UMIN-CTR Clinical Trial

Basic information
Public title	Comparison between stereotactic body radiotherapy and radiofrequency ablation for hepatocellular carcinoma: Meta-analysis and systematic review.
Acronym	Comparison between stereotactic body radiotherapy and radiofrequency ablation for hepatocellular carcinoma: Meta-analysis and systematic review.
Scientific Title	Comparison between stereotactic body radiotherapy and radiofrequency ablation for hepatocellular carcinoma: Meta-analysis and systematic review.
Scientific Title:Acronym	Comparison between stereotactic body radiotherapy and radiofrequency ablation for hepatocellular carcinoma: Meta-analysis and systematic review.
Region	Japan

Condition
Condition	Hepatocellular carcinoma
Classification by specialty	Gastroenterology Radiology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	In the Barcelona Clinic Liver Cancer staging and treatment strategy (BCLC) guideline, surgery, radiofrequency ablation (RFA), and trans-arterial chemoembolization (TACE) are considered as standard treatment for hepatocellular carcinoma (HCC). Although stereotactic body radiotherapy (SBRT) has been recognized as novel local therapy for HCC, SBRT is still not mentioned in BCLC guideline due to lack of randomized control trials. Recently, meta-analysis which compared SBRT and RFA for HCC has published. However, reports analyzed in the meta-analysis were heterogeneous in quality. In recent years, there are several retrospective studies which compared SBRT and RFA using propensity score matching (PSM). Aim of current meta-analysis is to summarize data from quality studies compared SBRT and RFA using PSM.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Hazard ratio of overall survival
Key secondary outcomes

Base
Study type	Others,meta-analysis etc

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	We will include observational studies using propensity score matching that compared SBRT and RFA for HCC. Articles were published as full reports, brief reports, or conference abstracts, regardless of their primary end point. Non-English reports were excluded.
Key exclusion criteria	NA
Target sample size

Research contact person
Name of lead principal investigator	1st name Takahisa Middle name Last name Eriguchi
Organization	Ofuna Chuo Hospital
Division name	Radiation Oncology Center
Zip code	2470056
Address	6-2-24
TEL	0467452111
Email	eriguchitakahisa@gmail.com

Public contact
Name of contact person	1st name Takahisa Middle name Last name Eriguchi
Organization	Ofuna Chuo Hospital
Division name	Radiation Oncology Center
Zip code	2470056
Address	6-2-24
TEL	0467452111
Homepage URL
Email	eriguchitakahisa@gmail.com

Sponsor
Institute	Ofuna Chuo Hospital
Institute
Department

Funding Source
Organization	NA
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	NA
Address	NA
Tel	0467452111
Email	eriguchitakahisa@gmail.com

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2020 Year 10 Month 01 Day

Related information
URL releasing protocol	N/A
Publication of results	Published

Result
URL related to results and publications	https://pubmed.ncbi.nlm.nih.gov/33856722/
Number of participants that the trial has enrolled	2107
Results	Three BCLC factor matched studies were identified. Stereotactic body radiotherapy led to comparable OS and significantly better LC. We also identified three additional BCLC factor unmatched studies. However, considerable heterogeneity was observed for HR of OS between BCLC factor matched and unmatched studies.
Results date posted	2022 Year 07 Month 29 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	In the selected six studies, 2107 patients with HCC treated with SBRT or RFA were analyzed; 1241 and 866 patients were categorized as having RFA and SBRT, respectively. Basic information about the included studies is summarized in Table 1, and the clinical information is shown in Table 2. Hara et al. included 13.2% of hypofractionated radiotherapy. The total NOS score to assess the quality of observational studies was 9 points in one study, 8 points in three studies, and 7 points in two studies (a score of 9 suggests the best study quality) (Table S4). We requested the authors to provide the HR for OS or LC and log rank of p values that were unavailable in the studies by Wahl et al. and Hara et al. The HR for OS in the study by Feng et al. was calculated from the Kaplan Meier curve in their poster. Information in Tables 1 and 2 was not only from articles and abstracts but also from posters and data provided by authors.
Participant flow	N/A
Adverse events	Complications related to treatments were available in four studies. The rates of grade 3 or higher toxicities ranged from 0 to 11 percent, which were not significantly different between RFA and SBRT. The uncompensated liver cirrhosis and liverrelated deaths 12 months after treatment was significantly higher in the SBRTHFRT in the report by Hara et al. However, the 3year liver failure mortalities after propensity score matching were similar (p, 0.52). Although CP score deterioration more than 2 at 3 months was higher in patients treated with SBRT in the report by Kim et al.8 it recovered at 6 months posttreatment (p, 0.278).
Outcome measures	The adjusted HR for OS as the primary endpoint was assessed based on six retrospective studies consisting of 2107 patients. A randommodel metaanalysis of these studies comprised 866 patients who underwent SBRT and 1241 patients who underwent RFA, the three metaanalyses of BCLCfactormatched studies revealed that SBRT led to equivalent OS compared with RFA. We identified three additional PS studies that did not use BCLCfactors in the PS analysis. Among them, the HR of OS was significantly higher in RFA than in SBRT. However, considerable heterogeneity was observed in the HR of OS between BCLCfactomatched and unmatched studies.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2020 Year 10 Month 01 Day
Date of IRB	2020 Year 10 Month 01 Day
Anticipated trial start date	2020 Year 10 Month 01 Day
Last follow-up date	2020 Year 10 Month 01 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other

Other related information

Study Search We will systematically search PubMed, the Cochrane database, EMBASE, and Web of Science as of October 1, 2020. The search strategy for PubMed will be as follows: (hepatoma[title] OR hepatomas[title] OR HCC[title] OR ((hepatocellular[title] OR hepatic[title] OR liver[title]) AND (cancer[title] OR carcinoma[title] OR malignancy[title] OR tumor[title] OR neoplasm[title] OR neoplasms[title] OR carcinomas[title] OR malignancies[title]))) AND (RFA OR ((radiofrequency OR thermal) AND (ablation OR ablative))) AND (SBRT OR SRT OR SABR OR stereotactic OR radiotherapy OR radiation OR irradiation) AND (randomized OR randomized OR RCT OR randomly OR phase III OR phase 3 OR propensity OR PSM OR Inverse probability of treatment weighting OR Doubly Robustness) Reference lists in the included articles and review articles will be also hand searched. Data synthesis HR from propensity score matched studies will be pooled. Prior to generic inverse variance meta-analysis using RevMan 5.0 (Cochrane Collaboration, London, UK), HR will be log converted. Subgroup analyses which focus on liver function will be performed. Statistical significance will be judged by P < 0.05.

Management information
Registered date	2020 Year 09 Month 29 Day
Last modified on	2022 Year 07 Month 29 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047710