2 The procedure

2.1 Indications and current treatments

2.1.1 The most common types of primary liver cancer are hepatocellular carcinoma (also known as hepatoma) and cholangiocarcinoma.

2.1.2 Treatment for primary liver cancer depends on a number of factors, including the location and stage of the cancer and how well liver function is preserved. Treatment options include surgical resection, thermal ablation, systemic chemotherapy, transarterial chemoembolisation and selective internal radiation therapy. Liver transplantation may be appropriate for some patients. For most patients, treatment with curative intent is not possible. Irreversible electroporation is a non-thermal cell-destruction technique, which is claimed to allow targeted destruction of cancerous cells with less damage to surrounding structures (such as major blood vessels and bile ducts) than other types of treatment.

2.2 Outline of the procedure

2.2.1 The aim of irreversible electroporation is to destroy cancerous cells by subjecting them to a series of short electrical pulses using high-voltage direct current. This creates multiple holes in the cell membrane, irreversibly damaging the cell's homeostasis mechanisms and leading to cell death.

2.2.2 The procedure is performed with the patient under general anaesthesia. A neuromuscular blocking agent is essential to prevent uncontrolled severe muscle contractions caused by the electric current. Bipolar or unipolar electrode needles are introduced percutaneously (or by open surgical or laparoscopic approaches) and guided into place in and adjacent to the target tumour using imaging guidance. A series of very short electrical pulses is delivered over several minutes to ablate the tumour. The electrodes may then be repositioned to extend the zone of electroporation until the entire tumour and an appropriate margin have been ablated. Cardiac synchronisation is used to time delivery of the electrical pulse within the refractory period of the heart cycle, minimising the risk of arrhythmia.

Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview.

2.3 Efficacy

2.3.1 A case series of 38 patients including 11 patients with primary liver cancer (22 tumours) reported a complete response in 64% (14/22) of these primary tumours, progressive disease in 14% (3/22) and stable disease in 23% (5/22) at 3-month follow-up, assessed by modified 'Response Evaluation Criteria in Solid Tumors' (modified RECIST). In patients with primary hepatocellular carcinoma, 82% (14/17) of targeted tumours were completely ablated at 3-month follow-up.

2.3.2 A case series of 44 patients (including 14 patients with hepatocellular carcinoma) reported local recurrence-free survival of 90% at 6 months and 50% at 12 months.

2.3.3 The Specialist Advisers listed key efficacy outcomes as completeness of tumour ablation, survival and relapse-free interval.

2.4 Safety

2.4.1 The case series of 38 patients reported transient cardiac arrhythmia in 6 patients (4 patients had ventricular tachycardia, 1 patient had supraventricular tachycardia and 1 patient had atrial fibrillation). Two of these patients had cardiac synchronisation and 4 did not. All of the arrhythmias resolved without treatment except for atrial fibrillation in 1 patient, which was treated by cardioversion.

2.4.2 A case series of 21 patients with primary or metastatic cancer (liver, kidney and lung) reported transient ventricular tachycardia during 25% (7/28) of procedures. In 4 of the 7 procedures, arterial blood pressure was 'markedly decreased' (not defined).

2.4.3 A case series of 49 patients with hepatocellular carcinoma or colorectal liver metastases reported pneumothorax in 4% (2/49) of patients. In the case series of 38 patients, 1 pneumothorax was related to liver ablation and a Heimlich valve was inserted with resolution 'in a few hours'. In the case series of 21 patients with primary or metastatic cancer, 1 pneumothorax occurred after transabdominal placement of electrodes in the liver and the other 2 were in patients having treatment for lung metastases. The case series of 21 patients with primary hepatocellular carcinoma reported pneumothorax in 1 patient, which was managed conservatively.

2.4.4 A case series of 26 patients with hepatocellular carcinoma reported haemothorax due to a needle puncture of an intercostal artery (treated by drainage) in 1 patient.

2.4.5 A case series of 44 patients with primary or metastatic liver cancer reported 1 patient with a neurogenic bladder, which resolved without treatment within 30 days.

2.4.6 The case series of 26 patients reported transient hepatic decompensation in 1 patient, which resolved without treatment.

2.4.7 The case series of 38 patients reported increases in alanine aminotransferase (ALT) level of between 19 and 1747 international units per litre 24 hours after 95% (40/42) of procedures (ALT levels available for 42 of 49 liver tumour ablation procedures). Levels returned to normal or baseline at 1-month follow-up after 98% (39/40) of the procedures.

2.4.8 The Specialist Advisers listed theoretical adverse events as tumour seeding along the needle tracks; injury to structures such as bile ducts, blood vessels, diaphragm and lung; nerve damage; portal vein thrombosis; and liver abscess.

2.5 Other comments

2.5.1 The Committee noted that most of the published studies included patients with different tumour types and that only a few patients had primary liver cancer.

2.5.2 The Committee noted the claim that this procedure may be associated with less damage to surrounding structures (such as major blood vessels and bile ducts) than other ablative techniques, but considered that more evidence is needed to support this.

  • National Institute for Health and Care Excellence (NICE)