Introducing GIST
Gastrointestinal stromal tumour usually forms on the stomach or the upper intestine. Occasionally it is found lower down the GI system. It is a cancer of the cells which form the structure of the stomach and intestine, not a cancer of the linings of the organ itself (that would be a carcinoma). This means that it is usually painless and until it causes a swelling, or discomfort by pressing on other organs, or ruptures causing blood loss and anaemia, it may remain undetected.
Many low grade GISTs are found during other forms of GI surgery and are removed. They may be identified as a benign tumour, or one with a very low risk of recurrence, and in the past some surgeons did not even tell their patients what they had found. It does mean that there are many people who have had a GIST removed and remain unaware of the fact. A review of these diagnoses, including re-testing retained tissue samples, is underway in some areas to try and see how many people might be affected. It also means that the number of patients diagnosed each year is uncertain. Evidence from Scandinavia suggests that there may be as many as 900 cases a year in the UK and Ireland, which would make GIST the most common sarcoma.
GIST tests positive in the pathology laboratory for c-KIT/CD117. It is a test which requires expertise so should be carried out by a properly experienced pathologist. The test offers a definitive diagnosis of GIST. The test reveals a molecule on the tumour cell which switches the cancer on or off c-KIT. A CD117 positive, or c-KIT + tumour, offers a definitive diagnosis of GIST and opens the way to treatment with imatinib (GlivecŪ - a drug made by Novartis).
It is calculated that about 50% of all GIST patients are cured by surgery. Small and low-grade tumours are unlikely to spread but today patients will be told of their risk. Because of the difficulty of identifying GIST early, many patients first present with large tumours and advanced disease. High grade GIST spreads (metastasises) readily - usually to the liver - so although a surgeon may be able to successfully remove the primary tumour it is not unusual for more advanced disease to set in quite quickly. Patients with large or high grade tumours are at a high risk of developing advanced GIST.
Radiotherapy is difficult to administer to organs which can move around in the body, and traditional chemotherapies do not have any impact on GIST. Until quite recently survival beyond a year with advanced GIST was very rare.
In the year 2000 a clinical trial of imatinib (Glivec) gained an 85% response rate with GIST patients, and the response was long-term. The prospect of survival for this group of patients changed almost overnight - it has been one of the great success stories of cancer research.
Glivec works by blocking the signal generated by c-KIT to instruct the tumour to reproduce. Its a bit like filling up a keyhole so a key cannot fit and a switch cannot work to turn the reproduction mechanism on.
Glivec can also have a role treating tumours prior to initial surgery. The surgeon would hope to reduce the size of tumours so that he needs to remove less tissue during the operation. This is not a licensed use of the drug but may be permitted under certain trial conditions. There is some evidence that in this case surgery can be less radical and patients can recover quicker and more completely.
About ten years on from its first use with patients with GIST a lot more is known about imatinib, how it works and how long its effect lasts. The body builds resistance to the drug over time. This can be countered by a larger dose, an alternative durg called sunitinib (Sutent from Pfizer), and other new drugs are in clinical trials.
Page reviewed December 2009