Elsevier

Cancer Treatment Reviews

Volume 32, Issue 8, December 2006, Pages 594-606
Cancer Treatment Reviews

Tumour review
Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies

https://doi.org/10.1016/j.ctrv.2006.08.002Get rights and content

Summary

Background

Although transarterial chemoembolization (TACE) improves survival in patients with hepatocellular carcinoma (HCC), it is not known if TACE combined with other treatments is beneficial. Aim: To evaluate the evidence for improved outcomes in HCC with a multimodal treatment approach involving TACE.

Method

PubMed search for all cohort and randomized trials (n = 84) evaluating TACE combined with other therapies; meta-analysis performed where appropriate.

Results

A meta-analysis involving 4 RCTs showed a significant decrease in mortality favouring combination treatment (TACE plus percutaneous ablation) compared to monotherapy in patients with either small (<3 cm) or large HCC nodules (>3 cm) (OR, 0.534; 95% CI, 0.288–0.990; p = 0.046). TACE combined with local radiotherapy improved survival in patients with tumour thrombosis of the portal vein in 7 non-randomized studies. Two RCTs and 13 non-randomized studies showed that TACE prior to hepatic resection does not improve survival nor tumour recurrence. Conversely, 2 RCTs and 5 comparative studies showed that transarterial injection of chemotherapeutic drugs mixed with lipiodol (TOCE) following hepatectomy confers survival benefit and less tumour recurrence. TACE before liver transplantation is safe and reduces drop-out rate from the waiting list, but there is no current evidence of improvement in subsequent survival or recurrence rate.

Conclusions

A combined approach involving TACE and percutaneous ablation improves survival. Adjuvant TOCE improves outcome after hepatectomy. TACE is useful to control tumours burden while on the waiting list for OLT. Multimodal treatment seems to be the best way to optimize TACE outcomes in HCC.

Introduction

Liver cancer is the fifth most common cancer in the world and its incidence is increasing worldwide. In 80% of cases hepatocellular carcinoma (HCC) is a complication of cirrhosis and is the main cause of death among these patients in Europe.1

Consensus about a common treatment strategy for patients with HCC has not been reached worldwide, even if several proposals have been published. The most recent one is the Barcelona-Clinic Liver Cancer (BCLC) staging classification and treatment schedule.1 Since radical therapies, including resection, liver transplantation and percutaneous ablation (percutaneous ethanol injection (PEI) and radiofrequency (RF)), are applicable in only 30–40% of patients with HCC1 according to this algorithm, the majority need different approaches.

Several alternative therapeutic strategies have been proposed but only chemoembolization has been shown to improve survival.2 Although this procedure is becoming more common in clinical practice, there is no consensus about the optimal schedule or technique of embolization.3

In particular, the role of transarterial chemoembolization (TACE) either compared to other therapies or combined with other therapies has not been subject to guidelines or been part of therapeutic algorithms. Therefore, the aim of this review is to evaluate the evidence for improved outcomes with TACE added to other therapies for HCC.

Section snippets

Search strategy and selection criteria

Studies were identified by searching Medline using the following key words: “hepatocellular carcinoma” or “HCC” or “hepatic tumour” or “liver tumour” or “hepatic cancer” or “liver cancer” and “TACE” or “TAE” or “chemoembolization” or “embolization” and “clinical trials” in English and non-English language. We also manually searched general reviews on HCC and references from published clinical trials.

Articles were excluded if they dealt with liver metastases, recurrence of HCC after hepatectomy,

Chemoembolization as sole therapy versus other therapies

There were 11 studies involving 5131 patients comparing TACE to other treatments: radiofrequency ablation (n = 1), percutaneous acetic acid injection (PAI) (n = 1), percutaneous ethanol injection (n = 1) 131iodine-lipiodol radiotherapy (n = 2), liver resection (n = 5) and transplantation (n = 1).

The median number of patients in each study was 117 (range: 39–3225). Two were RCTs4, 5 and three were multicenter;6, 7, 8 the mean duration of each study was 4 ± 1.5 years. Six were conducted in Asia (3 Japanese, 1

Conclusion

Chemoembolization has been used in patients with HCC not suitable for curative therapy according to the BCLC treatment schedule. In this subset of selected patients it improves survival compared to supportive treatment or systemic chemotherapy.2 Currently, none of the therapeutic algorithms used for HCC consider the role of TACE combined with other therapies. The aim of our review was to evaluate the evidence for improved outcomes in HCC with a multimodal treatment approach involving TACE.

Four

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