Selective internal radiation therapy for colorectal metastases in the liver (interventional procedures consultation)
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE
Interventional procedure consultation document
Selective internal radiation therapy for colorectal metastases in the liver
Colorectal liver metastasis is cancer that has spread to the liver from the bowel. Selective internal radiation therapy (known as SIRT) uses radiation put into the patient’s liver to kill the cancer cells. Tiny radioactive ‘beads’ are injected into the artery that supplies blood to the liver (the hepatic artery). The beads become trapped (embolise) in the tiny blood vessels surrounding the cancer, releasing radiation directly onto it. The treatment may be repeated.
The National Institute for Health and Clinical Excellence (NICE) is examining selective internal radiation therapy for colorectal metastases in the liver 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 selective internal radiation therapy for colorectal metastases in the liver.
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- The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.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).
NICE is committed to promoting through its guidance race and disability equality and 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 guidance on interventional procedures. In particular, we aim to encourage people and organisations from groups in the population who might not normally comment on our guidance to do so. We also ask consultees to highlight any ways in which draft guidance fails to promote equality or tackle discrimination and give suggestions for how it might be improved. 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 November 2009
Target date for publication of guidance: February 2010
1 Provisional recommendations
1.1 Current evidence on the safety of selective internal radiation therapy (SIRT) for colorectal metastases in the liver is adequate, but evidence on efficacy is inadequate in quantity. It is therefore recommended that all patients undergoing the procedure be entered into the current UK FOXFIRE trial [[details to be completed at publication]].
1.2 After recruitment to that trial has closed the procedure should only be used with special arrangements for clinical governance, consent and audit or research. These arrangements should also apply to any patients selected for SIRT who are not eligible for the FOXFIRE trial because they have received previous chemotherapy.
1.3 When recruitment to the UK FOXFIRE trial has closed, and for all ineligible patients, clinicians wishing to undertake SIRT for colorectal metastases in the livershould take the following actions.
- Inform the clinical governance leads in their Trusts.
- Ensure that patients and their carers understand the uncertainty about the procedure’s efficacy and provide them with clear written information. In addition, the use of NICE’s information for patients (‘Understanding NICE guidance’) is recommended (available from www.nice.org.uk/IPGXXXpublicinfo). [[details to be completed at publication]]
- Audit and review clinical outcomes of all patients having SIRT for colorectal metastases in the liver(see section 3.1).
1.4 NICE will review the procedure on publication of further evidence.
2 The procedure
2.1 Indications and current treatments
2.1.1 Colorectal cancer is the second most common cancer in women and the third most common cancer in men in the UK. The liver is the most common site for metastases.
2.1.2 Treatment for patients with liver metastases from colorectal cancer is most often done with the expectation of palliation or prolongation of life, rather than cure. For a minority of patients, liver resection with curative intent may be possible, depending on the number, location and size of the metastases. Treatment options currently include systemic chemotherapy, radiotherapy, cryotherapy, arterial embolisation with chemotherapeutic agents, and laser photocoagulation.
2.2 Outline of the procedure
2.2.1 SIRT is used for the treatment of diffuse non-resectable hepatic metastases secondary to colorectal cancer in the absence of extrahepatic disease, and often in combination with chemoembolisation.
2.2.2 The procedure aims to deliver radiation directly into the metastases, while minimising the risk of damage to healthy surrounding tissues. With the patient under sedation, glass or resin spheres containing a radioactive source are injected into the hepatic artery via a transfemoral catheter or a surgically implanted hepatic artery port catheter. The spheres are designed to embolise into the small vessels around the metastases. However, in some patients they may pass through the liver and lodge in the lungs, potentially causing radiation damage. A radioisotope scan is carried out to assess this risk before treatment and patients judged to be at risk receive a reduced dosage.
2.2.3 SIRT may be repeated after a few weeks if lesions persist.
| 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/IP228aoverview. |
2.3 Efficacy
2.3.1 In a randomised controlled trial (RCT) of 70 patients with non-resectable colorectal liver metastases, median survival of patients treated by hepatic artery chemoembolisation alone or in combination with SIRT was 18.4 and 23.5 months respectively (p = 0.14). In an RCT of 21 patients with colorectal liver metastases not treatable by resection or ablation, median survival of patients treated by systemic chemotherapy compared with systemic chemotherapy plus SIRT was 12.8 and 29.4 months respectively (p = 0.025). A case series of 100 patients with extensive colorectal liver metastases (not otherwise defined) reported that estimated survival after SIRT was 48% at 12 months, 18% at 24 months and 9% at 30 months.
2.3.2 In the RCT of 21 patients, median time to disease progression was significantly longer in the SIRT plus chemotherapy group (18.6 months) than in the chemotherapy alone group (3.6 months) (p < 0.0005).
2.3.3 The Specialist Advisers listed key efficacy outcomes as tumour response rates, increased survival and downstaging of disease to allow surgery or chemoresponsiveness.
2.4 Safety
2.4.1 In a case series of 100 patients, 1 patient died from radiation hepatitis 9 weeks after SIRT and another patient died from acute pancreatitis with peptic ulceration due to unintended perfusion of microspheres 10 weeks after SIRT.
2.4.2 In the SIRT plus systemic chemotherapy treatment arm of the RCT of 21 patients, radiation-induced cirrhosis was noted after 1 year in 1 patient and later resolved. A liver abscess occurred in 1 patient (timing not stated) and resolved after drainage.
2.4.3 A case report of 5 patients reported radiation pneumonitis after SIRT in 1 patient. The patient had an estimated 14.8% lung shunting of radiation spheres (symptoms improved with prednisone) (timing of event not stated).
2.4.4 Mild pancreatitis was reported in 3% (1/36) of patients after SIRT and hepatic artery chemotherapy and in 0% (0/34) of patients treated by hepatic artery chemotherapy alone in the RCT of 70 patients (significance and timing of event not stated).
2.4.5 The Specialist Advisers listed adverse events as pain, vomiting, anorexia, fatigue, portal hypertension, radiation sensitisation and potential problems in delivery and distribution of radioembolic material when antiangiogenic chemotherapeutic agents have previously been used. They considered theoretical adverse events to include cholecystitis and radiation dermatitis.
2.5 Other comments
2.5.1 The Committee noted that since publication of guidance in 2004 very little evidence has been published on this procedure. It was considered that recommending recruitment into the FOXFIRE trial would enhance the availability of published evidence for a future review by NICE.
3 Further information
3.1 This guidance requires that clinicians undertaking the procedure make special arrangements for audit. NICE has identified relevant audit criteria and is developing an audit tool (which is for use at local discretion), which will be available when the guidance is published.
3.2 This document is a review of the NICE interventional procedures guidance 93 published in 2004. For related NICE guidance see www.nice.org.uk.
Bruce Campbell
Chairman, Interventional Procedures Advisory Committee
October 2009
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.