Interventional procedure consultation document

Selective internal radiation therapy for primary hepatocellular carcinoma

Using internal radioactive beads to treat primary hepatocellular carcinoma

Hepatocellular carcinoma is a type of primary liver cancer (a cancer that begins in the liver).

Selective internal radiation therapy (known as SIRT) aims to kill cancer cells, causing as little damage to the surrounding tissues as possible. Tiny radioactive ‘beads’ are injected into branches of the artery that supplies blood to the liver. The beads then become trapped in the small blood vessels supplying the cancer, releasing radiation directly into the cancer cells and killing them.

The National Institute for Health and Clinical Excellence (NICE) is examining selective internal radiation therapy for primary hepatocellular carcinoma 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 primary hepatocellular carcinoma.

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• The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.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, advance equality of opportunity, 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: 17 December 2012

Target date for publication of guidance: March 2013

1                      Provisional recommendations

1.1                  Current evidence on the efficacy and safety of selective internal radiation therapy (SIRT) for primary hepatocellular carcinoma is adequate for use with normal arrangements for clinical governance, consent and audit. Uncertainties remain about its comparative effectiveness, and clinicians are encouraged to enter eligible patients into trials comparing the procedure against other forms of treatment.

1.2                  Patients with primary hepatocellular carcinoma should be selected for treatment by SIRT or for entry into trials by a multidisciplinary hepatobiliary cancer team.

1.3                  SIRT should only be carried out by clinicians with specific training in its use and in techniques to minimise the risk of side effects of the procedure.

1.4                  Clinicians undertaking the procedure for patients outside research studies should 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/guidance/IPG401/publicinfo).
• Clinicians should enter details for all patients undergoing selective internal radiation therapy for non resectable colorectal metastases in the liver onto the national SIRT register and review clinical outcomes locally.

 

2                      The procedure

2.1                  Indications and current treatments

2.1.1                      Hepatocellular carcinoma is the most common type of primary liver cancer.

2.1.2                      The choice of treatment for primary hepatocellular carcinoma depends on a number of factors, including the exact location, stage of the cancer and the patient’s liver function. The aim of treatment is normally to slow progression with a view to improving quality of life and prolonging survival.  In some patients surgical removal with curative intent may be possible: this may sometimes be achieved by downstaging the tumour using other treatment modalities first.  Treatment options include chemotherapy (intravenous or by hepatic artery infusion), surgical excision, transarterial chemo-embolisation (TACE) and radiofrequency ablation.

2.2                  Outline of the procedure

2.2.1                      SIRT for primary hepatocellular carcinoma involves infusion of microspheres loaded with yttrium-90, which aims to deliver radiation directly into the tumour, minimising the risk of radiation damage to healthy surrounding tissues.

2.2.2                      Before undertaking the treatment, a nuclear medicine liver-to-lung shunt study is usually carried out to assess the risk of radioactive microspheres causing lung damage. Radiographic imaging and selective coil embolisation of arteries to the stomach and duodenum are also commonly carried out.  

2.2.3                      With the patient under local anaesthesia, radioactive microspheres that are designed to embolise in the small arteries are injected into branches of the hepatic artery, usually by a percutaneous femoral approach.

2.2.4                      The procedure may be repeated depending on the response achieved.

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/1038/overview

2.3                  Efficacy

2.3.1                      A non-randomised comparative study of 86 patients, with 43 treated by SIRT and 43 treated by TACE, reported overall median survival of 42 months in the SIRT group compared with 19 months in the TACE group (p=0.008). A non-randomised comparative study of 71 patients, with 27 treated by SIRT and 44 treated by chemo-embolisation, reported 1-year survival rates of 16% (4/27) in patients treated by SIRT compared with 20% (9/44) in patients treated by chemo-embolisation (level of significance not reported).

2.3.2                      The non-randomised comparative study of 86 patients reported a partial response (assessed using World Health Organization [WHO] criteria) in 61% (26/43) of the patients treated by SIRT (median follow-up of 34 months) and 37% (13/35) of the patients treated by TACE (median follow-up of 52 months). This difference was not significant (p=0.07).

2.3.3                      The non-randomised comparative study of 86 patients reported downstaging from stage T3 to stage T2 in 58% (25/43) of patients in the SIRT group and 31% (11/35) of patients in the TACE group at a median time of ‘within 6 months’ (p=0.02).

2.3.4                      A case series of 291 patients treated by SIRT reported that 12% (34/291) of patients underwent treatment with curative intent: 32 went on to have liver transplants and 2 had resection of their tumours (median follow-up 31 months).

2.3.5                      A case series of 35 patients treated by SIRT reported that 8 patients were downstaged and underwent liver transplantation (timing ranged from 12 days to 210 months after treatment).

2.3.6                      The non-randomised comparative study of 86 patients reported a median time to overall progression of disease of 33 months in the SIRT group compared with 13 months in the TACE group (level of significance not reported).

2.3.7                      A non-randomised comparative study of 28 patients, with 14 treated by SIRT and 14 treated by cisplatin, reported health-related quality of life measured on the Functional Assessment of Cancer Therapy – Hepatobiliary (FACT-Hep) questionnaire (scored on a scale of 0–4; higher score indicating better quality of life or fewer symptoms). The overall health-related quality of life score was 47 for the SIRT group (n=9) and 52 for the cisplatin group (n=5) at 6-month follow-up. This difference was reported as not significant (p value not reported).

2.3.8                      The Specialist Advisers listed efficacy outcomes as tumour response, overall survival, quality of life, increased time to progression, downsizing or downstaging to potentially curative treatments, and bridging to liver transplantation.

2.4                  Safety

2.4.1                      Death within 30 days was reported in 7% (2/27) of patients treated by SIRT and in 9% (4/44) of patients treated by chemo-embolisation in the non-randomised comparative study of 71 patients.

2.4.2                      Radiation pneumonitis was reported in 4 patients between 1 and 6 months after treatment by SIRT (a scan to determine lung shunting had been performed before SIRT) in a case series of 80 patients. All patients were treated by steroids. Three patients died of progressive respiratory failure and 1 from progressive cancer.

2.4.3                      Ulceration caused by radiation was reported in 11% (3/27) of patients who were treated by SIRT (after prophylactic coil embolisation of the gastroduodenal arteries) and gastritis and/or temporary ulceration was reported in 20% (9/44) of patients treated by chemo-embolisation in the non-randomised comparative study of 71 patients. Two patients in the SIRT group  were treated by subtotal gastrectomy; there were no further details on the other patient. (median follow-up 6 months).

2.4.4                      Cholecystitis reported as ‘possibly related to treatment’ occurred in 2 patients in the case series of 80 patients treated by SIRT (both treated by emergency cholecystectomy 21 and 243 days after treatment).

2.4.5                      Radiation-induced biliary stricture was described in a case report. The patient became progressively jaundiced and fatigued, with mild or moderate bilirubin toxicity (timing not reported).

2.4.6                      Bone marrow suppression resulting in transient thrombocytopenia was reported 1 month after SIRT in a case report.

2.4.7                      Postembolisation syndrome was reported in 60% of patients in both the SIRT and TACE groups (absolute numbers not reported) in the non-randomised comparative study of 86 patients. The symptoms (fatigue and transient non-specific flu-like symptoms) lasted 7 to 10 days in the SIRT group (no further details).

2.4.8                      The Specialist Advisers listed additional anecdotal adverse events as fibrosis and skin ulceration; and additional theoretical adverse events as liver failure, portal hypertension, and radiation-induced liver disease.

2.5                  Other comments

2.5.1                      The Committee noted wide variation in the published evidence about prior and adjunctive treatments that patients received. This made interpretation of the effect of SIRT difficult. 

3                      Further information

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

Bruce Campbell

Chairman, Interventional Procedures Advisory Committee

November, 2012