What is Gastrointestinal Stromal Tumor (GIST)?

From the Guidelines

GIST (Gastrointestinal Stromal Tumor) is a rare type of cancer that begins in specialized cells found in the wall of the gastrointestinal tract, most commonly in the stomach or small intestine, and is typically caused by mutations in genes called KIT or PDGFRA, which lead to uncontrolled cell growth, as stated in the most recent guidelines 1.

Diagnosis and Treatment

The diagnosis of GIST relies on morphological assessment and immunohistochemistry (IHC), with the diagnosis being supported by CD117 and/or DOG1 immunopositivity 1.

• The most common symptoms of GIST include upper gastrointestinal bleeding and anaemia, whilst larger tumours may present with abdominal pain/discomfort and a palpable mass.
• Small bowel GISTs may remain silent for a long period before presenting with an acute event such as haemorrhage or rupture.
• Treatment usually involves surgical removal of the tumor when possible, followed by targeted therapy with medications like imatinib (Gleevec), sunitinib (Sutent), or regorafenib (Stivarga) for advanced or recurrent cases.

Prognosis and Monitoring

• Prognosis varies based on tumor size, location, mitotic rate (how quickly cells are dividing), and whether the cancer has spread, with complete surgical removal offering the best chance for cure in localized disease.
• Regular monitoring with CT scans or MRIs is essential to track treatment response, as recommended in the guidelines 1.

Molecular Analysis

• Molecular analysis has predictive value for sensitivity to molecular-targeted therapy, and prognostic value, and is highly recommended for all GISTs, particularly for resected moderate or high-risk GISTs, resected GISTs showing tumour rupture, and biopsies diagnostic of GIST prior to neoadjuvant or adjuvant therapy 1.

From the FDA Drug Label

1. 2 Gastrointestinal Stromal Tumors STIVARGA is indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate.

GIST Definition: Gastrointestinal Stromal Tumor (GIST) is a type of tumor that occurs in the digestive tract, specifically in the stomach or small intestine.

• Key Characteristics:
  • Locally advanced, unresectable, or metastatic
  • Previously treated with imatinib mesylate and sunitinib malate
• Treatment: STIVARGA (regorafenib) is indicated for the treatment of patients with GIST who have been previously treated with imatinib mesylate and sunitinib malate 2

From the Research

Definition and Characteristics of GIST

• Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, accounting for 1-3% of all gastrointestinal malignancies 3.
• GISTs are defined as mesenchymal tumors of the gastrointestinal tract expressing proto-oncogene protein CD117 4.
• They are presumed to arise from interstitial cells of Cajal or gastrointestinal pacemaker cells which control gut motility 4.
• GISTs have unpredictable biological behavior, and their prognosis is dependent on tumor size as well as mitotic count 4.

Clinical Presentations and Symptoms

• The clinical presentations of GIST are highly variable according to their site and size 3.
• The most frequent symptoms are anemia, weight loss, gastrointestinal bleeding, abdominal pain, and mass-related symptoms 3.
• Patients may present with acute abdomen, obstruction, perforation, or rupture and peritonitis 3.
• Gastrointestinal bleeding is a common presenting symptom, as seen in 45 patients in one study 3.

Treatment and Management

• Surgical resection is the "gold standard" for therapy of GIST 3.
• Radical surgical excision is the treatment of choice, and surgery is still the gold standard treatment in localized GIST 3, 4.
• Targeted therapy with inhibitors of tyrosine kinase receptors (imatinib) has been introduced for the management of advanced and metastatic tumors 3, 5, 6.
• Adjuvant therapy with imatinib mesylate or other tyrosine kinase inhibitors is recommended for high-risk patients after complete resection 5, 6.

Prognosis and Survival Rates

• The prognosis is strictly related to size and completeness of surgical resection 3.
• The 3 and 5-years overall survival rates for all patients were 92.1% and 81.4% respectively in one study 3.
• The 3 and 5-years disease-free survival rates for all patients were 73.2% and 64.5% respectively in one study 3.
• Recurrence is common, and the risk can be defined by surgical factors like incomplete resection, intraperitoneal rupture, or bleeding and tumor-associated factors like tumor size, mitotic index, or localization 5.