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. The may be identified as a benign tumour, though this is less likely today than it was before the discovery of Glivec. It does mean however that there are 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. 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. Because of the difficulty of identifying GIST early, many patients first present with 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. About 80% of patients with large or high grade tumours develop advanced GIST.
The disease is resistant to radiotherapy and traditional chemotherapies and until recently survival beyond a year with advanced GIST was very rare. When Glivec was first made available to advanced and metastatic GIST patients in 2000 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 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.