UMIN-CTR Clinical Trial

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

Hepatocellular carcinoma

Classification by specialty

Gastroenterology

Radiology

Classification by malignancy

Malignancy

Genomic information

NO

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

Primary outcomes

Hazard ratio of overall survival

Key secondary outcomes

Study type

Others,meta-analysis etc

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

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

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

Institute

Ofuna Chuo Hospital

Institute

Department

Personal name

Organization

NA

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

NA

Address

NA

Tel

0467452111

Email

eriguchitakahisa@gmail.com

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2020

Year

10

Month

01

Day

URL releasing protocol

N/A

Publication of results

Published

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

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 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.

Registered date

2020

Year

09

Month

29

Day

Last modified on

2022

Year

07

Month

29

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047710