Gastrointestinal Stromal Tumour

Gastrointestinal stromal tumours are rare cancerous growths that develop in the digestive system, most commonly in the stomach or small intestine, and can range from very small to large masses that cause serious symptoms.

Table of contents

• What is a gastrointestinal stromal tumour?
• Where these tumours occur
• Causes and risk factors
• Signs and symptoms
• How these tumours are diagnosed
• Treatment options
• What to expect
• Living with gastrointestinal stromal tumour

What is a gastrointestinal stromal tumour?

A gastrointestinal stromal tumour, also called a GIST, is a type of cancer that begins in the digestive system^[1]. It is the most common type of tumour that grows from the supporting tissues of the digestive tract, though it remains quite rare overall. Between 4,000 to 6,000 people are diagnosed with gastrointestinal stromal tumours each year in the United States^[2].

These tumours are thought to form from special nerve cells called interstitial cells of Cajal that are found in the walls of the digestive organs^[1]. These nerve cells help control the movement of food through the digestive system. When changes occur in the genes of these cells, they can begin to grow abnormally and form tumours^[8].

Gastrointestinal stromal tumours can happen in people at any age, but they are most common in adults between 60 and 70 years old and are very rare in children^[1]. They affect men and women with roughly equal frequency^[10].

GIST

Where these tumours occur

Gastrointestinal stromal tumours can develop anywhere along the digestive tract, but some locations are more common than others. The stomach is the most frequent site, accounting for 50 to 70 percent of cases^[9]. The small intestine is the second most common location, representing 20 to 35 percent of cases^[9].

Less commonly, these tumours appear in the colon and rectum, which together account for about 5 percent of cases^[9]. The esophagus is the least common site, with fewer than 1 percent of tumours forming there^[10]. In rare situations, gastrointestinal stromal tumours can develop outside the digestive tract itself, in nearby areas such as the large flat fatty tissue layer that covers the organs in the belly, called the omentum, or the thin lining of tissue that covers the organs and lines the inside of the belly, called the peritoneum^[7].

• Stomach
• Small intestine
• Colon
• Rectum
• Esophagus
• Omentum
• Peritoneum

Causes and risk factors

The cause of most gastrointestinal stromal tumours is not known^[1]. In most cases, these tumours occur sporadically, meaning they happen at random with no known reason^[22]. There are no known lifestyle factors, such as diet or smoking, that cause these tumours^[10].

A gastrointestinal stromal tumour starts when cells in the digestive system develop changes in their DNA, which is the material inside cells that carries genetic information^[1]. About 75 to 80 percent of cases involve a change in a gene called KIT, and 5 to 10 percent involve changes in another gene called PDGFRA^[8]. These genetic changes cause cells to produce abnormal proteins that tell the cells to multiply uncontrollably, leading to tumour formation^[2].

Certain rare genetic conditions can increase a person’s risk of developing a gastrointestinal stromal tumour. These inherited syndromes include neurofibromatosis type 1, also known as von Recklinghausen disease, which is caused by a defect in the NF1 gene^[9]. Another rare condition is Carney-Stratakis syndrome, which involves changes in genes related to an enzyme called succinate dehydrogenase^[8]. A third condition, called familial GIST syndrome, is extremely rare and runs in families. People with this syndrome may inherit abnormal KIT genes from a parent, which increases their chances of developing tumours at a younger age and having more than one tumour^[2].

Age is another risk factor. Gastrointestinal stromal tumours are most common in older people, typically those over the age of 50^[10].

Signs and symptoms

Small gastrointestinal stromal tumours may cause no symptoms at all^[1]. Many people learn they have a tumour when they have a test or surgery for another reason^[2]. These tumours may grow so slowly that they don’t cause problems at first. As a tumour grows larger, it can begin to cause symptoms.

The most common symptom is bleeding in the digestive system. This happens because the tumours are made up of many blood vessels and can become fragile as they grow^[22]. When bleeding occurs, a person may throw up blood, which can look like coffee grounds because it has been partially digested^[22]. Bleeding into the stomach or small intestine can cause black and tarry bowel movements, while bleeding into the large intestine can cause red blood in the stool^[22]. Slower bleeding over time can lead to a low red blood cell count, called anemia, which causes fatigue and weakness^[2].

Other symptoms may include pain in the belly area, nausea and vomiting, not feeling hungry when you would expect to, feeling full after eating only a small amount of food, and losing weight without trying^[1]. Some people may notice a lump or swelling in their belly that they can feel^[10]. If a tumour is in the esophagus, it may cause problems swallowing^[22].

If you experience any of these symptoms, it is important to see a doctor. While they may be caused by other, less serious conditions, they should always be checked^[7].

How these tumours are diagnosed

To diagnose a gastrointestinal stromal tumour, a doctor will start by asking about symptoms and health history, then perform a physical examination^[12]. If the doctor suspects a tumour, several tests may be needed to confirm the diagnosis.

Imaging tests help doctors find the tumour and determine its size. These may include ultrasound, CT scans (computed tomography scans that create detailed pictures using X-rays and computers), MRI scans (magnetic resonance imaging that uses magnets and radio waves), and PET scans (positron emission tomography that shows how tissues are functioning)^[12]. Not everyone needs every type of imaging test.

An upper endoscopy uses a long, thin tube with a light and camera on the end, which goes through the mouth and down the throat to look at the inside of the esophagus, stomach, and the first part of the small intestine^[12]. An endoscopic ultrasound is similar but has an ultrasound probe on the tip of the tube, which uses sound waves to make pictures of the tumour and show its size^[12].

To confirm the diagnosis, doctors need to examine a sample of tissue from the tumour. This is done through a biopsy. A fine-needle aspiration biopsy uses a thin, hollow needle on the tip of an endoscope to collect small amounts of tissue^[12]. Sometimes the needle can’t get enough cells, or the results aren’t clear, and surgery may be needed to collect the sample.

The tissue sample goes to a laboratory where specialists examine it under a microscope to determine if the cells are cancer cells. Other tests check for specific proteins and genetic changes that help doctors plan treatment^[12]. Testing for mutations in the KIT and PDGFRA genes is particularly important because it helps predict how well the tumour will respond to certain medications^[8].

Treatment options

Treatment for gastrointestinal stromal tumours depends on several factors, including the size and location of the tumour, whether it has spread to other parts of the body, the genetic changes present in the tumour, and the person’s overall health^[12].

Surgery to remove the tumour is the most common treatment and the only one that can cure the disease^[2]. The surgeon aims to remove the entire tumour along with a border of healthy tissue around it, called a clear margin^[7]. Having healthy tissue without any cancer cells around the removed tumour is important because it lowers the risk of the cancer coming back. Surgery may be the only treatment needed if the tumour is small^[2].

For larger tumours or those that have spread, treatment may combine surgery with medications called targeted therapies. These are drugs that work by blocking specific proteins that cause cancer cells to grow. The most commonly used targeted therapy is a medication called imatinib, also known by the brand name Gleevec^[12]. This drug blocks the abnormal proteins produced by mutations in the KIT or PDGFRA genes.

Sometimes targeted therapy is given before surgery to shrink a large tumour and make it easier to remove^[2]. This is called neoadjuvant therapy. After surgery, some people receive targeted therapy to reduce the chance of the cancer returning. This is called adjuvant therapy^[9]. For tumours that cannot be removed with surgery or have spread to other parts of the body, targeted therapy may be the main treatment.

The response to imatinib varies depending on which genetic mutation is present. Tumours with mutations in a specific part of the KIT gene called exon 11 respond best, with approximately 90 percent of patients responding^[19]. Tumours with mutations in another part called exon 9 are less sensitive, with about 50 percent responding. For these patients, doctors may start with a standard dose and increase it if the person can tolerate it^[19].

Some genetic mutations do not respond well to imatinib. Tumours with a specific PDGFRA mutation called D842V typically do not respond to standard treatments^[19]. For these patients, doctors generally do not recommend adjuvant therapy, though other options may be considered.

If imatinib stops working or causes severe side effects, other targeted therapy drugs may be used. These include sunitinib (brand name Sutent) and regorafenib^[12].

What to expect

The outlook for people with gastrointestinal stromal tumours varies depending on the size of the tumour, its location, how quickly the cells are dividing, and whether it has spread. Treatment can ease symptoms and sometimes cure the disease, but tumours can come back^[2].

Overall, 85 percent of people with gastrointestinal stromal tumour are alive five years after diagnosis^[2]. The survival rate is higher when the tumour has not spread. When the tumour stays in its original location, 95 percent of people are alive five years later. When it has spread to nearby tissues and organs, 84 percent are alive after five years^[2].

After treatment, regular follow-up appointments are important to check for signs of the cancer returning. These appointments typically occur every three to six months and may include CT scans, MRI scans, or PET scans^[2].

Living with gastrointestinal stromal tumour

Living with a gastrointestinal stromal tumour can affect many aspects of daily life. Both the tumour itself and its treatment can cause symptoms that interfere with normal activities. Eating may become difficult due to pain, nausea, and feeling full after small amounts of food^[20].

Surgery can change how food moves through the digestive system. Some people develop what is called dumping syndrome, where food moves too quickly through the digestive tract^[20]. To manage this, it may be helpful to eat smaller portions every two to three hours instead of three large meals. Limiting sugary foods and excess fluids can also help reduce symptoms. Adding more complex carbohydrates and protein to the diet may help you feel better^[20].

After surgery, the body may have trouble absorbing vitamins and minerals, so supplements may be helpful. A dietitian can help plan a menu of foods that are easier for the digestive system to handle^[20].

Fatigue is common, either from the cancer itself or from treatment. Getting enough rest is important. Aim to sleep at least 8 hours each night and take short naps during the day if needed^[20]. Exercise, with medical clearance, can help maintain physical and emotional fitness.

Planning daily activities can help manage energy levels. Schedule activities for times when you feel most energetic, and don’t hesitate to ask friends and family for help. If you work, talk to your employer about flexible hours, taking breaks, or taking a leave of absence if needed^[20].

It’s important to communicate openly with your healthcare team about any symptoms or treatment side effects. Medications are available to help relieve many treatment-related symptoms^[20]. The emotional and mental health impacts of cancer are also significant, and support is available through counseling, support groups, and other resources.