Management of Gastrointestinal Stromal Tumors in the Imatinib Era: Selected Case Studies

Abstract

The introduction of imatinib, an orally administered inhibitor of the KIT receptor tyrosine kinase, is prompting revision of the management algorithms that have traditionally guided the treatment of gastrointestinal stromal tumor (GIST). Historically, patients with GISTs have had substantial rates of relapse as well as limited long-term survival even after complete surgical resection of a primary tumor. Imatinib has been shown to induce durable tumor responses in more than half of the patients with malignant metastatic or unresectable GISTs and to halt disease progression in an additional third. These encouraging results have led to the initiation of clinical trials of imatinib as an adjuvant or neoadjuvant therapy with surgery. Until relevant data are reported to provide definitive direction for the management of operable or potentially operable GISTs, treatment decisions must be made on the basis of the available evidence and clinical experience with imatinib. This paper presents selected case studies describing approaches to the combined use of surgery and systemic therapy that have been applied in the treatment of individual GIST patients. The management of GIST in these cases required a coordinated, multidisciplinary approach involving medical oncologists, diagnostic radiologists, gastroenterologists, surgeons, and pathologists. The Oncologist 2006;11:9-20

Characterization of malignant gastrointestinal stromal tumors—a single center experience

“…Although many new drugs are currently under evaluation and alternative activated signaling pathway treatments have been discovered, surgery remains the only potentially curative remedy for primary localized GISTs (8) and the only curative option for locally advanced or recurrent GISTs. Unfortunately, the recurrence rate after surgery alone is as high as 50% at 5 years (9), and more than 50% of high-risk patients will develop a recurrence within 2 years (10).…”

Precision Medicine in Gastrointestinal Pathology

“…In those patients who achieved a complete resection, 5-year overall survival was between 35% and 65%, with chemotherapy and radiotherapy having little efficacy. 10 In 90% of GIST cases, imatinib targets the constitutively activated mutant KIT or the related PDGFRA receptor tyrosine kinase (rather than the ABL kinase in CML). One of the first applications of imatinib to metastatic GIST resulted in dramatic response with marked reduction in tumor volume.…”

Imaging of complications of oncological therapy in the gastrointestinal system

“…Other examples of targeted therapy are imatinib (inhibits specific protein kinases such as Abl seen in leukemias and Kit, the tyrosine protein kinase, which is also the stem cell growth factor receptor) found in gastrointestinal stromal tumors), erlotinib (tyrosine kinase inhibitor which acts on the epidermal growth factor receptor) and sunitinib (multi-targeted tyrosine kinase inhibitor) [3] . Targeted therapy can be used alone or in combination with traditional chemotherapy.…”