Symptoms

Individuals with a gastrointestinal stromal tumor (GIST) may experience a range of non-specific symptoms, which vary based on the tumor’s size, location, and extent of growth.

Symptoms of gastrointestinal stromal tumors include the following:

• Abdominal mass or swelling.
• Abdominal pain.
• Fatigue.
• Nausea and vomiting.
• Loss of appetite.
• Early satiety (feeling full after eating a small amount).
• Dark-colored stools, which may indicate gastrointestinal bleeding.

Diagnosis and Stages

Diagnosis of a gastrointestinal stromal tumor usually starts with a review of symptoms and medical history. If suspicion remains, further diagnostic tests may be required, such as the following:

• Imaging tests - These help locate the tumor and determine its size. This may include an ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) scans. Not all patients need every test. CT scans are often used to identify masses, MRIs can improve visualization of soft tissue, and PET scans can offer insight into tumor activity.
• Upper endoscopy - This procedure uses a thin, flexible tube with a light introduced through the mouth to examine the esophagus, stomach, and upper small intestine. It can detect masses in these areas
• Lower endoscopy can detect masses in the colon or rectum.
• Endoscopic ultrasound (EUS) - This procedure uses an endoscope with an ultrasound probe to visualize the tumor and measure its size. It also allows for the collection of tissue samples.
• Fine-needle aspiration and Fine-needle Biopsy - These tests use a thin, hollow needle, often guided by endoscopic ultrasound, to collect a tissue sample from the tumor for laboratory analysis. If the sample is insufficient or the results are inconclusive, minor surgery may be needed to obtain an adequate specimen. The tissue is then analyzed to determine if cancer cells are present.
  

Gastrointestinal stromal tumors often cause no symptoms in early stages and are frequently found incidentally during evaluations for other conditions.

Treatments

Treatment for gastrointestinal stromal tumors (GISTs) typically includes surgery and targeted therapy. Some GISTs, especially very small and asymptomatic ones, may not require immediate treatment. In these cases, regular monitoring is recommended, and treatment can begin if the tumor shows signs of growth.

Treatment decisions for GISTs are based on tumor size, location, cell division rate, and the likelihood of spread. At the CU Anschutz Cancer Center a multidisciplinary team develops a treatment plan that may include surgery and medication. If the tumor is removable, surgery is usually the primary approach. For tumors with a higher risk of recurrence, tyrosine kinase inhibitors (TKIs) such as imatinib are often prescribed after surgery. If the tumor cannot be removed, has spread, or recurs, systemic therapy is the main option, selected according to the tumor’s genetic profile.

Surgery

The primary goal of surgery is the complete removal of the GIST. Surgery is often the initial treatment for tumors that have not spread beyond their original location.

Surgery may not be appropriate if the tumor is very large or has invaded nearby structures. In such cases, targeted therapy is often used first to shrink the tumor, with surgery considered at a later stage.

 The type of surgery depends on the tumor's specific characteristics. Minimally invasive techniques are often possible (robotic and laparoscopic surgery), allowing surgeons to operate through small incisions rather than a single large one.

Radiation therapy is generally not used for GISTs, as these tumors respond poorly to radiation and the surrounding abdominal organs are highly sensitive. 

Targeted therapy

Targeted therapy uses medications that block specific molecules involved in cancer cell growth. In GISTs, these treatments target the tyrosine kinase enzyme, which promotes tumor growth, and have significantly improved GIST treatment, replacing less effective chemotherapy with targeted therapies that target specific genetic changes.

TKIs such as Imatinib (Gleevec) are commonly the first targeted therapy for GISTs. Targeted treatments may be administered:

• After surgery, to lower the risk that the cancer will come back.
• Before surgery, the tumor is reduced in size to make it easier to remove.
• As the first treatment, if the cancer has spread to other parts of the body.
• If the GIST comes back.
  

Other targeted therapies may be considered if imatinib is ineffective or loses effectiveness. Research in this area is advancing rapidly, and additional treatments are expected to become available.

First-Line Therapy

TKIs are typically the first-line treatment for unresectable, metastatic, or recurrent GISTs. Clinical studies have shown that imatinib benefits over 80% of patients by shrinking tumors or halting their growth, resulting in longer progression-free intervals.

Neoadjuvant Therapy

Imatinib given before surgery can be helpful for GISTs that are large or in tricky places, where surgery right away could cause serious problems or mean losing an organ. This treatment before surgery tries to shrink the tumor, make it easier to remove, and save organ function. This approach also allowed for less extensive surgery.

Because some tumors do not respond to imatinib, genetic testing is essential before starting preoperative therapy. Tumors located in challenging areas such as the rectum, duodenum, or gastroesophageal junction are suitable candidates for this approach, as surgery in these locations can be complex and may require major procedures.

Second- and Third-Line Therapies

For patients whose cancer stops responding to imatinib or who cannot take it, Sunitinib is the usual second treatment. Regorafenib is used as a third treatment and was shown to help people who had already tried both imatinib and sunitinib go longer without their cancer getting worse.

Fourth-Line and Subsequent Therapies

Ripretinib is used as a fourth-line therapy for GIST and targets multiple genetic mutations. Avapritinib is highly effective for patients with the PDGFRA D842V mutation, which is resistant to most other treatments.