Gastrointestinal Stromal Tumor (GIST)

What a GIST is

GISTs arise from the interstitial cells of Cajal, which act as the gut's pacemaker, coordinating muscle contractions. Unlike most stomach and bowel cancers, which start in the inner lining, GISTs grow within the muscle wall, so they often bulge outward and can grow large before causing symptoms.

About 4,000 to 6,000 GISTs are diagnosed each year in the US. They occur mostly in people aged 50 to 70.

Causes and genetics

• KIT mutations in about 75 to 80% of GISTs drive tumor growth.
• PDGFRA mutations in about 5 to 10%; one variant (D842V) does not respond to imatinib.
• "Wild-type" GISTs without these mutations include SDH-deficient tumors (often in children and young adults, sometimes with Carney-Stratakis syndrome) and those in neurofibromatosis type 1.

Most GISTs are not inherited. Genetic testing of the tumor guides treatment.

Symptoms

• black, tarry stools or vomiting blood from bleeding
• tiredness and breathlessness from anemia
• abdominal pain or discomfort
• early fullness or bloating
• nausea and vomiting
• a palpable lump in the abdomen
• weight loss

Small GISTs are often discovered during endoscopy, CT scans or surgery done for other reasons.

Diagnosis

• CT scan with contrast of the abdomen and pelvis: the main imaging test for size, location and spread (most often to the liver and lining of the abdomen).
• Upper endoscopy and endoscopic ultrasound (EUS): show a smooth submucosal bulge and allow a needle biopsy.
• Biopsy: pathologists confirm GIST with markers such as KIT (CD117) and DOG1 on immunostaining.
• Mutational analysis of KIT and PDGFRA to guide drug choice.
• MRI for rectal GISTs, and PET-CT in selected cases.

Risk assessment

Doctors estimate the chance of a GIST coming back after surgery using:

Very small stomach GISTs (under 2 cm) may simply be monitored with endoscopic ultrasound in some cases.

Treatment

Surgery

Complete surgical removal with clear margins is the main treatment for localized GIST. Because GISTs rarely spread to lymph nodes, surgeons remove the tumor with a margin of normal tissue rather than wide lymph node dissection. Laparoscopic surgery is possible for many stomach GISTs. Care is taken not to rupture the tumor.

Targeted therapy

• Imatinib blocks the KIT and PDGFRA proteins. It is used: - after surgery (adjuvant) for 3 years in high-risk tumors, which improves survival - before surgery (neoadjuvant) to shrink large tumors or those in difficult locations - for advanced or metastatic GIST, often controlling disease for years
• Sunitinib and regorafenib are used when imatinib stops working.
• Ripretinib for later lines of therapy.
• Avapritinib for GISTs with the PDGFRA D842V mutation.

Common side effects of imatinib include swelling around the eyes, fluid retention, muscle cramps, nausea, diarrhea, rash and fatigue. They are often manageable.

Other treatments

Chemotherapy and radiation are generally ineffective for GIST. Liver surgery or ablation may be used for limited metastases.

Follow-up

Regular CT scans, often every 3 to 6 months for several years after surgery, depending on risk. Recurrence is most common in the liver and abdominal lining.

Outlook

Outlook depends on size, location, mitotic rate and mutation type. Many small, low-risk GISTs are cured by surgery alone. For advanced GIST, targeted therapy has turned a previously untreatable cancer into one that many people live with for years. Five-year survival for localized GIST is over 90%.

Frequently asked questions

Is a GIST cancer?

Yes. GISTs are a type of sarcoma, a cancer of connective tissue. However, their behavior ranges widely: small, low-risk GISTs are often cured by surgery, while large or high-risk ones are more likely to recur or spread.

What are the symptoms of a GIST?

Many have no symptoms. When present, symptoms include black stools or vomiting blood from bleeding, tiredness from anemia, abdominal pain, early fullness, nausea and a lump in the abdomen.

How is GIST treated?

Surgery to remove the tumor is the main treatment. Imatinib, a targeted pill, is given after surgery for high-risk tumors, before surgery to shrink large ones, and for advanced disease. Other targeted drugs are used if imatinib stops working.

What is the survival rate for GIST?

Five-year survival is over 90% for GISTs that have not spread. For advanced GIST, targeted drugs allow many people to live for years. Your outlook depends on tumor size, location, growth rate and genetic mutation.