Outcome of Metastatic GIST in the Era before Tyrosine Kinase Inhibitors
- 332 Downloads
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.
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.
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.
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.
KeywordsGastrointestinal stromal tumor GIST Imatinib mesylate Gleevec Surgery
Supported in part by: PO1 CA 47179 (MFB), ACS MRSG CCE-106841 (CRA), and CA94503 and CA102613 (RPD).
- 6.Fujimoto Y, Nakanishi Y, Yoshimura K, Shimoda T. Clinicopathologic study of primary malignant gastrointestinal stromal tumor of the stomach, with special reference to prognostic factors: analysis of results in 140 surgically resected patients. Gastric Cancer 2003; 6(1):39–48PubMedCrossRefGoogle Scholar
- 10.van Oosterom AT, Judson IR, Verweij J, et al. Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group. European Journal of Cancer 2002; 38(Supplement 5):S83-S87PubMedCrossRefGoogle Scholar
- 12.Benjamin RS, Rankin C, Fletcher C, et al. Phase III dose-randomized study of imatinib mesylate (STI571) for GIST: Intergroup S0033 early results. Proc Am Soc Clin Oncol 2003; 22:814 (abstract 3271)Google Scholar
- 13.Blanke C, Joensuu H, Demetri G, et al. Long-term follow up of advanced gastrointestinal stromal tumor (GIST) patients treated with imatinib mesylate. 2004 Gastrointestinal Cancers Symposium. San Francisco, California, 2004 (abstract 2).Google Scholar
- 21.Blanke CD, Joensuu H, Demetri GD, et al. Outcome of advanced gastrointestinal stromal tumor (GIST) patients treated with imatinib mesylate: Four-year follow-up of a phase II randomized trial. Gastrointestinal Cancers Symposium. San Francisco, California, 2006 (abstract 7)Google Scholar
- 22.Maki RG, Fletcher JA, Heinrich MC, et al. Results from a continuation trial of SU11248 in patients (pts) with imatinib (IM)-resistant gastrointestinal stromal tumor (GIST). J Clin Oncol 2005; 23(16S):9011Google Scholar
- 23.Demetri G, van Oosterom AT, Garrett C, et al. Improved survival and sustained clinical benefit with SU11248 (SU) in pts with GIST after failure of imatinib mesylate (IM) therapy in a phase III trial. Gastrointestinal Cancers Symposium. San Francisco, California, 2006 (abstract 8)Google Scholar
- 34.Heinrich MC, Shoemaker JS, Corless CL, et al. Correlation of target kinase genotype with clinical activity of imatinib mesylate (IM) in patients with metastatic GI stromal tumors (GISTs) expressing KIT (KIT+). J Clin Oncol 2005; 23(16S):7Google Scholar
- 35.Debiec-Rychter M, Dumez H, Judson I, et al. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2004; 40(5):689–95PubMedCrossRefGoogle Scholar