肝动脉化疗栓塞术联合阿帕替尼治疗中晚期原发性肝癌疗效评价

  目的  评价肝动脉化疗栓塞术（transarterial chemoembolization,TACE）联合口服阿帕替尼治疗中晚期肝癌的近期疗效。   方法  收集2016年6月至2016年10月于首都医科大学附属北京友谊医院接受TACE联合口服阿帕替尼250 mg/d治疗的21例中晚期原发性肝癌（hepatocellular carcinoma,HCC）患者的临床资料;采用影像学中最新修订的实体瘤疗效评价标准（modified responseevaluation criteria in solid tumors,mRECIST）,回顾性分析联合治疗1个疗程（平均约28 d）后患者的治疗效果,并对不良反应进行分析。   结果  21例患者中,完全缓解（complete response,CR）3例（14.3%）,部分缓解（patial response,PR）6例（28.6%）,疾病稳定（stable disease,SD）5例（23.8%）。疾病控制率（disease control rate,DCR）为61.9%,客观缓解率（objective rate,ORR）为38.1%。疾病进展（progressive disease,PD）2例（9.5%）。21例患者治疗中出现的不良反应:乏力17例（94.4%）,胃肠道症状14例（66.7%）,手足综合征4例（19.0%）,血压升高4例（19.0%）,并出现不同程度的声音嘶哑、头痛头晕、蛋白尿等。   结论  TACE联合阿帕替尼对中晚期原发性肝癌的临床治疗近期效果满意,治疗过程中不良反应发生率较高,需给予积极处理。      

TACE序贯联合PMCT治疗原发性肝癌的预后因素分析

  目的  分析影响动脉化疗栓塞术(transarterial chemoemlolization, TACE)序贯联合微波凝固消融(percutaneous micro wave coagulation therapy, PMCT)治疗原发性肝癌预后的主要因素。   方法  本研究收集本科收治的97例接受TACE序贯联合PMCT治疗的原发性肝癌患者。对可能影响预后的各变量进行单因素分析, 再利用多因素Cox逐步回归分析影响预后的主要因素。   结果  本组肝癌患者的1、2、3、5年累积生存率分别为68.2%、43.2%、28.8%、13.4%。单因素分析与预后有关的因素为肿瘤大小、临床分期(BCLC)、Child-Pugh分级、门脉癌栓、动静脉瘘、PMCT治疗次数及体力状况(ECOG评分)。Cox逐步回归多因素分析与预后有关并具有显著意义的因素为肿瘤大小、临床分期、门脉癌栓、PMCT治疗次数及体力状况。   结论  适当重复PMCT治疗可以延长肝癌患者的生存期限。大肝癌、门脉癌栓为预后的危险性因素, 巨块型肝癌及伴门脉主干癌栓患者的中位生存时间明显缩短。      

The outcomes of elderly patients with hepatocellular carcinoma treated with transarterial chemoembolization

BACKGROUND:

The authors evaluated and compared the treatment outcomes of transarterial chemoembolization (TACE) between young (≤70 years) and elderly (>70 years) patients at their institute over an 18‐year period.

METHODS:

Advanced hepatocellular carcinoma (HCC) patients who received TACE at the authors' center were analyzed retrospectively. The demographic data, TACE‐related morbidities, and survival outcome were compared between these 2 age groups.

RESULTS:

Between 1989 and 2006, 843 patients who were ≤70 years old and 197 patients who were >70 years old received TACE treatment for advanced HCC. There were significantly more comorbid illnesses associated with the elderly patients than the young patients (64 % vs 33%, P < .01). Moreover, elderly patients who received TACE treatment for HCC were at earlier stages of disease (P < .01). Both the overall median survival (14.0 months vs 8.1 months, P < .003) and disease‐specific survival (15.2 months vs 8.7 months, P < .001) were significantly higher in elderly than young patients. The most commonly encountered TACE‐related morbidity in both age groups was liver function derangement. Young patients had a significantly higher rate of developing liver derangement after TACE than elderly patients (21% vs 11%, P < .01). Conversely, the elderly patients had a significantly higher rate of developing peptic ulcer disease with TACE treatment than young patients (2.5% vs 0.5%, P = .01). Overall, there was no significant difference in TACE‐related mortality between the young and elderly patients (3% vs 4%, P = .49).

CONCLUSIONS:

This study has confirmed the comparable efficacy and tolerability in using TACE for the treatment of advanced HCC in young and elderly patient populations. Cancer 2009. © 2009 American Cancer Society.     

TACE联合抗血管生成药治疗肝癌的研究进展

肝癌是最常见、最致命的恶性肿瘤之一。肝动脉化疗栓塞（transarterial chemoembolization,TACE）是公认的肝癌非手术治疗中最常用的方法之一。TACE在阻断肿瘤组织血供的同时,也增加了肿瘤血管再生及形成侧支循环的风险。新生血管与恶性肿瘤的发生和发展关系密切。抗血管生成药能抑制血管内皮细胞的迁移和增殖,从而抑制肿瘤的生长。本文就TACE联合抗血管生成药治疗肝癌的进展进行综述。     

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。     

TACE versus TAE as therapy for hepatocellular carcinoma

Transarterial chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, best anticancer agent and best technique are still unclear. TACE may not be better than transarterial embolization (TAE). HCC is very chemoresistant, thus embolization may be more important than chemotherapy. Lipiodol cannot be considered as an embolic agent and there are no data to show that it can release chemotherapeutic agents slowly. It can mask residual vascularity on CT imaging and its use is not recommended. Both TACE and TAE result in hypoxia, which stimulates angiogenesis, promoting tumor growth; thus combination of TACE with antiangiogenic agents may improve current results. To date, there is no evidence that TACE pre-liver transplantation or resection helps to expand current selection criteria for patients with HCC, nor results in less recurrence after surgery. Combination with other techniques, such as radiofrequency ablation and drugs, may enhance the effect of TACE. New trials are being conducted to clarify these issues.     

Stereotactic body radiation therapy for nonpulmonary primary tumors

Stereotactic body radiation therapy (SBRT) represents a novel treatment modality for cancer and has been used to treat various types of primary cancer with curative intent. Data on the use of SBRT for various primary sites are emerging. While the largest body of data is concerned with early-stage lung cancer, there is also a fair amount of experience in the treatment of nonpulmonary primary sites with SBRT. This article will provide an overview of radiobiologic, technical and clinical aspects of the use of this emerging treatment modality for various nonpulmonary primary tumors.     

A preclinical study on the combination therapy of everolimus and transarterial chemoembolization in hepatocellular carcinoma

Transarterial chemoembolization (TACE) is commonly used for the treatment of locally advanced hepatocellular carcinoma (HCC) by its dual effects of chemotherapy and ischemic hypoxia. However, one of the side effects of TACE is the introduction of hypoxic condition, which in turn activates hypoxia-induced survival pathways and enhances VEGF-induced neovascularization by stabilizing HIF-1α expression. Herein, the preclinical therapeutic efficacy of the combined treatment of everolimus, a novel mTOR inhibitor and TACE for the treatment of HCC was investigated. The MHCC-97L cells were used for the study of the effect of combined treatment on cell proliferation and cellular apoptosis. HUVEC cells were used for the study on tube formation under different treatments. Inhibitions on the Akt/mTOR pathways were also studied. Finally, the effect on tumor growth was further study using an in vivo orthotopic model. The results demonstrated that everolimus enhanced the therapeutic efficacy of TACE in inhibiting cell proliferation, promoting apoptosis and inhibiting tube formation of endothelial cells by blocking the Akt/mTOR signaling pathway in vitro and inhibiting tumor growth and neoangiogenesis in vivo. Based on this preclinical study, the potential of combining everolimus with TACE was guaranteed which suggested the use of the combination therapy in the clinical treatment of advanced HCC patients.     

Stereotactic body radiation therapy for metastasis to the adrenal glands

Many primary cancers can metastasize to the adrenal glands. Adrenalectomy via an open or laparoscopic approach is the current definitive treatment, but not all patients are eligible or wish to undergo surgery. There are only limited studies on the use of conventional radiation therapy for palliation of symptoms from adrenal metastasis. However, the advent of stereotactic body radiation therapy (SBRT) – also named stereotactic ablative radiotherapy for primary lung cancer, metastases to the lung, and metastases to the liver – have prompted some investigators to consider the use of SBRT for metastases to the adrenal glands. This review focuses on the emerging data on SBRT of metastasis to the adrenal glands, while also providing a brief discussion of the overall management of adrenal metastasis.     

Gelatin sponge microparticles for transarterial chemoembolization combined with regorafenib in hepatocellular carcinoma: a single-center retrospective study

BackgroundThe treatment of advanced hepatocellular carcinoma (HCC) is challenging. The positive effect of gelatin sponge microparticles for transarterial chemoembolization (GSMs-TACE) in the treatment of Barcelona Clinic Liver Cancer (BCLC) stage C and large HCC has been confirmed by previous studies. This study initially explored the efficacy and safety of GSMs-TACE combined with regorafenib in patients with unresectable HCC who failed first-line sorafenib and/or lenvatinib therapy.MethodsThis retrospective study collated the data of patients who presented at the Affiliated Zhongshan Hospital of Dalian University between December 2018 and June 2021. Patients were treated with GSMs-TACE, followed by regorafenib 1 week later. Follow-up was conducted every 3 to 5 weeks after combination therapy. If the treatment was changed due to disease progression, the patients were followed up every 3 months to obtain overall survival (OS) time. The OS, progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) was used to evaluate the efficacy of the treatment, while adverse events (AEs) was used to assess its safety.ResultsA total of 47 patients were included in the study. The age of patients was 64.4±6.8 years; There were 43 (91.5%) males and 4 (8.5%) females; the number of Child-Pugh grade A was 22 (46.8%) and B was 25 (53.2%); the longest tumor diameter was 5.1 cm [interquartile range (IQR), 3.8, 8.9 cm]; the number of BCLC grade B was 14 (29.8%) and grade C was 33 (70.2%). The median follow-up time was 11.6 months [95% confidence interval (CI): 10.8 to 14.0 months]. The median number of GSMS-TACE sessions was 3. The initial doses of regorafenib were 80 mg/d (n=17, 36.2%), 120 mg/d (n=23, 48.9%), and 160 mg/d (n=7, 14.9%). The median PFS was 6.0 months (95% CI: 4.5 to 7.5 months), and the median OS was 14.3 months (95% CI: 11.8 to 16.8 months). The ORR and DCR were 21.3% and 85.1%, respectively. The incidence of grade 3/4 AEs was 8 out of 47 patients (17.0%).ConclusionsThe study indicated that GSMs-TACE combined with regorafenib may be efficient and safe in patients with unresectable HCC. Future prospective large-scale studies should be conducted to verify these results.     

Stereotactic body radiation therapy for liver metastases

Over the years, early diagnosis of metastatic disease has improved and the prevalence of oligometastatic patients is increasing. Liver is a most common site of progression from gastrointestinal, lung and breast cancer and in the setting of oligometastatic patients, surgical resection is associated with increased survival. Approximately 70-90% of liver metastases, however, are unresectable and an effective and safe alternative therapeutic option is necessary for these patients. The role of stereotactic body radiation therapy (SBRT) was investigated in the treatment of oligometastatic patients with promising results, thanks to the ability of this procedure to deliver a conformal high dose of radiation to the target lesion and a minimal dose to surrounding critical tissues. This paper was performed to review the current literature and to provide the practice guidelines on the use of stereotactic body radiotherapy in the treatment of liver metastases. We performed a literature search using Medical Subject Heading terms “SBRT” and “liver metastases”, considering a period of ten years.     

Hepatic resection alone versus in combination with pre- and post-operative transarterial chemoembolization for the treatment of hepatocellular carcinoma: A systematic review and meta-analysis

Background and Aims

The prognosis of hepatocellular carcinoma (HCC) treated with hepatic resection may be improved by the adjunctive use of transarterial chemoembolization (TACE). This study aimed to systematically compare the outcomes between hepatic resection with and without TACE groups.

Methods

All relevant randomized controlled trials (RCTs) and non-RCTs were searched by the PubMed, EMBASE, and Cochrane Library databases. Overall survival (OS) and disease-free survival (DFS) were two major outcomes. Meta-analyses were performed according to the timing of TACE (pre- or post-operative TACE). Subgroup analyses were also performed. Hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated.

Results

Overall, 55 papers were included (14 RCTs and 41 non-RCTs). Overall meta-analyses demonstrated that OS and DFS were statistically similar between hepatic resection with and without pre-operative TACE groups (HR = 1.01, 95%CI = 0.87–1.19, P = 0.87; HR = 0.91, 95%CI = 0.82–1.01, P = 0.07). Subgroup analyses of RCTs or non-RCTs showed that OS and DFS remained statistically similar between hepatic resection with and without pre-operative TACE groups. Subgroup analysis of incomplete or no tumor necrosis showed that OS was worse in hepatic resection with pre-operative TACE group than in hepatic resection without pre-operative TACE group. By contrast, subgroup analysis of complete tumor necrosis showed that DFS was better in hepatic resection with pre-operative TACE group than in hepatic resection without pre-operative TACE group.Overall meta-analyses demonstrated that OS and DFS were better in hepatic resection with post-operative TACE group than in hepatic resection without post-operative TACE group (HR = 0.85, 95%CI = 0.72–1.00, P = 0.06; HR = 0.83, 95%CI = 0.73–0.94, P = 0.004). Subgroup analyses of RCTs, vascular invasion, or large HCC showed that OS and DFS remained better in hepatic resection with post-operative TACE group than in hepatic resection without post-operative TACE group. By contrast, subgroup analyses of non-RCTs, no vascular invasion, or small HCC showed that OS and DFS were statistically similar between the two groups.

Conclusions

Post-operative TACE, rather than pre-operative TACE, may be considered as an adjunctive treatment option for HCC treated with hepatic resection.     

Stereotactic body radiation therapy in patients with hepatocellular carcinoma: A mini-review

Stereotactic body radiation therapy (SBRT) is an emerging treatment for hepatocellular carcinoma. This technique results in excellent local control rates with favorable toxicity profile despite being predominantly used in heavily pretreated patients or those unsuitable for other local therapies. SBRT may be used as a sole treatment or in combination with other local therapies as well as a bridging strategy for patient awaiting liver transplants. This brief review describes current practice of SBRT with respect to radiation technique, patient selection and treatment concepts. It summarizes available evidence from retro- and prospective studies evaluating SBRT alone, SBRT in combination with other treatments and SBRT compared to other local treatment approaches.