Regional Therapies for Colorectal Liver Metastases: Systematic Review and Clinical Practice Guideline

BackgroundResection is the foundation for cure for colorectal cancer (CRC) liver metastases; however, only 20% of patients are suitable for surgery. Those suitable would be considered for resection or local therapies before being considered for regional therapies. Noncurative treatment is usually systemic chemotherapy. For patients with liver-only or liver-predominant metastases that are unresectable, regional therapies [conventional transarterial chemoembolization (cTACE), drug-eluting bead transarterial chemoembolization (DEB-TACE), and transarterial radioembolization (TARE)] may be considered. We review the current evidence for regional therapies for CRC liver metastases.Patients and MethodsLiterature searches (January 2000 to March 2019 or January 2010 to March 2019 depending on the specific systematic review question) were conducted, including Medline, Embase, Cochrane Library, and 2018 American Society of Clinical Oncology (ASCO) abstracts.ResultsA total of 4100 articles were identified; 15 studies were included in the review. There were no comparative data regarding the resectable population. There was either insufficient evidence (cTACE or DEB-TACE) or evidence against (TARE) the addition of regional therapies to systemic therapy in the first line in the unresectable population. There was either no evidence (cTACE) or weak evidence (DEB-TACE or TARE) for the addition of regional therapies with or without systemic therapy in the second line or later in the unresectable population.ConclusionLimited evidence supports the delivery of percutaneous regional therapies in patients with unresectable CRC liver metastases. There are strong data demonstrating positive effects of TARE within the liver, but they do not translate to a benefit in patient-important outcomes. DEB-TACE appears to offer a survival benefit in the second-line setting, although the evidence is limited by small sample size and larger trials are needed.     

大分割三维适形放疗联合化疗治疗中晚期肝癌45例疗效分析

 目的 探讨大分割三维适形放射治疗联合化疗治疗中晚期肝癌的疗效。 方法 对45例不能手术的中晚期肝癌患者进行介入治疗两次, 其中22例结合大分割三维适形放射治疗, 采用6MV X线, 单剂量为3~5Gy, 隔日1次,总剂量为DT 45～55Gy 23例单纯介入治疗。 结果 大分割三维适形放疗联合介入治疗组近期有效率(CR+PR)为85.7%,对照组为52.3%,两组差异有统计学意义;1、2、3年的生存率联合治疗组为68.7%,56.8%, 39.8%,对照组为51.2%, 28.7%, 15.7%,两者差异有统计学意义。两组间不良反应差异无统计学意义(P>0.05）。 结论 对于不能手术切除的中晚期肝癌患者, 大分割3DCRT结合TACE有较好的疗效,不良反应可以耐受。     

肝细胞癌TACE治疗中C臂CT扫描方法和应用范围的探索

目的探索肝细胞癌（HCC）动脉化疗栓塞治疗（TACE）过程中采用C臂CT的扫描方法及其应用范围。方法80例HCC患者于2012年9月至2013年3月在我院接受TACE治疗时行C臂CT扫描。以指导介入操作和评估TACE疗效为目的,探索C臂CT扫描方法,评价C臂CT的应用范围。结果在TACE治疗HCC中,C臂CT扫描使用稀释的非离子型造影剂,采用平扫、动脉早期、动脉实质期三个时相扫描,可以满足病灶的检出、供血动脉显示、异常供血动脉和动脉异常走行的显示需要,可以便捷、准确、全面地评估病灶存活肿瘤、碘油沉积、供血动脉栓塞是否完全等情况,即时评价TACE疗效的效果满意。C臂CT扫描未明显增加X线辐射剂量,手术时间平均延长9.5min。结论在TACE治疗HCC过程中应用C臂CT扫描安全、有效,对于术前制定计划、术中指导操作以及术后即时评估疗效等有较大帮助。     

Metastatic disease to the liver: Locoregional therapy strategies and outcomes

Secondary cancers of the liver are more than twenty times more common than primary tumors and are incurable in most cases. While surgical resection and systemic chemotherapy are often the first-line therapy for metastatic liver disease, a majority of patients present with bilobar disease not amenable to curative local resection. Furthermore, by the time metastasis to the liver has developed, many tumors demonstrate a degree of resistance to systemic chemotherapy. Fortunately, catheter-directed and percutaneous locoregional approaches have evolved as major treatment modalities for unresectable metastatic disease. These novel techniques can be used for diverse applications ranging from curative intent for small localized tumors, downstaging of large tumors for resection, or locoregional control and palliation of advanced disease. Their use has been associated with increased tumor response, increased disease-free and overall survival, and decreased morbidity and mortality in a broad range of metastatic disease. This review explores recent advances in liver-directed therapies for metastatic liver disease from primary colorectal, neuroendocrine, breast, and lung cancer, as well as uveal melanoma, cholangiocarcinoma, and sarcoma. Therapies discussed include bland transarterial embolization, chemoembolization, radioembolization, and ablative therapies, with a focus on current treatment approaches, outcomes of locoregional therapy, and future directions in each type of metastatic disease.     

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.     

复合型栓塞剂在肝癌介入治疗中的价值

目的 探讨在肝癌的介入治疗中复合型栓塞剂的价值。方法 将原发性肝癌患者188例分为常规组103例,复合组85例。观察并比较两组的碘油沉积、有效率、手术切除、病理改变、生存率和并发症。结果 在巨块型、结节型的多血供肝癌患者中,碘油沉积表现为完全填充型和致密型。常规组和复合组碘油沉积分别为59．2％和89．4％;有效率（CR＋PR）两组分别为32．0％和56．5％;手术切除率分别为5．8％和15．3％;肿瘤完全坏死率分别为1．0％和4．7％。常规组1,2,3年生存率分别为57．7％、42．8％和8．4％,复合组1,2,3年生存率分别为79．8％、55．3％和38．5％,两组比较,差异有统计学意义。并发症两组间基本相同。结论 肝癌患者的介入治疗疗效与栓塞剂的用量及种类相关。对于巨块型、结节型的多血供肝癌患者,应提倡超选择复合栓塞治疗;少血供、弥漫型和不能超选择插管的肝癌患者应常规治疗。     

TACE联合冷循环PMCT治疗原发性肝癌的临床应用

目的：评价肝动脉化疗栓塞（TACE）联合冷循环经皮微波凝固治疗（PMCT）原发性肝癌的临床疗效。方法：71例确诊为原发性肝癌的患者,分期是Ⅰa～Ⅲa,随机分为治疗组（PMCT和TACE联合治疗组）33例,对照组（TACE组）38例。治疗组患者先行TACE治疗,2～4周后根据复查的AFP和CT/MR等的影像学检查决定再次行TACE或者PMCT。随访时间5～48个月（平均25.5个月）,随访内容包括AFP、肝功能、影像学资料、并发症等。根据随访的生存时间、复发情况作统计学分析。结果：治疗组和对照组治疗的肝癌患者的1、2、3年累积生存率分别是84.23%、72.29%、61.96%和55.84%、22.79%、11.40%,治疗组和对照组治疗的肝癌患者的6个月、12个月、24个月累积复发率分别6.06%、9.09%、24.24%和7.89%、31.57%、60.52%。TACE联合PMCT治疗肝癌没有严重并发症,对肝功能的损害轻。治疗组33例有5例合并动静脉瘘（AVF）,经动脉栓塞治疗后2例AVF消失,3例治疗后效果不理想的患者行PMCT后AVF消失。结论：本组研究初步显示,TACE联合PMCT治疗原发性肝癌是安全、有效、可行的方法,在治疗原发性肝癌的临床应用近、中期的效果好。PMCT提供了治疗肝癌合并AVF新的方法。     

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.     

原发性肝细胞癌局部介入治疗新进展

原发性肝细胞癌是全球第6大常见恶性肿瘤，肿瘤相关性死亡中排名第三。我国肝癌发病率和病死率在男性和女性中均位列前五，且呈逐年上升趋势，而就诊时可手术切除的患者不到30%。随着医学技术的不断发展，介入治疗已在肝癌治疗中发挥着关键性作用。本文将重点对经动脉化疗栓塞、经动脉放射栓塞、经皮射频消融、微波消融等介入治疗方式，以及介入治疗与分子靶向、免疫联合治疗方面的最新进展作一综述。     

Transarterial chemoembolization <i>vs.</i> liver resection as initial treatment for hepatocellular carcinoma occurring exclusively in caudate lobe: A retrospective propensity matching analysis

Treatment of hepatocellular carcinoma (HCC) in the caudate lobe is technically challenging. This retrospective study was designed to evaluate the clinical outcome of both superselective transcatheter arterial chemoembolization (TACE) and liver resection (LR) for HCC occurring exclusively in the caudate lobe. From January 2008 to September 2021, a total of 129 patients were diagnosed with HCC of the caudate lobe. The Cox proportional hazard model was used to analyze the potential clinical factors and established prognostic nomograms with interval validation. Of the total number of patients, 78 received TACE and 51 received LR. The overall survival (OS) rates (TACE vs. LR) at 1, 2, 3, 4, and 5 years were 83.9% vs. 71.0%; 74.2% vs. 61.3%; 58.1% vs. 48.4%; 45.2% vs. 45.2%; and 32.3% vs. 25.0%, respectively. However, subgroup analysis revealed that TACE was superior to LR for treating patients with stage IIb Chinese liver cancer (CNLC-IIb) in the entire cohort (p = 0.002). Interestingly, no difference was found between TACE and LR in the treatment outcomes of CNLC-IIa HCC (p = 0.6). Based on Child-Pugh A and B calculations, TACE tended to lead to a better OS than LR (p = 0.081 and 0.16, respectively). Multivariate analysis showed that Child-Pugh score, CNLC stage, ascites, alpha fetoprotein (AFP), tumor size, and anti-HCV are related to OS. Predictive nomograms for 1, 2, and 3 years were performed. Based on this study, TACE may provide a longer OS than liver resection for patients with CNLC-IIb HCC of the caudate lobe. Because this suggestion is limited by the study design and relatively small sample size, additional randomized controlled trials are needed.     

Advanced age is not a contraindication for liver resection in cases of large hepatocellular carcinoma

Background

The role of surgery in the management of large hepatocellular carcinomas (HCCs) is controversial. Advanced age and comorbidities are taken into account when major surgery is considered.

Purpose

To compare the outcomes of liver resection (LR) and transarterial chemoembolization (TACE) for resectable HCC in patients aged 70 years or older.

Patients and materials

This study included 70 patients aged 70 years or older treated for large HCCs (≥5 cm) between January 2007 and December 2012: 37 underwent LR and 33 underwent TACE. The outcomes of these patients were retrospectively analyzed. Univariate and multivariate Cox proportional hazard models were established. Kaplan–Meier survival curves were generated, and survival data were compared using the log-rank test.

Results

Hospital stay was significantly longer in the LR group than in the TACE group (10 days vs 8.5 days; P = 0.003). Treatment-related complications were more frequent in the TACE group, but this difference was not statistically significant. LR was associated with a better disease-free survival rate, median survival rate and cumulative overall survival rate.

Conclusion

Our results showed that LR could be a safe and effective treatment option for HCC tumors ≥5 cm in patiets aged 70 years or older.     

经导管肝动脉化疗栓塞联合索拉非尼治疗中晚期肝细胞癌的临床观察

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癌的有效性和安全性.方法 40例已接受过TACE治疗的中晚期肝细胞癌患者口服索拉非尼单药治疗,400mg,2次/d,直至病情进展或出现不可耐受的毒性反应.按照实体瘤疗效评价标准(RECIST)评价疗效,按照美国国立癌症研究所常见毒性事件标准(NCI-CTCAE)评价不良反应.结果 40例中晚期肝细胞癌患者中,获得完全缓解1例,部分缓解7例,疾病稳定19例,疾病进展13例,疾病控制率为67.5%.全组患者的生存时间为1～18个月,1年生存率为54.0%.主要不良反应为手足皮肤反应,其次是腹泻和血小板计数降低.结论 TACE联合索拉非尼治疗中晚期肝细胞癌是有效和安全的.     

Sorafenib With and Without Transarterial Chemoembolization for Advanced Hepatocellular Carcinoma With Main Portal Vein Tumor Thrombosis: A Retrospective Analysis

Background.

The survival benefit of combining sorafenib and transarterial chemoembolization (TACE) therapy compared with sorafenib monotherapy for patients with advanced hepatocellular carcinoma (HCC) and main portal vein tumor thrombosis (MPVTT) is unclear.

Methods.

Between January 2009 and June 2013, 183 consecutive patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) and MPVTT were retrospectively reviewed. Of these, 89 patients with advanced HCC and MPVTT were enrolled in this study: 45 were treated with combination therapy (sorafenib-TACE group), and the other 44 treated with sorafenib monotherapy (sorafenib group).

Results.

The mean number of TACE sessions per patient was 2.6 (range: 1–5). The median duration of sorafenib in the sorafenib-TACE group and sorafenib group was 5.6 months and 5.4 months, respectively. The disease control rate was similar between the two groups. Median time to progression was 3.0 months (95% confidence interval [CI]: 2.2, 3.7) in the sorafenib-TACE group, and 3.0 months (95% CI: 2.1, 3.8) in the sorafenib group (p = .924). Median overall survival was 7.0 months (95% CI: 6.1, 7.8) and 6.0 months (95% CI: 4.7, 7.3) in the sorafenib-TACE group and the sorafenib group, respectively (p = .544). The adverse events related to sorafenib were comparable between the two groups. Twenty-one adverse events of grade 3–4 related to TACE occurred in 12 patients (26.7%), and 2 of them died (4.4%).

Conclusion.

This study demonstrated no advantage of combination therapy over sorafenib monotherapy. Considering the patients’ morbidity after TACE, sorafenib monotherapy is appropriate for managing patients with advanced HCC and MPVTT.

Implications for Practice:

For patients with advanced hepatocellular carcinoma (HCC) and main portal vein tumor thrombosis (MPVTT), no benefit was seen in this study in terms of disease control rate, time to progression, and overall survival for patients receiving sorafenib and transarterial chemoembolization compared with those receiving sorafenib monotherapy. Considering the patients’ morbidity after combination therapy, monotherapy is appropriate for managing patients with advanced HCC and MPVTT.     

盐酸格拉司琼预防肝癌患者介入治疗后恶心呕吐的疗效观察

目的探讨盐酸格拉司琼对预防肝癌患者介入治疗后引起的恶心、呕吐的疗效。方法将60例行介入治疗的患者随机分为格拉司琼治疗组（治疗组）和胃复安＋安定对照组（对照组）。治疗组在介入治疗术中未灌注化疗药物前，通过导管向动脉内注射盐酸格拉司琼。对照组在介入治疗术前30min肌注胃复安和安定。观察2组患者术后的恶心、呕吐等不良反应。结果盐酸格拉司琼组的止吐疗效明显高于对照组，2组比较有显著性差异（P〈0．05）；治疗组其他不良反应发生次数明显少于对照组。结论盐酸格拉司琼对介入化疗栓塞术患者是有效的止吐药物，值得临床推广应用。