Percutaneous ethanol injection for liver metastases

Is local destruction of the cancer that spread to the liver with percutaneous ethanol injection beneficial?

Review question

What is the effect of using percutaneous ethanol injection (PEI) to destroy any cancer metastases in the liver? Metastases are new cancer sites that are found in parts of the body other than the site of the original cancer. We were looking for any randomised trial (a study in which patients are allocated to groups by a play of chance) assessing effects of PEI in people with metastases in the liver from cancer of any location compared with no PEI with or without co-interventions. We looked at effects of PEI on risk of death, progression of disease, health-related quality of life, and adverse events (unwanted effects caused by the intervention).

Background

When cancer spreads in the body (metastasis), one of the most common sites of metastasis is the liver. Besides cancers of the liver (primary liver cancer), liver metastases from colorectal cancer are the most common cancers affecting the liver. More than half of people who have cancer spread to the liver die of complications. Metastases in the liver can be destroyed by several different methods, one of them being PEI. This procedure is performed under ultrasound or computed tomography guidance; a special needle is placed at the cancer site and is subsequently used to inject alcohol with the goal of killing cancer tissues. Ultrasound and computed tomography are imaging procedures. Alcohol induces tumour destruction by drawing water out of tumour cells (dehydrating them), thereby altering (denaturing) the structure of the cellular proteins.

Search results and study characteristics

We last searched for evidence on 10 September 2019. We included only one randomised trial comparing percutaneous intratumour ethanol injection in combination with transcatheter arterial chemoembolisation (TACE; a liver-directed treatment whereby chemotherapy is administered through the catheter directly to blood vessels supplying the tumour) to TACE alone. Forty-eight people with liver metastases were included; 25 received PEI with TACE, and 23 received TACE alone. Primary tumours were colon, stomach, pancreas, lung, breast, and ovary cancers.

The included study did not provide information on funding nor on conflict of interest.

Key results

Results of one small randomised clinical trial do not show beneficial or harmful effects of adding percutaneous intratumour ethanol injection to TACE in people with liver metastases with respect to mortality or local recurrence in comparison with TACE alone. Participants were followed for between 10 and 43 months. The tumour necrosis was larger in the combined treatment group. Trial authors reported some adverse events but gave very few details. We found no data on time to mortality, failure to clear liver metastases, recurrence of liver metastases, health-related quality of life, or time to progression of liver metastases.

Quality of evidence

We judged the evidence to be of very low certainty because the identified study was at high risk of bias, had a relatively small sample size, described few events overall, and reported inconclusive results.

Authors' conclusions: 

Evidence for the effectiveness of PEI plus TACE versus TACE in people with liver metastases is of very low certainty and is based on one small randomised clinical trial at high risk of bias. Currently, it cannot be determined whether adding PEI to TACE makes a difference in comparison to using TACE alone. Evidence for benefits or harms of PEI compared with no intervention, other ablation methods, or systemic treatments is lacking.

Read the full abstract...
Background: 

The liver is affected by two of the most common groups of malignant tumours: primary liver tumours and liver metastases from colorectal carcinoma or other extrahepatic primary cancers. Liver metastases are significantly more common than primary liver cancer, and the reported long-term survival rate after radical surgical treatment is approximately 50%. However, R0 resection (resection for cure) is not feasible in the majority of patients; therefore, other treatments have to be considered. One of these is percutaneous ethanol injection (PEI), which causes dehydration and necrosis of tumour cells, accompanied by small-vessel thrombosis, leading to tumour ischaemia and destruction of the tumour.

Objectives: 

To assess the beneficial and harmful effects of percutaneous ethanol injection (PEI) compared with no intervention, other ablation methods, or systemic treatments in people with liver metastases.

Search strategy: 

We searched the following databases up to 10 September 2019: the Cochrane Hepato-Biliary Group Controlled Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE Ovid; Embase Ovid; Science Citation Index Expanded; Conference Proceedings Citation Index – Science; Latin American Caribbean Health Sciences Literature (LILACS); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We also searched clinical trials registers such as ClinicalTrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the US Food and Drug Administration (FDA) (17 September 2019).

Selection criteria: 

Randomised clinical trials assessing beneficial and harmful effects of percutaneous ethanol injection and its comparators (no intervention, other ablation methods, systemic treatments) for liver metastases.

Data collection and analysis: 

We followed standard methodological procedures as outlined by Cochrane. We extracted information on participant characteristics, interventions, study outcomes, study design, and trial methods. Two review authors performed data extraction and assessed risk of bias independently. We assessed the certainty of evidence by using GRADE. We resolved disagreements by discussion.

Main results: 

We identified only one randomised clinical trial comparing percutaneous intratumour ethanol injection (PEI) in addition to transcatheter arterial chemoembolisation (TACE) versus TACE alone. The trial was conducted in China and included 48 trial participants with liver metastases: 25 received PEI plus TACE, and 23 received TACE alone. The trial included 37 male and 11 female participants. Mean participant age was 49.3 years. Sites of primary tumours included colon (27 cases), stomach (12 cases), pancreas (3 cases), lung (3 cases), breast (2 cases), and ovary (1 case). Seven participants had a single tumour, 15 had two tumours, and 26 had three or more tumours in the liver. The bulk diameter of the tumour on average was 3.9 cm, ranging from 1.2 cm to 7.6 cm.

Participants were followed for 10 months to 43 months. The trial reported survival data after one, two, and three years. In the PEI + TACE group, 92%, 80%, and 64% of participants survived after one year, two years, and three years; in the TACE alone group, these percentages were 78.3%, 65.2%, and 47.8%, respectively. Upon conversion of these data to mortality rates, the calculated risk ratio (RR) for mortality at last follow-up when PEI plus TACE was compared with TACE alone was 0.69 (95% confidence interval (CI) 0.36 to 1.33; very low-certainty evidence) after three years of follow-up. Local recurrence was 16% in the PEI plus TACE group and 39.1% in the TACE group, resulting in an RR of 0.41 (95% CI 0.15 to 1.15; very low-certainty evidence). Forty-five out of a total of 68 tumours (66.2%) shrunk by at least 25% in the PEI plus TACE group versus 31 out of a total of 64 tumours (48.4%) in the TACE group. Trial authors reported some adverse events but provided very few details. We did not find data on time to mortality, failure to clear liver metastases, recurrence of liver metastases, health-related quality of life, or time to progression of liver metastases.

The single included trial did not provide information on funding nor on conflict of interest.

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