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KSR Number: KSRA54078

Survival benefit of hepatic resection versus transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombus: a systematic review and meta-analysis

Risk of Bias Assessment

Overall summary: Low risk of bias in the review

Bottom Line

Current evidence suggests hepatic resection may improve overall survival in patients with hepatocellular carcinoma and type I or II portal vein tumour thrombus (PVTT) vs transarterial chemoembolisation; but no difference was reported for type III or IV PVTT patients. The results should be interpreted cautiously due to significant heterogeneity between the studies with some outcomes. A large number of adequately powered well-designed randomised controlled trials are needed to support these findings.

Risk of Bias Assessment

Overall summary Low risk of bias in the review

Low

The authors acknowledged the presence of significant heterogeneity between the studies in the limitations.

A. Did the interpretation of findings address all of the concerns identified in Domains 1 to 4? Probably yes
B. Was the relevance of identified studies to the review's research question appropriately considered? Probably yes
C. Did the reviewers avoid emphasizing results on the basis of their statistical significance? Probably yes
Risk of bias in the review Low

Details of Review

Number of studies 12
Number of participants 3,129
Last search date January 2017
Review type Intervention
Objective To compare the effectiveness of hepatic resection and transarterial chemoembolisation for hepatocellular carcinoma with portal vein tumour thrombus patients.
Population Hepatocellular carcinoma (HCC) with various types of portal vein tumour thrombus (PVTT).

Studies including advanced HCC patients without PVTT were excluded.
Interventions Hepatic resection (HR).
Comparator Transarterial chemoembolisation (TACE).
Outcome Six months or 1, 2, 3, 5-years overall survival (OS), recurrence rate and disease-free survival (DFS).
Study design Retrospective controlled studies.

Narrative reviews, case reports, current affairs reviews, letters, comments or studies unrelated to the topics were excluded.

Results

The pooled analysis reported that the 1- (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.41 to 0.57, 11 studies, 3069 participants), 2- (OR 0.21, 95% CI 0.12 to 0.38, 5 studies, 1835 participants), 3- (OR 0.35, 95% CI 0.28 to 0.44, 10 studies, 3024 participants) and 5-year (OR 0.28, 95% CI 0.14 to 0.54, 5 studies, 2490 participants) overall survival (OS) rates were improved with hepatic resection (HR) compared to transarterial chemoembolisation (TACE). The 6 month OS rate varied from 14.2% to 86.5% for HR and from 34.2% to 34.6% for TACE, respectively.

Subgroup analysis based on the type of portal vein tumour thrombus (PVTT), also reported better 1-, 2-, 3, 5-year OS rates for type I and type II PVTT with HR than TACE. However, no differences were found regarding outcomes 1-, 2-, 3, 5-year OS rates for type III and type IV PVTT between the HR and TACE groups. None of the included trials reported on outcomes recurrence rate and DFS.

Full Risk of Bias Assessment

The research objective was clearly stated and appropriate inclusion criteria were defined. No restrictions were reported based on study characteristics and sources of information.

1.1 Did the review adhere to pre-defined objectives and eligibility criteria? Probably yes
1.2 Were the eligibility criteria appropriate for the review question? Probably yes
1.3 Were eligibility criteria unambiguous? Probably yes
1.4 Were all restrictions in eligibility criteria based on study characteristics appropriate (e.g. date, sample size, study quality, outcomes measured)? Probably yes
1.5 Were any restrictions in eligibility criteria based on sources of information appropriate (e.g. publication status or format, language, availability of data)? Probably yes
Concerns regarding specification of study eligibility criteria Low

Studies were identified by searching PubMed, Cochrane Library, EMBASE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), VIP, Wanfang and Sino Med databases. Additionally, ClinicalTrials.gov was searched. The search terms and search strategy were reported and appeared to be adequate (although not supported in line with relevant reporting guidelines). No restrictions were reported based on the date, publication format, or language. Two reviewers were independently involved in the study selection process.

2.1 Did the search include an appropriate range of databases/electronic sources for published and unpublished reports? Probably yes
2.2 Were methods additional to database searching used to identify relevant reports? Probably yes
2.3 Were the terms and structure of the search strategy likely to retrieve as many eligible studies as possible? Probably yes
2.4 Were restrictions based on date, publication format, or language appropriate? Probably yes
2.5 Were efforts made to minimise error in selection of studies? Probably yes
Concerns regarding methods used to identify and/or select studies Low

Two reviewers were independently involved in the data extraction process and disagreements were resolved by discussion with the third reviewer. Sufficient individual study characteristics have been extracted to allow interpretation of the results. Relevant study results appear to have been extracted. Methodological quality assessment of included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. No information was provided on the number of reviewers involved in the risk of bias assessment.

3.1 Were efforts made to minimise error in data collection? Yes
3.2 Were sufficient study characteristics considered for both review authors and readers to be able to interpret the results? Probably yes
3.3 Were all relevant study results collected for use in the synthesis? Probably yes
3.4 Was risk of bias (or methodological quality) formally assessed using appropriate criteria? Probably yes
3.5 Were efforts made to minimise error in risk of bias assessment? No information
Concerns regarding methods used to collect data and appraise studies Unclear

The synthesis appeared to have included all relevant studies. The method of analysis was explained and appeared appropriate. Significant heterogeneity was found between the studies in the pooled analysis of some outcomes. However, this limitation was acknowledged by the authors. Publication bias was assessed with funnel plots, Begg’s test and Egger’s test.

4.1 Did the synthesis include all studies that it should? Probably yes
4.2 Were all pre-defined analyses reported or departures explained? Probably no
4.3 Was the synthesis appropriate given the degree of similarity in the research questions, study designs and outcomes across included studies? Probably yes
4.4 Was between-study variation minimal or addressed in the synthesis? Probably no
4.5 Were the findings robust, e.g. as demonstrated through funnel plot or sensitivity analyses? Probably yes
4.6 Were biases in primary studies minimal or addressed in the synthesis? No information
Concerns regarding synthesis and findings High

Keywords