of subsequent responders at the 1-year landmark (stable disease [SD] after first transarterial chemoembolization but CR or PR after repeated transarterial chemoembolization; n = 61; 46.2 vs 40.1 months, respectively; P = .145). Likewise, the median OS of initial CR patients (n = 326) was not significantly different from that of the subsequent CR group (n = 126) at the 1-year landmark (PR or SD after first transarterial chemoembolization but CR after repeated transarterial chemoembolization; 53.4 vs 46.3 months, respectively; P = .455). Multivariate Cox analyses showed that the objective responses, the initial responses (hazard ratio [HR], 0.638; P = .001), and the best responses (HR, 0.304; P < .001) had the significant prognostic significance for OS.ConclusionsBoth the initial and best responses during repeated transarterial chemoembolization were significantly associated with OS in patients with intermediate-stage HCC and preserved liver function.     

Safety and Efficacy of Doxorubicin Drug-eluting Bead Transarterial Chemoembolization in Patients with Advanced Hepatocellular Carcinoma

PurposeTo investigate the safety and efficacy of transarterial chemoembolization using doxorubicin drug-eluting beads (DEBs) in patients with Barcelona Clinic Liver Cancer (BCLC) C stage hepatocellular carcinoma (HCC).MethodsConsecutive patients with initial staging of BCLC C HCC who received DEB transarterial chemoembolization over the last 5 years were studied. The study included 121 patients (mean age, 61.2 years old). Adverse events (AEs) after DEB transarterial chemoembolization were studied in detail and were recorded as per the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 criteria. Survivals were analyzed according to parameters from the time of first DEB transarterial chemoembolization. Kaplan-Meier method by log-rank test and Cox proportional hazard model were used for survival analysis.ResultsAEs occurred in 30.2% of patients. No AEs were greater than Common Terminology Criteria for Adverse Events grade III. Grade I and II AEs included nausea and vomiting in 7.8% of patients and abdominal pain in 23.8% of patients. Grade III AEs were noted in 1.06% of patients. There were no gastrointestinal or hepatic complications. There were no deaths within 30 days after DEB transarterial chemoembolization. The overall median survival was 13.5 months. Among the Child-Pugh class A patients, those without PVT and metastasis (28.9%) had better survival when treated with DEB transarterial chemoembolization than those with PVT and metastases (9.9%) (18.8 mo versus 4.4 mo, P = .001). Ascites, performance status, Okuda stage HCC, serum alpha fetoprotein levels, and etiologic factor for chronic liver disease predicted survival.ConclusionsDEB transarterial chemoembolization appears to be a safe and effective treatment option for patients with BCLC C HCC. Patients with Child-Pugh class A without PVT and metastasis benefited most from DEB transarterial chemoembolization.     

Transarterial Radioembolization versus Transarterial Chemoembolization Plus Percutaneous Ablation for Unresectable,Solitary Hepatocellular Carcinoma of ≥3 cm: A Propensity Score–Matched Study

PurposeTo compare the safety and effectiveness of transarterial radioembolization (TARE) and transarterial chemoembolization with drug-eluting embolic agents combined with percutaneous ablation (transarterial chemoembolization [TACE] + ablation) in the treatment of treatment-naïve, unresectable, solitary hepatocellular carcinoma (HCC) of ≥3 cm.Materials and MethodsTwenty-nine patients with treatment-naïve, unresectable, solitary HCC of ≥3 cm received combined TACE + ablation, and 40 patients received TARE at a single institution. Local tumor response, tumor progression-free survival (PFS), overall survival, need for reintervention, bridge to transplant, and major complications were compared. Clinical variables and outcomes were compared before and after propensity score matching (PSM).ResultsBefore PSM, patients who underwent TARE had a larger tumor size (3.7 vs 5.5 cm; P = .0005) and were older (61.5 vs 69.3 years; P = .0014). After PSM, there was no difference in baseline characteristics between the 2 groups, with the mean tumor sizes measuring 3.9 and 4.1 cm in the TACE + ablation and TARE cohorts, respectively. After PSM (n = 19 in each group), no statistically significant difference was observed in local radiological response (disease control rates, 100% vs 94.7%; P = .31), survival (subdistribution hazard ratio [SHR], 0.71; 95% confidence interval [CI], 0.28–1.80; P = .469), PFS (SHR, 0.61; 95% CI, 0.21–1.71; P = .342), bridge to transplant (21.1% vs 31.6%, P = .46), and major adverse event rates (15.8% vs 10.5%, P = .63) between the 2 groups. The mean total number of locoregional interventions was higher in the TACE + ablation cohort (1.9 vs 1.3 sessions, P = .02), with an earlier median reintervention trend (SHR, 0.61; 95% CI, 0.20–1.32; P = .167).ConclusionsThe present study showed that TARE and the combination of TACE and ablation are comparable in safety and effectiveness for treating treatment-naïve, unresectable, solitary HCC of ≥3 cm.     

Survival benefit of chemoembolization plus Iodine125 seed implantation in unresectable hepatitis B-related hepatocellular carcinoma with PVTT: a retrospective matched cohort study

Objectives

To investigate the survival benefit of transarterial chemoembolization (TACE) plus Iodine125 seed implantation (TACE-Iodine125) in hepatitis B-related HCC patients with portal vein tumour thrombus (PVTT) and the underlying prognostic factors.

Methods

A retrospective matched cohort study was performed on consecutive HCC patients with PVTT from January 2011 to June 2014. Seventy patients (TACE-Iodine125 group) who underwent TACE-Iodine125 were compared with a historical case-matched control group of 140 patients (TACE group) who received TACE alone. The survival of patients and the underlying prognostic factors were analysed.

Results

The median survival times of the TACE-Iodine125 and TACE groups were 11.0 and 7.5 months, respectively (p?<?0.001). The survival probability at 12, 24, and 36 months was 50 %, 14.5 %, and 14.5 % vs. 25 %, 9 %, and 5 % in the TACE-Iodine125 and TACE groups, respectively (p?<?0.001). The PVTT responders had better survival than the PVTT non-responders (p?<?0.001). For the PVTT non-responders, there were no differences in the survival curves between the groups (p?=?0.353). Multivariate analysis showed that type III PVTT (p?<?0.001) and APS (p?<?0.001) were independent predictors of poor prognosis. In contrast, the treatment modality of TACE-Iodine125 (p?<?0.001) and PVTT response (p?=?0.001) were favourable prognostic features.

Conclusions

TACE combined with Iodine125 seed implantation may be a good choice for selected HB-HCC patients with PVTT.

Key Points

? TACE-Iodine125 was more effective than TACE for patients with HCC-PVTT. ? The TACE-Iodine125 procedure was safe. ? TACE-Iodine125 was conditional for patients with HCC-PVTT. ? TACE-Iodine125 resulted in a better PVTT response compared to TACE alone. ? A good PVTT response is a favourable prognostic factor.

     

Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials

PURPOSE: To review the available evidence of chemoembolization for unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Computerized bibliographic searches with MEDLINE and CANCERLIT databases from 1980 through 2000 were supplemented with manual searches, with the keywords "hepatocellular carcinoma," "liver cell carcinoma," "randomized controlled trial [RCT]," and "chemoembolization." Studies were included if patients with unresectable HCC were enrolled and if they were RCTs in which chemoembolization was compared with nonactive treatment (five RCTs) or if different transarterial modalities of therapy (13 RCTs) were compared. Data were extracted from each RCT according to the intention-to-treat method. Five of the RCTs with a nonactive treatment arm were combined by using the random-effects model, whereas all 18 RCTs were pooled from meta-regression analysis. RESULTS: Chemoembolization significantly reduced the overall 2-year mortality rate (odds ratio, 0.54; 95% CI: 0.33, 0.89; P =.015) compared with nonactive treatment. Analysis of comparative RCTs helped to predict that overall mortality was significantly lower in patients treated with transarterial embolization (TAE) than in those treated with transarterial chemotherapy (odds ratio, 0.72; 95% CI: 0.53, 0.98; P =.039) and that there is no evidence that transarterial chemoembolization is more effective than TAE (odds ratio, 1.007; 95% CI: 0.79, 1.27; P =.95), which suggests that the addition of an anticancer drug did not improve the therapeutic benefit. CONCLUSION: In patients with unresectable HCC, chemoembolization significantly improved the overall 2-year survival compared with nonactive treatment, but the magnitude of the benefit is relatively small.     

CT-guided radiofrequency ablation after with transarterial chemoembolization in treating unresectable hepatocellular carcinoma with long overall survival improvement

Purpose

To assess the time to disease progression (TTP), long-term survival benefit and safety of patients with unresectable hepatocellular carcinoma (HCC) treated with computed tomography (CT)-guided radiofrequency ablation (RFA) with transarterial chemoembolization chemoembolization (TACE).

Methods

This study was approved by the institutional review board. We reviewed the records of patients with intermediate and advanced HCC treated with CT-guided RFA with TACE between January 2000 and December 2009. Median TTP, overall survival (OS) and hepatic function were analyzed with the Kaplan–Meier method and log-rank tests.

Results

One hundred and twenty-two patients (112 men and 10 women, mean age 53 years, range 18–86 years) were included in the study. The median follow-up time was 42 months (range 6–89 months), TTP was 6.8 months, the median OS was 31 months, and the 1-, 3-, and 5-year OS were 88.5%, 41.0%, and 10.7%. The results of the univariate analysis revealed that intrahepatic lesion, AJCC stage, and Child-Pugh stage were predictors of OS (P < 0.01). In the multivariate analysis, the AJCC stage system showed a statistically significant difference for prognosis. Procedure-related death was 0.21% (1/470) within 1 month, and a statistical difference was found between the TACE and RFA of liver decompensation and Child-Pugh stage (P < 0.05).

Conclusions

The survival probabilities of OS increased with CT-guided RFA with TACE, as observed in randomized studies from Europe and Asia. The longest TTP was observed for the intermediate stage HCC. The procedures were well tolerated with acceptable minor and major complications in unresectable HCC patients.