Navigating Recurrent Gastrointestinal Stromal Tumors – a Case Report and a Short Review Of The Literature

Abstract

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Tyrosine kinase inhibitors (TKIs) have markedly improved outcomes in metastatic GIST, but acquired resistance and disease recurrence remain major challenges. We report a case of a 56-year-old male with metastatic jejunal GIST who underwent multiple surgical debulking procedures and sequential TKI therapies over nearly five years.

Summary: The patient presented in August 2018 to the emergency department with abdominal pain, vomiting, and melena. A CT scan of the abdomen and pelvis revealed an abscessed mesenteric tumor. Emergency surgery confirmed a high-grade jejunal GIST with peritoneal metastases. Post-operative imaging revealed hepatic and peritoneal metastases. First-line imatinib 400 mg daily was initiated with subsequent escalation to 800 mg daily at hepatic progression. On further progression, second-line sunitinib achieved prolonged radiological disease stabilization. Cytoreductive surgery was subsequently undertaken during radiological disease control, followed by third-line regorafenib. Following multi-line progression and in the context of limited access to standard later-line TKIs, metastatic-tissue molecular profiling was performed late in the disease course to define an acquired resistance mechanism. Next-Generation Sequencing (NGS) identified a secondary KIT exon 17 mutation consistent with resistance to imatinib and sunitinib and supported subsequent off-label cabozantinib. The patient underwent further palliative debulking procedures and received one cycle of Gemcitabine/Oxaliplatin without clinical benefit and died in June 2023 after 58 months of overall survival (OS).

Conclusion: This case illustrates the prolonged disease control that can be achieved in metastatic GIST through multimodal management combining TKIs and surgery, as well as the limitations once multi-line TKI resistance develops. It highlights the importance of molecularly targeted therapy, the debated role of debulking surgery in advanced GIST, and the need for novel treatments or clinical trials after standard options are exhausted.