Nonsurgical management of advanced hepatocellular carcinoma: a clinical practice guideline

Background Practice guidelines based on a systematic review of the literature regarding the nonsurgical management of hepatocellular carcinoma (hcc) in North America are lacking. Resection and transplantation are the foundations for cure of hcc; however, most patients are diagnosed at an advanced stage, precluding those curative treatments. A number of local or regional therapies are used and are followed by systemic therapy for advanced or progressive disease. Other treatments are available, but their efficacy, compared with those standards, is not well known. Methods First, systematic review questions were developed. Literature searches of the medline, embase, and Cochrane library databases (January 2000 to July 2018 or January 2005 to July 2018 depending on the question) were conducted; in addition, abstracts from the 2018 annual meeting of the American Society of Clinical Oncology were reviewed. A practice guideline was drafted that was then scrutinized by internal and external reviewers. Results Seventy-seven studies were included in the guideline: no guidelines, two systematic reviews, and seventyfive primary studies published in full (including one pooled analysis). Five recommendations were developed. Conclusions There is no evidence for or against the use of local or regional interventions other than transarterial chemoembolization for the treatment of intermediate- or advanced-stage hcc. Furthermore, there is no evidence to support the addition of sorafenib to any local or regional therapy. Sorafenib or lenvatinib are recommended for firstline systemic treatment of intermediate-stage hcc. Regorafenib or cabozantinib provide survival benefits when given as second-line treatment. Antiviral treatment is recommended in individuals with advanced hcc who are positive for the hepatitis B surface antigen.

Download Full-text

Health economic evaluation of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma: a systematic review

Cost Effectiveness and Resource Allocation ◽

10.1186/s12962-019-0198-z ◽

2020 ◽

Vol 18 (1) ◽

Cited By ~ 2

Author(s):

Haiyin Wang ◽

Chunlin Jin ◽

Liang Fang ◽

Hui Sun ◽

Wendi Cheng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Economic Evaluation ◽

Cost Effectiveness ◽

Stereotactic Body Radiotherapy ◽

Health Economic Evaluation ◽

Cochrane Library ◽

Economic Evaluations ◽

Advanced Hepatocellular Carcinoma ◽

Noninvasive Treatment

AbstractStereotactic body radiotherapy (SBRT) is a novel noninvasive treatment for hepatocellular carcinoma. SBRT can achieve effective local control, but it requires a relatively high input of resources; this systematic review was performed to assess the cost effectiveness of SBRT in the treatment of hepatocellular carcinoma to provide a basis for government pricing and medical insurance decision-making. The PubMed, EMBASE, Cochrane Library, CNKI, Wanfang and SinoMed databases were searched to collect economic evaluations of SBRT for the treatment of hepatocellular carcinoma from the date of database inception through December 31, 2018. Two reviewers independently screened the studies, extracted the data and performed a descriptive analysis of the basic characteristics, methods of economic evaluation and main results, as well as the quality and heterogeneity of the reports. A total of 5 studies were included. Among them, the level of heterogeneity was relatively acceptable, with a median score of 90%. Four studies were cost-utility analyses (CUAs), and 1 was a cost-effectiveness analysis (CEA). The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was US $114,795 per quality-adjusted life year gained (cost/QALY) in patients with advanced hepatocellular carcinoma. The ICER for proton beam therapy compared to SBRT was US $6465 in patients with inoperable advanced hepatocellular carcinoma. The ICER for SBRT compared to RFA was US $164,660 for patients with unresectable colorectal cancer (CRC) with liver metastases and US $56,301 for patients with early-stage hepatocellular carcinoma. For patients with inoperable localized hepatocellular carcinoma, compared with RFA–SBRT therapy, the ICERs for SBRT–SBRT and SBRT–RFA were US $558,679 and US $2197,000, respectively; RFA–RFA was dominated. In conclusion, there is limited evidence suggesting that SBRT could be cost-effective for highly specific subpopulations of HCC patients, and further economic evaluations based on randomized controlled trials (RCTs) or cohort studies are needed.

Download Full-text

Adjuvant Transarterial Chemoembolization Following Curative-Intent Hepatectomy Versus Hepatectomy Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cancers ◽

10.3390/cancers13122984 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2984

Author(s):

Stepan M. Esagian ◽

Christos D. Kakos ◽

Emmanouil Giorgakis ◽

Lyle Burdine ◽

J. Camilo Barreto ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Randomized Controlled Trials ◽

Transarterial Chemoembolization ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Controlled Trials ◽

Curative Intent ◽

Randomized Controlled

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.

Download Full-text

Therapies for advanced stage hepatocellular carcinoma with macrovascular invasion or metastatic disease: A systematic review and meta-analysis

Hepatology ◽

10.1002/hep.29486 ◽

2017 ◽

Vol 67 (1) ◽

pp. 422-435 ◽

Cited By ~ 64

Author(s):

Richard S. Finn ◽

Andrew X. Zhu ◽

Wigdan Farah ◽

Jehad Almasri ◽

Feras Zaiem ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Metastatic Disease ◽

Meta Analysis ◽

Advanced Stage

Download Full-text

Multidisciplinary Treatment of Advanced Hepatocellular Carcinoma

Case Reports in Gastroenterology ◽

10.1159/000506185 ◽

2020 ◽

Vol 14 (1) ◽

pp. 98-102

Author(s):

Zhe Yang ◽

Bulat Abdrakhimov ◽

Shuo Wang ◽

Qin-Fen Xie ◽

Shu-Sen Zheng

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Pulmonary Resection ◽

Multidisciplinary Treatment ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Stage ◽

Receive Treatment

Current strategy for treatment of hepatocellular carcinoma (HCC) based on Barcelona-Clinic Liver Cancer (BCLC) criteria dictates that patients with advanced-stage HCC are to only receive treatment with tyrosine kinase inhibitors. However, they prolong overall survival just by slightly more than 6 months. In this article, we present a patient with HCC diagnosed at an advanced stage who received multidisciplinary treatment consisting of transarterial chemoembolization, hepatic resection, pulmonary resection, radiofrequency ablation, tyrosine kinase inhibitors, and radiotherapy, and has survived for more than 2 years since diagnosis and counting.

Download Full-text

Systematic review with meta-analysis: effectiveness of direct-acting antiviral treatment for hepatitis C in patients with hepatocellular carcinoma

Alimentary Pharmacology & Therapeutics ◽

10.1111/apt.15598 ◽

2019 ◽

Vol 51 (1) ◽

pp. 34-52 ◽

Cited By ~ 5

Author(s):

Sichan He ◽

Ian Lockart ◽

Maryam Alavi ◽

Mark Danta ◽

Behzad Hajarizadeh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Hepatitis C ◽

Meta Analysis ◽

Antiviral Treatment ◽

Direct Acting Antiviral ◽

Direct Acting

Download Full-text

Efficacy and Safety of Bevacizumab for the Treatment of Advanced Hepatocellular Carcinoma: A Systematic Review of Phase II Trials

PLoS ONE ◽

10.1371/journal.pone.0049717 ◽

2012 ◽

Vol 7 (12) ◽

pp. e49717 ◽

Cited By ~ 39

Author(s):

Ping Fang ◽

Jin-hua Hu ◽

Zhi-gang Cheng ◽

Zhe-feng Liu ◽

Jin-liang Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Phase Ii ◽

Advanced Hepatocellular Carcinoma ◽

Efficacy And Safety ◽

Phase Ii Trials

Download Full-text

Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio as Prognostic Predictors for Hepatocellular Carcinoma Patients with Various Treatments: a Meta-Analysis and Systematic Review

Cellular Physiology and Biochemistry ◽

10.1159/000485396 ◽

2017 ◽

Vol 44 (3) ◽

pp. 967-981 ◽

Cited By ~ 59

Author(s):

Jun Zheng ◽

Jianye Cai ◽

Hui Li ◽

Kaining Zeng ◽

Liying He ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Meta Analysis ◽

Palliative Therapy ◽

Neutrophil To Lymphocyte Ratio ◽

Cochrane Library ◽

Platelet To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Poor Outcomes ◽

The Cochrane Library

Background/Aims: Systemic inflammatory response (SIR) is widely considered as a preoperative risk factor for hepatocellular carcinoma (HCC) outcomes. The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), two of the prognostic indices, have been investigated in post-therapeutic recurrence and survival of HCC. Here, we quantify the prognostic value of these two biomarkers and evaluate their consistency in different HCC therapies. Methods: A systematic review of electronic database of the Web of Science, Embase, PubMed and the Cochrane Library was conducted to search for associations between the NLR and PLR in the blood and clinical outcomes of HCC. Overall survival (OS) and recurrence-free survival (RFS) were the primary outcomes, and hazard ratios (HRs) and 95% confidence intervals (95% CIs) were explored as effect measures. Subgroup analyses were performed to explore the heterogeneity of different therapies. Results: A total of 24 articles comprising 6318 patients were included in the meta-analysis. Overall, the pooled outcomes revealed that a high NLR before treatment predicted a poor OS (HR: 1.54, 95% CI: 1.34 to 1.76, p<0.001) and poor RFS (HR: 1.45, 95% CI: 1.16 to 1.82, p=0.001). Moreover, an increased PLR predicted a poor OS (HR: 1.63, 95% CI: 1.34 to 1.98, p<0.001) and earlier HCC recurrence (HR: 1.52, 95% CI: 1.21 to 1.91, p<0.001). In addition, both the NLR and PLR were identified as independent risk factors for predicting OS and RFS in HCC patients in a subgroup analysis of different treatment types, including curative or palliative therapy; however, these results were not found in the sorafenib subgroup due to limited clinical research. Conclusion: An increased NLR or PLR indicated poor outcomes for patients with HCC. The NLR and PLR may be considered as reliable and inexpensive biomarkers for making clinical decisions regarding HCC treatment.

Download Full-text