What is a Gastrointestinal Stromal Tumor (GIST)?

From the Guidelines

The primary treatment for GIST (Gastrointestinal Stromal Tumor) involves surgical removal of the tumor when possible, with targeted therapy using tyrosine kinase inhibitors like imatinib being the standard first-line treatment for advanced, metastatic, or unresectable GISTs. According to the most recent guidelines, for localized GISTs, complete surgical resection is the primary treatment, while for advanced cases, imatinib at 400-800 mg daily is the standard first-line treatment 1. Imatinib works by blocking specific proteins that drive tumor growth. If imatinib fails, second-line options include sunitinib or regorafenib.

Some key points to consider in the diagnosis and treatment of GIST include:

• Genetic testing of the tumor is crucial as different mutations respond differently to treatments 1
• The diagnosis of GIST relies on morphological assessment and immunohistochemistry (IHC), with CD117 and/or DOG1 immunopositivity supporting the diagnosis 1
• Molecular analysis has predictive value for sensitivity to molecular-targeted therapy and prognostic value, and should be performed on all resected moderate or high-risk GISTs, biopsies diagnostic of GIST prior to neoadjuvant or adjuvant therapy, and specimens from patients with unresectable and/or metastatic GIST 1
• Regular follow-up with CT scans or MRIs every 3-6 months is essential to monitor treatment response

It's also important to note that GISTs arise from interstitial cells of Cajal in the digestive tract wall and are characterized by mutations in KIT or PDGFRA genes, which cause abnormal cell growth and division. Prognosis depends on tumor size, location, mitotic rate, and whether it has spread. The British Sarcoma Group clinical practice guidelines provide a comprehensive overview of the diagnosis, treatment, and follow-up of GISTs, and recommend a multidisciplinary approach to management 1.

From the FDA Drug Label

The safety of sunitinib was evaluated in Study 1, a randomized, double-blind, placebo-controlled trial in which previously treated patients with GIST received sunitinib 50 mg daily on Schedule 4/2 (n = 202) or placebo (n = 102). Table 3 summarizes the adverse reactions for Study 1. Table 3 Adverse Reactions Reported in ≥ 10% of GIST Patients Who Received Sunitinib in the Double-Blind Treatment Phase and More Commonly Than in Patients Given Placebo* in Study 1 The most common adverse reactions (≥ 25%) were fatigue/asthenia, diarrhea, mucositis/stomatitis, nausea, decreased appetite/anorexia, vomiting, abdominal pain, hand-foot syndrome, hypertension, bleeding events, dysgeusia/altered taste, dyspepsia, and thrombocytopenia Sunitinib is used to treat GIST.

• Common adverse reactions in GIST patients who received sunitinib include:
  • Fatigue/asthenia
  • Diarrhea
  • Mucositis/stomatitis
  • Nausea
  • Decreased appetite/anorexia
  • Vomiting
  • Abdominal pain
  • Hand-foot syndrome
  • Hypertension
  • Bleeding events
  • Dysgeusia/altered taste
  • Dyspepsia
  • Thrombocytopenia 2

From the Research

Definition and Epidemiology of GIST

• Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal tract associated with high rates of malignant transformation 3.
• GISTs are the most common mesenchymal tumors of the gastrointestinal tract, accounting for 1-3% of all gastrointestinal malignancies 4.
• The majority of GISTs harbor gain of function mutations in either KIT or PDGFRα 5.

Clinical Presentation and Diagnosis

• Most GISTs present asymptomatically, but the clinical presentations can be highly variable according to their site and size 4.
• The most frequent symptoms are anemia, weight loss, gastrointestinal bleeding, abdominal pain, and mass-related symptoms 4.
• GISTs are best identified by computed tomography (CT) scan and most stain positive for CD117 (C-Kit), CD34, and/or DOG-1 3.

Treatment and Management

• Surgical resection is the "gold standard" for therapy of GIST, and the approaches to treating GISTs include resecting primary low-risk tumors, resecting high-risk primary or metastatic tumors with imatinib, or neoadjuvant imatinib followed by surgical resection for unresectable tumors 3.
• Targeted therapy with inhibitors of tyrosine kinase receptors (imatinib) has been introduced for the management of advanced and metastatic tumors 4.
• Second and third line options include sunitinib and regorafenib, respectively, and yield low response rates and limited clinical benefit 5.
• Recent FDA approvals for GIST include ripretinib in the fourth-line setting and avapritinib for PDGFRA exon 18-mutant GIST 5.

Prognosis and Survival

• The prognosis is strictly related to size and completeness of surgical resection 4.
• The 3 and 5-years overall survival rates for all patients were 92.1% and 81.4% respectively, and the 3 and 5-years disease-free survival rates for all patients were 73.2% and 64.5% respectively 4.
• High-risk tumors should be monitored for recurrence with serial abdominal CT scans 3.