Gastrointestinal Stromal Tumours (GIST)

A gastrointestinal stromal tumour (GIST) is a rare type of sarcoma (cancerA disease where abnormal cells split without control and spread to other nearby body tissue and/or organs. Cancer cells can also spread to other parts of the body through the bloodstream and lymph systems. arising from bones or soft tissues) that forms in lining of the gastrointestinal tract. More specifically, they develop in interstitial cells
• the smallest, living parts of the body. Cells work together to form or build the body
• a human is made up of millions of Cells
• Cells reproduce themselves to make sure a body stays working
• sometimes Cells can be abnormal or damaged and these can be cancer cells
of Cajal (ICC), which play a critical role in the intestinal contractions required for digestion. The gastrointestinal tract is primarily responsible for food digestion and nutrient uptake, and is made up of organs such as the stomach, small intestine, and large intestine (colon
• The large intestine (also known as big bowel) which is the lower part of your digestive system from the end of the small intestine to the rectum (back passage; bum) which absorbs water from the food you eat and turns the leftover waste into faeces (stools; poo).
• Rectal cancer is found in the colon.
).

GISTs in adults are slightly more common in males and are generally diagnosed in people between the ages of 50 and 70. They are most commonly found in either the stomach, or the small intestine. While this disease has higher incidence in adults, children and teenagers are also able to develop this disease. In paediatric cases, GISTs are more common in girls and tends to be diagnosed in the teen years. In children and teenagers, GISTs are usually found in the stomach.

Treatment

If a GIST is detected, it will be staged and graded based on size, metastasisKnown as secondary cancer, it grows/spreads from the original/ primary cancer. (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.

Cancers can be staged using the TNM staging system:

• T (tumour) indicates the size and depth of the tumour.
• N (nodes) indicates whether the cancer has spread to nearby lymphA clear fluid that moves through the body through the lymphatic system, carrying cells that fight infection. nodes.
• M (metastasis) indicates whether the cancer has spread to other parts of the body.

This system can also be used in combination with a numerical value, from stage 0-IV:

• Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissue.
• Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
• Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localisedOnly to one area/place of body. cancer.
• Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
• Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advancedAt a late stage, far along or metastatic cancer.

Cancers can also be graded based on the rate of growth and how likely they are to spread:

• Grade
  • A score that tells how quickly a tumour might spread and grow by looking at how the abnormal cells and tissue look under a microscope.
  • Grade is not the same as stage.
  • Grading is different depending on the type of cancer.
  I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
• Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.
• Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.

Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.

Treatment is dependent on several factors, including age, location, stage of disease and overall health.

Treatment of Childhood GIST

Due to the rarity of GIST in childhood, there are fewer treatment options than adults with GIST. Treatment options for childhood GIST may include:

• Surgery, potentially including:
  • Keyhole surgery (laparoscopyLooking into the abdomen with a small, flexible camera called an endoscope.).
  • Gastrectomy (partial/total removal of the stomach).
  • Intestine resection (partial/total removal of intestine).
  • Abdominoperineal resection (partial/total removal of the anusEntry to the back passage; bum., rectum and sigmoid colon).
  • Pancreaticoduodenectomy, also known as a Whipple procedure (removal of portions of the pancreas, small intestine/duodenum, gall bladderA small, elastic/muscle type sac/bag in the body, where urine (wee) is stored for urinating/weeing. Is found in the lower abdomen/belly area. and/or stomach).
• Targeted therapies.
• Clinical trials.
• Palliative careLessening pain without curing the disease..

Treatment of GIST in adults

Adults with GIST have more treatment options that children with this disease. However, like childhood GIST, chemotherapy
• a chemical drug treatment to kill or slow-growing cancer Cells
• these drugs are called cytotoxic drugs
and radiation therapy are not often used to treat this type of cancer.

Treatment options for GISTs in adults may include:

• Surgery, potentially including:
  • Keyhole surgery (laparoscopy).
  • Gastrectomy (partial/total removal of the stomach).
  • Intestine resection (partial/total removal of intestine).
  • Abdominoperineal resection (partial/total removal of the anus, rectum and sigmoid colon).
  • Pancreaticoduodenectomy, also known as a Whipple procedure (removal of portions of the pancreas, small intestine/duodenum, gall bladder and/or stomach).
• Targeted therapies.
• Watch and wait.
• Clinical trials.
• Palliative care.

For more information on the treatment options, please refer to the Rare Cancers Australia Treatment Options page.

Some of the information regarding treatment was obtained from the Gastrointestinal Stromal Tumors Treatment (Adult) (PDQ) and the Childhood Gastrointestinal Stromal Tumours Treatment (PDQ) pages published by the National Cancer Institute.

Risk factors

The risk factors for developing GIST, as an adult or a child, include having genetic conditions such as:

• Neurofibromatosis type 1 (NF1).
• Carney triad.
• Carney-Stratakis dyad.
• Familial GIST syndrome.

Certain genetic mutations have also been linked to the development of GIST. The genes commonly affected include:

• Tyrosine c-KIT.
• PDGFRA (platelet derived growth factor receptor alpha) receptors.

Some fewer common genes affected can include:

• Succinate Dehydrogenase (SDH).
• Neurofibromatosis gene 1 (NF1).
• BRAF V600
• Rat sarcoma (RAS).

Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.

Symptoms

GIST may appear asymptomatic in the early stages. Adults and children with GIST may experience some of the following symptoms:

• Bloodhello in stool and/or vomit.
• Abdominal pain and/or massA growth of cells that come together to make a lump, either big or small, and may or may not be cancer..
• Bloating.
• Fatigue.
• Difficulties/pain when swallowing.
• Unexplainable weight loss/loss of appetite.\
• Nausea and/or vomiting.
• AnaemiaWhere the number of red blood cells have dropped. This can make people feel tired, breathless and unwell and affects how the body fights infection (low levels of red blood cells).
• Blocked intestinesThe tubes/organs that work between the end of the stomach to the anus (back passage; bum)., which carry its own set of symptoms:
  • Abdominal cramping and/or swelling
  • Nausea and/or vomiting.
  • DiarrhoeaWhere watery or loose faeces (stools; poo) is frequently/often released discharged from the body. Also called ‘the runs’..
  • Constipation.

Not everyone with the symptoms above will have cancer, but see your GP if you are concerned.

Diagnosis/diagnosing

If your doctor suspects you have a GIST, they may order the following tests to confirm the diagnosisUsing medical test results, identify and name a disease and/or condition. and refer you to a specialist for treatment.

Genetic testing

In addition to guiding treatment, genetic testing can be used to help diagnose certain conditions. GIST has been linked to mutations in the KIT (receptor tyrosine kinase gene), PDGFA (platelet-derived growth factor A gene) and SDH (succinate dehydrogenase gene) genes, which all change specific protein functions. These changes can lead to cell abnormalities and, in extreme cases, cancer. Your doctor may perform genetic testing to better understand your condition.

Physical examination

Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.

Imaging & blood tests

The doctor will take images of your body using magnetic resonance imagingTaking images/photos of inside body parts using magnet rather than x-ray. (MRITaking images/photos of inside body parts using magnet rather than x-ray.), a computed tomography scan (CT scanA 3-D (three dimensional) x-ray pictures that gives more information than a normal x-ray.), and/or positron emission tomography (PET scanA test that uses a radioactive drug to show a picture of how your tissues and organs are working. Also known as a positron emission tomography scan.), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and looks for signs of metastasis. Additionally, a blood test may be taken to assessTo measure, look at and learn from. your overall health and help guide treatment decisions.

Endoscopy & biopsy

An endoscopyLooking inside the body with an endoscope. is a surgical procedure that involves inserting a long, flexible tube with a light and small camera through oesophagus, stomach and the first part of the small intestine. You will be given a sedative or anaestheticA drug used to get rid of or reduce the feeling of pain by putting you to sleep throughout the procedure. You will be asked to fast for several hours prior to the procedure. An endoscopy is often done as a day surgery. Your doctor will discuss the risks and any possible complications prior to the procedure.

Throughout the procedure, your doctor may also perform an endoscopic ultrasound to guide the needle during a biopsyTo take a small piece of body tissue and test it in a laboratory., or to check for signs of cancer metastasis.

If any abnormalities are observed, your doctor will remove a small tissue sample for analysis.

References

• GI Cancer Institute
• Mayo Clinic
• National Cancer Institute - Adult GIST
• National Cancer Institute - Childhood GIST