Drug-eluting bead transarterial chemoembolisation for unresectable hepatocellular carcinoma

  • Protocol
  • Intervention

Authors

  • Wenbo Shao,

    Corresponding author
    1. Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Department of Surgical Oncology (Interventional Therapy), Jinan, Shandong, China
    • Wenbo Shao, Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, 440 Jiyan Road,, Jinan, Shandong, 250117, China. shaowenbomd@gmail.com. shaowenbo1974@sina.com.

    Search for more papers by this author
  • Jinlong Song

    1. Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Department of Surgical Oncology (Interventional Therapy), Jinan, Shandong, China
    Search for more papers by this author

Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the beneficial and harmful effects of drug-eluting bead transarterial chemoembolisation for unresectable hepatocellular carcinoma.

Background

Description of the condition

Hepatocellular carcinoma is the fifth most common cancer and the third most common cause of cancer mortality in the world (El-Serag 2007a). It has a high incidence in East and South-East Asia and in Middle and Western Africa where chronic hepatitis B viral infection is prevalent, with the exception of Japan where the major risk factor for hepatocellular carcinoma is chronic hepatitis C virus infection (Lai 2005). Hepatocellular carcinoma is less common in Europe and the US (El-Serag 1999; McGlynn 2001; El-Serag 2012), but it is on the increase in these regions because of the rising incidence of cirrhosis due to alcohol, obesity (El-Serag 2007), and especially chronic hepatitis C virus infection (Davila 2004). One-year survival for untreated patients with hepatocellular carcinoma is 17.5% and two-year survival is 7.3% (Cabibbo 2010).

Many people with hepatocellular carcinoma cannot be diagnosed at an early stage because there are no specific symptoms in early or even intermediate stage of the cancer. In countries where no systematic screening of cirrhotic patients is performed, more than 50% patients with hepatocellular carcinoma are diagnosed at an advanced stage of the carcinoma (Bruix 2005). Such patients are precluded from curative treatment options such as transplantation, surgical resection, and percutaneous ablation. Several therapies have been proposed for patients with unresectable hepatocellular carcinoma. According to the Barcelona Clinic Liver Cancer (BCLC) tumour staging system, which is endorsed by the European Association for the Study of Liver Disease (EASL) (Bruix 2001) and the American Association for the Study of Liver Disease (AASLD) (Bruix 2005). Patients at intermediate stage (BCLC stage B) may benefit from treatment with transarterial chemoembolisation, whereas patients at an advanced stage (BCLC stage C) may benefit from treatment with sorafenib (Keating 2009; Bruix 2011; Oliveri 2011). Finally, patients at end-stage (BCLC stage D) should receive palliative care (Forner 2010). Studies from Asia have evaluated the safety and survival of transarterial chemoembolisation in patients with portal vein thrombosis and have suggested that selected patients at an advanced stage (BCLC stage C) should undergo transarterial chemoembolisation (Kim 2009; Luo 2011).

Description of the intervention

Transarterial chemoembolisation is considered a mainstay of treatment for unresectable hepatocellular carcinoma. Asymptomatic patients with multinodular non-invasive tumours (BCLC stage B) are considered the best candidates for transarterial chemoembolisation, particularly in Child-Pugh A compensated cirrhosis. According to the Society of Interventional Radiology guidelines, chemoembolisation is currently defined as the infusion of a mixture of chemotherapeutic agents with or without iodised oil, followed by embolisation with particles (Brown 2007). The concept of conventional transarterial chemoembolisation is to administer a high dose of chemotherapeutic agent(s), typically emulsified in lipiodol into the hepatic arteries supplying the tumour, and, then, embolising the tumour-feeding vessels with agents such as gelfoam, polyvinyl alcohol, or acrylic copolymer gelatin particles to prolong the chemotherapeutic-to-tumour interaction time. Lipiodol acts as a carrier of chemotherapeutic agents that are released slowly from the lipiodol mixture (Nakamura 1989; Raoul 1992), but some studies argue that there is no difference in terms of pharmacokinetic parameters with intra-arterial administration of adriamycin with or without lipiodol (Johnson 1991; Dodds 1996). Transarterial chemoembolisation currently has no uniformly adopted protocol. Specifically, there are variations at different institutions in position of the catheter within the liver (selective or superselective), choice of chemotherapeutic agent, properties of the embolisation device (permanent or temporary), and schedule or interval of retreatment (Marelli 2007). This wide variety of clinical practice may lead to difficulties in the effect assessment of the various interventions. Two randomised clinical trials (Llovet 2002; Lo 2002) and two meta-analyses (Camma 2002; Llovet 2003) have demonstrated a survival benefit of transarterial chemoembolisation. However, one Cochrane review concluded that there was no firm evidence to support or refute transarterial chemoembolisation for patients with unresectable hepatocellular carcinoma (Oliveri 2011).

In an attempt to simplify and standardise the embolisation and chemotherapy delivery aspects of transarterial chemoembolisation, drug-eluting beads were developed. To date, there are two different types of drug-eluting beads: polyvinyl alcohol (PVA)-based microspheres (DC Bead®) and superabsorbent polymer (SAP) microspheres (HepaSphere® (Europe)/QuadraSphere® (USA)) (Grosso 2008; Lewis 2009; van Malenstein 2011). Both types of drug-eluting beads can lead to persistent and sustained drug elution (Sottani 2012). Drug-eluting beads have two functions in transarterial chemoembolisation, one as an embolic material and the other as an anticancer drug delivery vehicle that can elute the agent in a sustained and controlled manner. Drug-eluting bead transarterial chemoembolisation represents a relatively new dimension to the field of chemoembolisation. It is performed using similar materials (microcatheter, beads, and drug), similar technique (superselective), and with similar retreatment time intervals as conventional transarterial chemoembolisation (Poon 2007; Varela 2007; Lewandowski 2011). Drug-eluting beads add to the standardisation of transarterial chemoembolisation and may reduce the heterogeneity of the transarterial chemoembolisation procedure (Lewandowski 2011).

The main adverse effects of conventional transarterial chemoembolisation include post-embolisation syndrome, which is characterised by nausea, vomiting, fever, and right upper quadrant pain. In addition, there are other adverse effects such as bone marrow aplasia, renal failure, and cardiac toxicity. A minority of patients may develop severe infectious complications such as hepatic abscess or cholecystitis (Meza-Junco 2012). Drug-eluting bead transarterial chemoembolisation is better than conventional transarterial chemoembolisation in reducing the incidence and severity of adverse events including liver function parameters and cardiac function (Vogl 2011).

How the intervention might work

The main difference between drug-eluting bead transarterial chemoembolisation and conventional transarterial chemoembolisation is the drug-delivery mechanism (Varela 2007). Beads preloaded with anticancer drugs can be trapped within the hepatocellular carcinoma vascular network, blocking the supply of nutrition and oxygen, and inducing ischaemic necrosis (Lewis 2006). At the same time, anticancer drugs can be released in a sustained and controlled manner, achieve higher intratumoural levels of the chemotherapeutic compared with conventional transarterial chemoembolisation, and allow for prolonged contact time with cancer cells (Hong 2006; Lewis 2006). In addition, the high intratumoural concentrations of the chemotherapeutic do not result in diffusion of chemotherapeutic in the systemic circulation as opposed to conventional transarterial chemoembolisation, and so may lead to less systemic and liver toxicity (Poon 2007; Varela 2007).

Why it is important to do this review

Many studies on drug-eluting bead transarterial chemoembolisation including retrospective studies and randomised clinical trials have shown a good local response, lower number of complications without systemic toxicity, and better results in patients with more advanced hepatocellular carcinoma patients compared with conventional transarterial chemoembolisation (Varela 2007; Malagari 2008; Lammer 2010; Malagari 2010). An assessment of drug-eluting bead transarterial chemoembolisation on survival benefit is underway (Malagari 2010). Drug-eluting bead transarterial chemoembolisation is more expensive than conventional transarterial chemoembolisation and it is important for policy makers to find out whether drug-eluting bead transarterial chemoembolisation surpasses no intervention, sham intervention, or conventional transarterial chemoembolisation for unresectable hepatocellular carcinoma. During our search, we could not find any meta-analyses or systematic reviews of randomised clinical trials evaluating the beneficial and harmful effects of drug-eluting bead transarterial chemoembolisation for unresectable hepatocellular carcinoma. Thus, we consider it important to study the effects of drug-eluting bead transarterial chemoembolisation for patients with unresectable hepatocellular carcinoma.

Objectives

To assess the beneficial and harmful effects of drug-eluting bead transarterial chemoembolisation for unresectable hepatocellular carcinoma.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised clinical trials (published or unpublished), irrespective of language, blinding, and publication status. We will consider non-randomised studies retrieved with the searches for the reports of harms and we will extract information on harms.

Types of participants

Patients diagnosed with hepatocellular carcinoma who are unsuitable for liver transplantation, resection, or percutaneous ablation.

Types of interventions

Experimental intervention: drug-eluting bead transarterial chemoembolisation.

Control intervention: no intervention; sham or placebo intervention; other interventions (eg, conventional transarterial chemoembolisation or transarterial embolisation).

We will allow the co-interventions of best supportive care delivered in a similar way to both the experimental and control groups.

Types of outcome measures

Primary outcomes
  1. All-cause mortality.

  2. Adverse events: they will be defined as any untoward medical occurrence not necessarily having a causal relationship with the treatment, but resulting in the discontinuation of treatment. Severe adverse events will be defined according to the International Committee on Harmonization guidelines as any event that would increase mortality; is life threatening; requires inpatient hospitalisation; results in a persistent or significant disability; or any important medical event that may jeopardise the patient or require intervention to prevent it (ICH-GCP 1997).

  3. Quality of life according to the measures used in the individual trials.

Secondary outcomes
  1. Tumour response according to criteria of the EASL (Bruix 2001):

    1. progressive disease: increase 25% or greater or new lesions;

    2. complete response: decrease = 100%;

    3. partial response: decrease 50% or greater;

    4. stable disease: decrease less than 50% or increase less than 25%.

  2. Proportion of patients without post-embolisation syndrome (nausea, vomiting, fever, and right upper quadrant pain).

  3. Proportion of patients without post-embolisation changes of liver enzymes compared with baseline.

  4. Duration of hospital stay.

Search methods for identification of studies

We will follow the guidance of the Cochrane Handbook of Systematic Reviews of Interventions (Higgins 2011), and the Cochrane Hepato-Biliary Group Module (Gluud 2013), to collect and analyse data.

Electronic searches

We will search the Cochrane Hepato-Biliary Group Controlled Trials Register (Gluud 2013), The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (OvidSP), EMBASE (OvidSP), Science Citation Index Expanded (Royle 2003), and The Chinese Biomedical Literature Database.

We have presented the preliminary search strategies in Appendix 1 with the expected time span for the searches. We will not limit the search strategies by year of publication, language, or publication type.

Searching other resources

We will try to identify additional trials by searching the citations and reference lists of articles and the latest conference meetings. We will contact the manufacturer of drug-eluting beads and ask if they are aware of additional trials for inclusion, including unpublished trials. We will contact the authors of included trials asking them if they are aware of any ongoing or published randomised clinical trials on drug-eluting beads.

Data collection and analysis

We will perform the review and meta-analyses following the recommendations of The Cochrane Collaboration and the Cochrane Hepato-Biliary Group Module (Gluud 2013). The analyses will be performed using Review Manager 5 (RevMan 2012).

Selection of studies

Two review authors (WS and JS) will independently scan the abstracts, titles, or both sections of every record retrieved. We will exclude papers definitely failing the inclusion criteria. We will investigate all potentially relevant articles as full text. We will resolve inter-rater disagreement for study selection by discussion. If resolving a disagreement is not possible, we will add the article to those 'awaiting assessment' and will contact study authors for clarification. If we receive no reply from study authors, the differences in opinion will be resolved by a third review author, Jinpeng Li (JL), who will join our work on the review at the review stage. A copy of a data collection form is presented in Appendix 2.

Data extraction and management

For trials that fulfil inclusion criteria, two review authors (WS and JS) will independently extract trial characteristics (design, sample size, duration/follow-up, and quality assessment criteria), participant-related data (diagnostic criteria, eligibility criteria, exclusion criteria, baseline characteristics, number of people allocated to each group, numbers of withdrawals and drop-outs), intervention scheme (drug, dose, and route for experimental and control interventions), adverse events, and time-to-event summary data using data collection forms provided by the Cochrane Hepato-Biliary Group, and will resolve any disagreements by discussion, or if required by a third party. We will seek any relevant missing information on the trial from the original author(s) of the article, if required.

Assessment of risk of bias in included studies

Two review authors (WS and JS) will assess each trial independently, using a specific tool recommended by The Cochrane Collaboration (recommendations in the Cochrane Handbook for Systematic Reviews of Interventions) (Higgins 2011) for assessing risk of bias in each included study. We will resolve disagreements by discussion. If discussion does not help in resolving disagreements, the third review author (JL) will make the final decision. The domains for risk of bias and their definitions according to which we will judge the risk of bias of each individual trial are provided below (Schulz 1995; Moher 1998; Kjaergard 2001; Wood 2008; Lundh 2012; Savović 2012; Savović 2012a).

Allocation sequence generation
  • Low risk of bias: sequence generation was achieved using computer random number generation or a random number table. Drawing lots, tossing a coin, shuffling cards, and throwing dice will be adequate if performed by an independent research assistant not otherwise involved in the trial.

  • Uncertain risk of bias: the method of sequence generation was not specified.

  • High risk of bias: the sequence generation method was not random.

Allocation concealment
  • Low risk of bias: the participant allocations could not have been foreseen in advance of, or during, enrolment. Allocation was controlled by a central and independent randomisation unit. The allocation sequence was unknown to the investigators (eg, if the allocation sequence was hidden in sequentially numbered, opaque, and sealed envelopes).

  • Uncertain risk of bias: the method used to conceal the allocation was not described so that intervention allocations may have been foreseen in advance of, or during, enrolment.

  • High risk of bias: the allocation sequence was likely to be known to the investigators who assigned the participants.

Blinding of participants, personnel, and outcome assessors
  • Low risk of bias: blinding was performed adequately, or the assessment of outcomes was not likely to be influenced by lack of blinding.

  • Uncertain risk of bias: there was insufficient information to assess whether blinding was likely to induce bias on the results.

  • High risk of bias: no blinding or incomplete blinding, and the assessment of outcomes were likely to be influenced by lack of blinding.

Incomplete outcome data
  • Low risk of bias: missing data were unlikely to make treatment effects depart from plausible values. Sufficient methods, such as multiple imputation, have been employed to handle missing data.

  • Uncertain risk of bias: there was insufficient information to assess whether missing data in combination with the method used to handle missing data were likely to induce bias on the results.

  • High risk of bias: the results were likely to be biased due to missing data.

Selective outcome reporting
  • Low risk of bias: all outcomes were pre-defined (eg, in the published trial protocol) and reported, or all clinically relevant and reasonably expected outcomes were reported.

  • Uncertain risk of bias: it is unclear whether all pre-defined and clinically relevant and reasonably expected outcomes were reported.

  • High risk of bias: one or more clinically relevant and reasonably expected outcomes were not reported, and data on these outcomes were likely to have been recorded.

For a trial to be assessed with low risk of bias in the selective outcome reporting domain, the trial should have been registered either on the www.clinicaltrials.gov website or a similar register, or there should be a protocol (eg, published in a paper journal). In the case when the trial was run and published in the years when trial registration was not required, we will attempt to scrutinise carefully all publications reporting on the trial to identify the trial objectives and outcomes. If usable data on all outcomes specified in the trial objectives are provided in the publications results section, then the trial can be considered a low risk of bias trial in the selective outcome reporting domain.

Industry bias or vested interest bias
  • Low risk of bias: the trial appears to be free of vested interests that could put it at risk of bias. 

  • Uncertain risk of bias: the trial may or may not be free of vested interests that could put it at risk of bias.

  • High risk of bias: there are factors in the trial that could put it at risk of bias (eg, for-profit involvement, authors have conducted trials on the same topic, etc).

Other bias
  • Low risk of bias: the trial appears to be free of other components (eg, sufficient sample size calculation and no early stopping) that could put it at risk of bias. 

  • Uncertain risk of bias: the trial may or may not be free of other components that could put it at risk of bias.

  • High risk of bias: there are other factors in the trial that could put it at risk of bias.

If we judge the risk of bias in a trial as low in all the above domains, the trial will fall into the category of 'low risk of bias'. If we judge the risk of bias to be 'uncertain' or 'high', then the trial will fall into the group of trials with 'high risk of bias'. Two review authors will independently assess all the above bias risk domains. We will resolve disagreements between the authors by discussion. If discussion does not help in resolving disagreements, the third review author (JL) will make the final decision.

Measures of treatment effect

Dichotomous data

We will calculate the risk ratios with 95% confidence intervals (CI) by both the fixed-effect (DeMets 1987), and random-effects (DerSimonian 1986), models for dichotomous data. In case of discrepancy between the two models (eg, one giving a significant intervention effect, the other no significant intervention effect), we will report both results; otherwise, we will report only the results from the fixed-effect model.

Continuous data

We will calculate mean differences with 95% CI for continuous outcome measures (DeMets 1987). We will use the standardised mean difference (SMD) to combine trials that measure the same outcome but that have used different methods.

Unit of analysis issues

Intervention groups of patients in randomised clinical trials. We will give special attention to the cross-over design of the randomised clinical trial. We will only include data from the first period of the randomised cross-over trial, following the suggestions of the Cochrane Handbook of Systematic Reviews of Interventions (Higgins 2011).

Dealing with missing data

If data are missing in a published report, the review authors will:

  • Whenever possible, contact the original investigators to request missing data.

  • Make explicit the assumptions of any methods used to cope with missing data: for example, that the data were assumed missing at random, or that missing values were assumed to have a particular value such as a poor outcome.

  • Perform sensitivity analyses to assess how sensitive results are to reasonable changes in the assumptions that are made.

Address the potential impact of missing data on the findings of the review in the 'Discussion' section.

Assessment of heterogeneity

We will assess the statistical heterogeneity by inspecting the forest plots (Egger 1997). We will assess heterogeneity using the Chi2 test of heterogeneity and quantity of heterogeneity by the Chi2 measure of inconsistency (Higgins 2002; Higgins 2003).

Assessment of reporting biases

We will use funnel plots to show evidence of bias, plotting effect estimates against study size where data allow. We will use two tests to assess funnel plot asymmetry - adjusted rank correlation test and regression asymmetry test (Egger 1997). There are a number of explanations for the asymmetry of a funnel plot, including true heterogeneity of effect with respect to study size and risk of bias in small studies. Therefore, we will interpret the results carefully.

Data synthesis

Meta-analysis

We will use Review Manager 5 (RevMan 2012), the statistical software provided by The Cochrane Collaboration to synthesise the data. We will most likely do the evidence synthesis in a narrative way, but where possible and meaningful (data are clinically homogeneous), we will use meta-analyses. We will present text, tables, and figures to summarise the data and to allow the reader to judge the results based on the differences and similarities of included trials and their risk of bias assessment. We will group the trials by intervention, patient characteristics, and outcomes, and we will describe the most important characteristics of the included trials, including a detailed review of the methodological shortcomings of the trial.

Trial sequential analysis

Where possible, we will examine apparent significant beneficial and harmful intervention effects with trial sequential analyses (Thorlund 2011; CTU 2012), in order to evaluate if these effects could be caused by random error ('play of chance') (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009; Wetterslev 2009; Thorlund 2010). The trial sequential analyses will use an alpha error of 0.05, beta error of 0.20, the control event proportion obtained from the results of the meta-analysis and a relative risk reduction of 20% for mortality and other dichotomous outcomes, and the observed diversity of the meta-analysis (Thorlund 2011; CTU 2012).

Subgroup analysis and investigation of heterogeneity

We will perform the following subgroup analyses whenever relevant or possible in order to explore important clinical differences among the trials that might alter the magnitude of the treatment effect:

  • Trials with low risk of bias compared to trials with high risk of bias.

  • Patients' characteristics: we will classify patients according to their Child-Pugh class (A/B or C) and Eastern Cooperative Oncology Group performance status (0/1).

  • Characteristics of the tumours: bilobar disease (yes/no).

Sensitivity analysis

We will analyse data with both fixed-effect model and random-effects model analyses. In the text, we will only report the fixed-effect model if the two analyses reach a similar conclusion.

'Summary of findings' table

We will create a 'Summary of findings' table including, where possible, survival, response, recurrence, and adverse event, using GRADEpro (ims.cochrane.org/revman/other-resources/gradepro).

Acknowledgements

We thank the Cochrane Hepato-Biliary Group for their help during the development of this protocol.

Peer reviewers: Ken Sato, Japan; Geert Maleux, Belgium.
Contact editors: Ronald Koretz, USA; Davor Stimac, Croatia.

Appendices

Appendix 1. Search strategies

Name of database Time span Search strategy
Cochrane Hepato-Biliary Group Controlled Trials RegisterDate will be given at review stage('drug eluting bead*' OR DEB OR 'DC bead*') AND (((transcatheter OR transarterial) AND (emboli* OR chemoemboli*)) OR TAE OR TACE) AND ('hepatocellular carcinoma*' OR HCC* OR hepatoma*)
Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane LibraryLatest issue

#1 drug eluting bead* OR DEB OR DC bead*

#2 MeSH descriptor embolisation, Therapeutic explode all trees

#3 ((transcatheter or transarterial) and (emboli* or chemoemboli*)) or TAE or TACE

#4 (#2 OR #3)

#5 MeSH descriptor Carcinoma, Hepatocellular explode all trees

#6 hepatocellular carcinoma* OR HCC* OR hepatoma*

#7 (#5 OR #6)

#8 (#1 AND #4 AND #7)

MEDLINE (OvidSP)1948 to the date of search

1. (drug eluting bead* or DEB or DC bead*).mp. [mp=protocol supplementary concept, rare disease supplementary concept, title, original title, abstract, name of substance word, subject heading word, unique identifier]

2. exp embolisation, Therapeutic/

3. (((transcatheter or transarterial) and (emboli* or chemoemboli*)) or TAE or TACE).mp. [mp=protocol supplementary concept, rare disease supplementary concept, title, original title, abstract, name of substance word, subject heading word, unique identifier]

4. 2 or 3

5. exp Carcinoma, Hepatocellular/

6. (hepatocellular carcinoma* or HCC* or hepatoma*).mp. [mp=protocol supplementary concept, rare disease supplementary concept, title, original title, abstract, name of substance word, subject heading word, unique identifier]

7. 5 or 6

8. 1 and 4 and 7

EMBASE (OvidSP)1980 to the date of search

1. (drug eluting bead* or DEB or DC bead*).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]

2. exp artificial embolism/

3. (((transcatheter or transarterial) and (emboli* or chemoemboli*)) or TAE or TACE).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]

4. 2 or 3

5. exp liver cell carcinoma/

6. (hepatocellular carcinoma* or HCC* or hepatoma*).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]

7. 5 or 6

8. 1 and 4 and 7

9. (random* or blind* or placebo* or meta-analysis).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword]

10. 8 and 9

Science Citation Index Expanded (apps.webofknowledge.com)1945 to the date of search

#6 #5 AND #4

#5 TS=(random* or blind* or placebo* or meta-analysis)

#4 #3 AND #2 AND #1

#3 TS=(hepatocellular carcinoma* or HCC* or hepatoma*)

#2 TS=(((transcatheter or transarterial) and (emboli* or chemoemboli*)) or TAE or TACE)

#1 TS=(drug eluting bead* or DEB or DC bead*)

Appendix 2. Data collection form

Drug eluting beads TACE for unresectable hepatocellular carcinoma (review title)

 

Study ID (surname of first author and year of the first full report of the trial when published, eg, Smith 2001)
 

 

Report IDs of other reports of this study (eg, duplicate publications, follow-up studies)
 

 

Notes:      

 

 

 

1. General Information

 

Date form completed (dd/mm/yyyy) 
Name/ID of person extracting data 

Report title

(title of paper/ abstract/ report that data are extracted from)

 

Report ID

(if there are multiple reports of this study)

 

Reference details

 

 
Report author contact details 

Publication type

(eg, full report, abstract, letter)

 

Study funding source

(including role of funders)

 

Possible conflicts of interest

(for study authors)

 

Notes:      

 

 

 

2. Eligibility

 

Study Characteristics

Review Inclusion Criteria

(Insert inclusion criteria for each characteristic as defined in the protocol)

YesNoUnclear

Location in text

(pg and

/fig/table)

Type of studyRandomised clinical trial    

Controlled clinical trial

(quasi-randomised trial)

    

Controlled before and after study

  • Contemporaneous data collection

  • Comparable control site

  • At least 2 x intervention and 2 x control cluster

    

Interrupted time series

  • At least 3 time points before and 3 times after the intervention

  • Clearly defined intervention point

      

Other design (specify):

Prospective pilot study 

    

Participants

 

XX patients with surgically unresectable hepatocellular carcinoma

 

    
Types of intervention

  

Drug-eluting bead TACE

 

    
Types of outcome measures

Primary outcomes:

Secondary outcomes:

 

    
INCLUDE  EXCLUDE  

Reason for exclusion

 

 

Notes:        

 

 

Contributions of authors

Wenbo Shao drafted the protocol and Jinlong Song revised it.
All authors agreed on the final protocol version.

Declarations of interest

None known.

Sources of support

Internal sources

  • Shandong Cancer Hospital, China.

    Salary support

  • the Johns Hopkins Hospital, USA.

    Library databases support

External sources

  • The Health Department of Shandong Province, China.

    Financial support to Wenbo Shao for his stay at the Johns Hopkins Hospital to observe drug-eluting bead transcatheter arterial chemoembolisation for hepatocellular carcinoma

Ancillary