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In the In the name of name of

AllaAlla

Transarterial chemoembolization in

combination with percutaneous ablation therapy in

unresectable hepatocellular carcinoma:

a meta-analysisPrepared by: Dr. Samah Ali Mansoor Mater

Under supervision by : Ass. Prof. Dr. Abdul Hakeem Atamimi

May/2010

The contributersThe contributers::

Wei Wang, Jian Shi and Wei-fen xie

Department of Gasteroenterology,

Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China

INTRODUCTION

Hepatocellular carcinoma (HCC)

The 6th common cancer in the world

Small proportion with early stage may benefit from radical options

Surgical resection isn’t the 1st treatment of choice in the presence of large lesion or poor liver function

Transcatheter arterial chemoembolization (TACE) and percutaneous ablation (PA) are prescribed to prevent and relive suffering and improve qulity of life

Percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) are highly effective in the treatment of small lesion

Transcatheter arterial chemoembolization (TACE) improve the survival in large and multiple lesions

Some viable tumor cells remain after transcatheter arterial chemoembolization (TACE)

Recent evidence suggest that the combination of transcatheter arterial chemoembolization (TACE) with percutaneous ethanol injection (PEI) or radiofrequency ablation (RFA) may have a synergistic effect in treating large lesions that don’t response adequately to either procedure alone

For 5 cm lesions, 90-100% of complete response rate at 1 year was reported by applying radiofrequency ablation (RFA) after transcatheter arterial chemoembolization (TACE)

Kirioshi et al. reported better results in tumor response and overall survival with combination of transcatheter arterial chemoembolization (TACE) and percutaneous ablation (PA) as compared with either procedure alone

However, several studies found no significant difference in the overall survival between combination and monotherapy

Aim of the presented study

Identify the survival benefits of

this combination therapy for patients

with unresectable hepatocellular

carcinoma (HCC) with those of

either procedure alone.

PATIENTS AND

METHODS

Study objectives

The primary outcome The survival rate

The secondary outcome The initial complete response rate, and

The tumour recurrence rate

Search strategy Trials assesed the survival benefit or tumour recurrence

for patients with unresectable hepatocellular carcinoma (HCC) were searched :

- On PubMed, Embase and Web of Science ( all from 1990 to July 2009 )

- On Cochrane library database ( 2009, issue 2 )

- Manually, in general reviews on hepatocellular carcinoma (HCC) and references from published clinical trials

• A prospective randomized-controlled A prospective randomized-controlled clinical trialsclinical trials

• Above 18 years old patientsAbove 18 years old patients

• Patients were scheduled to undergo Patients were scheduled to undergo transcatheter arterial chemoembolization transcatheter arterial chemoembolization (TACE) with percutaneous ethanol (TACE) with percutaneous ethanol injection (PEI) or radiofrequency ablation injection (PEI) or radiofrequency ablation (RFA) (RFA)

Including critereaIncluding criterea

• Non-randomized studiesNon-randomized studies

• Recurrence of the tumour after Recurrence of the tumour after hepatectomy, liver metastaseshepatectomy, liver metastases

• Non of the three interventionNon of the three intervention procedures was appliedprocedures was applied

• No clinical data were collected forNo clinical data were collected for primary and secondary outcomesprimary and secondary outcomes

Exclusion critereaExclusion criterea

Jadad composite scale

used to score the included trials (from 0 to 5

points ) as assesses descriptions of :

Randomization ( 0-2 point )

Blinding ( 0-2 point )

dropouts or withdrawals ( 0-1 point )

_______________________________________

** High-quality reports at least with 3 points.

** Low-quality reports with 2 points or less.

Qualitative analysis

All calculations for the current meta-analysis were performed using REVIEW MANAGER (version 5.0 for Windows; the Cochrane Collaboration, Oxford, UK).

This article follows the QUARUM and the Cochrane Collection guidelines (http:// www.cochrane.de ) for reporting meta-analysis.

Statistical methods The meta-analysis was carried according to the Cochrane Reviewer’s Handbook recommended by Cochrane Collaboration. Pooled odd ratio (OR) was calculated using

DerSimonian and Laird method (random- affected model).

The quantitative heterogeneity between trials was evaluated by the DLQ statistic.

A funnel plot was used to test potential publication bias.

RESULTS

Identification of eligible randomized-controlled trials from different medicine databases.

-Clinical data from 595 patients from those 10 trials were pooled to comparing for the current

meta-analysis.

- One trial was with no difference in most baseline characteristics.

- Two trials involved 3 study arms. - No overlapping cases were among the 10 trials.

Baseline characteristics of randomized trials included in the meta-analysis

Qualitative analysis of randomized trials - 9 trials including 512 patients reported the

1-year survival rate.

- 7 trials reported the 2-years and 3-years survival rate separately.

- 1 trial assessed the qualiy of life and used in calculating the secondary outcome.

Treatment arms among the 10 selected randomized controlled studies

Methodological characteristics of randomized trials included in the meta-analysis

Child-Pugh scoreParameter 1 Point 2 Points 3 Points_________________________________________________

Serum bilirubin <2 2–3 >3 (mg/dL)Albumin (g/dL)  >3.5 2.8–3.5 <2.8Prothrombin time 1–3 4–6 >6 ( ↑ S)Ascites None Slight SignificantEncephalopathy None 1–2 3–4_________________________________________________

Grades:A, 5 to 6 points B, 7 to 9 pointsC, 10 to 15 points

Sensitivity analysis of survival

Prognosis of patients reported in the randomized controlled trials included in the meta-analysis

DISCUSSION

The presented study demonstrated that the combination of transcatheter arterial chemoembolization (TACE) with percutaneous ablation (PA) was superior to transcatheter arterial chemoembolization (TACE) or percutaneous ablation (PA) alone for the significant benefit of survival and decrease of tumour recurrence for hepatocellular carcinoma patients.

No enough adverse events data can be pooled for systematic analysis among the selected randomized controlled trials (RCTs), so no safety profile and risk analysis with the different interventions was established in this meta-analysis presentation.

The conclusion The combination of transcatheter arterial

chemoembolization (TACE) with percutaneous

ablation (PA):

1. Improve the overall survival status, especially with percutaneous ethanol injection (PEI), more significantly than a single monotherapy.

2. Decrease the tumour recurrence rate compared with that of monotherapy.

THANKTHANKSS