What is the management of a Patient (Pt) with a Platelet count of 3 (Pt3) Gastrointestinal Stromal Tumor (GIST)?

From the Guidelines

Pt3 GIST is typically managed with complete surgical excision of the lesion, with no dissection of clinically negative lymph nodes, and adjuvant therapy with imatinib 400 mg/day for 3 years for patients with a significant risk of relapse. The goal of surgery is to achieve R0 excision, but in cases where R0 surgery implies major functional sequelae, the decision can be made with the patient to accept possible R1 (microscopically positive) margins 1.

Key Considerations

• The standard treatment approach involves surgical excision, with laparoscopic excision planned according to the principles of oncological surgery 1.
• Adjuvant imatinib therapy is recommended for patients with a significant risk of relapse, with the dose and duration tailored to the individual patient's risk factors and mutation status 1.
• For patients with KIT exon 9 mutation, a higher dose of imatinib (800 mg daily) may be considered for 3 years 1.
• PDGFRA exon 18 D842V-mutated GISTs should not be treated with adjuvant imatinib, and adjuvant treatment should be avoided in NF1-related and SDH expression-negative GISTs 1.

Management Approach

• Preoperative systemic therapy with imatinib may be considered for patients with locally advanced GIST where immediate resection is likely to be morbid 1.
• Neoadjuvant imatinib is recommended for locally advanced GIST where upfront surgery with major sequelae cannot be avoided and/or R0 surgery is not feasible, with a recommended duration of 6-12 months 1.
• Close monitoring of the response to neoadjuvant therapy is essential to avoid delayed local therapy in case of lack of response 1.

Ongoing Care

• Patients require close monitoring with tumor markers and imaging after treatment, with the frequency of follow-up tailored to the individual patient's risk factors and response to 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.

Management of Pt3 GIST

• The FDA-approved treatment for unresectable or metastatic GIST is imatinib mesylate 2 or regorafenib 3 for patients who have been previously treated with imatinib mesylate and sunitinib malate.
• Imatinib mesylate is used as a first-line treatment for GIST, while regorafenib is used as a third-line treatment.
• The recommended dose of regorafenib for GIST is 160 mg taken orally once daily for the first 21 days of each 28-day cycle 3.
• The recommended dose of imatinib mesylate for GIST is 400 mg or 800 mg orally daily continuously until disease progression or unacceptable toxicity 2.

From the Research

Management of Pt3 GIST

The management of Pt3 GIST involves a combination of surgical resection and adjuvant therapy with tyrosine kinase inhibitors (TKIs) such as imatinib.

• Surgical resection is the primary treatment for resectable tumors, with the goal of achieving complete (R0) resection 4, 5, 6, 7, 8.
• Adjuvant therapy with imatinib is recommended for patients with high-risk GIST, including those with large tumors or high mitotic rates 4, 6, 7.
• The duration of adjuvant therapy is typically at least 3 years, although the optimal duration is unknown 4, 6.
• Neoadjuvant therapy with imatinib may be considered for patients with unresectable tumors or those requiring extensive surgery, with the goal of shrinking the tumor to allow for organ preservation and less extensive surgery 6, 7, 8.
• Monitoring for recurrence with serial abdominal CT scans is recommended for patients with high-risk GIST 5.
• Other treatment options, such as sunitinib, ponatinib, and regorafenib, may be considered for patients with specific mutations or refractory disease 5, 6.

Risk Stratification

Risk stratification is essential in determining the management of Pt3 GIST.

• The National Institutes of Health (NIH) consensus risk criteria, the Armed Forces Institute of Pathology criteria, and the modified NIH criteria are commonly used to estimate the risk of recurrence 4.
• Patients with intermediate-risk GIST may pose a challenge in determining the need for adjuvant therapy, and the modified NIH risk stratification criteria may be useful in this setting 4.
• Analysis of tumor tissue for KIT and PDGFRA mutations is recommended to exclude patients with imatinib-insensitive mutations from adjuvant therapy 4.