MATERIALS AND METHODS

Study design and inclusion criteria

Clinical trials on the prognostic factors of RFA in HCC patients were considered, excluding randomized controlled trials comparing RFA and surgery, studies with insufficient data to estimate the outcomes, and studies on RFA with microwave and ethanol. A primary analysis was planned to evaluate the clinical prognostic factor of OS. RFS was the secondary aim. OS was defined as the time interval between the day of start of treatment until the day of death or last follow-up visit. The RFS was defined as the observation time during the follow-up period during which the patient developed a intrahepatic distant recurrence, extrahepatic recurrence, or death.


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Search strategy

We conducted a bibliographic search of the PubMed, Embase, Cochrane Library. Keywords used included “radiofrequency AND hepatocellular carcinoma”, “radiofrequency AND liver cancer”. Articles published in English until September 2017 and reporting data of studies conducted on human participants were retrieved. Relevant reviews and meta-analyses of loco-regional treatments of unresectable HCC were also examined for potential suitable studies and data. The 2000–2017 proceedings of the Annual Meeting of the American Society of Clinical Oncology (ASCO and ASCO Gastrointerstinal), European Society of Clinical Oncology (ESMO and ESMO Gastrointerstinal), European Association for the Study of the Liver, American Association for the Study of Liver Diseases, and International Liver Cancer Association were systematically reviewed for relevant unpublished data.

The computer search was supplemented with a manual search of the primary studies referenced in all of the retrieved review articles. When the results of a study were reported in multiple subsequent analyses, only the most recent and complete version was considered.

Data extraction and management

Two review authors (ACG and MV) independently screened the titles of all the selected studies, and read the abstracts of potentially eligible papers. Whenever discrepancies in trial search or selection occurred between the 2 review authors, they were discussed with a third review author (FGF) to reach an agreement. All selected trials published as full-text articles in peer-reviewed journals were analyzed and classified using the Newcastle–Ottawa Quality Assessment Scale for Cohort Studies. ACG and MV independently performed the qualitative and quantitative analysis of the selected articles. Whenever discrepancies occurred, they were discussed with FGF to reach an agreement.

Statistical analysis

All analyses were carried out using Stata version 15.0 (Stata Corporation, College Station, TX, USA). HR reported in each study was used as an outcome measure of the prognostic value. The summary estimates were generated using a fixed-effect model (Mantel–Haenszel method) or a random-effect model49 depending on the absence or presence of heterogeneity.

The inter-study heterogeneity was examined by the Cochran’s Q and I-squared statistic with an I-squared >50% representing significant heterogeneity.7

We assessed the potential of publication bias by visually inspecting the funnel plot symmetry and Egger’s test for asymmetry.8

Sensitivity analyses were conducted by excluding 1 study at a time and reanalyzing the remaining to test whether the results had changed substantially by any individual study. A value of P<0.05 was regarded as statistically significant for all statistical analyses. All tests were 2-sided.