To Transarterial Chemoembolization Research Articles

Erratum to: Unresectable Hepatocellular Carcinoma: Radioembolization Versus Chemoembolization: A Systematic Review and Meta-analysis.

Transarterial radioembolization (TARE) has emerged as a newer regional therapy to transarterial chemoembolization (TACE) for treatment of unresectable hepatocellular carcinoma (HCC). The aim of this study is to compare clinical outcomes of both the techniques. Online search for studies comparing TARE to TACE from 2005 to present was performed. Primary outcome was overall survival rate for up to 4 years. Secondary outcomes included post-treatment complications and treatment response. Quality of included studies was evaluated by STrengthening the Reporting of OBservational studies in Epidemiology criteria. Relative risk (RR) and 95 % confidence intervals (CI) were calculated from pooled data. The search strategy yielded 172 studies, five met selection criteria and included 553 patients with unresectable HCC, 284 underwent TACE and 269 underwent TARE. Median ages were 63 and 64 years for TACE and TARE, respectively. Meta-analysis showed no statistically significant difference in survival for up to 4 years between the two groups (HR = 1.06; 95 % CI 0.81–1.46, p = 0.567). TACE required at least one day of hospital stay compared to TARE which was mostly an outpatient procedure. TACE had more post-treatment pain than TARE (RR = 0.51, 95 % CI 0.36–0.72, p < 0.01), but less subjective fatigue (RR = 1.68, 95 % CI 1.08–2.62, p < 0.01). There was no difference between the two groups in the incidence of post-treatment nausea, vomiting, fever, or other complications. In addition, there was no difference in partial or complete response rates between the two groups. TARE appears to be a safe alternative treatment to TACE with comparable complication profile and survival rates. Larger prospective randomized trials, focusing on patient-reported outcomes and cost–benefit analysis are required to consolidate these results.

Elevated serum plasma fibrinogen is associated with advanced tumor stage and poor survival in hepatocellular carcinoma patients.

Hyperfibrinogenemia has been reported to be a predictor of poor prognosis in cancer patients, and in hepatocellular carcinoma (HCC) patients, survival remains uncertain and unpredictable. The aim of the present study was to evaluate the association between the level of plasma fibrinogen and overall survival in HCC patients.Overall, 308 patients with histologically proven HCC were included in our study. Univariate and multivariate analyses were performed to identify predictive risk factors for the rates of overall survival and tumor recurrence.Patients in the high-fibrinogen-level group were more likely to have advanced stage HCC, portal vein invasion, and tumors that were greater in number and larger in diameter than were patients in the low-fibrinogen-level group (all P < .05). The long-term overall survival rate of patients in the high-fibrinogen group was much lower than that of patients in the normal-fibrinogen group (P = .008), and similar outcomes were observed in the subgroup of patients who underwent radical therapies for HCC (P = .003). The results of the univariate and multivariate analyses indicated that high plasma fibrinogen remained independently associated with poorer overall survival. In addition, high plasma fibrinogen levels were associated with nonresponse to transarterial chemoembolization (TACE) (P < .001).Elevated plasma fibrinogen was independently associated with advanced HCC stage, poor prognosis, and nonresponse to TACE and may, therefore, serve as a valuable clinical biomarker for predicting prognosis in HCC patients.

Tumor SOCS3 methylation status predicts the treatment response to TACE and prognosis in HCC patients.

BackgroundSuppressor of cytokine signaling (SOCS) 1 and 3 methylation have been associated with clinical features and outcomes of cancer patients. However, their roles in determining the treatment response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) remain unknown.ResultsWe found that presence of SOCS3 methylation is significantly associated with the major clinical features of HCC patients, including tumor stage, lymph node and vascular invasion. Of note, we observed that the presence of SOCS3 methylation is closely related to TACE response. In prognosis analyses, HCC patients with SOCS3 methylation presence have a poorer prognosis indicated by lower 3-, and 5-year survival rates and shorter mean survival period, than those without. Multivariate COX analysis confirms the prognostic role of the presence of SOCS3 methylation in HCC patients receiving TACE treatment.Materials and MethodsA total of 246 HCC patients receiving TACE were enrolled in this study. Tumor samples was obtained from echo-guided fine needle aspiration and genomic DNA from tumor samples was purified. SOCS1 and SOCS3 methylation status were detected using methylation-specific polymerase chain reaction. The treatment responses to TACE of patients were evaluated after procedure and all patients were followed for prognosis analysis.ConclusionsThis finding suggests that the presence of SOCS3 methylation is a marker to predict treatment response and prognosis in HCC patients receiving TACE therapy.

Stereotactic body radiotherapy vs. TACE or RFA as a bridge to transplant in patients with hepatocellular carcinoma. An intention-to-treat analysis

There is limited information on the use of stereotactic body radiotherapy (SBRT) as a bridge to liver transplantation for hepatocellular carcinoma and no study comparing its efficacy to transarterial chemoembolization (TACE) and radiofrequency ablation (RFA). We aimed to ascertain the safety and efficacy of SBRT on an intention-to-treat basis compared with TACE and RFA as a bridge to liver transplantation in a large cohort of patients with hepatocellular carcinoma. Outcomes between groups were compared from the time of listing and from the time of transplant. Between July 2004 and December 2014, 379 patients were treated with either SBRT (n=36, SBRT group), TACE (n=99, TACE group) or RFA (n=244, RFA group). The drop-out rate was similar between groups (16.7% SBRT group vs. 20.2% TACE group and 16.8% RFA group, p=0.7); 30 patients were transplanted in the SBRT group, 79 in the TACE group and 203 in the RFA group. Postoperative complications were similar between groups. Patients in the RFA group had more tumor necrosis in the explant. The 1-, 3- and 5-year actuarial patient survival from the time of listing was 83%, 61% and 61% in the SBRT group vs. 86%, 61% and 56% in the TACE group, and 86%, 72% and 61% in the RFA group, p=0.4. The 1-, 3- and 5-year survival from the time of transplant was 83%, 75% and 75% in the SBRT group vs. 96%, 75% and 69% in the TACE group, and 95%, 81% and 73% in the RFA group, p=0.7. In conclusion, SBRT can be safely utilized as a bridge to LT in patients with HCC, as an alternative to conventional bridging therapies. Patients with liver cancer included in the waiting list for liver transplantation are at risk of tumor progression and death. Stereotactic body radiotherapy may be a good alternative to conventional therapies to reduce this risk.

Patterns of sorafenib and TACE treatment of unresectable hepatocellular carcinoma in a Chinese population: subgroup analysis of the GIDEON study.

To analyze safety and efficacy of patterns of sorafenib and TACE therapy under real-life clinical practice conditions. A total of 338 Chinese patients with unresectable hepatocellular carcinoma (HCC) from the international database of the GIDEON non-interventional trial were included in this analysis. Endpoints were overall survival (OS), progression-free survival (PFS), time to progression (TTP) and safety. Two major patterns in the use of sorafenib observed in current Chinese clinical practice were: sorafenib administration subsequent to transarterial chemoembolization (TACE) treatment (n = 226, 66.9%) and sorafenib administration concomitant to TACE (n = 80, 35.4%). Patients receiving TACE prior to sorafenib had worse liver function (43.8% BCLC stage Cat diagnosis and 62.1% BCLC stage C at study entry) than those receiving TACE concomitant to sorefenib (35.0% BCLC stage C at diagnosis and 51.3% BCLC stage three at study entry). For patients undergoing prior TACE and concomitant TACE treatment, median OS time was 354 days vs. 608 days, PFS time was 168 days vs. 201 days, and TTP was 214 days vs. 205 days; and the percentage of patients who experienced drug-related adverse effects after sorafenib therapy in these two groups were 33.3 and 50.0%, respectively. Sorafenib treatment is usually administered in cases of tumor progression or poor liver function status after TACE treatment in China. Under such conditions, patients still gained a relatively satisfactory survival outcome. In addition, the present study suggests that concomitant sorafenib and TACE treatments may lead to a better prognosis, although differences in baseline characteristics may have contributed in part to the better outcomes.

MRECIST response combined with sorafenib-related adverse events is superior to either criterion alone in predicting survival in HCC patients treated with TACE plus sorafenib.

The mRECIST and dermatologic adverse events (AEs) can be used to assess the patient response to transarterial chemoembolization (TACE) and/or sorafenib for hepatocellular carcinoma (HCC). Here, we aimed to combine the two criteria to stratify the prognosis in patients with unresectable HCC receiving TACE plus sorafenib (TACE-S). In total, 176 consecutive HCC patients treated with TACE-S were enrolled. CT scans and laboratory tests were conducted pretreatment (at baseline, 5-7 days before the TACE-S) and post-treatment (at 1, 2 and 3 months). The radiological response was assessed according to mRECIST. Sorafenib-related AEs were recorded every 2 weeks after oral administration, and patients with dermatologic AEs of Grade 2 or more were defined as dermatologic responders. The earliest time at which mRECIST and dermatologic responses correlated with survival was 2 months after therapy. The mRECIST-dermatologic AE combination assessment stratified patients into three different prognoses; responders on both assessments exhibited the longest median overall survival (OS), followed by responders on one assessment and non-responders on both assessments (30.5, 17.4 and 8.3 months, respectively; p < 0.001). Achieving the highest C-index, the mRECIST-dermatologic AE combination showed better performance in predicting survival than either mRECIST or dermatologic AEs alone. Furthermore, the mRECIST-dermatologic AE combination remained a significant predictor of OS, even when the patients were stratified according to the BCLC stage, ECOG score or alpha-fetoprotein (AFP) value. This study showed that the combination of mRECIST response and dermatologic AEs is superior to either criterion used alone for predicting the survival of HCC patients treated with TACE-S.

C-arm computed tomography and volume perfusion computed tomography (VPCT)-based assessment of blood volume changes in hepatocellular carcinoma in prediction of midterm tumor response to transarterial chemoembolization: a single center retrospective trial.

BackgroundThis study aims to evaluate immediate changes in perfusion parameters in hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) in C-arm computed tomography (CT) and volume perfusion CT (VPCT) and prediction of midterm tumor response.MethodsTwenty-five patients (median age 66, range 61 to 75 years) with 62 HCC lesions undergoing TACE received immediate pre- and post-interventional assessment by C-arm CT and VPCT. Cross-sectional imaging was analyzed at baseline and approximately 12 weeks after TACE according to modified RECIST criteria. Outcome was defined as objective response (OR, > 30 % reduction of viable tumor) or non-OR. Perfusion parameters were evaluated in C-arm CT [parenchymal blood volume (PBV)] and VPCT [blood volume (BV) and blood flow (BF)]. Ratios of perfusion parameters before and after TACE within the tumor and the non-affected liver parenchyma were calculated.ResultsCorrelation between tumor PBV and BV revealed a moderate correlation (rho = 0.45, p = 0.005). In non-affected liver parenchyma, a significant decrease in PBV was seen, compared to a significant increase in BF and BV. Perfusion ratios in HCC lesions were significantly (p < 0.05) increased in OR group compared to non-OR patients in C-arm CT and VPCT: PBV ratio (0.95 (0.06) to 0.67 (0.38), BV ratio 0.63 (0.34) to 0.15 (0.6), and BF ratio 0.6 (0.32) to 0.22 (0.51). Logistic regression including PBV and BF allowed prediction of OR (sensitivity 88 %/specificity of 83 %).ConclusionsPerfusion parameters acquired by C-arm CT and VPCT cannot simply be substituted by each other, but show similar capability in prediction of midterm tumor response.

Time of Dropout From the Liver Transplant List in Patients With Hepatocellular Carcinoma: Clinical Behavior According to Tumor Characteristics and Severity of Liver Disease.

Prolonged time on the waiting list affects post-transplant survival of patients with hepatocellular carcinoma (HCC). However, it is not yet known which patients will be at higher risk for early dropout from the list. We investigate specific risk factors for early waiting list dropout in patients with HCC. This was a single-center, intention-to-treat analysis of adults with HCC, within the Milan criteria, from July 2006 through September 2013. Patients were divided into groups according to waiting list time. The main end point was dropout from the list. The dropout rates of the study cohort at 3, 6, and 12-months were 6.4%, 12.4%, and 17.7%, respectively. Patients who dropped out from the list tended to be older, with blood types A and O, and with higher Child-Pugh and Model for End-Stage Liver Disease (MELD) scores. They also had larger nodules, responded poorly to trans-arterial chemo-embolization (TACE), and had a higher alpha-fetoprotein. Those with blood types B and AB appeared to be protected for dropout (odds ratio [OR]= 0.21, P= .02). Patients who responded to TACE were also protected (OR= 0.22, P< .001). When we looked into time to dropout, the only baseline characteristic that stood out was a higher MELD score (13 for those dropping out up to 90 days vs 10 for those dropping out after 180 days, P= .0025). We conclude that patients who drop out early from the list are primarily driven by the severity of liver disease. Patients who had progressive HCC had a high tumor load and poor response to loco-regional therapies, dropping out from the list after 180 days of inclusion.

Hypo-Vascular Liver Metastases Treated with Transarterial chemoembolization: Assessment of Early Response by Volumetric Contrast-Enhanced and Diffusion-Weighted Magnetic Resonance Imaging

OBJECTIVE: To evaluate the value of anatomic and volumetric functional magnetic resonance imaging (MRI) in early assessment of response to trans-arterial chemoembolization (TACE) in hypovascular liver metastases. METHODS: This retrospective study included 52 metastatic lesions (42 targeted and 10 non-targeted) in 17 patients who underwent MRI before and early after TACE. Two reviewers reported response by anatomic criteria (Response Evaluation Criteria in Solid Tumor [RECIST], modified RECIST [mRECIST], and European Association for the Study of Liver Disease [EASL]) and functional criteria (volumetric apparent diffusion coefficient and contrast enhancement). Treatment endpoint was RECIST at 6 months. A 2-sample paired t test was used to compare the mean changes after intra-arterial therapy. P < .05 was considered statistically significant. RESULTS: Reduction in mRECIST and EASL at 1 month was significant in the whole cohort as well as in responders by RECIST at 6 months, and the changes fulfilled partial response criteria for both metrics in responders. Responders also had significant changes in volumetric apparent diffusion coefficient (P = .01 and P = .03) and contrast enhancement (P < .0001 and P < .0001) at 1 month for both readers, respectively. CONCLUSION: At 1 month post treatment, responders did not fulfill RECIST criteria but fulfilled mRECIST and EASL criteria. In addition, volumetric contrast-enhanced and diffusion-weighted MRI may be helpful in evaluating early treatment response after TACE in hypovascular liver metastases in patients who have failed to respond to initial chemotherapy.

Stereotactic body radiotherapy (SBRT) as an alternative to transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).

4087Background: TACE is a standard treatment for patients (pts) with HCC. SBRT is a newer, noninvasive therapy. There have been no comparative studies to date. Thus, we examined TACE and SBRT outco...

Serum microRNA-199a/b-3p as a predictive biomarker for treatment response in patients with hepatocellular carcinoma undergoing transarterial chemoembolization.

ObjectiveThe aim of this study was to investigate whether the level of serum microRNA-199a/b-3p (miR-199a/b-3p) can serve as a predictor of treatment response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC).MethodsSerum miR-199a/b-3p expression level was measured in 132 patients with HCC before TACE (t1) and 3–5 days after TACE (t2). Additionally, 126 patients of these 132 patients had levels measured 4 weeks after TACE (t3) and 3–5 days after second TACE (t4). Serum miR-199a/b-3p expression levels were compared with those of 50 healthy controls. Correlations between miR-199a/b-3p expression levels and clinicopathologic factors and tumor responsiveness were analyzed. The modified Response Evaluation Criteria in Solid Tumors assessment was conducted at t3.ResultsA lower mean baseline miR-199a/b-3p expression level was observed in patients with HCC compared with healthy controls (0.68±0.81 vs 2.50±2.16, P<0.001). A negative correlation between baseline miR-199a/b-3p expression levels and tumor size (P<0.001) was observed. The nonresponder group had significantly lower miR-199a/b-3p expression levels than the responder group at t1 (0.77±1.09 vs 1.96±1.32, P<0.001). In addition, the decrease in miR-199a/b-3p at t2 was greater in the responder group than in the nonresponder group (P=0.011). A higher proportion of the responder group achieved a >25% decrease in serum miR-199a/b-3p expression levels compared with the nonresponder group (64% vs 39%).ConclusionSerum miR-199a/b-3p may represent a novel biomarker for predicting efficacy of TACE in patients with HCC.

3:27 PMAbstract No. 380 - Neutrophil/Lymphocyte ratio as a prognostic indicator of tumor response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC)

3:27 PMAbstract No. 380 - Neutrophil/Lymphocyte ratio as a prognostic indicator of tumor response to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC)

Randomized Clinical Trial Comparing Proton Beam Radiation Therapy with Transarterial Chemoembolization for Hepatocellular Carcinoma: Results of an Interim Analysis

To describe results of a planned interim analysis of a prospective, randomized clinical trial developed to compare treatment outcomes among patients with newly diagnosed hepatocellular carcinoma (HCC). Eligible subjects had either clinical or pathologic diagnosis of HCC and met either Milan or San Francisco transplant criteria. Patients were randomly assigned to transarterial chemoembolization (TACE) or to proton beam radiation therapy. Patients randomized to TACE received at least 1 TACE with additional TACE for persistent disease. Proton beam radiation therapy was delivered to all areas of gross disease to a total dose of 70.2 Gy in 15 daily fractions over 3 weeks. The primary endpoint was progression-free survival, with secondary endpoints of overall survival, local tumor control, and treatment-related toxicities as represented by posttreatment days of hospitalization. At the time of this analysis 69 subjects were available for analysis. Of these, 36 were randomized to TACE and 33 to proton. Total days of hospitalization within 30 days of TACE/proton was 166 and 24 days, respectively (P<.001). Ten TACE and 12 proton patients underwent liver transplantation after treatment. Viable tumor identified in the explanted livers after TACE/proton averaged 2.4 and 0.9 cm, respectively. Pathologic complete response after TACE/proton was 10%/25% (P=.38). The 2-year overall survival for all patients was 59%, with no difference between treatment groups. Median survival time was 30 months (95% confidence interval 20.7-39.3 months). There was a trend toward improved 2-year local tumor control (88% vs 45%, P=.06) and progression-free survival (48% vs 31%, P=.06) favoring the proton beam treatment group. This interim analysis indicates similar overall survival rates for proton beam radiation therapy and TACE. There is a trend toward improved local tumor control and progression-free survival with proton beam. There are significantly fewer hospitalization days after proton treatment, which may indicate reduced toxicity with proton beam therapy.

Unresectable hepatocellular carcinoma: Is radio-embolization an alternative for chemo-embolization?

323 Background: Transarterial Radio-embolization (TARE) has emerged as a newer regional technique to Transarterial Chemo-embolization (TACE) for treatment of unresectable hepatocellular carcinoma (HCC). The aim of this study is to evaluate clinical outcomes of both techniques. Methods: Online search for studies comparing TARE to TACE from 2005 to present was performed. Primary outcome was overall survival rate for up to 4 years. Secondary outcomes included post-treatment complications and treatment response. Quality of included studies was evaluated by STROBE criteria. Relative Risk (RR) and 95% Confidence Intervals (CI) were calculated from pooled data. Results: The search strategy yielded 172 studies, 5 met our selection criteria and included 653 patients undergoing embolization for unresectable HCC. Of these patients, 284 underwent TACE and 269 underwent TARE. Median age was 63 and 64 years for TACE and TARE, respectively. Meta-analysis showed no statistically significant difference in survival for up to 4 years between the two groups (HR = 1.06; 95% CI: 0.81-1.46, p = 0.567). TACE required at least one day of hospital stay compared to TARE which was mostly an outpatient procedure. TACE had more post-treatment pain than TARE (RR = 1.96, 95% CI: 1.40-2.75, p &lt; 0.01), but less subjective fatigue (RR = 0.62, 95% CI: 0.48-0.80, p &lt; 0.01). There was no difference between the two groups in the incidence of post-treatment nausea, vomiting, fever or other complications. In addition, there was no difference in partial or complete response rates between the two groups. Conclusions: TARE appears to be a safe alternative treatment to TACE with similar complication profile and survival rates. Larger prospective randomized trials, focusing on patient-reported quality-of-life are required to consolidate these results, and to evaluate cost vs benefit for both techniques.

Hepatic Resection Improved the Long-Term Survival of Patients with BCLC Stage B Hepatocellular Carcinoma in Asia: a Systematic Review and Meta-Analysis

ObjectiveHepatic resection has been increasingly performed in patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), but the current evidence supporting its efficacy remains controversial. The aim of this systematic review was to investigate the long-term survival and safety of hepatic resection compared to transarterial chemoembolization (TACE) alone for BCLC stage B HCC. MethodsEligible trials that compared hepatic resection with TACE alone for intermediate HCC were identified from the Embase, PubMed, Web of Science, and Cochrane databases. The study outcomes included overall survival (OS) rate and treatment-related complication rate. Hazard ratios (HRs) with a 95 % confidence interval were used to measure the pooled effect according to a random-effects or fixed-effects model, depending on the heterogeneity among the included studies. The heterogeneity among these trials statistically was evaluated using the χ2 and I2 tests. Sensitivity analyses were also performed. ResultsA total of 9 studies containing 4958 patients were included. The comparison between hepatic resection and TACE revealed a pooled HR for 3-year OS of 0.403 (95 % CI 0.364–0.446, p = 0.000; I2 = 0 %, p = 0.643) and a pooled HR for 5-year OS of 0.433 (95 % CI 0.394–0.475, p = 0.000; I2 = 0 %, p = 0.468). An AFP level >400 ng/ml and being HBV-positive were factors significantly correlated with overall survival. For treatment-related complications, the overall odds ratio (OR) for hepatic resection versus TACE was 0.990 (95 % CI 0.934–1.049; p = 0.728; I2 = 64.5 %, p = 0.060). ConclusionHepatic resection likely improved overall survival compared with TACE alone in BCLC stage B HCC patients, but did not increase the incidence of treatment-related complications. An AFP level >400 ng/ml and HBV positivity were significantly correlated with poor OS.

TRIP: a pathological score for transarterial chemoembolization resistance individualized prediction in hepatocellular carcinoma.

Although potentially very useful in optimizing patient selection and follow-up, the individual response to transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) is generally unpredictable. The aim of this study was to identify tissue predictors of tumour resistance to TACE for use in clinical practice on pretreatment biopsies. We investigated the association of residual tumour in post-TACE-resected HCC with pathological and immunophenotypical features, mainly related to hypoxia and angiogenesis. Comparison of tumour phenotype between post-TACE HCC and both paired pre-TACE biopsies and control TACE-untreated HCC was performed. Cases showing >50% residual tumour (RT) were defined as TACE-resistant. A consecutive series of 108 HCC from 41 patients was studied. Overall, 45/108 (44%) HCC were classified as TACE-resistant. Among these, 32 (71%) and 40 (89%) showed diffuse CD34 vascular staining and negative VEGF staining respectively (p<0.05). The association of these two parameters in a weighted score (TRIP) was able to predict TACE resistance with 81% accuracy, 89% sensitivity and 59% specificity. The effectiveness of TRIP was validated in an independent series of 28 HCC biopsies from patients subsequently treated with TACE and for whom radiological follow-up was available. This study demonstrates the potential value of pretreatment tumour biopsy as predictors of TACE resistance in HCC.

Serum miR-335 Level is Associated with the Treatment Response to Trans-Arterial Chemoembolization and Prognosis in Patients with Hepatocellular Carcinoma

Aim: To identify the role of serum MicroRNA-335 (miR-335) in determining the treatment response to Trans-arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and their prognosis after TACE. Methods: A total of 125 HCC patients were enrolled in this study. All these patients underwent TACE and the treatment response was evaluated. All patients were followed for prognosis analyses. Serum miR-335 levels immediate before and 30 days after TACE were determined. Results: HCC patients had significantly lower miR-335 levels than hepatitis patients and healthy controls. Lower serum miR-335 levels were closely associated with more progressive clinical features, including a higher mean serum AFP level, more vascular invasion, cirrhosis and larger tumor size. Response rates were higher in patients with high miR-335 compared to those with low miR-335 level. Patients with lower serum miR-335 levels had significantly poorer prognosis than patients with higher serum miR-335 levels. Conclusion: Our data suggest that serum miR-335 can be used as a molecular marker to predict the treatment response and clinical outcome in HCC patients receiving TACE.

Transarterial radioembolization for hepatocellular carcinoma: An update and perspectives.

In the last decade trans-arterial radioembolization has given promising results in the treatment of patients with intermediate or advanced stage hepatocellular carcinoma (HCC), both in terms of disease control and tolerability profile. This technique consists of the selective intra-arterial administration of microspheres loaded with a radioactive compound (usually Yttrium(90)), and exerts its therapeutic effect through the radiation carried by these microspheres. A careful and meticulous selection of patients is crucial before performing the radioembolization to correctly perform the procedure and reduce the incidence of complications. Radioembolization is a technically complex and expensive technique, which has only recently entered clinical practice and is supported by scant results from phase III clinical trials. Nevertheless, it may represent a valid alternative to transarterial chemoembolization (TACE) in the treatment of intermediate-stage HCC patients, as shown by a comparative retrospective assessment that reported a longer time to progression, but not of overall survival, and a more favorable safety profile for radioembolization. In addition, this treatment has reported a higher percentage of tumor shrinkage, if compared to TACE, for pre-transplant downsizing and it represents a promising therapeutic option in patients with large extent of disease and insufficient residual liver volume who are not immediately eligible for surgery. Radioembolization might also be a suitable companion to sorafenib in advanced HCC or it can be used as a potential alternative to this treatment in patients who are not responding or do not tolerate sorafenib.

Radioembolization with Yttrium-90 microspheres in hepatocellular carcinoma: Role and perspectives.

Transarterial radioembolization (TARE) is a form of brachytherapy in which intra-arterially injected yttrium-90-loaded microspheres serve as a source for internal radiation purposes. On the average, it produces disease control rates exceeding 80% and it is a consolidated therapy for hepatocellular carcinoma (HCC); however, current data are all based on retrospective series or non-controlled prospective studies since randomized controlled trials comparing it with the other liver-directed therapies for intermediate and locally advanced stage HCC are still underway. The data available show that TARE provides similar or even better survival rates when compared to transarterial chemoembolization (TACE). First-line TARE is best indicated for both intermediate-stage patients (staged according to the barcelona clinic liver cancer staging classification) who have lesions which respond poorly to TACE due to multiple tumors or a large tumor burden, and for locally advanced-stage patients with solitary tumors, and segmental or lobar portal vein tumor thrombosis. In addition, emerging data have suggested the use of TARE in patients who are classified slightly beyond the Milan criteria regarding radical treatment for downstaging purposes. As a second-line treatment, TARE can also be applied in patients progressing to TACE or sorafenib; a large number of phase II/III trials are ongoing with the purpose of evaluating the best association with systemic therapies. Transarterial radioembolization is very well tolerated and has a low rate of complications which are mainly related to unintended non-target tissue irradiation, including the surrounding liver parenchyma. The complications can be additionally reduced by accurate patient selection and a strict pre-treatment evaluation including dosimetry and assessment of the vascular anatomy. Since a correct treatment algorithm for potential TARE candidates is not clear and standardized, this comprehensive review analyzes the best selection criteria for patients who really benefit from TARE and also the new advances of this therapy, which can be a very important weapon against HCC.

Selective internal radiotherapy (SIRT) of liver tumors

Selective internal radiotherapy (SIRT) is a safe and efficacious, minimally invasive procedure to treat primary and secondary unresectable liver tumors. For hepatocellular carcinoma (HCC), SIRT has proven to be a well-tolerated therapy option even in advanced stages of disease. In cases of portal vein thrombosis SIRT is the alternative to transarterial chemoembolization (TACE). The role of SIRT regarding downstaging and bridging to transplantation is promising and SIRT has also been shown to be highly effective and well-tolerated in metastastic liver disease. The results of prospective randomized trials are awaited to prove the efficiency and safety of SIRT described in numerous retrospective and prospective non-randomized studies. The indications are established within the framework of a tumor board.