Efficacy and safety of various primary treatment strategies for very early and early hepatocellular carcinoma: a network meta-analysis

Abstract Background Several treatments are available for treatment of early and very early-stage Hepatocellular Carcinoma, also known as small Hepatocellular Carcinoma (SHCC). However, there is no consensus with regards to the efficacies of these methods. We aimed at identifying the most effective initial treatment strategy for SHCC through Bayesian network meta-analyses. Methods Studies published between January, 2010, and February, 2021 were searched in EMBASE, Cochrane Library, PubMed and Web of science databases, and conference proceedings for trials. The included studies reported the survival outcomes of very early and early Hepatocellular Carcinoma patients subjected to radiofrequency ablation (RFA), microwave ablation (MWA), surgical resection (SR), transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), minimally invasive liver surgery (MIS), stereotactic body radiotherapy (SBRT) and cryoablation (CA). Then, data were extracted from studies that met the inclusion criteria. Patient survival data were retrieved from the published Kaplan–Meier curves and pooled. A Bayesian random-effects model was used to combine direct and indirect evidence. Results A total of 2058 articles were retrieved and screened, from which 45 studies assessing the efficacies of 8 different treatments in 11,364 patients were selected. The included studies had high methodological quality. Recurrence free survival* (progression/recurrence/relapse/disease/tumor-free survival were combined and redefined as RFS*) and overall survival (OS) outcomes were highest in MIS-treated patients (HR 0·57, 95% confidence intervals [CI] 0·38–0·85; HR 0.48,95% CI 0.36–0.64, respectively), followed by SR-treated patients (HR 0.60, 95% CI 0.50–0.74; HR 0.62, 95% CI 0.55–0.72, respectively). TACE was highly efficacious (58.9%) at decreasing the rates of major complications. Similar findings were obtained through sensitivity analysis, and in most of the prognostic subgroups. Conclusions MIS and SR exhibited the highest clinical efficacies, however, they were associated with higher rates of complications. Ablation is effective in small tumors, whereas SBRT is a relatively promising treatment option for SHCC. More well-designed, large-scale randomized controlled trials should be performed to validate our findings.

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Comparison of the survival outcomes of laparoscopy versus laparotomy in treatment of early-stage ovarian cancer: a systematic review and meta-analysis

Journal of Ovarian Research ◽

10.1186/s13048-021-00793-1 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Qingduo Kong ◽

Hongyi Wei ◽

Jing Zhang ◽

Yilin Li ◽

Yongjun Wang

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Early Stage ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Survival Outcomes ◽

Free Survival ◽

Review Manager ◽

Early Stage Ovarian Cancer

Abstract Background Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC. Methods According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2). Results A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008). Conclusions Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.

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Comparison between percutaneous ethanol injection (PEI) and transarterial chemoembolization (TACE) in patients with small hepatocellular carcinoma (HCC)

Journal of Hepatology ◽

10.1016/s0168-8278(00)80968-x ◽

2000 ◽

Vol 32 ◽

pp. 167

Author(s):

G. Cioni ◽

F. Turrini ◽

E. Baraldi ◽

P.G. Pedrazzini ◽

E. Ventura ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transarterial Chemoembolization ◽

Percutaneous Ethanol Injection ◽

Small Hepatocellular Carcinoma ◽

Ethanol Injection

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Percutaneous ethanol injection (PEI) in the treatment of small hepatocellular carcinoma (HCC)

Journal of Microwave Surgery ◽

10.3380/jmicrowavesurg.14.89 ◽

1996 ◽

Vol 14 ◽

pp. 89-94

Author(s):

Masaaki Ebara ◽

Hiroyuki Fukuda ◽

Masaharu Yoshikawa ◽

Nobuyuki Sugiura ◽

Hiromitsu Saisho

Keyword(s):

Hepatocellular Carcinoma ◽

Percutaneous Ethanol Injection ◽

Small Hepatocellular Carcinoma ◽

Ethanol Injection

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What is the long-term efficacy of percutaneous ethanol injection for small hepatocellular carcinoma?

Nature Clinical Practice Gastroenterology &#38 Hepatology ◽

10.1038/ncpgasthep0408 ◽

2006 ◽

Vol 3 (2) ◽

pp. 78-79

Author(s):

Morris Sherman

Keyword(s):

Hepatocellular Carcinoma ◽

Percutaneous Ethanol Injection ◽

Small Hepatocellular Carcinoma ◽

Ethanol Injection ◽

Term Efficacy

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Prognostic Value of Lactate Dehydrogenase in Patients with Hepatocellular Carcinoma: A Meta-Analysis

BioMed Research International ◽

10.1155/2018/1723184 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Weihao Kong ◽

Xiaomin Zuo ◽

Hao Liang ◽

Jingxiong Hu ◽

Huabing Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Sensitivity Analysis ◽

Lactate Dehydrogenase ◽

Publication Bias ◽

Subgroup Analysis ◽

Prognostic Value ◽

Meta Analysis ◽

Progression Free Survival ◽

Cochrane Library ◽

Free Survival

Background. Previous studies have shown the prognostic value of lactate dehydrogenase (LDH) in hepatocellular carcinoma (HCC), but the results are not persuasive. Therefore, the purpose of our study was to quantitatively explore the prognostic value of LDH in hepatocellular carcinoma.Methods. We searched the Web of Science, Embase, PubMed, and the Cochrane Library for literature published before October 2018 on the prognostic value of LDH in patients with hepatocellular carcinoma. The combined hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized to assess the prognostic value of LDH in overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) of HCC. Subgroup analysis, sensitivity analysis, and metaregression were used to explore the source of heterogeneity. Funnel plots with Begg’s test and Egger’s test were used to detect potential publication biases. Furthermore, combined odds ratios (ORs) were utilized to assess the correlation between LDH and clinicopathological features.Results. A total of 10 nonrandomized controlled studies were included in this meta-analysis. The combined effects of LDH on HCC patients’ OS, RFS/DFS, and PFS were HR = 2.07, 95% CI: 1.63-2.62, P < 0.001; HR = 1.62, 95% CI: 1.37-1.90, P < 0.001; and HR = 1.96, 95% CI: 1.14-3.36, P = 0.014, respectively. Subgroup analysis and sensitivity analysis showed that the outcome was stable, and the results of the metaregression also identified statistical models as an important source of heterogeneity. Potential publication bias was detected in the OS studies, so the trim-and-fill method was used to explore publication bias, and the results showed stability. Furthermore, the combined OR suggests that LDH was significantly correlated with gender, Child-Pugh grade, alpha-fetoprotein, vascular invasion, and tumor size.Conclusions. Preoperative LDH elevation is significantly associated with poor prognosis in patients with HCC, which may be a promising factor in assessing the prognosis of patients with HCC.

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Flash echo gray scale imaging with subtraction in assessment of small hepatocellular carcinoma treated with percutaneous ethanol injection: preliminary report.

Journal of Ultrasound in Medicine ◽

10.7863/jum.2001.20.5.539 ◽

2001 ◽

Vol 20 (5) ◽

pp. 539-544 ◽

Cited By ~ 7

Author(s):

J H Wang ◽

S N Lu ◽

C S Changchien ◽

C M Lee ◽

H D Tung ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Preliminary Report ◽

Percutaneous Ethanol Injection ◽

Small Hepatocellular Carcinoma ◽

Gray Scale ◽

Ethanol Injection

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Liquid biopsy in the clinical management of hepatocellular carcinoma

Gut ◽

10.1136/gutjnl-2019-320282 ◽

2020 ◽

Vol 69 (11) ◽

pp. 2025-2034 ◽

Cited By ~ 1

Author(s):

Johann von Felden ◽

Teresa Garcia-Lezana ◽

Kornelius Schulze ◽

Bojan Losic ◽

Augusto Villanueva

Keyword(s):

Hepatocellular Carcinoma ◽

Treatment Response ◽

Liquid Biopsy ◽

Clinical Management ◽

Early Stage ◽

Personalised Medicine ◽

Precision Oncology ◽

Early Hepatocellular Carcinoma ◽

Populations At Risk ◽

Circulating Tumour Dna

With increasing knowledge on molecular tumour information, precision oncology has revolutionised the medical field over the past years. Liquid biopsy entails the analysis of circulating tumour components, such as circulating tumour DNA, tumour cells or tumour-derived extracellular vesicles, and has thus come as a handy tool for personalised medicine in many cancer entities. Clinical applications under investigation include early cancer detection, prediction of treatment response and molecular monitoring of the disease, for example, to comprehend resistance patterns and clonal tumour evolution. In fact, several tests for blood-based mutation profiling are already commercially available and have entered the clinical field.In the context of hepatocellular carcinoma, where access to tissue specimens remains mostly limited to patients with early stage tumours, liquid biopsy approaches might be particularly helpful. A variety of translational liquid biopsy studies have been carried out to address clinical needs, such as early hepatocellular carcinoma detection and prediction of treatment response. To this regard, methylation profiling of circulating tumour DNA has evolved as a promising surveillance tool for early hepatocellular carcinoma detection in populations at risk, which might soon transform the way surveillance programmes are implemented. This review summarises recent developments in the liquid biopsy oncological space and, in more detail, the potential implications in the clinical management of hepatocellular carcinoma. It further outlines technical peculiarities across liquid biopsy technologies, which might be helpful for interpretation by non-experts.

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Hepatocellular Carcinoma More Than 3 cm in Diameter: A Systematic Review of Transcatheter Arterial Chemoembolization Plus Percutaneous Ethanol Injection versus Transcatheter Arterial Chemoembolization Alone

ISRN Gastroenterology ◽

10.1155/2013/526024 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 7

Author(s):

Shiying Wang ◽

Liping Zhuang ◽

Zhiqiang Meng

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Tumor Response ◽

Transcatheter Arterial Chemoembolization ◽

Survival Rates ◽

Percutaneous Ethanol Injection ◽

Cochrane Library ◽

Ethanol Injection ◽

Knowledge Infrastructure ◽

Arterial Chemoembolization

Objective. To identify the efficiency and safety of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol (PEI) for patients with hepatocellular carcinoma (HCC) more than 3 cm in diameter in comparison with those of transcatheter arterial chemoembolization monotherapy. Methods. All databases were searched up to February 22, 2013. The literature retrieval was conducted through Pubmed, Web of Science, and Cochrane Library. We also searched Chinese databases, including Chinese National Knowledge Infrastructure (CNKI), Chinese Biology Medicine (CBM), Wanfang database, and VIP Database for Chinese Technical Periodicals without language limitations. Results. Based on the criteria, we found 12 RCTs including 825 patients. Our results showed that TACE combined with PEI therapy compared with TACE monotherapy improved overall survival and tumor response. Conclusion. The combination of TACE and PEI compared with TACE monotherapy improved overall survival rates and tumor response of patients with large HCC. Besides, larger and more methodologically rigorous clinical trials are needed to confirm this outcome.

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