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19/88 Ablative and non-invasive therapies for hepatocellular carcinoma




The aim of the HTA Programme is to ensure that high quality research information on the effectiveness, costs and broader impact of health technology is produced in the most efficient way for those who use, manage, provide care in or develop policy for the NHS. Topics for research are identified and prioritised to meet the needs of the NHS. Health technology assessment forms a substantial portfolio of work within the National Institute for Health Research and each year about fifty new studies are commissioned to help answer questions of direct importance to the NHS. The studies include both primary research and evidence synthesis.

Research Question: What is the comparative clinical effectiveness of ablative and non-invasive therapies in the management of hepatocellular carcinoma, up to 3 cm in size?  


  1. Interventions: All forms of ablative and non-invasive therapies used in the UK.
  2. Patient/target group: Patients with hepatocellular carcinoma up to 3 cm.
  3. Setting: Secondary and tertiary care.
  4. Study design: An evidence synthesis by a systematic review and meta-analysis to include randomised and non-randomised studies of a wide range of technologies used in the UK, supplemented by a network meta-analysis where suitable evidence is available. The review should consider the use of sub group analyses or stratifying patients by stage of tumour and/or a suitable prognostic score. The research should assess the suitability of the findings to be used in an economic analysis.
    The development of a model of cost effectiveness is not expected as part of this research.
  5. Important outcomes: Overall survival, progression free survival, adverse events and quality of life.
    Other outcomes: Health care utilisation and costs; a list of registered, ongoing or unpublished trials with an assessment of their potential to contribute significantly to the findings of this meta-analysis; and if appropriate, recommendations for further primary research.


Hepatocellular carcinoma (HCC) is the most common primary liver cancer with around 6,000 cases diagnosed each year in the UK. Treatment for HCC depends on a number of factors, including the exact location and stage of the cancer, the state of liver function, patient’s age and general health, and types of treatment previously used. For most patients, treatment with curative intent (liver transplant or resection) is not possible.

However, there are a range of ablative and non-invasive therapies available for treating small HCC, up to 3 cm, when surgery is not an option. These are ablative therapies, which broadly fall into two categories; thermal (extreme heat and cold to cause tumour cell death) and chemical (injection of chemicals to cause tumour cell death).

By contrast, non-invasive therapies are those that do not use extreme temperatures or chemicals, but instead use energy (radiation or electrical currents) or embolisation (blocking blood vessels) to bring about cell damage.

Therapies can include, but are not limited to, the following:

  • Radiofrequency ablation
  • Microwave ablation
  • Laser ablation
  • High-intensity focussed ultrasound
  • Cryoablation 
  • Percutaneous ethanol injection
  • Percutaneous acid injection
  • Irreversible electroporation 
  • Stereotactic ablative radiotherapy 
  • Transarterial chemoembolisation
  • Transarterial embolisation
  • Radioembolisation

This is an active area of research with a wide range of different technologies in use. It is timely to undertake an evidence synthesis of these therapies to increase our understanding of their effectiveness and of their potential role. The Programme Oversight Committee has estimated that the cost of this work should be around £150,000.

Additional commissioning brief background information

A background document is available that provides further information to support applicants for this call. It is intended to summarise what prompted the call and the existing evidence base, including relevant work from the HTA and wider NIHR research portfolio. It was researched and written on the basis of information from a search of relevant sources and databases, and in consultation with a number of experts in the field. If you would like a copy please email

Making an application

If you wish to submit a Stage 1 application for this call, the online application form can be found on the Funding opportunities page.  To select this call, use the filters on the right of the screen or search using the call name and/or number.

Your application must be submitted on-line no later than 1pm on the 4th December 2019. Applications will be considered by the HTA Funding Committee at its meeting in January.

Guidance notes and supporting information for HTA Programme applications are available by clicking the links.

IMPORTANT: Shortlisted Stage 1 applicants will be given eight weeks to submit a Stage 2 application. The Stage 2 application will be considered at the Funding Committee in May.

Applications received after 1300 hours on the due date will not be considered.

Should you have any queries please contact us:


Telephone: Commissioning Funding Committee 02380 595510