A gastrointestinal stromal tumor (sometimes called a “GIST”) is an uncommon type of cancer that forms in cells of the digestive tract wall. Between 4,000 to 6,000 people are diagnosed with gastrointestinal stromal tumors each year in the United States, according to the American Cancer Society.

Although gastrointestinal stromal tumors may be diagnosed at any age—even in children (though this is very rare)—it occurs most often among men and women ages 50 or older.

Fortunately, several types of treatment are available for GISTs. These include surgery, which can cure the disease in some cases, and targeted therapies, which can help reduce—or delay—the recurrence of the cancer.

“Early and accurate diagnosis of these types of tumors is vital to our ability to optimize each patient’s personal treatment plan. This kind of proactivity and precision informs everything we do at Yale for our patients—from our research, to bedside treatment, and recovery,” says Nita Ahuja, MD, MBA, a surgical oncologist at Smilow Cancer Hospital, chair of surgery for Yale Medicine, and chief of surgery for Yale New Haven Hospital. “It is a journey that we take with each patient—as a partner—from day one.”

GISTs are a type of rare cancer that develops within the digestive (or gastrointestinal) tract. Most experts believe the tumors originate within cells known as the interstitial cells of Cajal (ICC). These are sometimes called the “pacemaker cells of the digestive tract” because they regulate the movement of food through the digestive system.

GISTs can form in any part of the digestive tract, although its prevalence varies by site:

• Between 50 and 60% of GISTs are located in the stomach.
• The small intestine accounts for 30 to 35% of cases.
• About 5% of GISTs are found in the colon and rectum.
• Less than 1% form in the esophagus.

GISTs begin when genetic mutations occur in certain genes, leading to uncontrolled cell growth. Over time, this uncontrolled cell growth leads to the formation of tumors. Around 75 to 80% of GIST cases have a mutation in a gene called KIT, and in 5 to 10% of cases, there is a mutation in another gene known as PDGFRA. Less commonly, additional gene mutations are involved.

Doctors may run tests to figure out the specific mutation involved because it helps determine the best course of treatment for GIST.

Certain risk factors for GISTs have been identified, including:

• Familial GIST syndromes (inheriting mutations in certain genes, in particular in KIT or PDGFRA)
• Certain other inherited syndromes (e.g., neurofibromatosis type 1 [NF1], Carney-Stratakis syndrome)
• Carney’s triad

In the vast majority of cases, however, GISTs are sporadic, meaning they arise in people who have not inherited variants of genes known to increase their chances of developing these tumors.

Some people with gastrointestinal stromal tumors don’t experience any symptoms; their tumors are found incidentally during imaging tests or surgery, when doctors are diagnosing or treating other conditions.

But, people who do have symptoms may experience:

• Abdominal pain or discomfort
• Bloody stools
• Feeling tired
• Nausea and vomiting
• Blood in vomit
• Difficulty swallowing
• Indigestion
• Loss of appetite
• Feeling full after eating a few bites of food or a small meal
• Diarrhea or constipation
• Increased volume of urine
• Palpable mass or swelling in the abdomen

To diagnose gastrointestinal stromal tumors, doctors usually take a medical history, perform a physical examination, and order diagnostic tests.

• Medical history. Your doctor will ask you about symptoms and whether you have any risk factors for a GIST.
• Physical exam. During the physical exam, the doctor will closely examine your abdominal area to check for a palpable mass or other signs of a GIST.
• Diagnostic tests. Even if your doctor suspects a GIST, additional tests are necessary to confirm the diagnosis and rule out other medical conditions. In most cases, you may have the following tests:
  • Imaging tests such as a computer tomography (CT) scan, magnetic resonance imaging (MRI) scan, or a positron emission tomography (PET) scan of the abdominal and pelvic area.
  • Blood tests, including a complete blood count (CBC), are also usually part of the initial workup. 
  • Endoscopy. In this procedure, a doctor inserts an endoscope—a flexible tube equipped with a camera—into the digestive tract to visually inspect the stomach, intestines, and other tissues.
    • Upper endoscopy: With this procedure, an endoscope is inserted into the mouth then directed into the stomach and upper portion of the large intestine. This allows the doctor to examine the upper digestive tract.
    • A colonoscopy,or lower endoscopy, is used to assess the tissues of the anus, rectum, and colon.
    • A capsule endoscopy may be used in some cases. In this procedure, the patient swallows a small camera, which takes pictures as it passes through the digestive tract.
    • An endoscopic ultrasound (EUS) may also be necessary. This procedure is similar to an upper or lower endoscopy; however, with EUS, a tiny ultrasound probe is attached to the end of the endoscope. Ultrasound uses sound waves to produce images of internal tissues.
  • Biopsy. If your doctor finds a tumor or an area of abnormal tissue, he or she may perform a biopsy. Often biopsies are done during endoscopy. In some cases, though, tissue samples are collected during a surgical procedure or with the use of a needle that is inserted through the skin and into the digestive tract.  
    
    After a tissue sample has been collected, a pathologist will examine it to check for the presence of cancer cells and to learn about its molecular makeup. If cancer is detected, additional tests will be run on tissue samples to determine the genetic makeup and other details of the cells.

Imaging tests such as a PET scan, CT scan, chest X-ray, or bone scan may be used to determine whether the cancer has spread to other parts of the body. These tests are used to stage the cancer and they allow doctors to make a prognosis and create a tailored treatment plan for each patient.

Treatment for GISTs includes:

• Monitoring. For some tumors less than 2 cm in size that are at low risk of spreading, doctors may recommend monitoring with EUS every 6 to 12 months.
• Surgery. Surgical removal of the tumor is the primary treatment for GISTs that have not spread to other parts of the body. In some cases, surgery is performed to remove primary and metastatic tumors. Small tumors may be removed using a minimally invasive surgical procedure known as laparoscopy. In some cases, surgery can be curative.
• Targeted therapy. This treatment uses drugs designed to target specific components of cancer cells that are not found in healthy cells. GISTs are treated with targeted drugs called tyrosine kinase inhibitors (TKIs). Several types of TKIs are available, including imatinib, sunitinib, regorafenib, and avapritinib, among others. Targeted therapy may be used before surgery to shrink the tumor or after surgery to destroy any cancer cells that remain. It is also used in cases in which cancer has spread to other parts of the body.
• Ablation and embolization. These treatments may be used in cases in which the cancer has spread to the liver, and if surgery is not an option. In ablation, chemicals, heat, cold, microwaves, or high energy radio waves are used to destroy cancer cells. In embolization, a doctor injects substances into blood vessels with the aim of starving cancer cells in the liver of a blood supply.
• Radiation therapy. Though radiation therapy is not usually used to treat GISTs, it may be used as part of palliative care to reduce pain.

The outlook for people with GISTs varies based on several factors. These include the size and location of the tumors, how aggressively they are growing, and whether they have spread to other parts of the body. If a GIST can be successfully removed with surgery, the procedure may be curative. Some tumors, however, cannot be fully removed or may have spread to other sites in the body. Often, patients take a targeted drug like imatinib after surgery to delay or reduce the chances of recurrence. Patients may need to continue to take these drugs for three years or longer.

Even after treatment, there is a chance that GISTs will return. Because of this risk, it is important that people who have had a GIST see their doctor for regular checkups and monitoring.

The 5-year relative survival rate for localized GISTs (tumors that have not spread beyond the site where they originally formed) is 93%. The 5-year survival rate for GISTs that have spread to distant parts of the body is 55%.

“We recognize that a cancer diagnosis can be life-changing, for our patients, their families, and friends. We are on a mission to make sure that each patient has access to the premier experts, clinical trials, and technologies that are available, in order to navigate a diagnosis and receive the best treatment available,” says Smilow Cancer Hospital surgical oncologist Sajid Khan, MD. “We face each diagnosis together as a partnered care team.”