Gastrointestinal stromal tumours or GIST tumours are cancers that occur in the digestive tract or system. The most common parts of the digestive system where these are seen are in the stomach and small intestine, but they can be present in any part of the tract. These are a type of sarcoma, but their treatment is different to that of a soft tissue sarcoma and hence discussed separately. These types of cancers are usually rare and make up about 1% of all cancers in the digestive system. GIST tumours can be benign or malignant. They usually grow around the site of origin but can spread to other parts of the body too.
GIST’s are common in people over the age of 50 but can occur at any age.
About 5% of all GIST tumours occur due to a genetic link in the family. The conditions that lead to this are familial GIST syndrome, Neurofibromatosis type 1 and Carney-Stratakis syndrome.
Common symptoms produced by a GIST tumour include pain in the abdomen, nausea, vomiting, weight loss, vomiting of blood, feeling of fullness in the stomach, passing blood in the motion or tiredness.
A GIST is commonly diagnosed by accident when tests are done for the above symptoms. Some tests done to diagnose a GIST include
Endoscopy is a test which involves passing a thin tube into the oesophagus and stomach to look for abnormalities. The tube has a camera at the end of it so that that the doctor doing the procedure can see all of the oesophagus and stomach. The test is done using mild sedation and is painless. The patient should not have eaten for a period of 6-8 hours prior to the procedure.
It is a day case procedure, so there is no need to stay overnight in hospital. If the doctor sees an abnormal area on endoscopy, a biopsy can be done at the same time. If a GIST is suspected on endoscopy, a biopsy may be done.
A CT or computed tomographic scan is done once a diagnosis of GIST is made on endoscopy or is done directly without an endoscopy. The CT scan uses x-rays to get detailed images of the inside of the body.
Therefore, it can give information about whether the cancer has spread to other parts of the body.
PET Scan or PET-CT Scan
A PET –CT scan is a specialized CT scan where a radioactive tracer is injected into the body prior to the CT scan. This tracer lodges in areas within the body where there is high requirement for glucose. As cancers need a lot of glucose to survive, they take up the tracer much more than the rest of the body. The cancer can then be easily spotted on the scan. A PET-CT scan is more sensitive than a standard CT scan to look for evidence of spread of cancer. It is a very important test in staging of GIST prior to treatment.
Endoscopic Ultrasound (EUS)
An Endoscopic ultrasound is a test that is like an endoscopy but has an ultrasound scanner at the end of it. This test uses sound waves to look for the cancer and can help in the diagnosis of a GIST. The scanner also helps to look for any enlarged lymph nodes that may be present around the cancer. The test is used to help get an accurate stage of the cancer and also to biopsy any abnormal lumps or nodes.
A biopsy of suspected GIST is done to confirm the diagnosis of the condition particularly in advanced cancers. The biopsy is done with the help of endoscopy or ultrasound or CT or other methods.
There are a few specific tests that are done on the biopsy sample to get a definite diagnosis of GIST. These tests also help in the decision process of treatment. The following tests are done.
Testing for CD 117 or C-KIT mutation by IHC is done on all suspected GIST patients. This test detects a mutation in the KIT protein. Majority of GIST tumours will be CD117 positive.
Testing will also be done for mutations in the PDGFRA gene. Those tumours that are KIT negative can be PDGFRA positive.
Molecular testing to look for mutations on Exon 11 and 9 are also recommended in patients with advanced GIST as this will help decide on the most appropriate treatment.
Treatment options for GIST tumours depend on the location and extent of disease in the body, KIT and PDGFRA mutation status and the general fitness and wishes of the patient.
Surgery or surgical removal of the tumour is an option of treatment for GIST tumours that can be safely removable. Some small tumours, those less than 2cm in size could be monitored closely without the need for surgery. However, these options should be discussed with the doctor.
The surgery involves removal of the mass or tumour along with a part of normal tissue or organ that is present around it to ensure completeness of its removal. Local lymph nodes are not removed unless enlarged. Surgery can be done by open surgery or laparoscopically depending on the location of the tumour.
For disease that is advanced or extensive or invading important structures, treatment with Imatinib is given first to reduce the tumour size(neo adjuvant therapy) and surgery is done after that.
Adjuvant treatment involves adding another treatment to a definitive treatment that was done to increase the chances of better control or cure. In patients who have had a surgical removal of a GIST tumour and the tumour characteristics show that it is a high risk one, adjuvant treatment with Imatinib for three years is advised. This helps in achieving better control of the tumour. Higher risk tumours are those which are more than 5cm in size, those that are incompletely removed by surgery and those that have ruptured at surgery, have a high mitotic rate, tumours in a location other than the stomach etc.
Advanced or Metastatic Disease
In patients where the GIST tumour or cancer is advanced locally in its place of origin or has spread to other parts of the body from its place of origin and are KIT or PDGFR positive, treatment is done with a drug called Imatinib. Imatinib is a targeted therapy drug called tyrosine kinase inhibitor and is quite effective in controlling GIST tumours. It is given as a tablet taken daily and is usually tolerated very well. Potential side effects include weight gain, swelling of face and legs, nausea, abdominal pain and low blood counts. Whilst on treatment, the disease can be monitored with serial CT or PET-CT scans to assess for response. The treatment is continued for as long as it is effective, and the patient is able to tolerate it well. The dose of Imatinib can be adjusted based on the extent of side effects.
Disease that is resistant to Imatinib or increases after initially responding to Imatinib is treated with other tyrosine kinase inhibitors like Sunitinib or Regorafenib.