Efficacy of combined transarterial radioembolization and sorafenib in the treatment of hepatocarcinoma: A meta-analysis.

BACKGROUND: Adjuvant sorafenib may further enhance the efficacy of transarterial radioembolization for the treatment of hepatocellular carcinoma. AIMS: To evaluate the efficacy and safety of radioembolization plus sorafenib in hepatocellular carcinoma patients. METHODS: With a literature search through October 2020, we identified 9 studies (632 patients). Primary outcome was overall survival. Results were expressed as pooled median, odds ratio, or hazard ratio and 95% confidence intervals. RESULTS: Pooled overall survival after radioembolization plus sorafenib was 10.79 months (95% confidence interval 9.19-12.39) and it was longer in Barcelona Clinic Liver Cancer (BCLC) B (14.47 months, 9.07-19.86) as compared to BCLC C patients (10.22 months, 7.53-12.9). No difference between combined therapy versus radioembolization alone was observed in terms of overall survival (hazard ratio 1.07, 0.89-1.30). Pooled median progression-free survival was 6.32 months (5.68-6.98), with 1-year progression-free survival pooled rate of 38.5% (12.7%-44.2%). No difference in progression-free survival (hazard ratio 0.94, 0.79-1.12) between the two treatments was observed. Pooled rate of severe adverse events was 48.9% (26.7%-71.2%), again with no difference between the two treatment regimens (odds ratio 1.52, 0.15-15.02). CONCLUSIONS: The association of sorafenib does not seem to prolong survival nor delay disease progression in patients treated with radioembolization.

The Prognosis of Hepatocellular Carcinoma Treated with Sorafenib in Combination with TACE.

OBJECTIVE: Sorafenib have been shown to be effective in the treatment of advanced HCC and has been standard therapy since its release in Japan in 2009 (Llovet et al., 2008; Cheng et al., 2009). However, due to a low response rate, more aggressive combination treatment has been utilized as a multimodal strategy. The present study aimed to determine the efficacy of sorafenib alone and in combination with transarterial chemoembolization (TACE) for the treatment of advanced HCC. METHODS: All patients with unresectable advanced HCC who were prescribed sorafenib at Kanto Rosai Hospital were included in the study. Five-year overall survival (OS) rates were estimated for patients treated with sorafenib alone or in combination with TACE. Multivariate and univariate regression analyses were performed to identify factors affecting OS. Analysis using propensity score matching and inverse-probability weights were also performed. RESULTS: A total of 46 patients were treated with sorafenib up to June 2018. The total sorafenib dose administered was higher in the TACE combination group (70900 mg vs. 24000 mg vs. with sorafenib alone), although the relative dose intensity was lower (11.7% vs. 17.6%, respectively). The 5-year survival prognosis estimated using the Kaplan-Meier method was longer in patients treated with sorafenib in combination with TACE versus sorafenib alone (36.3% vs. 7.7%). Combination with TACE was the only factor associated with improved OS in both univariate and multivariate analysis. Among cases matched by propensity scores the hazard rate for combination with TACE was 0.067 (95% CI 0.091-1.128). CONCLUSION: With an array of therapeutic options currently available, it is important to determine the efficacy of different multimodal strategies, such as sorafenib combined TACE, for patients with unresectable HCC.

Resection might be a meaningful choice for hepatocellular carcinoma with portal vein thrombosis: A systematic review and meta-analysis.

BACKGROUND: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the presence of portal vein tumor thrombosis (PVTT) is considered to indicate an advanced stage of hepatocellular carcinoma (HCC) with nearly no cure. Hepatic resection and transarterial chemoembolization (TACE) have recently been recommended for treatment of HCC with PVTT. METHODS: We conducted a systematic review to compare the overall survival between patients with HCC and PVTT undergoing hepatectomy, TACE or conservative treatment including sorafenib chemotherapy. The PubMed, Web of Science, and Cochrane Library databases were searched. All relevant studies were considered. Hazard ratios with 95% confidence intervals were calculated for comparison of the cumulative overall survival. Ten retrospective studies met the inclusion criteria and were included in the review. RESULTS: Overall survival was not higher in the hepatectomy group than TACE group. But survival rate was higher in hepatectomy group than conservative group. The subgroup analysis demonstrated that hepatectomy was superior in patients without PVTT in the main trunk than in patients with main portal vein invasion. In patients without main PVTT, hepatectomy has showed more benefit than TACE. However, there has been no significant difference between the hepatectomy and TACE groups among patients with main PVTT. CONCLUSION: For patients with resectable HCC and PVTT, hepatectomy might be more effective in patients without PVTT in the main trunk than TACE or conservative treatment.

Percutaneous thermal ablation combined with simultaneous transarterial chemoembolization for hepatocellular carcinoma ≤5 cm.

BACKGROUND/AIM: Percutaneous thermal ablation combined with transarterial chemoembolization (TACE) becomes a treatment option for unresectable hepatocellular carcinoma (HCC). This study aims to investigate the safety and feasibility of percutaneous thermal ablation combined with simultaneous TACE for patients with HCC ≤ 5 cm. MATERIALS AND METHODS: From June 2010 to February 2017, a total of 280 patients with HCC ≤ 5 cm who underwent percutaneous thermal ablation combined with simultaneous TACE were included in our study. Their clinical data were collected and analyzed. RESULTS: Major complications occurred in five cases (1.8%). The complete necrosis rate was 91.9%. The median overall survival (OS) was 66.5 months (95% confidence interval [CI] = 57.7-75.2). The OS rates in 1-, 3-, 5-, and 7-year were 96.7%, 76.0%, 59.7%, and 31.1%, respectively. Tumor size (hazard ratio = 1.826; 95% CI = 1.131-2.947; P = 0.014) was considered as independent prognostic factors of long-term survival. CONCLUSION: Percutaneous thermal ablation combined with simultaneous TACE is a safe and effective treatment for HCC ≤ 5 cm.

Combined Therapy with Transarterial Chemoembolization and Radiofrequency Ablation for Hepatocellular Carcinoma: Does the Degree of Ethiodized Oil Accumulation within the Tumor Affect the Therapeutic Efficacy?

PURPOSE: To evaluate the effects of the degree of ethiodized oil accumulation achieved by transarterial chemoembolization followed by radiofrequency (RF) ablation on the treatment efficacy for a single intermediate-sized hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 153 consecutive patients who underwent chemoembolization and RF ablation for a single intermediate-sized HCC (2-5 cm) were included. On the basis of the degree of ethiodized oil accumulation in HCC on cone-beam CT images, patients who underwent chemoembolization and RF ablation were classified into 2 groups: compact accumulation (≥ 75%) and noncompact accumulation (< 75%). The rates of cumulative local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) were compared between groups. RESULTS: Of the 153 patients, 89 were classified into the compact ethiodized oil accumulation group and 64 in the noncompact ethiodized oil accumulation group. There were no significant differences in patient demographic or HCC characteristics between groups except for the incidence of liver cirrhosis (P = .038) and the tumor margin morphology (P = .008). The cumulative LTP rate was significantly lower in the compact accumulation group than in the noncompact accumulation group (P = .013). There were no significant differences in the incidences of complications, DFS rates (P = .055), or OS rates (P = .184). CONCLUSIONS: The degree of ethiodized oil accumulation does not play a role in decreasing the OS or DFS rate after chemoembolization and RF ablation for intermediate-sized HCC; however, it may contribute to reducing the rate of LTP.

Comprehensive treatments for hepatocellular carcinoma with portal vein tumor thrombosis.

Portal vein tumor thrombosis (PVTT) is one of the most common complications in hepatocellular carcinoma (HCC). HCC with PVTT usually indicates poor prognosis, which has a number of characteristics including a rapidly progressive disease course, worse liver function, complications connected with portal hypertension, and poorer tolerance to treatment. The exact mechanisms of PVTT remain unknown, even though some concerned signal transduction or molecular pathways have been identified. In western countries, sorafenib is the only recommended therapeutic strategy regardless of PVTT types. However, multiple treatment options including transhepatic arterial chemoembolization, hepatectomy, radiotherapy, and sorafenib available in the clinic. In this review, we enumerate and discuss therapeutics against patients with HCC having PVTT available in the clinic and put forward directions for future research.

Comparison of Stable and Unstable Ethiodized Oil Emulsions for Transarterial Chemoembolization of Hepatocellular Carcinoma: Results of a Single-Center Double-Blind Prospective Randomized Controlled Trial.

PURPOSE: To compare the stability of stable and unstable water-in-oil emulsions and the efficacy and safety of these emulsions in a single-center, prospective double-blind trial of transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 812 patients with inoperable HCC were randomized (stable emulsion, n = 402; unstable emulsion, n = 410). The 2 emulsions were prepared by using the same protocol except that different solvents were used for chemotherapy agents, including epirubicin, lobaplatin, and mitomycin C. The solvent in the stable emulsion arm was contrast medium and distilled water, and the solvent in the unstable emulsion arm was distilled water. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), tumor response, adverse events (AEs), and plasma epirubicin concentrations. RESULTS: In vitro, stable emulsions did not occur until 1 day, and unstable emulsions, with a lower peak plasma concentration (P = .001) in vivo, exhibited rapid separation of the oil and aqueous phases after 10 minutes. Median OS times in the stable and unstable emulsion arms were 17.7 and 19.2 months, respectively (P = .81). No differences were found in TTP, tumor response, and AEs except for myelosuppression (anemia, 3.5% vs 7.6%; thrombocytopenia, 11.5% vs 17.7%), which was significantly more severe and frequent in the unstable emulsion arm (P = .013). CONCLUSIONS: Chemoembolization is equally effective with the use of stable and unstable emulsions, but the use of a stable emulsion has the advantage of less myelosuppression and a favorable pharmacokinetic profile.

Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver (RETNET): study protocol for a randomized controlled trial.

BACKGROUND: Neuroendocrine tumors (NETs) are the second most common gastrointestinal malignancy after colon cancer. Up to 90% of patients with NETs develop liver metastases, which are a major determinant of symptoms and survival. Current guidelines recommend embolotherapy for progressive or symptomatic NET liver metastases, but the optimal technique among bland embolization, lipiodol chemoembolization, and drug-eluting bead chemoembolization remains unknown and controversial. METHODS/DESIGN: A prospective, open-label, multicenter randomized controlled trial will be conducted in patients with progressive or symptomatic unresectable NET liver metastases. Patients will be randomized to treatment with bland embolization, lipiodol chemoembolization, or drug-eluting microsphere chemoembolization, with 60 enrollees per arm. The primary endpoint will be hepatic progression-free survival (HPFS) following initial embolotherapy by RECIST criteria. The sample size is powered to detect an HR of 1.78 for HPFS following chemoembolization compared with bland embolization, which was estimated on the basis of existing retrospective studies. Secondary endpoints include overall progression-free survival, duration of symptom control, quality of life, rate of adverse events, and interval between embolotherapy cycles. Interim safety analyses will be performed at 10 and 30 patients per arm. DISCUSSION: The RETNET trial is a prospective, multicenter randomized controlled trial designed to determine the optimal embolotherapy technique for NET liver metastases. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02724540 . Registered on March 31, 2016.

Survival of patients with non-resectable, chemotherapy-resistant colorectal cancer liver metastases undergoing conventional lipiodol-based transarterial chemoembolization (cTACE) palliatively versus neoadjuvantly prior to percutaneous thermal ablation.

PURPOSE: To determine overall (OS) and progression-free survival (PFS) for cTACE alone and in combination with percutaneous thermal ablation in patients with non-resectable, chemotherapy-resistant colorectal cancer liver metastases (CRLM). MATERIAL AND METHODS: The study included 452 patients undergoing 2654 repetitive cTACE treatments of CRLM. 233 patients were treated palliatively using only cTACE, whereas 219 patients were treated with cTACE in a neoadjuvant intend with subsequent thermal ablation (either microwave ablation or laser-induced thermotherapy). The chemotherapeutics agents used, in either single-, double-, or triple-combinations, included MitomycinC, Gemcitabine, Irinotecan, and Cisplatin. Several factors were analysed to determine their prognostic value in terms of OS and PFS. RESULTS: Palliative use of cTACE resulted in a median OS and PFS of 12.6 and 5.9 months, whereas the neoadjuvant use of cTACE showed a median OS and PFS of 25.8 and 10.8 months. The differences in OS and PFS between the two groups were statistically significant (p < 0.001). Extrahepatic metastases were a significant prognostic factor in the OS and PFS analysis of the palliative and neoadjuvant group. In addition, number, location, and mean size of metastases were significant prognostic factors for OS and PFS in the neoadjuvant group. Sex, primary tumor location, T- and N-parameters of the TNM staging system, time of liver metastases appearance, ablation method, and patient age did not significantly impact OS and PFS in either patient group. The most distinct response to cTACE was observed in metastases that were treated with a triple-combination of chemotherapeutics (p = 0.021). CONCLUSION: cTACE is an effective treatment option in advanced non-resectable CRLM. Chemoembolization followed by ablation further increases survival rates. A triple combination of chemotherapeutics improves response to cTACE.

Stereotactic Body Radiation Therapy as an Alternative to Transarterial Chemoembolization for Hepatocellular Carcinoma.

PURPOSE: To conduct a large single-institution comparison of transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) outcomes in similar groups of patients with hepatocellular carcinoma (HCC). METHODS AND MATERIALS: From 2006 to 2014, 209 patients with 1 to 2 tumors underwent TACE (n=84) to 114 tumors or image guided SBRT (n=125) to 173 tumors. Propensity score analysis with inverse probability of treatment weighting was used to compare outcomes between treatments while adjusting for imbalances in treatment assignment. Local control (LC), toxicity, and overall survival (OS) were retrospectively analyzed. RESULTS: The TACE and SBRT groups were similar with respect to the number of tumors treated per patient, underlying liver disease, and baseline liver function. Patients treated with SBRT were older (65 vs 61 years, P=.01), had smaller tumors (2.3 vs 2.9 cm, P<.001), and less frequently underwent liver transplantation (8% vs 18%, P=.01). The 1- and 2-year LC favored SBRT: 97% and 91%, respectively, for SBRT and 47% and 23% for TACE (hazard ratio 66.5, P<.001). For patients treated with TACE, higher alpha-fetoprotein (hazard ratio 1.11 per doubling, P=.008) and segmental portal vein thrombosis (hazard ratio 9.9, P<.001) were associated with worse LC. Predictors associated with LC after SBRT were not identified. Grade 3+ toxicity occurred after 13% and 8% of TACE and SBRT treatments, respectively (P=.05). There was no difference in OS between patients treated with TACE or SBRT. CONCLUSIONS: Stereotactic body radiation therapy is a safe alternative to TACE for 1 to 2 tumors and provides better LC, with no observed difference in OS. Prospective comparative trials of TACE and SBRT are warranted.

Association of hepatic vein Lipiodol tram-track sign during transcatheter arterial chemoembolization with perioperative death.

Objective To assess the relationship between the hepatic vein Lipiodol tram-track sign during transcatheter arterial chemoembolization (TACE) and perioperative death. Methods Patients treated for hepatic carcinoma at the Beijing Shijitan Hospital, Capital Medical University from January 2010 to December 2015 were retrospectively evaluated. The patients underwent hepatic TACE with Lipiodol. The incidence of the hepatic vein Lipiodol tram-track sign, prognosis, and possible risk factors were analyzed. Results A total of 5372 patients underwent hepatic TACE and had complete available intraoperative imaging data. Among them, nine patients showed the hepatic vein Lipiodol tram-track sign, including five who died intraoperatively. The patients who died had liver metastasis from hepatocellular carcinoma, cholangiocarcinoma, or breast cancer and had previously received doxorubicin. The survivors had metastasis from gastric or colorectal cancer and had not received doxorubicin. Conclusion Occurrence of the hepatic vein Lipiodol tram-track sign during hepatic TACE is likely to result in perioperative death.

Combination of TACE and Sorafenib Improves Outcomes in BCLC Stages B/C of Hepatocellular Carcinoma: A Single Centre Experience.

BACKGROUND AND AIM: Transarterial chemoembolization (TACE) or sorafenib is recommended for hepatocellular carcinoma BCLC stages B and C respectively. We studied the role of combination of TACE and sorafenib in BCLC stages B/C. MATERIAL AND METHODS: We undertook an observational study on a cohort of cirrhotics with HCC from August 2010 through October 2014. Patients in BCLC stages B/C who had received TACE and/or sorafenib were included. mRECIST criteria were used to assess tumor response. The primary end point was overall survival. RESULTS: Out of 124 patients, 47.6% were in BCLC-B and 52.4% in BCLCC. Baseline characteristics were comparable. The predominant etiology was cryptogenic (37.2% and 38.5%, p = NS). 49.1% in BCLC-B and 56.9% in BCLC-C had received TACE+sorafenib. In BCLC-B, the overall survival improved from 9 months (95% CI 6.3-11.7) using TACE only to 16 months (95% CI 12.9-19.1) using TACE+sorafenib (p < 0.05). In BCLC-C, addition of TACE to sorafenib improved the overall survival from 4 months (95%CI 3-5) to 9 months (95%CI 6.8-11.2) (p < 0.0001). As per mRECIST criteria, patients on TACE+sorafenib had reduced progressive disease (37.8% vs. 83.3%), improved partial response (43.2% vs. 3.3%) and one had complete response compared to those on sorafenib alone (p < 0.0001) in BCLC-C but not in BCLC-B group. Hand foot syndrome was noted in 27.7% patients on sorafenib and post TACE syndrome in 80.2% patients, but both were reversible. No major adverse events were noted. CONCLUSION: TACE+sorafenib was more effective than TACE or sorafenib alone in HCC BCLC stages B or C with a significant survival benefit and improved tumour regression especially in BCLC-C patients.

Practical Considerations of Real Life of Hepatocellular Carcinoma in a Tertiary Center of Brazil.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignancy that develops in cirrhotic livers. Its clinical and epidemiological characteristics and mortality rates vary according to geographical region. The objective of this study was to evaluate the clinical profile, epidemiological characteristics, laboratory parameters, treatment and survival of patients with HCC. MATERIAL AND METHODS: Patients with HCC seen between 2000 and 2012 were studied. The Kaplan-Meier method was used for survival analysis according to variables in question. RESULTS: The study included 247 patients with a mean age of 60 ± 10 years. There was a predominance of males (74%). The main etiologies of HCC were HCV infection (55%), excessive alcohol consumption (12%), and HBV infection (8%). Liver cirrhosis was present in 92% of cases. The mean tumor number and diameter were 2 and 5 cm, respectively. Patients meeting the Milan criteria corresponded to 43% of the sample. Liver transplantation was performed in 22.4% of patients of the Milan subset and in 10% of the whole sample. The overall mean survival was 60 months, with a 1-, 3- and 5-year survival probability of 74%, 40% and 29%, respectively. Lower survival was observed among patients with alcoholic etiology. Survival was higher among patients submitted to liver transplantation (P &lt; 0.001), TACE (P &lt; 0.001), or any kind of treatment (P &lt; 0.001). However, no difference was found for surgical resection (P = 0.1) or sorafenib (P = 0.1). CONCLUSION: Patients with HCC were mainly older men diagnosed at an advanced stage. Treatment was associated with better overall survival, but few patients survived to be treated.

Polyvinyl alcohol terminal chemoembolization for hepatocellular carcinoma with hepatic arteriovenous shunts: Safety, efficacy, and prognostic factors.

PURPOSE: To evaluate the safety and efficacy of polyvinyl alcohol (PVA) terminal chemoembolization and to identify the prognostic factors associated with survival in hepatocellular carcinoma (HCC) patients with hepatic arteriovenous shunts (HAVS). MATERIALS AND METHODS: Of 133 patients' managements were retrospectively analyzed. HAVS was classified into three types: slow-flow, intermediate-flow and high-flow. The size of the PVA used was determined following the scheme: slow-flow HAVS: 300-500µm PVA; intermediate-flow HAVS: 500-710µm PVA; high-flow HAVS: 710-1000µm PVA. The HCCs with slow-flow and intermediate-flow HAVS were embolized by PVA plus chemotherapeutic agents lipiodol emulsion, while the high-flow HAVS were treated by PVA with chemotherapeutic agents. Survival curves were calculated by Kaplan-Meier method and compared by log-rank test. The influence of possible prognostic factors on survival were analyzed by multivariate Cox proportional-hazards method. RESULTS: The median overall survival (OS) of 133 patients was 9.1 months. The median OS of the slow-flow type, intermediate-flow type and high-flow type patients were 10.8, 9.1 and 7.3 months, respectively. There was no statistically significant difference among different HAVS types (P=0.239). The 30-day mortality was 3.8%. Cox multivariate survival analysis revealed that initial preoperative AFP value≥400ng/ml (HR=2.105, P=0.006) was an independent risk factor. While multiple embolization (HR=0.482, P=0.011), tumor remission (HR=0.431, P=0.041) and multimodality therapy (HR=0.416, P=0.004) were independent protection factors. CONCLUSION: It is safe and effective for HCCs with HAVS treated by terminal chemoembolization therapy with PVA plus chemotherapeutic agents lipiodol emulsion (or PVA plus chemotherapeutic agents). The HCCs with HAVS achieves good prognosis with multiple embolization, tumor remission and multimodality therapy, while achieves poor prognosis with inital preoperative high AFP value (≥400ng/ml).

Retrospective analysis of transarterial chemoembolization and sorafenib in Chinese patients with unresectable and recurrent hepatocellular carcinoma.

We explored the hypothesis that sorafenib may improve the effect of transarterial chemoembolization (TACE) in patients with recurrent hepatocellular carcinoma (HCC) and that longer sorafenib duration was associated with additional survival benefits. In this retrospective, nested case-controlled study, 1126 cases of unresectable HCC were collected. Patients with unresectable disease treated with TACE+sorafenib (n=245) and TACE alone (n=245) and those with recurrence after surgery treated with TACE+sorafenib (n=127) and TACE alone (n=127) were identified and matched according to sex, age, and lesion size and number. The clinicopathological factors associated with survival were examined by univariate and multivariate analyses. The mean duration of sorafenib treatment was 10.8±10.51 months. Sorafenib significantly increased the median survival time as compared to TACE alone (unresectable HCC: 20.23 vs. 13.97 months, respectively; p=0.013 and recurrent HCC: 30.7 and 18.22 months, respectively; p=0.003). The survival of patients with unresectable HCC was associated with the presence of portal vein tumor thrombus (HR=1.47, p=0.004) and treatment method (TACE+sorafenib combination therapy; HR=0.72, p=0.003). For patients with recurrent HCC, the presence of extrahepatic metastasis (HR=1.71, p=0.012) and treatment method (TACE+sorafenib therapy; HR=0.60, p=0.002) also was associated with survival. For patients treated with TACE+sorafenib, multivariate analysis showed decreased hazard of death with longer duration of sorafenib treatment (HR=0.9, p<0.001). Thus, sorafenib plus TACE may provide survival benefits, which may be related with sorafenib treatment duration, particularly for patients with HCC recurrence. Further clinical studies are required to confirm these results and identify which patients are most likely to benefit from this therapeutic strategy.

Aggressive Treatment of Performance Status 1 and 2 HCC Patients Significantly Improves Survival - an Egyptian Retrospective Cohort Study of 524 Cases.

BACKGROUND: In the Barcelona Clinic Liver Cancer (BCLC) system, only sorafenib is suggested for HCC patients having performance status (PS) 1 or 2 even if they have treatable lesions. In the current study, we aimed to explore the outcome of using aggressive treatment for HCC patients with PS 1 and 2. MATERIALS AND METHODS: Five hundred and twenty four patients with HCC were enrolled in this study and divided into 2 groups: 404 PS 1 and 120 PS 2. Of the included 524 patients, 136 recceived non-aggressive supportive treatment and sorafenib, while 388 patients were offered aggressive treatment in the form of surgical resection, transplantation, percutaneous ablation, trans-arterial chemoembolization and/or chemoperfusion. All the patients were followed up for a period of 2 years to determine their survival. RESULTS: Most HCC patients were CHILD A and B grades (89.4% versus 85.0%, for PS1 and PS2, respectively). Patients with PS1 were significantly younger. Out of the enrolled 524 patients, 388 were offered aggressive treatment, 253 (65.2%) having their lesions fully ablated, 94 (24.2%) undergoing partial ablation and 41 patients with no ablation (10.6%). The median survival of the patients with PS 1 who were offered aggressive treatment was 20 months versus 9 months only for those who were offered supportive treatment and sorafenib (<0.001). Regarding HCC patients with PS 2, the median survivals were similarly 19.7 months versus 8.7 months only (<0.001). CONCLUSIONS: Aggressive treatment of HCC patients with PS 1 and 2 significantly improves their survival. Revising the BCLC guidelines regarding such patients is recommended.

The effect of locoregional therapies in patients with advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND & AIMS: It is unknown whether the addition of locoregional therapies (LRTx) to sorafenib improves prognosis over sorafenib alone in patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to assess the effect of LRTx in this population. METHODS: A retrospective analysis was performed of patients with advanced HCC as defined by extrahepatic metastasis, lymphadenopathy >2 cm, or gross vascular invasion. Sorafenib therapy was required for inclusion. Survival of patients who received LRTx after progression to advanced stage was compared to those who did not receive LRTx. RESULTS: Using an intention to treat analysis of 312 eligible patients, a propensity weighted proportional hazards model demonstrated LRTx as a predictor of survival (HR = 0.505, 95% CI: 0.407-0.628; P < 0.001). The greatest benefit was seen in patients with the largest tumor burden (HR = 0.305, 95% CI: 0.236-0.393; P < 0.01). Median survival in the sorafenib arm was 143 days (95% CI: 118-161) vs. 247 days (95% CI: 220-289) in the sorafenib plus LRTx arm (P < 0.001). CONCLUSIONS: These results demonstrate a survival benefit with the addition of LRTx to sorafenib for patients with advanced HCC. These findings should prompt a prospective clinical trial to further assess the role of LRTx in patients with advanced HCC.

Comprehensive treatments for hepatocellular carcinoma with tumor thrombus in major portal vein.

AIM: To evaluate the efficacy of transcatheter arterial chemoembolisation (TACE) compared with surgical intervention and sorafenib for treatment of hepatocellular carcinoma (HCC) in patients with tumor thrombus extending to the main portal vein. METHODS: From 2009 to 2013, a total of 418 HCC patients with tumor thrombus extending to the main portal vein were enrolled in this study and divided into four groups. These groups underwent different treatments as follows: TACE (n = 307), surgical intervention (n = 54), sorafenib (n = 15) and palliative treatment (n = 42). Overall survival rates were determined by Kaplan-Meier method, and differences between the groups were identified through log-rank analysis. Cox's proportional hazard model was used to identify the risk factors for survival. RESULTS: The mean survival periods for patients in the TACE, surgical intervention, sorafenib and palliative treatment groups were 10.39, 4.13, 5.54 and 2.82 mo, respectively. For the TACE group, the 3-, 6-, 12- and 24-mo survival rates were 94.1%, 85.9%, 51.5% and 0.0%, respectively. The corresponding rates were 60.3%, 22.2%, 0.0% and 0.0% for the surgical intervention group and 50.9%, 29.5%, 0.0% and 0.0% for the sorafenib group. Evidently, the results in the TACE group were significantly higher than those in the other groups (P < 0.0001). Furthermore, no significant difference among survival rates was observed between TACE with/without sorafenib (10.22 mo vs 10.52 mo, P = 0.615). No significant difference in survival rates was also found among the surgical intervention, sorafenib and palliative treatment groups (P > 0.05). These values significantly increased after TACE with/without sorafenib compared with other treatments (P < 0.05). CONCLUSION: For HCC patients with tumor thrombus extending to the main portal vein, TACE can yield a higher survival rate than surgical intervention or sorafenib treatment.

Single- versus Triple-Drug Chemoembolization for Hepatocellular Carcinoma: Comparing Outcomes by Toxicity, Imaging Response, and Survival.

PURPOSE: To determine the efficacy of single- versus triple-drug chemoembolization for the treatment of hepatocellular carcinoma, as measured by toxicity, tumor response, time to progression (TTP), and overall survival (OS). MATERIALS AND METHODS: A single-center retrospective review was performed on 337 patients who underwent chemoembolization over a 14-year period; 172 patients underwent triple-drug conventional transarterial chemoembolization, and 165 patients underwent single-agent doxorubicin chemoembolization. Imaging characteristics and clinical follow-up after conventional transarterial chemoembolization were evaluated to determine TTP. Imaging response was determined per World Health Organization and European Association for the Study of Liver criteria. OS from time of first chemoembolization was calculated. RESULTS: Median TTP was similar between groups: 7.9 months (95% confidence interval [CI], 7.1-9.4) and 6.8 months (95% CI, 4.6-8.6) for triple- and single-drug regimens, respectively (P > .05). For single-agent conventional transarterial chemoembolization, median OS varied significantly by Barcelona Clinic for Liver Cancer (BCLC) stage: A, 40.8 months; B, 36.4 months; C, 10.9 months (P < .01). Median OS for triple-drug therapy also varied significantly by BCLC: A, 28.9 months; B, 18.1 months; C, 9.0 months (P < .01). Single-drug conventional transarterial chemoembolization demonstrated longer median OS compared with triple-drug therapy (P < .05) for BCLC A/B patients. CONCLUSIONS: Single-agent chemoembolization with doxorubicin and ethiodized oil demonstrates acceptable efficacy as measured by TTP and OS. Results compare favorably with traditional triple-drug therapy.

Independent Analysis of Albumin-Bilirubin Grade in a 765-Patient Cohort Treated with Transarterial Locoregional Therapy for Hepatocellular Carcinoma.

PURPOSE: To assess validity of albumin-bilirubin (ALBI) grade as a predictor of survival in patients undergoing transarterial embolization for hepatocellular carcinoma. MATERIALS AND METHODS: Baseline albumin and bilirubin values of 765 consecutive patients treated with conventional transarterial chemoembolization or yttrium-90 ((90)Y) radioembolization at a single institution were used to determine liver function according to ALBI grade. Survival outcomes were stratified by ALBI grade using Kaplan-Meier and stratified by Child-Pugh (C-P) class and Barcelona Clinic Liver Cancer (BCLC) stage. Discriminatory ability was assessed by C-index. RESULTS: For 428 patients receiving (90)Y radioembolization, ALBI grade yielded distinct survival curves (P < .001). When stratified by C-P class and BCLC stage, ALBI grade revealed different survival outcomes for C-P B (P = .001), BCLC A (P < .001), BCLC B (P = .001), and BCLC C (P < .001). When substratified by BCLC stage, ALBI grade was a better discriminator of survival than C-P class (C-index 0.792, 0.763, respectively). For 337 patients receiving transarterial chemoembolization, ALBI grade yielded distinct survival curves (P < .001). When stratified by C-P class and BCLC stage, ALBI grade provided distinct survival curves for C-P B (P = .02), BCLC B (P = .001), and BCLC C (P = .02). When substratified by BCLC stage, ALBI grade was a better discriminator of survival than C-P class (C-index 0.739, 0.735, respectively). CONCLUSIONS: ALBI grade outperforms C-P class at discriminating survival in patients receiving transarterial chemoembolization or (90)Y radioembolization. ALBI grade is also valuable in patients with moderate liver dysfunction and BCLC B disease.