What is a Gastrointestinal Stromal Tumor (GIST) and what is its prognosis?

From the Guidelines

Gastrointestinal Stromal Tumors (GISTs) are rare cancers of the digestive tract with a prognosis that significantly varies based on tumor size, location, mitotic rate, and spread, and the current standard of care involves surgical removal followed by targeted therapy for high-risk or metastatic cases, as recommended by the most recent guidelines 1.

Key Factors Influencing Prognosis

• Tumor size: Smaller tumors (less than 5 cm) generally have a better prognosis
• Location: Gastric GISTs tend to have a better prognosis than those in the small bowel or rectum
• Mitotic rate: Lower rates indicate a better prognosis
• Spread: Presence of metastasis significantly worsens the prognosis

Diagnosis and Treatment

• Diagnosis is based on morphology and immunohistochemical positivity for CD117 and/or DOG1
• Surgical removal is the primary treatment, with targeted therapy (e.g., imatinib, sunitinib, regorafenib) for high-risk or metastatic cases
• Regular follow-up with CT scans or MRIs is crucial for monitoring recurrence

Recent Guidelines

• The 2018 ESMO-EURACAN clinical practice guidelines for diagnosis, treatment, and follow-up of GISTs emphasize the importance of anatomical site, histological type, size of tumor, depth of invasion, grade, M category, and mitotic rate as essential prognostic factors 1
• These guidelines also highlight the role of mutational status, particularly KIT and PDGFRA mutations, in determining the natural history and response to treatment

Management Approach

• Complete surgical excision is the standard treatment for localized GISTs, with no dissection of clinically negative lymph nodes
• Laparoscopic excision may be considered for smaller tumors, following the principles of oncological surgery
• Adjuvant imatinib for at least 3 years is recommended for high-risk patients after surgery, based on randomized trial results 1

From the FDA Drug Label

A total of 1,640 patients were enrolled into the two studies and randomized 1:1 to receive either 400 mg or 800 mg orally daily continuously until disease progression or unacceptable toxicity. Patients in the 400 mg daily treatment group who experienced disease progression were permitted to crossover to receive treatment with 800 mg daily The primary objective of the two studies was to evaluate either progression-free survival (PFS) with a secondary objective of overall survival (OS) in one study or overall survival with a secondary objective of PFS in the other study. Results from this combined analysis are shown in Table 26 Table 26: Overall Survival, Progression-Free Survival and Tumor Response Rates in the Phase 3 GIST

• Abbreviation: GIST, gastrointestinal stromal tumors. Imatinib Mesylate 400 mg N = 818 Imatinib Mesylate 800 mg N = 822 Progression-Free Survival (months) Median 18.9 23.2 95% CI 17.4–21.2 20.8–24.9 Overall Survival (months) 49 48.7 95% CI 45.3–60 45.3–51. 6 Best Overall Tumor Response Complete Response 43 (5.3%) 41 (5%) Partial Response 377 (46.1%) 402 (48.9%)

Gist Tumor Definition and Prognosis:

• A GIST (Gastrointestinal Stromal Tumor) is a type of tumor that occurs in the digestive tract, most commonly in the stomach or small intestine.
• The prognosis for GIST patients varies depending on the stage and location of the tumor, as well as the patient's overall health.
• According to the study, the median progression-free survival for patients with unresectable and/or metastatic malignant GIST was 18.9 months for the 400 mg imatinib mesylate group and 23.2 months for the 800 mg imatinib mesylate group 2.
• The overall survival rate was 49 months for the 400 mg group and 48.7 months for the 800 mg group.
• The best overall tumor response was a complete response in 5.3% of patients in the 400 mg group and 5% of patients in the 800 mg group, and a partial response in 46.1% of patients in the 400 mg group and 48.9% of patients in the 800 mg group.
• Another study showed that regorafenib can be used to treat GIST patients who have been previously treated with imatinib mesylate and sunitinib malate, with a median progression-free survival of 4.8 months compared to 0.9 months for the placebo group 3.

From the Research

Definition and Characteristics of GIST

• Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm in the gastrointestinal tract 4, 5, 6.
• GISTs are related to the interstitial cells of Cajal and are characterized by constitutive over-expression of the transmembrane tyrosine kinase receptor KIT 5.
• The majority of GISTs (up to 90%) have a mutation in the proto-oncogene c-kit, with exon 11 being the most frequently affected 5.

Prognosis and Treatment

• The prognosis of GIST depends on various factors, including tumor size, rate of mitosis, and the presence of mutations in the KIT or PDGFRα genes 4, 5.
• Surgery is the primary treatment for resectable non-metastatic GIST, with segmental colectomy with negative margins being the recommended approach 5.
• Medical therapeutic strategies, such as targeted molecular therapy with imatinib, have improved the outcome of GIST treatment 5, 6.
• Regorafenib, a multikinase inhibitor, has shown efficacy and safety in patients with GIST after failure of imatinib and sunitinib 7, 8.
• The disease control rate (DCR) and progression-free survival (PFS) are important endpoints in evaluating the efficacy of treatments for GIST 7, 8.

Epidemiology and Clinical Presentation

• The estimated incidence of GIST is approximately 10-20 per million people per year 6.
• The clinical presentation of GIST is variable, but common symptoms include the presence of a mass or bleeding 6.
• GISTs can occur in any part of the gastrointestinal tract, with the stomach being the most common site, followed by the small intestine and rectum 5.