Interventional procedure consultation document

Irreversible electroporation for treating primary lung cancer and metastases in the lung

Treating cancer in the lungs using pulses of electricity

Cancer that starts in the lungs is called primary lung cancer. When cancer has spread from other parts of the body to the lung the tumours are called lung metastases. Irreversible electroporation is a process that uses electrical pulses to kill cancer cells. They are applied directly to the tumour through special needles. The main difference between this procedure and thermal techniques for destroying tumours is that it does not produce extreme heat or cold. This means that it may cause less damage to healthy surrounding tissues than some other procedures.

The National Institute for Health and Clinical Excellence (NICE) is examining irreversible electroporation for treating primary lung cancer and metastases in the lung 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 treating primary lung cancer and metastases in the lung.

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• The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.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: 18 September 2012

Target date for publication of guidance: 23 January 2013

1   Provisional recommendations

1.1   Current evidence on the safety and efficacy of irreversible electroporation for treating primary lung cancer and metastases in the lung is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research. In particular, studies should report the effect of the procedure on local tumour control and patient survival.

2   The procedure

2.1   Indications and current treatments

2.1.1   Lung cancer is one of the most common cancers in the UK. The symptoms often do not appear until the disease is well established, and the prognosis is generally poor. There are 2 main types of primary lung cancer: small-cell lung cancer and non-small-cell lung cancer. The lung is also a common site for metastases from other primary cancers such as breast and colon cancer.

2.1.2   The choice of treatment for primary lung cancer and for metastases in the lung is influenced primarily by the type of tumour and stage of the disease. Treatments include surgical resection (open or thoracoscopic), chemotherapy, radiotherapy, photodynamic therapy or thermal ablation, or a combination of these. If the tumour protrudes into the major airways, interventional bronchoscopic treatments including diathermy, laser therapy, cryotherapy, brachytherapy or photodynamic therapy may be used. Irreversible electroporation is a non-thermal cell-destruction technique which may allow targeted destruction of cancerous cells with minimal damage to surrounding structures.

2.2   Outline of the procedure

2.2.1The aim of irreversible electroporation is to permanently damage cell membranes, leading to cell death. This is done by applying an intense electrical field using high-voltage direct current. This creates multiple holes in the cell membrane and damages the cell’s homeostasis mechanisms.

2.2.2   The procedure is performed with the patient under general anaesthesia. Use of 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 and positioned 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 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/1022/overview

2.3   Efficacy

2.3.1   A case series of 38 patients with a variety of tumours reported no satisfactory tumour response in any of the 4 patients treated for lung tumours and all 4 patients had progressive disease when assessed by the modified Response Evaluation Criteria in Solid Tumors at 3 months.

2.3.2   The Specialist Advisers listed key efficacy outcomes as patient survival, tumour response on follow-up imaging, local tumour control, time to disease progression, improvement in health-related quality of life and reduction in tumour-related symptoms.

2.4   Safety

2.4.1   The case series of 38 patients reported cardiac arrhythmia in 6 patients (4 ventricular tachycardia, 1 supraventricular tachycardia and 1 atrial fibrillation). Two of these patients had arrhythmias despite the use of cardiac synchronisation. All the arrhythmias resolved spontaneously except for the atrial fibrillation, which was treated by cardioversion. A case series of 21 patients (with different types of tumours) reported transient ventricular tachycardia during 2 out of 3 procedures in patients with lung tumours. In the same case series, arterial blood pressure was ‘markedly decreased’ (not defined) in 4 out of a total of 7 procedures where transient ventricular tachycardia occurred (not stated whether this occurred in the patients with lung tumours). Blood pressure and heart rhythm returned to normal immediately after treatment with no evidence of ischaemia on the electrocardiograph.

2.4.2   A case series of 45 patients (12 lung lesions) reported pneumothorax in 14% (7/50) of procedures. The case series of 38 patients (4 patients with lung cancer) reported 2 cases of pneumothorax (50% incidence). The case series of 21 patients (3 patients with lung cancer) reported 2 cases of pneumothorax (67% incidence).

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

2.4.4   The case series of 38 patients reported collapse of the right upper lobe in 1 patient with advanced lung cancer: the lobe re-expanded spontaneously.

2.4.5   One Specialist Adviser reported an anecdotal adverse event of sepsis. The Specialist Advisers listed theoretical adverse events as tumour seeding, bronchopleural fistula, residual necrotic tissue and changes such as fibrosis.

2.5   Other comments

2.5.1   The Committee noted that most of the published studies included patients with a variety of different types of tumour, among whom there were few with primary lung cancer or metastases in the lung.

2.5.2   The Committee noted the claim that this procedure may cause less damage to surrounding structures (such as major blood vessels) than other types of ablative treatment for lung cancer, but it considered that more evidence is needed to support this.

3   Further information

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

Bruce Campbell

Chairman, Interventional Procedures Advisory Committee

August, 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.}