Treatment algorithm for intermediate and advanced stage hepatocellular carcinoma: Korea

The practice guideline for hepatocellular carcinoma (HCC) in Korea was revised in 2009. It was based on clinical evidence. The treatment algorithm was divided into curative and noncurative treatments. According to Barcelona Clinic Liver Cancer (BCLC) staging, the curative treatment group included early stage HCC (BCLC-A), and the noncurative treatment group consisted of intermediate and advanced stages of HCC (BCLC-B, C). The intermediate stage of HCC stands for noncurative disease, and therefore surgical resection and radiofrequency ablation are not considered as primary treatment modalities. Transarterial chemoembolization (TACE) forms the backbone of the treatment for intermediate stage HCC with Child-Pugh A cirrhosis. Patients in whom complete necrosis is not achieved or early recurrence after TACE develops should receive individualized treatments such as systemic treatment or combined radiation therapy (RT). Liver transplantation (LT) can be carried out for intermediate stage HCCs. However, the long-term survival rate after LT for intermediate stage HCCs is inferior to that of early stage HCCs because intermediate stage HCCs exceed the Milan criteria. In patients with Child-Pugh C liver function, LT would be better than TACE in terms of survival gain if the tumor burden is acceptable by expert opinion standards. The treatment algorithm becomes very complicated when it comes to advanced stage HCC. Sorafenib, a multikinase inhibitor with antiangiogenic and antiproliferative properties, has been shown to prolong the median overall survival and the median time to radiological progression compared to placebo in randomized controlled trials (RCTs) and has become the current standard of care for patients with advanced-stage tumors not suitable for surgical or locoregional therapies. RT is in the process of becoming a modality with a high efficacy and minimum side effects for HCC treatment, with recent improvements in equipment as well as radiation methods. However, to discover whether RT is really beneficial in the treatment of large-sized intermediate and advanced stage HCC, prospective RCTs should be carried out.     

Asian consensus workshop report: expert consensus guideline for the management of intermediate and advanced hepatocellular carcinoma in Asia

Hepatocellular carcinoma (HCC) is a highly prevalent disease in many Asian countries, accounting for 80% of victims worldwide. Screening programs improve the detection of early HCC and have a positive impact on survival, but the majority of HCC patients in Asia still present with advanced stage disease. The treatment outcomes of HCC are affected by multiple variables, including liver function, performance status of the patient, and tumor stage. Therefore, it is not easy to apply a multidisciplinary therapeutic approach for optimal management. At present, limited numbers of HCC patients are eligible for curative therapies such as surgery or ablation in Asia. Therefore, most patients are eligible for only palliative treatments. For optimal management, the treatment choice is guided by staging systems and treatment guidelines. Numerous staging systems have been proposed and treatment guidelines vary by region. According to the Barcelona Clinic Liver Cancer (BCLC) guideline based on evidence from randomized clinical trials, only transarterial chemoembolization (TACE) is recommended for intermediate stage HCC and sorafenib for advanced stage HCC. However, treatment guidelines from Asian countries have adopted several other therapeutic modalities such as a surgical approach, hepatic arterial infusion chemotherapy, external radiation, and their combinations based on clinical experiences for intermediate and advanced stage HCC. Although TACE is the main therapeutic modality in the intermediate stage, overall therapeutic outcomes depend on the tumor size. In the advanced stage, the prognosis depends on the tumor status, e.g. major vessel invasion or extrahepatic spread. Thus, a new staging system representing prognoses suitable for Asian HCC patients and a corresponding optimal treatment algorithm should be further investigated using evidence-based data, which will finally bring about an Asian consensus for the management of intermediate and advanced stage HCC.     

The Comprehensive Analysis of Efficacy and Safety of CalliSpheres^® Drug-Eluting Beads Transarterial Chemoembolization in 367 Liver Cancer Patients: A Multiple-Center,Cohort Study

This study aimed to investigate the efficacy, safety, and prognostic factors of drug-eluting beads transarterial chemoembolization (DEB-TACE) in treating Chinese patients with liver cancer. A total of 367 liver cancer patients from 24 medical centers were consecutively enrolled in this multiple-center, prospective cohort study, including 275 hepatocellular carcinoma (HCC) cases, 37 intrahepatic cholangiocarcinoma (ICC) cases, and 55 secondary liver cancer cases. All the patients received CalliSpheres^® DEB-TACE treatment. Treatment response, overall survival (OS), change of liver function, and adverse events (AEs) were assessed. DEB-TACE treatment achieved 19.9% complete response (CR) and 79.6% objective response rate (ORR), with mean OS of 384 days [95% confidence interval (CI): 375–393 days]. CR and ORR were both higher in HCC patients compared with primary ICC patients and secondary liver cancer patients, while no difference was discovered in OS. Portal vein invasion was an independent risk factor for CR, while portal vein invasion, previous conventional TACE (cTACE) treatment, and abnormal blood creatinine (BCr) were independent risk factors for ORR. In addition, largest nodule size 5.0 cm, abnormal albumin (ALB), and abnormal total bilirubin (TBIL) independently correlated with unfavorable OS. Most liver function indexes were recovered to baseline levels at 1–3 months after DEB-TACE. Common AEs were pain, fever, vomiting, and nausea; most of them were at mild grade. CalliSpheres^® DEB-TACE is efficient and well tolerated in Chinese liver cancer patients. Portal vein invasion, previous cTACE treatment, largest nodule size, abnormal BCr, ALB, and TBIL correlate with worse prognosis independently.     

晚期原发性肝癌治疗的研究进展

原发性肝癌位居全球最常见恶性肿瘤的第五位,在癌症相关死亡原因中排名第三位.原发性肝癌治疗方法的选择很大程度上取决于肝脏功能,肿瘤大小,是否存在转移灶和血管侵犯.目前,原发性肝癌的根治方法包括肝切除术和肝移植手术,但是很多患者确诊时已进入晚期,失去了治愈的机会.全身系统性治疗对于晚期原发性肝癌的患者变得尤为重要,其中包括:分子靶向治疗、全身系统性化疗和免疫治疗.本文就近年来晚期原发性肝癌治疗的研究进展作一综述.     

Prospect of lenvatinib for unresectable hepatocellular carcinoma in the new era of systemic chemotherapy

The phase III clinical trial of the novel molecular targeted agent (MTA) lenvatinib for patients with advanced hepatocellular carcinoma (HCC) (REFLECT trial) found that lenvatinib was non-inferior to sorafenib in overall survival. Recently, the efficacy of multiple MTAs, including lenvatinib, in practice has been reported, and therapeutic strategies for Barcelona Clinic Liver Cancer (BCLC) intermediate stage HCC are undergoing major changes. Based on these results, lenvatinib could be recommended for patients with transcatheter arterial chemoembolization (TACE)-refractory, ALBI grade 1, within the up-to-seven criteria in the BCLC intermediate stage. Lenvatinib provides a more favorable outcome than TACE, even in cases with large or multinodular HCC beyond the up-to-seven criteria with Child-Pugh grade A. When patients meet the definitions of TACE-refractory or TACE-unsuitable, switching to systemic chemotherapy, including lenvatinib, is for favorable for preserving liver function. If initial treatment, including MTA, has a significant therapeutic effect and downstaging of HCC is obtained, additional TACE or surgical resection should be considered. Lenvatinib also has a therapeutic effect for poorly differentiated type and non-simple nodular type HCC thanks to the survival-prolonging effect of this drug. Furthermore, a significant therapeutic effect is expected in tumors with more than 50% liver involvement or main portal vein invasion, which have traditionally been considered to have a poor prognosis in patients. This suggests that at the start of lenvatinib treatment, HCC patients with ALBI grade 1 may be able to maintain liver functional reserve.     

Efficacy and Safety of CalliSpheres^® Drug-Eluting Beads Transarterial Chemoembolization in Barcelona Clinic Liver Cancer Stage C Patients

This study aimed to investigate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) treatment in Barcelona Clinic Liver Cancer (BCLC) stage C liver cancer patients. In 39 patients with BCLC stage C liver cancer, after the first cycle of DEB-TACE, 2 (5.1%) and 24 (61.5%) patients achieved complete response (CR) and partial response (PR) to give an overall objective response rate (ORR) of 66.7%. With respect to the second cycle of therapy, the ORR was higher in patients receiving DEB-TACE compared with those receiving cTACE (57.1% vs. 11.1%). After the first cycle of DEB-TACE treatment, the percentages of abnormal albumin (ALB), total protein (TP), total bilirubin (TBIL), and alanine aminotransferase (ALT) worsened at 1 week and recovered at 1 month. The number of patients with abnormal aspartate aminotransferase (AST) did not increase at 1 week but elevated at 1 month. After the second cycle of DEB-TACE or cTACE treatment, no difference was observed between cTACE and DEB-TACE in terms of all adverse events (AEs) at all visits, and most of the AEs did not change after the second cycle in both groups. The most common AEs after the first and second treatment cycles were pain, fever, and nausea/vomiting. These results demonstrate that DEB-TACE offers patients with BCLC stage C liver cancer a clinically active short-term treatment that is safe and relatively well tolerated.     

Chimioembolisation et hépatocarcinome: pour quel type de patient ?

Transarterial chemoembolization (TACE) is widely used in the treatment of Hepatocellular carcinoma. Recent technical advances (drug-eluting beads) have led to the standardization of injection techniques. Recognized indications for TACE are patients with an intermediate stage of cancer (BCLC classification). However the best indications are patients with well compensated liver cirrhosis (Child-Pugh A or B7), one or a few nodules of median size which can receive a selective embolization, without portal thrombosis, extra-hepatic metastases or severe comorbidities. For other intermediate-stage patients, systemic treatment with sorafenib would be the treatment of choice.     

Evolving strategies for the treatment of hepatocellular carcinoma: From clinical-guided to molecularly-taylored therapeutic options

Hepatocellular carcinoma (hepatocellular carcinoma, HCC) is the commonest primary liver cancer (80-90%) and represents the leading cause of cancer-related death, after lung and stomach cancer.The process of neoplastic transformation proceeds through the accumulation of mutations in the genes governing cell proliferation and apoptosis.It is currently difficult to determine the natural history of patients with untreated early-stage HCC, since most with early-stage tumor patients undergoes curative therapy. Survival rates at 3 years is 65% in patients with Child-Pugh A, and single untreated lesion. This proportion increases to 70% at 5 years after radical treatment. In patients included in randomized controlled clinical trials with advanced disease, survival at 1 and 2 years is respectively 72% and 50%.Surgery is the only potentially curative treatment for HCC. In carefully selected patients, resection and transplantation in fact, allow a 5 years survival from 60% to 70%.Unfortunately most patients in Western countries present with an intermediate or advanced HCC at diagnosis with the consequent inability to use curative treatments. These patients are therefore candidates to palliative therapies that include arterial embolization and chemoembolization and systemic treatments including chemotherapy, immunotherapy and hormonal therapy. Only recently the molecular targeted drug, Sorafenib, has been introduced among the therapeutic options for these patients.     

The cost-effectiveness of TheraSphere in patients with hepatocellular carcinoma who are eligible for transarterial embolization

IntroductionThe aim of the study is to estimate the cost-effectiveness of TheraSphere against other embolic treatments in a population with early to intermediate stage hepatocellular carcinoma (HCC) who are unresectable at presentation and are eligible for transarterial embolization (TAE), conventional transarterial chemoembolization (cTACE) or drug-eluting bead TACE (DEB-TACE).Materials and methodsA Markov model was constructed using a UK National Health Service (NHS) perspective, a 20-year time horizon, and four-week cycles. The eight health states included ‘watch and wait’, ‘transplantation’ (pre-, post and post (No HCC)), ‘resection’, ‘no HCC other’, ‘pharmacological management’ and ‘death’. Clinical data were sourced from literature and expert opinion. Resource use and costs were reflective of the NHS, and benefits were quantified using Quality-Adjusted Life Years (QALYs), with utility weights sourced from literature.Comparators were TAE, cTACE and DEB-TACE. The primary output was the Incremental Cost-Effectiveness Ratio (ICER) expressed as cost per QALY gained. An ICER of under £20,000/QALY gained for an intervention is cost-effective and represents efficient use of healthcare resources. Extensive deterministic and probabilistic sensitivity analyses were undertaken.ResultsTheraSphere patients were predicted to gain 0.7 additional QALYs compared to all other treatments. The base case ICERs for TheraSphere were £17,300, £17,279 and £23,020 per QALY gained compared to TAE, cTACE and DEB-TACE, respectively. In the TheraSphere cohort, 87% more patients were predicted to achieve downstaging compared to all other treatment options.ConclusionsThis study indicates that treatment with TheraSphere is a potentially cost-effective option for patients with early to intermediate stage HCC.     

Hepatocellular carcinoma in patients with chronic renal disease: Challenges of interventional treatment

Hepatocellular carcinoma (HCC) is a common malignancy worldwide, recognized as the fourth most common cause of cancer related death. Many risk factors, leading to liver cirrhosis and associated HCC, have been recognized, among them viral hepatitis infections play an important role worldwide. Patients suffering from chronic kidney disease (CKD), especially those on maintenance dialysis, show a higher prevalence of viral hepatitis than the general population what increases the risk of HCC onset. In addition, renal dysfunction may have a negative prognostic impact on both immediate and long-term outcomes after malignancy treatment. Several interventional procedures for the treatment of HCC are currently available: thermal ablation, transcatheter arterial chemoembolization, liver surgery or even liver transplantation. The Barcelona Clinic Liver Cancer system provides an evidence-based treatment algorithm to address different categories of patients to the most-effective treatment in consideration of the extension of disease, liver function and performance status. Liver resection and transplantation are usually reserved to patients with early stage HCC and acceptable performance status, while the other treatments are more indicated in case of impaired liver function or locally advanced or unresectable tumors. However, there is no validated treatment algorithm for HCC in CKD patients, mainly due to the rarity of reports in this cohort of patients. Hereby we discuss the available evidences on interventional HCC treatments in CKD patients, and briefly report up-to-date pharmacological therapy for HCC patients affected by viral hepatitis.     

Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma

Background:

Transcatheter arterial chemoembolisation (TACE) is the treatment of choice for intermediate stage hepatocellular carcinoma (HCC). Doxorubicin-loaded drug-eluting beads (DEB)-TACE is expected to improve the performance of conventional TACE (cTACE). The aim of this study was to compare DEB-TACE with cTACE in terms of time-to-tumour progression (TTP), adverse events (AEs), and 2-year survival.

Methods:

Patients were randomised one-to-one to undergo cTACE or DEB-TACE and followed-up for at least 2 years or until death. Transcatheter arterial chemoembolisation was repeated ‘on-demand''.

Results:

We enrolled 177 patients: 89 underwent DEB-TACE and 88 cTACE. The median number of procedures was 2 in each arm, and the in-hospital stay was 3 and 4 days, respectively (P=0.323). No differences were found in local and overall tumour response. The median TTP was 9 months in both arms. The AE incidence and severity did not differ between the arms, except for post-procedural pain, more frequent and severe after cTACE (P<0.001). The 1- and 2-year survival rates were 86.2% and 56.8% after DEB-TACE and 83.5% and 55.4% after cTACE (P=0.949). Eastern Cooperative Oncology Group (ECOG), serum albumin, and tumour number independently predicted survival (P<0.05).

Conclusions:

The DEB-TACE and the cTACE are equally effective and safe, with the only advantage of DEB-TACE being less post-procedural abdominal pain.     

Thalidomide Combined with Transcatheter Arterial Chemoembolization (TACE) for Intermediate or Advanced Hepatocellular Carcinoma: a Systematic Review and GRADE Approach

Objective:According to current guidelines, there is no clear second-line treatment for advanced liver cancer.In practice, clinicians have attempted to use thalidomide(TLD) combined with transcatheter arterial chemoembolization(TACE) for treating liver cancer. This study aims to assess the clinical efficacy and safety of TLD combined with TACEin patients with intermediate or advanced hepatocellular carcinoma. Methods: Medline, Embase, the Cochrane CentralRegister of Controlled Trials (CENTRAL), database of ClinicalTrials.gov, CBM, CNKI, VIP and Wanfang databasewere searched for eligible studies. Criteria for inclusion in our meta-analysis included a study that patients diagnosedwith intermediate or advanced HCC, the use of TACE plus TLD or its derivatives, and the availability of outcomedata for survival. A meta-analysis was conducted to summarize the evidences of randomized controlled trials (RCTs).And finally, the GRADE approach was used to assess the quality of these evidences. Results: Twelve RCTs involving894 Hepatocellular Carcinoma (HCC) patients were included. The meta-analysis results showed that TACE plus TLD wassignificantly superior than TACE alone in terms of 12-month survival rate (OR=2.55, 95% CI:1.78-3.64, P<0.01), 24-monthsurvival rate (OR=2.95, 95% CI:1.96-4.44, P<0.01), 36-month survival rate (OR=2.95, 95% CI:1.41-6.19, P<0.004),progression-free survival (PFS) (MD=2.23, 95% CI:1.19-3.28 , P<0.001), objective response rate (OR=1.84, 95%CI:1.34-2.52, P<0.0001), and disease control rate (OR=2.68, 95% CI:1.80-3.99). Subgroup analysis demonstratedno differences across related outcomes. Sensitivity analyses showed no important differences in the estimates ofeffects. Quality of evidence for all outcomes was rated moderate to very low after applying GRADE approach.Conclusions: Current evidence seemed to support the suggestion that TACE plus TLD as the second line treatment forpatients with intermediate or advanced HCC. However, this finding is not definitive due to the poor quality of includedstudies, more carefully designed and conducted RCTs are warranted to confirm above conclusions.     

A comparative study between Embosphere~ and conventional transcatheter arterial chemoembolization for treatment of unresectable liver metastasis from GIST简

Objective：Transcatheter arterial chemoembolization （TACE） is a standard treatment for hepatocellular carcinoma （HCC） and/or some unresectable liver metastasis tumors.Hypervascular liver metastatic lesions such as metastasis from gastrointestinal stromal tumor （GIST） are an indication for transcatheter arterial embolization （TAE）.The purpose of this study was to evaluate the efficacy and safety of Embosphere（㊣）-TAE （Embo-TAE） in comparison with conventional TACE （cTACE） for the treatment of liver metastasis from GIST.Methods：A total of 45 patients who underwent TACE between Aug 2008 and Feb 2013 were enrolled.Patients with GIST who underwent TAE with Embosphere（㊣） （n=19） were compared with controls who received cTACE （n=26）.The primary end points were treatment response and treatment-related adverse events.The secondary end points were progression-free survival （PFS） and overall survival （OS）.Results：The treatment response of Embo-TAE group was significandy higher than that of the cTACE group （P＜0.001）.The PFS was significandy better in the Embosphere（㊣）-group than in the cTACE group （56.6 and 42.1 weeks,respectively; P=0.003）.However,there was no statistically significant difference in liver toxicity between the two groups （P＞0.05）.The median OS in the Embo-TAE group was longer than that in the cTACE group （74.0 weeks,95％ CI：68.2-79.8 vs.61.7 weeks,95％ CI：56.2-67.2 weeks） （unadjusted P=0.045）.The use of Embo-TAE significantly reduced the risk of death in patients with GIST with liver metastases according to the Cox proportonal hazards regression model [hazard ratio （HR）：0.149; 95％ CI：0.064-0.475].Conclusions：TAE with Embosphcre（㊣） showed better treatment response and delayed tumor progression compared with cTACE.There was no significant difference in treatment-related hepatic toxicities.EmboTAE thus appears to be a feasible and promising approach in the treatment of liver metastasis from GIST.     

90 Y微球选择性内放射治疗在肝细胞癌中的应用及研究进展

肝细胞癌（hepatocellular carcinoma,HCC）是中国癌症相关死亡第二大常见原因。中国约85%的HCC患者在确诊时已是中晚期,系统治疗（包括化疗、靶向治疗、免疫治疗）联合局部微创治疗（如介入治疗、放射治疗等）是目前主要的治疗方式。钇-90（yttrium-90, ⁹⁰ Y）微球选择性内放射治疗（selective internal radiation therapy,SIRT）作为主要局部微创治疗手段在国外已有近20年的临床使用经验,临床研究证明了其治疗肝脏肿瘤的疗效和安全性。相关研究证实了 ⁹⁰ Y微球SIRT单用在HCC中的局部控制作用,以及其与手术、免疫药物、靶向药物联用的有效性及安全性,同时, ⁹⁰ Y微球SIRT对于肝段产生的“放射性切除”效应初步显示出其在HCC根治性治疗方面的应用前景。从HCC姑息治疗、转化治疗、放射性肝段切除等方面综述SIRT在HCC中的应用及研究进展。     

Transarterial chemoembolization combined with recombinant human adenovirus type 5 H101 prolongs overall survival of patients with intermediate to advanced hepatocellular carcinoma:a prognostic nomogram study

Background: Patients with intermediate to advanced hepatocellular carcinoma (HCC) are most commonly treated with transarterial chemoembolization (TACE). Previous studies showed that TACE combined with recombinant human adenovirus type 5 (H101) may provide a clinical survival benefit. In the present study, we aimed to determine the survival benefit of TACE with or without H101 for patients with intermediate to advanced HCC and to develop an effective nomogram for predicting individual survival outcomes of these patients. Methods: We retrospectively collected data from 590 patients with intermediate to advanced HCC who were treated at Sun Yat-sen University Cancer Center between January 2007 and July 2015. After propensity score matching, 238 patients who received TACE with H101 (TACE with H101 group) and 238 patients who received TACE without H101 (TACE group) were analyzed. Overall survival (OS) was evaluated using the Kaplan–Meier method; the nomogram was developed based on Cox regression analysis. Discrimination and calibration were measured using the concordance index (c-index) and calibration plots. Results: Clinical and radiologic features were similar between the two groups. OS rates were significantly lower in the TACE group than in the TACE with H101 group (1-year OS rate, 53.8% vs. 61.3%; 2-year OS rate, 33.4% vs. 44.2%;3-year OS rate, 22.4% vs. 40.5%; all P < 0.05). Multivariate Cox regression analysis for the entire cohort showed that alpha-fetoprotein level, alkaline phosphatase level, tumor size, metastasis, vascular invasion, and TACE with or without H101 were independent factors for OS, all of which were included in the nomogram. Calibration curves showed good agreement between nomogram-predicted survival and observed survival. The c-index of the nomogram for predict-ing OS was 0.716 (95% confidence interval 0.686–0.746). Conclusions: TACE plus H101 extends the survival of patients with intermediate to advanced HCC. Our proposed nomogram provides individual survival prediction and stratification for patients with intermediate to advanced HCC who receive TACE with or without H101.     

射频消融治疗原发性肝癌的生命质量对比评价

背景与目的以往对原发性肝癌(hepatocellularcarcinoma,HCC)各种治疗疗效的评价主要从治愈率、生存率和生存时间方面进行,近年来生命质量(qualityoflife,QOL)研究倍受关注,能较全面地反映肝癌患者体能恢复状况和切身感受而被广泛应用于癌症、慢性病的疗效评价。目前对于经皮射频消融(radiofrequencyablation,RFA)、经动脉插管栓塞化疗(transcatheterhepaticarterialchemo-embolization,TACE)治疗意义的评价大多关注局部肿瘤灭活率及患者生存率,而对治疗后患者生命质量的研究尚不多见。本研究从患者整体角度对比评估原发性肝癌经皮射频消融治疗后患者的生命质量。方法采用国内肝癌特异性生命质量量表(QOL-LCV2.0),对80例HCC经RFA治疗后QOL进行评定;并与同期40例经动脉插管栓塞化疗(TACE组)以及TACE RFA(联合组)40例分别进行比较。3组患者在年龄、性别、临床分期等方面分布均衡,无明显差异。结果RFA组的QOL总分中位数(168.6)高于TACE组(146.8),差异有显著性(P=0.025);RFA组和联合组在症状/副作用领域的得分中位数45.5、46.0,分别优于单纯TACE组38.1(P<0.01);RFA组躯体功能领域得分呈略高于TACE组的趋势。患者的年龄、收入、治疗后Child-Pugh分级、治疗后新生/复发率、并发症等方面与患者生命质量相关。TACE组和联合组于治疗后Child-Pugh分级提高的比例分别高于RFA组;TACE组新生/复发的比例明显高于RFA组。RFA组的1年、2年和3年生存率(92.8%、89.3%和76.5%)与联合治疗组(94.1%、87.4%、60.0%)比较无统计学差异,但高于TACE组(74.3%、48.2%、48.2%)。结论RFA治疗肝癌,多数患者可获得较好的疗效,严重的副作用少。TACE与RFA联合治疗与单纯TACE相比,可减少患者肝功能损伤,有利于提高原发性肝癌患者的生命质量。     

New concepts in embolotherapy of HCC

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths worldwide with rapidly growing incidence rates in the USA and Europe. Despite improving surveillance programs, most patients are diagnosed at intermediate to advanced stages and are no longer amenable to curative therapies, such as ablation, surgical resection and liver transplantation. For such patients, catheter-based image-guided embolotherapies such as transarterial chemoembolization (TACE) represent the standard of care and mainstay therapy, as recommended and endorsed by a variety of national guidelines and staging systems. The main benefit of these therapies is explained by the preferentially arterial blood supply of liver tumors, which allows to deliver the anticancer therapy directly to the tumor-feeding artery while sparing the healthy hepatic tissue mainly supplied by the portal vein. The tool box of an interventional oncologist contains several different variants of transarterial treatment modalities. Ever since the first TACE more than 30 years ago, these techniques have been progressively refined, both with respect to drug delivery materials and with respect to angiographic micro-catheter and image-guidance technology, thus substantially improving therapeutic outcomes of HCC. This review will summarize the fundamental principles, technical and clinical data on the application of different embolotherapies, such as bland transarterial embolization, Lipiodol-based conventional transarterial chemoembolization as well as TACE with drug-eluting beads (DEB-TACE). Clinical data on ⁹⁰Yttrium radioembolization as an emerging alternative, mostly applied for niche indications such as HCC with portal vein invasion, will be discussed. Furthermore, we will summarize the principle of HCC staging, patient allocation and response assessment in the setting of HCC embolotherapy. In addition, we will evaluate the role of cone-beam computed tomography as a novel intra-procedural image-guidance technology. Finally, this review will touch on new technical developments such as radiopaque, imageable DEBs and the rationale and role of combined systemic and locoregional therapies, mostly in combination with Sorafenib.     

Locoregional radiological treatment for hepatocellular carcinoma; Which, when and how?

Hepatocellular carcinoma (HCC) is one of the most frequent and deadliest cancers worldwide. Liver transplantation, surgical resection or local ablation offer the best survival advantages but most patients either present when the tumor is in an advanced stage or the degree of underlying liver disease precludes these options. Several therapies have been proposed for these patients with proven survival benefits. These therapies comprise the locoregional treatment for HCC, and include percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and drug-eluting bead (DEB). PEI and RFA are considered curative treatments for early stage HCC; whereas TACE is a standard of care for intermediate stages. Additionally, evaluation of response to locoregional treatment in HCC is important, as objective response may become a surrogate marker for improved survival. Currently, there are several criteria for response assessment, including the World Health Organization (WHO), the Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver Criteria (EASL), and the modified RECIST (mRECIST); however, there has been poor correlation between the clinical benefit provided by locoregional interventional therapies and conventional methods of response assessment.The aim of our study was to review and analyze the current evidence for radiological interventions in HCC, and to propose evidence based recommendations to improve the management of these patients.     

Experiences of Family of Patient with Newly Diagnosed Advanced Terminal Stage Hepatocellular Cancer

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the thirdleading cause of cancer-related death worldwide due to its generally poor prognosis. Caregiver burden for livercancer cases is higher than with other cancer and needs especial attention. Methods: To explore the experiencesof families of patients with newly diagnosed advanced terminal stage hepatocellular cancer by interview. Results:Nine participants were recruited in this study. Content analysis of the interviews revealed four themes: blamingoneself, disrupting the pace of life, searching all possible regimens, and not letting go. Conclusions: This studyprovides new insight into the needs and support of family members especially when they are facing loved oneswith newly diagnosed advanced terminal stage HCC. These results will inform future supportive care servicedevelopment and intervention research aimed at providing assistance in reducing unmet supportive care needsand psychological distress of these family members.     

A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cause of cancer death throughout the world. The majority of patients are not suitable for curative resection either because of the advanced stage of the disease at the time of presentation or because of underlying cirrhosis. Transcatheter intraarterial lipiodol chemoembolization (TACE) has been reported to be one of the most effective palliative measures for HCC. However, its severe side effects continue to make its use controversial. METHODS: In the current study, the authors prospectively evaluated 197 sessions of TACE performed in 59 patients with HCC. RESULTS: Acute hepatic decompensation occurred in 20% of the 197 sessions with 3% of cases being irreversible. Significant elevation of bilirubin was associated with the dosage of cisplatin used (P = 0.0001), basal bilirubin level (P = 0.0001), basal prothrombin time (P =0.004), basal aspartate aminotransferase (AST) level (P = 0.013), and stage of cirrhosis (P < 0.0001). Patients with irreversible hepatic decompensation were more likely to have higher pre-TACE bilirubin levels (P = 0.009), more prolonged prothrombin time (P = 0.015), received a higher dose of cisplatin (P = 0.033), and more advanced cirrhosis (P < 0.0001). The majority of the other side effects were self-limiting with the exception of one patient who died of liver and splenic abscesses. Approximately 36% of the patients achieved a tumor response, 39% achieved stable disease, and 29% developed progressive disease. CONCLUSIONS: The results of the current study identified factors that appeared to predispose patients to irreversible hepatic decompensation after TACE. Despite the high percentage of patients who developed hepatic decompensation after TACE, irreversible damage occurred in only a minority.