Interventional procedure consultation document

Irreversible electroporation for the treatment of liver metastases

Treating cancer that has spread to the liver using focused electrical fields

When cancer has spread from other parts of the body to the liver the tumours are called liver metastases. Irreversible electroporation is a process that uses electrical fields to kill cancer cells. It is applied directly to the tumour through special needles. The main difference between this procedure and thermal techniques for destroying liver metastases is that it does not produce extreme heat or cold.

The National Institute for Health and Clinical Excellence (NICE) is examining irreversible electroporation for the treatment of liver metastases and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. NICE’s Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about irreversible electroporation for the treatment of liver metastases.

This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:

• comments on the provisional recommendations
• the identification of factual inaccuracies
• additional relevant evidence, with bibliographic references where possible.

Note that this document is not NICE’s formal guidance on this procedure. The recommendations are provisional and may change after consultation.

The process that NICE will follow after the consultation period ends is as follows.

• The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
• The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.

For further details, see the Interventional Procedures Programme manual, which is available from the NICE website (www.nice.org.uk/ipprogrammemanual).

Through its guidance NICE is committed to promoting race and disability equality, equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our interventional procedures guidance. In particular, we aim to encourage people and organisations from groups who might not normally comment on our guidance to do so.

In order to help us promote equality through our guidance, we should be grateful if you would consider the following question:

Are there any issues that require special attention in light of NICE’s duties to have due regard to the need to eliminate unlawful discrimination and promote equality and foster good relations between people with a characteristic protected by the equalities legislation and others?

Please note that NICE reserves the right to summarise and edit comments received during consultations or not to publish them at all where in the reasonable opinion of NICE, the comments are voluminous, publication would be unlawful or publication would otherwise be inappropriate.

Closing date for comments: 22 May 2012

Target date for publication of guidance: 25 August 2012

 

1   Provisional recommendations

1.1   Current evidence on the safety and efficacy of irreversible electroporation for the treatment of liver metastases is limited in quantity and quality. Therefore, this procedure should only be used in the context of research. In particular, studies should report local and systemic safety outcomes and the effect of the procedure on local tumour control and survival.

 

2   The procedure

2.1   Indications and current treatments

2.1.1   Liver metastases are most commonly caused by colorectal cancer but may also result from other malignancies, such as lung and gastric cancer. Treatment of liver metastases depends on their extent and location. Treatment options include surgical resection, thermal ablation, chemotherapy, different types of arterial embolisation, external beam radiotherapy and selective internal radiation therapy. Irreversible electroporation is a non-thermal cell-destruction technique which may allow more targeted destruction of cancerous cells with less damage to surrounding supporting connective tissue, for example nearby blood vessels and nerves, compared with 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 cells to a powerful electrical field using high-voltage direct current. This creates multiple holes in the cell membrane, irreversibly damaging 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 used to prevent muscle spasms. 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 under imaging guidance. A series of very short electrical field pulses are delivered over several minutes to ablate the tumour. The electrodes are then repositioned to extend the zone of electroporation until the entire tumour and an appropriate margin have been ablated. Cardiac synchronisation is used to minimise the risk of arrhythmias.

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, available at www.nice.org.uk/guidance/IP/838/overview

 

2.3   Efficacy

2.3.1   In a case series of 38 patients (including 69 procedures for tumours in the liver, lung and kidney), a response rate of 50% was reported in 45 procedures to treat liver metastases (patient number not reported; response rate was not defined; exact timing of assessment unclear). Liver metastases larger than 5 cm in any dimension showed no response in terms of tumour control and all patients with liver metastases had other lesions which progressed.

2.3.2   The Specialist Advisers listed key efficacy outcomes as survival (including progression-free survival and overall survival), local tumour control and/or tumour recurrence rate, and preservation of vascular and biliary structures.

 

2.4   Safety

2.4.1   The case series of 38 patients reported cardiac arrhythmia in 6 patients (4 patients had ventricular tachycardia, 1 patient had supraventricular tachycardia and 1 patient had atrial fibrillation. Four of these patients had electrocardiography (ECG) synchronisation and 2 did not. All the arrhythmias resolved spontaneously except for atrial fibrillation in 1 patient, which was treated by cardioversion.

2.4.2   A case series of 21 patients reported transient ventricular tachycardia in 25% (7/28) of procedures. In 4 of the 7 procedures arterial blood pressure was ‘markedly decreased’ (not defined). A case series of 18 procedures reported ventricular tachycardia associated with a fall in blood pressure in 1 patient; ECG synchronisation was not used in this patient.

2.4.3   A case series of 45 patients, and the case series of 38 and 21 patients (all with different types of tumours) reported pneumothorax in 14% (7/50), 4% (3/69) and 11% (3/28) of procedures respectively. In the case series of 45 patients, 6 were treated with small calibre thoracostomy tubes (it was not stated whether patients were treated for lesions in the liver). 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, 1 pneumothorax occurred after transabdominal placement of electrodes in the liver; the other 2 occurred in the lung treatment group as a result of electrode insertion.

2.4.4   The case series of 21 patients reported contractions of the entire upper body, similar to that seen with a grand mal seizure, after each electrical pulse stimulation in inadequately paralysed patients (patient number not reported).

2.4.5   An analysis of 45 patients treated by irreversible electroporation for primary and secondary liver cancer, recorded in the Soft Tissue Ablation Register dataset (n = 150), reported 9 adverse events in 10% (5/51) of procedures. These included acute renal failure, cholangitis caused by biliary stent occlusion, neurogenic bladder, abdominal pain, flank pain, dehydration, leukocytosis and urinary tract infection. All these resolved (with or without treatment).

2.4.6   The case series of 21 patients reported transient increases in systolic blood pressure of approximately 20 to 30 mm Hg after treatment cycles in all patients. The case series of 45 patients reported transient hypertension during the procedure in 1 patient.

2.4.7   The case series of 38 patients reported increases in alanine aminotransferase (ALT) level of between 19 and 1747 U/L 24 hours after 95% (40/42) of procedures (ALT levels available for 42 of 49 liver tumour ablation procedures only). Levels returned to normal or baseline at 1-month follow-up after 98% (39/40) of the procedures. The same case series reported transient increases in bilirubin level, which returned to normal or baseline levels at 1-month follow-up, in 18% (9/49) of liver tumour ablation procedures.

2.4.8   The Specialist Advisers reported an anecdotal adverse event of post-ablation syndrome (flu-like symptoms, tiredness and lethargy lasting for 2–3 days). They listed theoretical adverse events as puncture or damage of non-target organs, sepsis, tumour seeding in needle tracks and bleeding.

 

3   Further information

3.1   For related NICE guidance see www.nice.org.uk

Bruce Campbell

Chairman, Interventional Procedures Advisory Committee

April, 2012

_{Personal data will not be posted on the NICE website. In accordance with the Data Protection Act names will be anonymised, other than in circumstances where explicit permission has been given.}

_{It is the responsibility of consultees to accurately cite academic work in order that they can be validated.}