Your GIST Treatment Guide

Medically Reviewed by Arnold Wax, MD on May 09, 2012
From the WebMD Archives

If you’ve been diagnosed with a gastrointestinal stromal tumor (GIST), there’s good news. GIST has become a treatable disease, thanks to advances in research and treatment over the last 15 years.

How Is GIST Treated?

The primary treatment for GIST is surgery. During surgery, the tumor is removed completely in approximately 85% of cases.

“More than half of all GIST tumors are small, not very aggressive, and easily removed during surgery,” says George Demetri, MD, associate professor of medicine at Harvard Medical School and director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute and Brigham and Women's Hospital in Boston.

After surgery, experts study the tumor under a microscope to determine the proper diagnosis and the likelihood of the tumor recurring.

There are three main factors that help determine what kind of treatment you will have next:

  • Tumor size. Tumors that are less than two centimeters in size are less likely to recur than larger tumors. The larger the tumor, the more likely it is to recur.
  • The “mitotic index.” This is a measure of how many cells in the tumor are dividing. More dividing cells means a more aggressive tumor.
  • Tumor location. GIST cancers that are found in the stomach are less likely to return than those found in the small intestine or the rectum.

The recurrence of GIST is most likely within the first two years after surgery. Therefore, monitoring is recommended at intervals of every 3-6 months, with CT scans. PET scans are not a substitute for CT scans.

What Are GIST Targeted Therapies?

For patients who have a more aggressive form of GIST and are at high risk of recurrence, the standard treatment is imatinib (Gleevec). This drug targets cells that have the C-KIT mutation, which is present in 87% of GIST tumors.

Gleevec has been shown to be effective in preventing GIST from recurring. In a study in which imatinib was given after surgery for high- risk GIST, one year of therapy was superior to no therapy after surgery.

A recent study that compared three years of imatinib after surgery to one year of therapy demonstrated superiority for the longer treatment. The FDA has now approved three years of postsurgical imatinib for GIST.

In certain circumstances, Gleevec may not be recommended after surgery. These circumstances may include KIT negative tumors (13%) or the presence of the PDGFRA gene (4%). In the latter instance, the PDGFRA gene conveys imatinib resistance, but also reduces the risk of GIST recurrence.

“There are different kinds of mutations in GIST tumor cells,” says Demetri. “About one out of five GISTs is driven primarily by something called the PDGFRA gene. This makes them resistant to Gleevec, so there’s no point to taking it. The good thing is that this mutation also makes the tumor act like a pussycat; it might be very big, but it rarely would come back. That’s why it’s important that your tumor cells undergo molecular testing, so that you don’t spend years on a treatment that won’t do anything for you.”

Gleevec is a “targeted therapy,” known as a tyrosine kinase inhibitor (TKI). These drugs interfere with the signals sent out by cancer cells, specifically those with the KIT mutation.

“Most people tolerate Gleevec very well,” says Demetri. However, as with all medications, there are side effects. The most common side effects of imatinib include:

Some patients cannot tolerate imatinib and have to discontinue the drug. The most serious side effect -- severe liver dysfunction -- may result in the withdrawal therapy.

In this case, or for tumor recurrence or resistance during imatinib therapy, the drug sunitinib (Sutent) is used. This drug has a GIST control rate of more than 50% with 2-year survival rates.

“Sutent targets a different genetic signaling switch than Gleevec does, so it has different toxicities. You don’t get the swelling you see with Gleevec, but instead you get others, like mouth sores and change in taste, and most commonly high blood pressure, which doctors will need to monitor closely,” says Demetri.

The drug regorafenib (Stivarga) is used to treat patients who have tumors that cannot be surgically removed and no longer respond to other GIST treatments.

Other agents being evaluated for GIST include sorafenib (Nexavar), dasatinib (Sprycel) and nilotinib (Tasigna).

Is GIST Treatment Working?

With most cancers, doctors measure whether or not a treatment is working with one main yardstick: is the tumor shrinking, growing, or staying the same? If the tumor isn’t growing, or is even getting smaller, that’s a sign that the treatment is effective. When a tumor grows while a patient is on a certain drug, doctors will usually stop that drug since it isn’t controlling the cancer.

GIST is different. In the metastatic setting, when GIST is evaluated by CT scan or MRI scan to check treatment response, tumors may enlarge, or stay the same size, even though the patient is improving. A PET scan can help in these cases because they show tumor activity instead of tumor size. This fact is unique to GIST.

Treatments You Probably Won’t Need

Chemotherapy and/or radiation are not appropriate for use in GIST, although radiation may be used to control bleeding from a GIST tumor.

What Happens if the Cancer Spreads?

For some people diagnosed with GIST, the disease has already metastasized at the time of initial diagnosis. Metastasis is defined as tumor spread outside of the primary tumor site. If GIST comes back after treatment at its original site, it is known as local recurrence. Metastatic disease cannot be removed surgically, but a localized recurrence may be able to be surgically removed.

“Between 10% and 20% of GIST patients have disease that’s spread right from the start,” says Demetri. “That’s frightening, but the good news is that Gleevec is very effective in controlling metastatic GIST. It works in about nine out of 10 patients and keeps the disease under control for an average of about 2 years. But about 17% of our patients with metastatic disease who were in the initial trial that we did of Gleevec to treat GIST are still alive and taking the drug today, 12 years later,” he says.

GIST that has metastasized to the liver is sometimes also treated with a procedure called hepatic artery embolization. “If the tumor is deep in the liver where a surgeon can’t take it out without risking the blood supply to that organ, for example, surgeons might use embolization to decrease blood flow to the tumor,” Demetri says.

“In well over half of cases, GIST is either completely controlled with surgery alone, or with surgery and Gleevec to prevent recurrence,” says Demetri.

Show Sources


GIST Support International.

George Demetri, MD, associate professor of medicine, Harvard Medical School; Director, Center for Sarcoma and Bone Oncology, the Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston. Telephone interview.

Nikhil Khushalani, MD, section chief for Soft Tissue and Melanoma, the Roswell Park Cancer Institute, Buffalo, NY. Telephone interview.

Joensuu H, Eriksson M, Hatrmann J, et al. Twelve versus 36 months of adjuvant imatinib (IM) as treatment of operable GIST with a high risk of recurrence: Final results of a randomized trial (SSGXVIII/AIO). Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago. Abstract LBA1.

News release, FDA.

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