Gastrointestinal stromal tumors (GISTs) are a rare type of soft-tissue sarcoma that forms in the wall of the digestive tract. These tumors originate from specialized nerve cells called the interstitial cells of Cajal, which regulate digestive processes. While GISTs can occur anywhere along the gastrointestinal path, they are most commonly found in the stomach and small intestine. Treatment has become highly specialized, using targeted approaches that have significantly improved patient outcomes.
Determining the Treatment Approach
A patient’s treatment plan is formulated after an evaluation of several diagnostic factors. The size of the tumor is a primary consideration; tumors larger than 2 cm are recommended for removal. The location of the GIST also plays a role, as a tumor in the stomach may be approached differently than one in the small intestine. Another factor is the mitotic rate, which measures how quickly cancer cells are dividing and provides insight into the tumor’s aggressiveness.
The most significant factor in GIST treatment is the tumor’s genetic profile. Over 85% of these tumors are driven by mutations in the KIT or PDGFRA genes, which cause cells to receive constant growth signals. Identifying the exact mutation through genetic testing is a standard part of the diagnostic process because it directly influences which medications will be most effective.
For example, a GIST with a PDGFRA D842V mutation will not respond to the common targeted drug, imatinib. Instead, a different medication, avapritinib, is used as the first-line therapy for this subtype. This level of precision allows oncologists to tailor treatment to the individual biological characteristics of the tumor.
Treatment for Localized Tumors
For GISTs that are confined to their original location, surgery is the primary treatment. The objective of the operation, known as a resection, is the complete removal of the tumor with an intact pseudocapsule and clean margins, meaning a border of healthy tissue is also taken out. GISTs rarely spread to the lymph nodes, so removal of nearby nodes is not necessary.
In some cases, targeted therapy is used to assist the surgical process. When a tumor is very large or located in a difficult-to-reach area, a treatment called neoadjuvant therapy may be recommended. This involves taking a targeted drug, usually imatinib, for up to 12 months before surgery to shrink the tumor, which can make the subsequent operation safer and more effective.
Following surgery, some patients may receive adjuvant therapy to lower the risk of the cancer returning. This involves taking a targeted drug, most commonly imatinib, for at least three years. Adjuvant therapy is recommended for patients whose tumors are determined to have a high risk of recurrence, based on factors like size, location, and mitotic rate.
Treatment for Advanced or Metastatic Tumors
When a GIST cannot be surgically removed or has already metastasized to other parts of the body, such as the liver or peritoneum, targeted therapy becomes the main form of treatment. Traditional chemotherapy and radiation are not effective against GISTs, which makes molecularly targeted drugs the standard of care. These drugs, known as tyrosine kinase inhibitors (TKIs), work by blocking the specific proteins that the cancer cells use to grow and divide.
Treatment for advanced GIST follows a sequential path known as lines of therapy. If a tumor develops resistance to one drug or a patient cannot tolerate it, they move to the next line. The standard sequence of these targeted drugs includes:
- First-line: Imatinib (Gleevec), effective for most patients with KIT or PDGFRA mutations.
- Second-line: Sunitinib (Sutent), used when imatinib is no longer effective.
- Third-line: Regorafenib (Stivarga), used if the tumor progresses further.
- Fourth-line: Ripretinib (Qinlock), an option after the first three drugs have been used.
Monitoring and Follow-Up Care
After the initial treatment for a GIST is completed, ongoing monitoring is a standard part of long-term care. The primary goal of this surveillance is to detect any signs of tumor recurrence or progression as early as possible. This is important for GISTs, as they have the potential to return even after successful initial treatment.
Follow-up care involves a regular schedule of imaging scans. Computed tomography (CT) or magnetic resonance imaging (MRI) scans are the most common methods used to monitor the original tumor site and check for any new growths. The frequency of these scans will depend on the individual’s risk of recurrence, with higher-risk patients being monitored more closely.
The oncology team also plays an ongoing role in managing any long-term side effects from targeted therapies. These medications can cause issues that require management, and the medical team can adjust dosages or provide supportive care to help maintain the patient’s quality of life. This continuous relationship with the care team ensures any changes in the patient’s health are addressed promptly.