Treating a Patient Newly Diagnosed With GIST

Initial presentation, evaluation, and work-up

A 63-year-old male initially presented to his PCP for evaluation of melena. The patient reported that he noticed black tarry stools for the last 3 weeks. Additionally, he’s noticed a decrease in his appetite recently and only eats about 50% of his dinner before getting full. Notably he has been taking oral iron supplements for many years to help with his energy.

On physical exam, his PCP noted a firm mass in the left upper quadrant, but no abdominal pain or tenderness upon palpation. He recommended the patient discontinue his iron supplements and ordered a CBC and abdominal x-ray. Results indicated a hemoglobin of 10.2 g/dL and a suspicious mass adjacent to the stomach. The patient went for an urgent CT of the abdomen, which revealed a 6.9 x 8.0 x 7.2 cm mass arising from the gastric body. His PCP put in an urgent referral to the GI oncology team.

This patient met with the surgical oncology team which recommended obtaining a tissue biopsy given the size and location of the mass and their concern for significant morbidity with upfront surgical resection. A CT-guided biopsy was performed, which confirmed a gastrointestinal stromal tumor (GIST). IHC was positive for CD117, with a mitotic count of 8 mitosis/50 HPFs.  

He was referred to the medical oncology team who ordered next-generation sequencing test which revealed a cKIT exon 11 mutation. They recommended the patient start neoadjuvant imatinib and re-image in 3 months to assess disease response.  

Discussion

GISTs often present with GI symptoms associated with tumor growth, which often includes GI bleeding, abdominal pain, and early satiety. Additionally, in approximately 25% of cases GIST may be incidentally found. In patients with small tumors (<2 cm) and no symptoms, active surveillance may be appropriate given a patient’s age, comorbidities, and preferences.¹ 

For those patients with larger masses (≥2 cm) or who present with symptoms from their tumor, additional evaluation is warranted. If resection is feasible, it should be performed upfront without the need of a prior tissue biopsy. However, if there is concern for adequate surgery or significant morbidity given tumor location and size, a tissue biopsy should be obtained to confirm the diagnosis of GIST as neoadjuvant therapy may be appropriate.² CD117 is present in ~95% of GIST and is a hallmark of diagnosis.  

Risk stratification for GIST recurrence involves various features of the GIST, including primary site, tumor size, and proliferation rate (Table 1). With all other factors being equal, patients with non-gastric primaries are at higher risk of disease recurrence compared to patients with gastric primaries. Tumors of greater size have a greater risk of recurrence, with risk stratification tools separating tumors into categories of <2 cm, 2-≤5 cm, 5-≤10 cm, or >10 cm. Proliferation rate is quantified using mitotic rate, and those patients with >5 mitosis/50 HPFs are at greater risk of disease recurrence. It’s important to acknowledge that despite this criteria, mitotic rate is a linear value and not binary, so it is critical to evaluate the actual number when assessing patient risk.  

Table 1: Overview of the National Comprehensive Cancer Network Criteria for Risk Assessment in Primary GIST^1,3,4

Obtaining additional sequencing information during GIST evaluation is essential given these tumors are not responsive to chemotherapy but may be highly responsive to small molecule inhibitors depending on specific genetic alterations. A broad-panel sequencing platform is preferred given its ability to detect sensitive oncogenic driver mutations such as KIT, PDGFR, NTRK and BRAF, as well as identify patients with mutations that do not have a targeted option such as SDH and NF1. This information is important in selecting the most appropriate systemic treatment for GIST patients based on their line of therapy.² 

References 

1. Schaefer IM, DeMatteo RP, Serrano C. The GIST of advances in treatment of advanced gastrointestinal stromal tumor. Am Soc Clin Oncol Educ Book. 2022;42:1-15. doi:10.1200/EDBK_351231 
2. Casali PG, Blay JY, Abecassis N, et al. Gastrointestinal stromal tumours: ESMO-EURACAN-GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(1):20-33. doi:10.1016/j.annonc.2021.09.005 
3. NCCN Guidelines: Gastrointestinal stromal tumors. Version 2.2024; July 31, 2024
4. Board, PDQ Adult Treatment Editorial. "Gastrointestinal Stromal Tumors Treatment (PDQ®)." PDQ Cancer Information Summaries [Internet]. National Cancer Institute (US), 2011