Treatment of GIST

This section explains the approach to the treatment of GISTs in the UK and what this should mean for patients.  GISTs are sarcomas so their treatment falls under the national guidelines for sarcomas with additional guidelines specific to GISTs.

Everyone's GIST journey is different but the key elements for most patients are:

• Being treated by GIST specialists - medical experts who have experience of treating large numbers of GIST patients and who have developed first hand experience of this rare cancer.  This means treatment at specialist hospitals or their designated partners.
• Support from a Multi Disciplinary Team (MDT) - there can be two MDTs involved in your care. The first will be the team who will remove your tumour and they will be specialists in the part of your body where the tumour is e.g. stomach, intestines, rectum. This is the Site Specific MDT. The second will be the team concerned with your on-going treatment with drugs, or just surveillance. This is the Sarcoma MDT.
• Identification of the GIST type (Mutational Analysis) - the outcome of this will affect the treatment pathway.
• Surgery - to remove the GISTs if possible.
• Drug treatment - this can be pre-surgery to reduce the tumour size to facilitate its removal and/or post- surgery to reduce the chances of recurrence.
• Monitoring - post initial treatment to check that there has been no recurrence.

Further details can be found below and in our publications especially GIST for Beginners.

The relevant National Institute for Clinical Excellence (NICE) guideline is Improving outcomes for people with sarcoma (2006) which has guidance for the public.  The key aspects include:

• the importance of prompt treatment
• good communication between patients, their families and healthcare professionals
• the importance of treatment being carried out by specialists through referral to a diagnostic clinic at, or linked to, a sarcoma treatment centre (see below).
• the nature of the specialists who should make up your Sarcoma MDT
• the support and rehabilitation that should be available after surgery

The NHS service specification (2019) for the provision of care for people with sarcoma cancer, including gastrointestinal stromal sarcomas states:

People with suspected GIST must be referred according to Network guidelines to a designated diagnostic centre. People with GIST must have their care plan confirmed by a Sarcoma MDT and treatment delivered by services designated by the Sarcoma Advisory Group (SAG). The medical management of GIST cases must be supervised by cancer specialists with experience in the management of people with GIST. These specialists must participate in national audit, contribute to national/international clinical trials where available and be core or designated members of the sarcoma MDT. It is recommended that these specialists have an annual new case load to a service of 24 per annum. Management will be in accordance with British Sarcoma Group guidelines.

The British Sarcoma Group guidelines for the management of GIST (2024) are aimed at specialist medical practitioners but may be of interest if you want to understand more about GISTs, the associated risk factors and possible treatments.  The guidelines include sections on Incidence, Causes (Aetiology), Diagnosis, including risk assessment, Treatment and Follow-up.  They draw on a review of the literature supported by the results of clinical trials or substantive retrospective reports and represent 'a consensus view of current best clinical practice'.

Mutational analysis is a key predictor for the course of the disease and will determine treatment options after the primary GIST has been removed or a biopsy has been taken.  Some mutations respond well to standard drug treatment whilst others are unaffected.  Thus, knowing more about the mutational nature of the GIST guides treatment.

Most GISTs have mutations in either the KIT (ca 80%) or PDGFRA (ca 8%) genes in parts called ‘exons’ which are pieces of DNA that encode proteins.  Other variations include inherited KIT mutated GISTs and BRAF Mutated & NTRK fusion GISTs.

The recommended treatment for each mutation is shown in the National Clinical Practice Guidelines (Figure 1).  Most mutations respond to standard drug treatment but for those that don't consider referral to the specialist PAWS-GIST clinic so that a detailed plan for treatment can be developed.

It is not always easy to identify the specialist sarcoma MDTs that have experience of GISTs (the Service specification covers all sarcomas). A supporting indicator of GIST expertise is to look at where clinical trials are being carried out and whether a hospital is able to perform mutational testing of tumour tissue. which is increasingly important for the treatment of GIST. Hospitals we believe to be currently involved are:

• Beatson Cancer Institute in Glasgow
• Northern Centre for Cancer Care in Newcastle
• The Christie Hospital in Manchester
• Weston Park Hospital in Sheffield
• Queen Elizabeth Hospital Birmingham
• Addenbrooke’s Hospital in Cambridge
• University College Hospital in London
• The Royal Marsden Hospital in London and Sutton (Surrey)
• Velindre Hospital in Cardiff
• Bristol Royal Infirmary
• St James's University Hospital, Leeds
• Oxford University Hospitals NHS Trust
• Royal Liverpool and Broadgreen University Hospitals (including Clatterbridge)

There may be others, and if you know of them do please let us know. All these hospitals receive positive feedback from GCUK members.

There are also hospitals where members of GCUK are very confident in their medical team, and where they have a close relationship with one of the specialist centres listed above.

Surgery to remove all the tumour, or tumours, is usually the first choice, provided this is possible. The tumour, with part of the organ it is attached to, will be removed. The aim is always to remove as much of the surrounding tissues as necessary to ensure that all the GIST cells have gone. In surgical terms this is known as an "R0 resection"

GIST in the Stomach

This will mean removing part or all of the stomach and possibly the spleen as well. The surgeons will try not to remove all the stomach unless it is absolutely necessary, because life after a total gastrectomy is much more difficult than life after a partial gastrectomy. Loss of the spleen is not a big problem: the patient just has to be careful as bacterial infections develop very fast. The patient may be put on antibiotics for life. We have two booklets available giving tips on living with a gastrectomy (partial or total). These are "Living after GI surgery for GIST" and "No Stomach?".  They can both be downloaded from our Publications page.

There is also a very good description of stomach surgery available at www.cancerhelp.org.uk. Follow the links for surgery for stomach cancer.  You can find useful information on eating after  a total or partial gastrectomy on the US National Cancer Institute website - Search for diet and nutrition.

GIST in the intestines

Again, the tumour will be removed with as much of the gut as is necessary to be sure that it has all gone. Losing part of your gut is not usually much of a problem afterwards.

After a GIST has been completely removed (from the stomach or the intestines), some patients have no further problems, especially if the tumour was small, on the stomach, and only growing slowly.

GIST in the liver

GISTs do not usually affect the liver first. GISTs in the liver are almost always secondaries from the stomach or gut. Liver surgery has only been possible fairly recently. Great advances are being made in the methods used, and it is now sometimes possible to remove GISTs from the liver surgically. It is also sometimes possible to use a technique called Radio Frequency Ablation (or RFA). This is done through a tiny hole, and is much less invasive than surgery, but is only used on small tumours.

Imatinib

GIST Drug Treatments - GLIVEC and SUTENT

Imatinib is a targeted drug designed with a very specific molecular shape to fit into a space in a specific molecule. In this case it fits into a tyrosine kynase molecule and stops it working. Imatinib is available in a number of versions provided by different manufacturers and with different brand names e.g. Glivec, Accord, Teva, Amarox and Sandoz,

See a: Summary of the NICE guidelines for the use of Glivec® for the treatment of GIST.

If a GIST cannot easily be removed, either because it is too large, or it is in a difficult place, imatinib will usually be prescribed. In 85% of patients it will stop the GIST growing and in many cases the tumour will shrink. This may mean that surgery to remove it becomes possible.

Imatinib does not "cure" the underlying condition. The condition sends out messages "make tumours" to the body. Imatinib stops the messages getting through, so growth of the tumour is inhibited.  Typically patients are on imatinib for three years post-surgery.

Treatment with Sutent®

Sutent is the trade name for the generic drug called sunitinib, marketed by Pfizer. Both these terms are used. Sutent is a tyrosine kinase inhibitor working through multiple targets to deprive tumour cells of the blood and nutrients needed to grow.

Patients whose tumours become resistant to Glivec, or who cannot tolerate the drug, can be treated with Sutent. Sutent has been proved to be a valuable drug for GIST patients, increasing the average overall survival. There is evidence that patients who have Exon 9 mutatons, or Wild-type GIST tend to respond best to Sutent.

Treatment with Regorafenib (Stivarga)

This drug has now been approved for GIST in the European Union and is available for oncologists to prescribe after patients have progressed or are intolerant to imatinib and/or sunitinib. Regorafenib is the standard third line treatment for GIST patients in England, Scotland and Wales. If you live in Northern Ireland your doctor can apply to your local Health and Social Care (HSC) Trusts through the Individual Funding Requests (IFR) process.

Other Drugs

Other drugs are being developed, and some are now being tested in clinical trials. (See our Clinical Trials page.)