What is a Gastrointestinal Stromal Tumor (GIST)?

From the Guidelines

The diagnosis and management of GIST should prioritize obtaining a pre-operative diagnosis, especially in larger, more complex tumors, to guide treatment and improve patient outcomes, as recommended by the British Sarcoma Group clinical practice guidelines 1.

Key Considerations

• The diagnosis of GIST relies on morphological assessment and immunohistochemistry, with CD117 and/or DOG1 immunopositivity being key diagnostic markers 1.
• Molecular analysis, including KIT and PDGFRA mutational analysis, is essential for predicting sensitivity to molecular-targeted therapy and has prognostic value 1.
• Small asymptomatic submucosal lesions <2 cm in diameter may be kept under surveillance, while larger lesions require a histological diagnosis, preferably through fine needle aspirate or core needle biopsy under endoscopic ultrasound (EUS) guidance 1.
• Multidisciplinary treatment planning, involving pathologists, radiologists, surgeons, and medical oncologists, is crucial for optimal management of GIST patients, and treatment should be carried out in reference centers for sarcomas and GISTs 1.

Diagnostic Approach

• Endoscopic ultrasound assessment and follow-up are recommended for small oesophagogastric or duodenal nodules <2 cm in size, with excision reserved for patients whose tumor increases in size or becomes symptomatic 1.
• Biopsy or excision is recommended for tumors >2 cm in size, and multiple core needle biopsies should be obtained through EUS guidance or an ultrasound/CT-guided percutaneous approach for masses, especially if surgery is likely to be a multivisceral resection 1.

Treatment and Follow-up

• The standard approach to tumors >2 cm in size is biopsy/excision, and immediate laparoscopic/laparotomic excision is an option on an individualized basis, especially if surgery is limited 1.
• Pathological diagnosis should be centralized in a laboratory enrolled in an external quality assurance program, and fresh frozen tissue should be collected to allow for new molecular pathology assessments 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.

The drug regorafenib (STIVARGA) is indicated for the treatment of patients with locally advanced, unresectable or metastatic GIST who have been previously treated with imatinib mesylate and sunitinib malate 2.

• Key points:
  • GIST treatment: regorafenib (STIVARGA) is used for GIST treatment.
  • Previous treatments: imatinib mesylate and sunitinib malate must have been previously used.
  • Disease stage: locally advanced, unresectable or metastatic GIST.

From the Research

Gastrointestinal Stromal Tumors (GISTs)

• GISTs are rare neoplasms of the gastrointestinal tract associated with high rates of malignant transformation 3
• Most GISTs present asymptomatically and are best identified by computed tomography (CT) scan 3
• GISTs are characterized by the expression of the protein-tyrosine kinase KIT (CD117) and are the most common mesenchymal tumor arising in the gastrointestinal tract, mesentery, or omentum 4

Treatment of GISTs

• Surgical resection is the first-line intervention for operable GISTs, particularly localized primary tumors 4
• Imatinib is a potent, specific inhibitor of KIT that has demonstrated significant activity and tolerability in the treatment of malignant unresectable or metastatic GIST 4
• The standard therapy for unresectable or metastatic GISTs includes first-line imatinib, second-line sunitinib, and third-line regorafenib 5
• Preoperative imatinib can decrease tumor volume and is associated with complete surgical resection in locally advanced primary GISTs 6

Management of Advanced GIST

• Continuous imatinib treatment in patients with advanced GIST is associated with reduced risk of progression 7
• For patients progressing on or intolerant of imatinib, continuing therapy with TKIs sunitinib followed by regorafenib is recommended 7
• Maintenance of therapy with TKIs is the key to successful treatment of GIST 7
• Patients may benefit from continuation of TKIs beyond disease progression and from rechallenge of TKIs used previously 5