Yttrium microsphere radioembolisation for advanced hepatocellular carcinoma (primary liver cancer)

Review question

What are the benefits and harms of yttrium-90 microsphere radioembolisation in people with advanced liver cancer compared with other available therapies?

Background
Hepatocellular carcinoma (that is, primary liver cancer) is the most common malignant tumour of the liver and the fifth most common malignant tumour worldwide. In the majority of people, hepatocellular carcinoma is diagnosed at an advanced stage. For these people, treatment options include ablation therapy (which destroys the tumour), embolisation therapy (the use of substances to block or decrease the flow of blood through the hepatic artery to the tumour), radiotherapy, or sorafenib, which is a targeted therapy (a treatment that uses a substance to identify and attack cancer cells while avoiding normal cells). Yttrium microsphere radioembolisation involves the injection of very small spheres that have radioactive material attached to them into the blood supply of the tumour. The radioactivity is supposed to destroy the liver tumour without affecting other parts of the body.

Study characteristics

The review authors searched published medical articles to clarify the role of yttrium microsphere radioembolisation in the treatment of people with advanced liver cancer. The review authors looked for randomised clinical trials (where people were allocated at random to one of two or more treatments groups) in order to perform statistical analysis on which to form conclusions about the intervention. Evidence was current to December 2015.

Key results

The review authors found two small randomised clinical trials, in which 68 people with advanced liver cancer were randomised. One trial compared radioembolisation with chemoembolization. The other trial presented the safety analysis of a study that compared radioembolisation plus sorafenib versus sorafenib alone. These two small trials suggested that this intervention may be as safe as other standard therapies for this disease. We identified five ongoing randomised clinical trials, the results of which have not been finalised.

Quality of the evidence and conclusions

The evidence obtained from the two low quality randomised trials was insufficient to reach conclusions on the potential beneficial and harmful effects of yttrium-90 microsphere radioembolisation for people with advanced hepatocellular carcinoma. More randomised clinical trials are needed.

Authors' conclusions: 

There was insufficient evidence to assess the beneficial and harmful effects of yttrium-90 microsphere radioembolisation for people with unresectable hepatocellular carcinoma. Further randomised clinical trials are mandatory to better assess the potential beneficial and harmful outcomes of yttrium-90 microsphere trans-arterial radioembolisation either as a monotherapy or in combination with other systemic or locoregional therapies versus placebo, no treatment, or other systemic or locoregional therapies for people with unresectable hepatocellular carcinoma.

Read the full abstract...
Background: 

Hepatocellular carcinoma is the most common liver neoplasm and the fifth most common cancer worldwide. Moreover, its incidence has increased dramatically since the mid-2000s. While surgical resection and liver transplantation are the main curative treatments, only around 20% of people with early hepatocellular carcinoma may benefit from these therapies. Current treatment options for unresectable hepatocellular carcinoma include various ablative and trans-arterial therapies in addition to the drug sorafenib.

Objectives: 

To determine the benefits and harms of yttrium-90 microsphere trans-arterial radioembolisation either as a monotherapy or in combination with other systemic or locoregional therapies versus placebo, no treatment, or other similar systemic or locoregional therapies for people with unresectable hepatocellular carcinoma.

Search strategy: 

We reviewed data from the Cochrane Hepato-Biliary Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded. We also checked reference lists of primary original studies and review articles manually for further related articles (cross-references) up to December 2015.

Selection criteria: 

Eligible studies included all randomised clinical trials comparing yttrium-90-90 microsphere radioembolisation either as a monotherapy or in combination with other systemic or locoregional therapies versus placebo, no treatment, or other systemic or locoregional therapies for unresectable hepatocellular carcinoma.

Data collection and analysis: 

The two review authors independently extracted the relevant information on participant characteristics, interventions, study outcomes, and data on the outcomes for this review, as well as information on the design and methodology of the studies. The two review authors assessed risk of bias of the included trials using pre-defined risk of bias domains. We used Trial Sequential Analysis to control the risk of random errors. We assessed the methodological quality with GRADE.

Main results: 

Two randomised clinical trials with 68 participants fulfilled our inclusion criteria. Both trials were at high risk of bias, and we rated the evidence as very low quality. One of the included trials compared radioembolisation versus chemoembolization for intermediate stage hepatocellular carcinoma as classified by the Barcelona Clinic Liver Cancer (BCLC) staging system, while the other included trial was an interim analysis of a randomised trial assessing radioembolisation combined with sorafenib versus sorafenib monotherapy in participants with BCLC-advanced stage hepatocellular carcinoma. The available data were insufficient to perform the planned analyses. Neither of the two trials reported data on all-cause mortality, cancer-related mortality, or time to progression of the tumour. The trial comparing radioembolisation with chemoembolization reported quality of life and serious adverse events, and there were no statistically significant differences between the trial groups with regard to these outcomes at week 12. On the basis of the two included randomised clinical trials, single-session radioembolisation appeared to be as safe as multiple sessions of chemoembolization for intermediate stage hepatocellular carcinoma and had a similar impact on quality of life, but data were too sparse to exclude even major differences. Radioembolisation followed by sorafenib appeared to be as well tolerated as sorafenib alone for advanced stage hepatocellular carcinoma, but data were too sparse to exclude even major differences. We also identified five ongoing studies evaluating the topic of our review.

Share/Save