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Outcome of Metastatic GIST in the Era before Tyrosine Kinase Inhibitors

Departments of Surgery (JSG, SMV, SS, MFB, RPD), Epidemiology and Biostatistics (MG), Medicine (RGM), and Pathology (CRA), Memorial Sloan-Kettering Cancer Center, New York, New York, USA

Correspondence: Address correspondence and reprint requests to: Ronald P. De Matteo, MD; Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA; E-mail: dematter{at}mskcc.org

Background: Treatment of metastatic GIST with imatinib mesylate results in a 2-year survival of approximately 72%. The outcome of patients with metastatic GIST not treated with tyrosine kinase inhibitors is not well defined.

Methods: One hundred nineteen patients with metastatic GIST diagnosed prior to July 1, 1998 (approximately 2 years prior to the use of imatinib for GIST) were identified from an institutional database of patients with pathologically confirmed GIST. Mutational analysis was performed in cases with available tissue. The log rank test and Cox regression models were used to assess prognostic factors.

Results: Median survival was 19 months with a 41% 2-year survival and a 25% 5-year survival. Resection of metastatic GIST was performed in 81 patients (68%), while 50 (42%) received conventional chemotherapy. Twelve patients (10%) were eventually started on imatinib. Primary tumor size <10 cm, <5 mitoses/50 HPF in the primary tumor, epithelioid morphology, longer disease-free interval, and surgical resection were independent predictors of improved survival on multivariate analysis. Mutational status did not predict outcome. In patients who underwent resection, the 2 year survival was 53%, and negative microscopic margins also independently predicted improved survival.

Conclusions: Treatment with imatinib appears to improve 2-year survival of metastatic GIST by approximately 20% when compared to surgery alone. The combination of imatinib and surgery for the treatment of metastatic GIST therefore warrants investigation.

Key Words: Gastrointestinal stromal tumor • GIST • Imatinib mesylate • Gleevec • Surgery