Risk Stratification of Gastrointestinal Stromal Tumors (GISTs)

GISTs are a rare type of soft tissue sarcoma — a general term for cancers beginning in connective tissues surrounding and protecting organs of the body. While these tumors can occur anywhere along the gastrointestinal (GI) tract, most begin in the stomach and small intestine. GISTs originate from specialized cells called the interstitial cells of Cajal (ICCs), which are found in the muscularis propria layer of the GI wall. Known as the ‘pacemaker’ cells of the gut, ICCs are responsible for sending signals to trigger muscular contractions that move stomach food and liquid along the digestive tract (peristalsis).

GISTs are mostly indolent (slow-growing), and smaller than 2 cm, with a low risk of spreading to other parts of the body. As they are not life-threatening, you usually may not need any treatment if you have an indolent GIST. Instead, your doctors may recommend monitoring it with regular endoscopies every 6 to 12 months. On the other hand, GISTs which are usually 2 cm or larger can grow into nearby tissues and spread to other organs.

Early-stage GISTs may be best treated with surgery while advanced-stage GISTs would likely require treatments, such as targeted therapy, that reach all parts of the body.

When your doctor first suspects that you may have a GIST, they will order a series of diagnostic tests to confirm whether you have the condition. In the case of GISTs, a biopsy is needed to diagnose this type of tumor. If the tumor is confirmed to be a GIST, these tests will provide some information that determines the stage of your cancer. This includes the size of the tumor and which parts of the body the cancer has spread to.

While cancer is typically staged when it is first diagnosed and before any treatment, in some cases, it can be staged again over the course of your treatment journey.

If surgery is done to remove the GIST, doctors can determine the tumor’s pathological (or surgical) stage. This is derived from the results of earlier tests as well as those from the surgery. The pathological stage often gives more precise information about the cancer, which makes it a much more accurate indicator of its actual progression within the body.

Some patients may receive other types of treatment, such as targeted therapy, before surgery. This is known as neoadjuvant therapy, which is done to reduce the size of the GIST so that there is a higher chance of successfully removing it from the body.

Assessing the severity and risk of spread of GISTs can be done by the Miettinen classification (also known as the Armed Forces Institute of Pathology (AFIP) classification). This will be based on the mitotic rate (a measure of the speed of cancer cell growth and division). The recommended adjuvant treatment will then depend on both the risk score, and the mutational status of the GIST. 

Those with a tumor size of over 5 cm and a high mitotic rate face a higher risk of metastasis, while those under 2 cm still face a low risk of metastasis.

For resectable GISTs, surgery is the preferred treatment as long as there are no significant predicted risks with surgical removal. For metastatic GISTs where surgery is no longer possible, imatinib is the first-line targeted therapy used for treatment. However, if the GIST does not have imatinib-sensitive mutations, other tyrosine kinase inhibitors may be used instead.

Despite how rare GISTs are, rest assured that strong guidelines are in place to predict and manage the risk of metastasis. Having a GIST is a serious condition and understanding the stage of your tumor is crucial in comprehending the severity of your diagnosis and overall health. It’s essential to communicate any doubts or questions about your condition with your cancer care team. By doing so, you can take control of your health and make informed decisions about your treatment options.