The role of surgical cytoreduction before imatinib therapy in patients with advanced GIST.

Abstract

10093 Background: Despite dramatic improvement of survival with introduction of imatinib mesylate, resistance to imatinib eventually develops in most of patients with advanced gastrointestinal stromal tumor (GIST). It is well known that baseline tumor size is an important factor related to imatinib resistance. We hypothesize that decreasing tumor size by surgery before starting imatinib may delay the emergence of resistance and improve prognosis in patients with advanced GIST. Methods: From 2001 to 2010, 102 patients with initially metastatic GIST and 147 patients with recurrent GIST were enrolled in this analysis. Patients with local relapse only were excluded because they were potentially curable by surgery alone. Patients were categorized into two groups according to the extent of cytoreduction; i.e., patients whose initial tumor bulk reduced >75% surgically before starting imatinib (group A) and the others (group B). Results: Among total 249 patients, 62 patients received initial surgery. 35 (14%) patients whose tumor bulk reduced > 75% were categorized into group A, and the remaining 214 (86%) were in group B. In group A, the median age was younger; more patients were initially metastatic; peritoneal metastases were more frequent; but liver metastases were less. The total tumor size was significantly reduced from median 122 mm before cytoreduction to 0 mm after on CT scans in group A. With a median follow-up of 42.7 months, progression-free survival (PFS) tended to be better in group A than in group B in univariate analysis (HR=0.60; 95% CI, 0.36-1.02; p=0.061), but PFS was not statistically different between the two groups in multivariate analysis (p=0.488). Meanwhile, absence of KIT exon 11 mutation (p=0.007), baseline total tumor size > 150mm (p=0.043), and granulocyte count > 5000/mm3 (p=0.009) remained independent poor prognostic factors. Conclusions: Despite marked decrease of total tumor size, the outcomes were not significantly improved in patients receiving initial cytoreduction more than 75% of baseline tumor bulk before starting imatinib. These results suggest that initial cytoreduction does not have beneficial role in advanced GIST, so imatinib should be still the first treatment of choice in this population.