GISTs comprise a very small fraction of GI tumors (approximately 1%). It is estimated that around 3.2-1.9 individuals per million are affected by GISTs. In the US, approximately 3,300 to 6000 new cases are diagnosed per year. 

Men and women appear to be affected equally. Although it was generally believed that GISTs are distributed across all ethnic groups, there is emerging evidence that in the US, the African-American population is most commonly affected. GISTs are mostly present in individuals aged 50-80. 

Generally, GISTs occur in individuals with no family history, but there are also cases where this tumor runs in the family.

 GISTs that occur in children and young adults are much rarer and represent 15% of the GISTs that are diagnosed. They are considered different and appear more commonly in females. 

Most cases of GIST are not inherited and are caused by genetic abnormalities acquired during lifetime. The majority of GIST cases are caused by a mutation in either KIT or PDGFRA genes. These are genes that encode proteins that belong to a family known as tyrosine kinases that are involved in promoting cell growth and division. They are typically inactive in ICCs unless the body needs to make more ICCs. When mutated in GISTs, these genes become activated which causes ICCs to rapidly divide and grow. About 75% of GISTs are due to a KIT mutation and about 10% are due to a PDGFRA mutation. Most GISTs have a mutation in either KIT or PDGFRA but not in both.

In about 15% of GISTs, there are no identifiable KIT or PDGFRA mutations. 

While most GISTs are not inherited, a small fraction are associated with inherited conditions:

• Primary familial GIST syndrome: individuals affected by this syndrome inherit a KIT or less commonly PDGFRA mutation from their parents which increases their chances of developing a GIST. In such cases, GIST tends to present at a younger age compared to the general population. 

• Neurofibromatosis type 1: this is a genetic condition due to a mutation in the neurofibromin 1 (NF1) gene which encodes the neurofibromin protein which is involved in the regulation of cell growth. Individuals affected by neurofibromatosis type 1 develop non-cancerous nerve tumors called neurofibromas and are at a higher risk of developing GISTs, particularly in the small intestine.

• Carney-Stratakis syndrome: this is an inherited condition due to a mutation in one of the genes of the succinate dehydrogenase (SDH) gene family. SDH genes are responsible for encoding the succinate dehydrogenase enzyme, an enzyme involved in producing energy from sugar molecules. This syndrome increases the risk of GIST as well as paragangliomas which are a type of nerve tumor. Affected individuals develop GISTs at a younger age and more often in the stomach.

Symptoms of GIST depend on the location and the size of the tumor. General symptoms of cancer include fatigue, weight loss, fever, and night sweats. Depending on the location of the tumor, individuals may experience difficulty swallowing (esophageal tumor), feeling full (if the tumor compresses the stomach), abdominal pain, or an abdominal lump (location depends on the location of the tumor), nausea and vomiting.

GISTs are fragile tumors and might rupture and cause bleeding. This bleeding may occur in small amounts over a long time causing anemia (low iron and red blood cells) which is associated with paleness of the skin, fatigue, and shortness of breath. It can also be in larger amounts leading to the presence of visible blood in the stool (if the tumor is in the lower GI tract) or vomiting blood if the tumor is in the upper GI tract. If the tumor is in the esophagus, individuals may vomit bright red blood. If it is in the stomach, they may vomit blood that has a coffee ground appearance due to partial digestion. Bleeding in the small intestine can make stool appear dark and bleeding in the large intestine leads to the presence of bright red blood in the stool. GI bleeding is the most common manifestation of GISTs.

Depending on the size of the tumor, it might compress the GI tract, leading to obstruction which is associated with abdominal pain and vomiting.

Diagnosis of GISTs is usually suspected due to the onset of symptoms or as incidental findings during medical exams or investigations for other health conditions. When the diagnosis is suspected, medical history such as family history, other genetic conditions that increase the risk of GISTs, and more specific signs and symptoms. A physical exam can help identify an abdominal lump or other signs of a GI tumor.

Abdominal imaging tests can be used to diagnose GISTs but they are also important for staging. Staging is done after a tumor is diagnosed and is used to describe how much the tumor has spread in the body, how large it is, etc. GIST stages are I-IV and an increasing number indicates the further spread of the tumor. The diagnosis can be confirmed by performing a biopsy, a procedure in which a sample of the suspected tissue is removed and assessed. Genetic tests can be performed to identify mutations in KIT, PDGFRA, or SDH. 

The most commonly done tests to diagnose GISTs are computed tomography (CT) scans and magnetic resonance imaging (MRI). Both these techniques can create detailed images of the soft tissues of the body, find the location and size of GISTs, and whether they have spread to other body parts. Although MRIs may be performed in some cases, CT scans are usually sufficient to visualize the tumors.

In some cases, CT scans can also be used to guide a biopsy needle precisely into a suspected cancer. However, this can be risky if the tumor might be a GIST (because of the risk of bleeding and a possible increased risk of tumor spread), so these types of biopsies are usually done only if the result might affect the decision on treatment. (See the biopsy information below.)

Another type of imaging used to diagnose GI abnormalities is barium X-ray. In this technique, the individual is asked to drink a fluid containing barium. Once the lining of the GI tract is coated by barium, it can more easily be visualized on X-rays.

Positron emission tomography (PET) scan is another imaging technique that is often used for staging and determining how much the tumor has spread.

Another diagnostic test that might be performed to diagnose GISTs is endoscopy. In this procedure, a camera is attached to the tip of a long, flexible tube that is passed through the GI tract to visualize the inside of the digestive organs. An upper endoscopy is used to visualize the esophagus, the stomach, and the beginning of the small intestine by passing the tube down through the mouth. A colonoscopy is a type of endoscopy in which the tube is passed to the large and small intestine through the anus. Depending on the location of the GIST, an upper endoscopy, a colonoscopy, or both may be performed. Endoscopy can also be used to take samples from internal organs for further evaluation. This is known as a biopsy where a piece of tissue is removed and assessed under a microscope or using other techniques to determine whether the tissue contains cancerous cells. Other than endoscopic biopsy, samples may be taken using a hollow needle through the skin (needle biopsy), or surgically. The biopsy technique depends on the size and location of the tumor. 

The sample that is used during a biopsy can also be used for genetic testing. The presence of KIT, PDGFRA, or SDH mutations supports a GIST diagnosis, but their absence does not exclude the diagnosis. 

There are a number of treatment options for GISTs. The choice of treatment or treatment combinations depends on characteristics of the tumor such as size, location, and how much it has spread. Treatment options are: 

• Surgery: Surgery is considered the main treatment for GISTs with the goal of removing all cancerous tissue. Depending on the size of the tumor, surgery may be done laparoscopically by passing surgical tools and a small camera attached to a small tube or via a larger incision. Additionally, depending on whether the tumor has spread to the nearby tissues, parts of adjacent organs may also be removed.

• Targeted drug therapy: targeted drugs are drugs that damage cancerous cells specifically, as opposed to traditional chemotherapy drugs that affect all rapidly-growing cells in the body. Most targeted drugs that are used in the treatment of GISTs are tyrosine kinase inhibitors (TKI). The proteins involved in the development of GISTs such as KIT and PDGFRA belong to the family of tyrosine kinases. These drugs are effective in GISTs that have KIT or PDGFRA mutations by blocking the signal that GISTs need to grow. Genetic testing is often performed to determine whether an individual can benefit from targeted drugs and to determine the most appropriate drug.

• Radiation therapy and traditional chemotherapy are often not effective in GISTs. GIST cells are highly resistant to chemotherapy, rendering this form of treatment ineffective. Radiation therapy may be used to control bone pain if cancer has extensively spread, affecting the bones.

To determine the best course of treatment, GISTs can be divided into resectable, unresectable, and metastatic. A resectable tumor is one that can be fully removed by surgery. Unresectable tumors are tumors that are either too large to be removed surgically, or they are in a location that is technically challenging and their surgical removal may cause too much damage. Metastatic tumors are those that have spread extensively making surgery an unpractical treatment. 

Treatment of resectable GIST

Surgery is the main treatment for resectable GISTs with the goal of complete removal of the cancerous tissue. In some cases, tyrosine kinase inhibitors may be used after surgery to lower the risk of recurrence and destroy any residual cancer cells that remain after surgery. 

Treatment of unresectable GIST

For unresectable tumors, tyrosine kinase inhibitors may be initiated to shrink the tumor to a size that is resectable. If this leads to a successful downsizing of the tumor, surgery follows, followed by more tyrosine kinase therapy to reduce the risk of recurrence.

Treatment of metastatic GIST

Surgery is not a common treatment for metastatic GISTs. Tyrosine kinase inhibitors are not curative but are helpful in slowing the progression of cancer, allowing individuals to live longer.

Treatment of refractory GIST

Many GISTs treated with a tyrosine kinase inhibitor (TKI) become refractory (stop responding) to the drug after a while. Treatment is usually a clinical trial with a different TKI or a clinical trial of a new drug.

Prognosis depends on a number of factors including the stage of cancer, whether it is resectable or not, and the overall health of the affected individual. Additionally, the genetic profile of the tumor also determines whether the individual will respond to tyrosine kinase inhibitors. 

The 5-year survival rate is the percentage of individuals who are alive 5 years after diagnosis and is used to describe the prognosis of a disease. The 5-year survival of GISTs is 93% if the tumor is completely localized without spreading to any nearby organs and tissues. It is 80% if the tumor is regional, meaning that it has only spread to some local lymph nodes without entering the blood. It is 55% if cancer has spread to distant body parts via blood. 

Often, affected individuals are anxious about the potential side effects of the various treatment options for GISTs. It is best to ask your healthcare provider the details of any side effects and how to cope with them. Patients and their families are recommended to share their feelings with each other and their healthcare provider to develop coping strategies to deal with the emotional stress that can arise from the disease.

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