Gastrointestinal Stromal Tumor (GIST)


Gastrointestinal tumors (GISTs) are rare soft-tissue tumors that develop from the interstitial cells of Cajal (ICC), which are nerve cells located in the wall of the gastrointestinal (GI) tract.1-3 The tumors may occur anywhere in the GI tract, but most commonly in the stomach (60%) or small intestine (35%).3,4 They may also develop in the esophagus, colon, or rectum.4 GISTs can be noncancerous or cancerous, and in the latter case, they are also called soft-tissue sarcomas.2 

GISTs account for approximately 1% of all GI tumors. The 5-year survival rate of patients with a GIST is 83%.4 The worldwide incidence is estimated to be 1 to 2 per 100,000 people, and the prevalence is estimated to be 13 per 100,000.3 Most commonly, GISTs occur in persons older than 60 years; both men and women are affected.3

Most GISTs develop in individuals with a non-inherited mutation of the KIT or PDGFRA gene.1 However, mutations in approximately 20 other genes have been associated with GISTs, most of which are not inherited.1 Familial GISTs, such as neurofibromatosis type 1, Carney-Stratakis syndrome, and Carney triad, are rare. The presentations are distinct, characterized by urticaria pigmentosa and hyperpigmentation.5

Symptoms and Diagnosis

The symptoms of a GIST depend on its size and location.1 In many cases, patients are asymptomatic, typically presenting with nonspecific symptoms such as early satiety, and remain so until the tumor grows to approximately 6 cm.1,3 Patients may also have anemia, hematemesis, abdominal pain, and bloody bowel movements.2 About 20% of patients have metastatic disease at the time of diagnosis.3 All GISTs have the potential to metastasize, usually to sites within the abdominal cavity and the liver, and less frequently to lymph nodes.1,3

A GIST can be diagnosed with percutaneous biopsy or endoscopic biopsy.1 The use of immunohistochemistry to detect certain proteins in various tissues, such as the KIT protein or the transmembrane phosphoglycoprotein CD34, can aid in diagnosing the tumor.3 Computed tomography CT), positron emission tomography (PET), magnetic resonance imaging (MRI), and ultrasonography can be used to determine if a tumor has metastasized and may provide additional information when the diagnosis is uncertain.1,3

The prognosis of a patient with a GIST depends on the size and location of the tumor, and whether it is cancerous. Whether metastasis is present, the potential for tumor rupture, and the possible requirement for resection are other factors affecting the prognosis.2,3

Read more about GIST symptoms

Treatment

The first-line treatment for localized tumors is complete surgical excision2; however, approximately 10% of tumors recur after surgery.3 It is important that care be taken to avoid tumor rupture. Surgery can also be performed after the patient has undergone chemotherapy.3 

The treatment of unresectable and recurrent tumors or of metastatic disease relies on the use of tyrosine kinase inhibitors (TKIs). Imatinib mesylate (Gleevec®) is commonly the first option for patients with advanced/metastatic disesase.6 Sunitinib malate (Sutent®) may be administered as second-line therapy when treatment with imatinib mesylate has been unsuccessful.2 When a patient does not respond to first- and second-line treatment, the TKI regorafenib (Stivarga®) may be prescribed.2 Imatinib mesylate may also be a neoadjuvant option to reduce tumor size before surgery, facilitating resection.3,7

Other TKIs have recently been developed for GIST treatment, including the fourth-line therapy ripretinib (Qinlock®). Avapritinib (Ayvakit™) can be administered as first-line therapy to patients with specific platelet-derived growth factor receptor alpha (PDGFRA) gene mutations.8

Read more about GIST treatment

Follow-up

Patients with GISTs require long-term follow-up. CT or MRI is routinely used to monitor disease progression. For patients with low-risk tumors, follow-up assessments every 6 to 12 months for 5 years may be appropriate. For patients undergoing adjuvant therapy, monitoring with imaging can be done every 3 to 6 months for 3 years. Once adjuvant therapy has been completed, monitoring can be done every 3 months for 2 years to assess for tumor recurrence. Follow-up can then be scheduled every 6 months for 5 years, then once a year.9 

References

1. Gastrointestinal stromal tumors. National Organization for Rare Disorders (NORD). Accessed May 1, 2022.

2. Gastrointestinal stromal tumors. Genetic and Rare Diseases Information Center (GARD). Accessed May 1, 2022.

3. Mantese G. Gastrointestinal stromal tumor: epidemiology, diagnosis, and treatment. Curr Opin Gastroenterol. 2019;35(6):555-559. doi:10.1097/MOG.0000000000000584

4. Gastrointestinal stromal tumor – GIST: statistics. Cancer.Net. Approved February 2022. Accessed May 1, 2022.

5. Stanek M, Pisarska M, Budzyńska D, et al. Gastric gastrointestinal stromal tumors: clinical features and short- and long-term outcomes of laparoscopic resection. Wideochir Inne Tech Maloinwazyjne. 2019;14(2):176-181. doi:10.5114/wiitm.2019.83868

6. Serrano C, George S. Gastrointestinal stromal tumor: challenges and opportunities for a new fecade. Clin Cancer Res. 2020;26(19):5078-5085. doi:10.1158/1078-0432.CCR-20-1706

7. Watson GA, Kelly D, Melland-Smith M, et al. Get the GIST? An overview of gastrointestinal stromal tumours. Ir J Med Sci. 2016;185(2):319-26. doi:10.1007/s11845-016-1410-1

8. Patel SR, Reichardt P. An updated review of the treatment landscape for advanced gastrointestinal stromal tumors. Cancer. 2021;127(13):2187-2195. doi:10.1002/cncr.33630

9. Casali PG, Abecassis N, Aro HT, et al. Gastrointestinal stromal tumours: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):iv68-iv78. doi:10.1093/annonc/mdy095

Reviewed by Hasan Avcu, MD, on 5/27/2022.

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