Updated use of TACE for hepatocellular carcinoma treatment: How and when to use it based on clinical evidence

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the sixth leading cause of cancer and the third leading cause of cancer-related mortality. Patient stratification and treatment allocation are based on tumor stage, liver function, and performance status. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, transarterial chemoembolization (TACE) is the first-line treatment for patients with intermediate stage HCC, including those with large or multinodular HCC, well-preserved liver function, and no cancer-related symptoms or evidence of vascular invasion or extrahepatic spread. Two TACE techniques have been used since 2004, conventional TACE (cTACE) and TACE with drug-eluting beads (DEB-TACE). cTACE was evidenced first to treat intermediate stage HCC patients. It combines the transcatheter delivery of chemotherapy using Lipiodol-based emulsion plus an embolizing agent to achieve strong cytotoxic and ischemic effects. Drug-eluting beads (DEBs) were developed in order to slowly release chemotherapeutic agents, and to increase ischemia intensity and duration. Recent advances allow TACE treatment of both early stage patients (i.e. those with a solitary nodule or up to 3 nodules under 3 cm) and some advanced stage patients. Here we review recent clinical evidence related to TACE treatment of patients with early, intermediate, and advanced stage HCC. Based on the 2014 TACE algorithm of Raoul et al., this international expert panel proposes an updated TACE algorithm and provides insights into TACE use for patients at any HCC stage.     

Treatment of intermediate/advanced hepatocellular carcinoma in the clinic: how can outcomes be improved?

Hepatocellular carcinoma (HCC) is a complex condition associated with a poor prognosis. Treatment outcomes are affected by multiple variables, including liver function, performance status of the patient, and tumor stage, making a multidisciplinary approach to treatment essential for optimal patient management. Only ～30% of patients are eligible for curative therapies (surgery or ablation); palliative treatments include transcatheter arterial chemoembolization (TACE) and sorafenib. Treatment choice is guided by staging systems and treatment guidelines, although numerous systems exist and treatment guidelines vary by region. The current standard of care for patients unsuitable for potentially curative therapy is locoregional therapy with TACE. This treatment is associated with survival benefits, but there is no consensus regarding the optimum treatment/retreatment strategy. For patients with more advanced disease or who have failed locoregional therapy, sorafenib is the standard of care. Sorafenib is a targeted agent with proven survival benefits as monotherapy in these patients, and ongoing studies will clarify its role in combination with other agents and in patients with impaired liver function. Although other novel agents and therapeutic approaches are emerging, such as radioembolization and various targeted agents, further suitably designed randomized clinical trials (RCTs) comparing these agents with the standard of care are needed. In addition to RCTs, the collection of real-life data will also be important to allow physicians to make fully informed treatment decisions. The Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON) study is a global, noninterventional study of patients with unresectable HCC receiving sorafenib. The aim of that study is to compile a large robust database to evaluate local, regional, and global factors influencing the management of patients with HCC. It is hoped that findings from the GIDEON study along with phase III RCT data will lead to better outcomes for patients with intermediate-advanced HCC.     

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.     

Therapeutic efficacy of transcatheter arterial chemoembolization as compared with hepatic resection in hepatocellular carcinoma patients with compensated liver function in a hepatitis B virus-endemic area: a prospective cohort study.

PURPOSE: Identifying a special subgroup of hepatocellular carcinoma (HCC) patients who may benefit from transcatheter arterial chemoembolization (TACE) when compared with the standard treatment of hepatic resection (HR) warrants research in Asian countries. PATIENTS AND METHODS: From January 1993 to December 1994, 182 patients with operable HCC (Child-Pugh class A and International Union Against Cancer [UICC] stage T1-3N0M0) were enrolled. After initial TACE and lipiodol computed tomography, 91 received HR and 91, who refused the operation, received repeated sessions of TACE. After stratification according to the tumor stage (UICC and Cancer of the Liver Italian Program [CLIP]) and lipiodol retention pattern, the survival rates of the two treatment groups were compared. The median follow-up period was 83 months. RESULTS: As of December 31, 2000, 48 patients who underwent HR and 68 patients who underwent TACE had died. In a subgroup analysis according to tumor stage, the HR group survival rate was significantly higher than the TACE group in both UICC T1-2N0M0 (P =.0058) and CLIP 0 (P =.0027) subgroups. However, there was no significant difference in either UICC T3N0M0 (P =.7512) or CLIP 1-2 (P =.5366) subgroups. Even in patients with UICC T1-2N0M0 HCC, when lipiodol was compactly retained, the survival rate of the HR group was comparable to that of the TACE group (P =.0596). CONCLUSION: TACE proved to be as effective as HR in the subpopulations with UICC T3N0M0 or CLIP 1-2 HCC and adequate liver function, and even with UICC T1-2N0M0 HCC when lipiodol was compactly retained in the tumor. In such cases, the choice of treatment modality between TACE and HR may be left to the patient's preference.     

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.     

肝癌经肝动脉化疗栓塞术后复发的临床相关因素研究

目的：研究中晚期肝细胞肝癌经肝动脉化疗栓塞术（TACE）后肝内复发的临床相关因素,为原发性肝癌患者制定合理的治疗方案及为介入治疗预后提供理论依据。方法：收集2006年1月-2011年10月经TACE治疗的454例中晚期肝细胞肝癌,进行单因素分析和Cox比例风险模型分析。结果：治疗有效率有意义的影响因素为：有无乙肝、是否手术、单发与多发、有无腹水、介人次数。预后有意义的影响因素为：谷丙转氨酶、白蛋白、胆红素、有无动静脉瘘、肿瘤类型、门脉癌栓、是否手术、介入次数、治疗间隔。结论：中晚期肝癌经TACE术后复发由多种因素决定,对谷丙转氨酶、白蛋白、胆红素正常,肿瘤相对局限、手术后患者,无门静脉癌栓的患者积极行介入化疗术,可获得较好的疗效。TACE术前评估肝癌术后复发的相关因素有利于治疗方法的选择及判断预后。     

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.     

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.     

The clinical management of hepatocellular carcinoma in the United States,Europe, and Asia: A comprehensive and evidence‐based comparison and review

Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, represents 1 of the leading causes of cancer deaths in the world with an estimated 21,670 deaths in the United States in 2013. In contrast to other malignancies, there is an array of treatment options for HCC involving several specialties in the multidisciplinary care of the patient. Consequently, vast heterogeneity in management tendencies has been observed. The objective of this report was to review and compare guidelines on the management of HCC from the United States (National Comprehensive Cancer Network), Europe (European Association for the Study of the Liver‐European Organization for Research and Treatment of Cancer), and Asia (consensus statement from the 2009 Asian Oncology Summit). By and large, all 3 guidelines are similar, with some variance in surveillance and treatment allocation recommendations because of regional differences in disease and other variables (diagnosis, staging systems) secondary to the lack of a concrete, high level of evidence. In contrast to other cancers, the geographic differences in tumor biology and resources make it impractical to have a globally universal guideline for all patients with HCC. Recommendations from the 3 groups are influenced by geographic differences in the prevalence and biology of the disease (ie, areas of increased hepatitis B prevalence) and available resources (organ availability for transplantation, finances, and accessibility to treatment). It is important for both physicians and policy makers to include these considerations when treating patients with HCC as well when structuring policies and guidelines. Cancer 2014;120:2824–2838. © 2014 American Cancer Society.     

ＴＡＣＥ联合索拉非尼治疗中晚期肝细胞肝癌的初步观察

目的：观察经导管肝动脉化疗栓塞（ＴＡＣＥ）联合索拉非尼治疗中晚期肝细胞肝癌（ＨＣＣ）的初步疗效和毒性反应。方法：选取病理证实或临床诊断及符合受试标准的中晚期ＨＣＣ患者１７例,行ＴＡＣＥ治疗,术后口服索拉非尼,４００ｍｇ／次,每日２次,每４～６周根据ＲＥＣＩＳＴ标准进行肿瘤应答的评价,并记录不良反应的发生情况。结果：近期疗效无部分缓解病例,进行独立评价的１２例患者中,共１０例获得疾病稳定。观察时间内的患者总体存活率为７６.５％。１７例患者中不良反应发生率为８２.３％,经相应处理后绝大多数获得明显缓解。结论：ＴＡＣＥ联合索拉非尼治疗中晚期ＨＣＣ患者有可能获得较长的生存时间和疾病稳定状态,安全性好,值得扩大病例进一步观察。     

Interim analysis of START: Study in asia of the combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular carcinoma trial

Transarterial chemoembolization (TACE) represents a first‐line noncurative therapy for hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown to be effective and safe monotherapy in patients with advanced HCC and the current study reports the interim results of a prospective Phase II, open label, trial investigating the safety and efficacy of the combination of sorafenib and conventional TACE in patients from the Asia‐Pacific region with intermediate HCC. Patients with histologically or clinically diagnosed HCC were treated with conventional TACE followed by sorafenib 4 to 7 days later. TACE was performed by selective transarterial chemotherapy in the vessels feeding the tumor with an emulsion of lipiodol (5–20 ml) and doxorubicin (30–60 mg) followed by embolization with absorbable particles (gel foam). TACE/sorafenib cycles were repeated every 6–8 weeks. Primary objectives were to evaluate the safety and tolerability, in addition to the efficacy of TACE combined with sorafenib for HCC. A total of 147 patients were included in the intention‐to‐treat analysis and received at least one dose of sorafenib. Gastrointestinal AEs were reported by 62.6% of patients while 57.8% reported skin AEs although most were mild to moderate. The mean number of cycles undertaken was 2.1 and 63.3% of patients achieved either partial response or stable disease. Clinically, the disease control rate was 91.2% while the overall response rate was calculated as 52.4%. Our study shows that concurrent sorafenib and TACE therapy is safe and effective with no unexpected side effects.     

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.     

阿帕替尼联合肝动脉化疗栓塞治疗中晚期肝癌的疗效及安全性分析

目的:观察阿帕替尼联合肝动脉化疗栓塞（transarterial chemoembolization,TACE）治疗中晚期肝癌的疗效和安全性。方法:纳入2017年3月至2017年9月中晚期肝癌患者40例，给予阿帕替尼联合TACE治疗，按修订的实体瘤疗效评价标准评价治疗效果。结果:在40例病人中，37例可评价疗效，完全缓解1例，部分缓解14例，疾病稳定15例，疾病进展7例，客观缓解率和疾病控制率分别为40.54%和81.08%，中位无进展生存期是6.0个月，与阿帕替尼相关的主要不良反应为高血压、手足综合征、乏力、蛋白尿。结论:阿帕替尼联合TACE治疗中晚期肝癌是安全、有效的，需要更进一步大样本随机对照临床研究来加以验证。     

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.     

Advances in Management of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor and a high impact health problem worldwide. The prevalence of HCC is particularly high in many Asian and African countries. Some HCC patients have no symptoms prior to diagnosis and many of them therefore present at late stage and have a grave prognosis. The well-established causes of HCC are chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection or alcoholic cirrhosis and nonalcoholic steatohepatitis. The Barcelona Clinic Liver Cancer (BCLC) Staging System remains the most widely used for HCC management guidelines. To date, the treatments for HCC are still very challenging for physicians due to limited resources in many parts of the world, but many options of management have been proposed, including hepatic resection, liver transplantation, ablative therapy, chemoembolization, sora nib and best supportive care. This review article describes the current evidence-based management of HCC with focus on early to advance stages that impact on patient overall survival.     

Comparison of hepatocellular carcinoma in Eastern versus Western populations

Hepatocellular carcinoma (HCC) is a heterogeneous disease that remains highly prevalent in many Asian countries and is the second most common cause of cancer‐related mortality worldwide. Significant differences exist between Eastern and Western populations on many key aspects of HCC, contributing to the potential different treatment outcomes and challenges of clinical trial design and data interpretation. In this review, the authors compare HCC in Asia versus the West and highlight 1) differences in terms of epidemiology and trends and their correlation with etiology, 2) differences in genetics and how they relate to underlying etiology, 3) differences in treatment approaches based on existing guidelines and consensus statements, and 4) differences in clinical outcomes for Asian versus non‐Asian patients with HCC in clinical trials and the implications for future clinical trial design. Cancer 2016;122:3430–3446 . © 2016 American Cancer Society     

8cm以上肝癌术后残癌的肝动脉栓塞化疗预后因素分析

目的：了解肝动脉栓塞化疗对直径大于8cm肝癌术后残癌的疗效和影响预后的因素。方法：肝癌切除术后2个月内经超声和动脉造影证实有残癌的肝癌患者，行肝动脉栓塞化疗；采用COX模型研究影响疗效的因素。结果：治疗后1，2，3，4年生存率为74.9%，44.2%，36.8%，18.4%。肝癌切除术后残癌的TNM分期是影响疗效的独立因素（P=0.003)。而原发癌的肿瘤分期，手术方式（局部切除或肝叶切除），肝动脉栓塞化疗的次数，不是影响预后的独立因素。结论：肝癌术后行肝动脉栓塞化疗是可行的，术后残癌的分期是影响肝动脉栓塞化疗效果的主要因素，大体积肿瘤术后尽早行肝动脉栓塞化疗是必要的。     

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic oesophageal cancer: a JSMO–ESMO initiative endorsed by CSCO,KSMO, MOS,SSO and TOS

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of oesophageal cancer was published in 2016, and covered the management and treatment of local/locoregional disease, limited disease, locally advanced disease and the management of advanced/metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic oesophageal cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic oesophageal cancer representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.     

中晚期肝细胞癌的化学免疫疗法

对74例无手术切除指征的中晚期肝细胞癌(HCC)患者采用化学免疫治疗(CIT),即经肝动脉化学栓塞治疗后1～2周,序贯地施行LAK或CD3AK过继免疫治疗,并以同期单用经肝动脉化学栓塞治疗的41例相同患者作对比。结果表明,化学免疫治疗组和经肝动脉化学栓塞治疗组的Ⅱ,Ⅲ期HCC患者的缓解率差异显著,分别为72.4％与40.496(P<0.05)和48.9％与14.3％(P<0.05)。化学免疫治疗和经肝动脉化学栓塞治疗组相比,Ⅲ期HCC患者的半年、1年生存率和Ⅱ期患者的2年生存率差异也显著,分别为62.2％与23.8％(P<0.05),46.0％与9.5％(P<0.05)以及48.3％与15.0％(P<0.05)。化学免疫治疗组1年内肝外转移发生率为25.9％(15/58),明显较经肝动脉化疗栓塞治疗组(58.1％,18/31)为低(P<0.05)。研究结果表明,化学免疫治疗这一有机序贯结合在治疗中晚期肝细胞癌患者方面确属合理、有效的综合治疗方案。     

Clinical study of transarterial chemoembolization combined with 3-dimensional conformal radiotherapy for hepatocellular carcinoma

Background

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Monotherapy is not very effective for intermediate or advanced stage HCC. Efficacy of combined therapy using transarterial chemoembolization (TACE) with three-dimensional conformal radiotherapy (3-DCRT) for advanced HCC should be evaluated.

Methods

HCC patients were selected from our patient database. The sequence of treatments that patients underwent was several courses of TACE followed in 2-4 weeks by 3-DCRT. The median tumor irradiation dose was 44Gy. Toxicity, tumor response, and overall survival rate were analyzed.

Results

140 HCC patients were followed up by the last follow-up time. Among these patients, hepatic toxicities due to treatment were notable in 15 cases. Gastrointestinal bleeding after the overall treatment occurred in 3 cases. Leukopenia of grade III was detected in 1 case. Radiation-induced liver disease (RILD) was observed in 3 patients. Among 140 patients, 27, 97, and 16 cases achieved partial response, stable disease, and progressive disease, respectively. The overall survival rates of 1-year, 3-years, and 5-years were 66%, 29%, and 13%, respectively, with a median survival time of 18 months. Both Child-Pugh grade and radiation dose were determined to be independent predictors for overall survival from multivariate analysis.

Conclusion

The combined modality of TACE and 3-DCRT is a promising treatment for unresectable HCC. A large-scale, prospective randomized trial should be performed to confirm the utility of this combined therapy.