Prognostic Factors for Residual Lesion Surgery Following Disease Control with Standard Dose Imatinib (IM) Treatment in Patients (pts) with Advanced Gastrointestinal Stromal Tumor (GIST)

Several retrospective studies have demonstrated the efficacy of residual lesion surgery in pts with advanced GIST responding to IM. However, to date, no studies have comprehensively evaluated the prognostic factors, especially pathologic factors, for the efficacy of residual lesion surgery. Between September 2002 and December 2015, a total of 107 pts with histologically documented initially metastatic or distant recurrent GIST received residual lesion surgery following disease control with IM 400 mg/day in Asan Medical Center, Seoul, Korea. Among these pts, 88 had complete data for potential clinical and pathologic prognostic factors and were included in the analysis. Median age was 57 years and 55 pts (62.5%) were male. Stomach (n=41, 46.6%) was the most common primary site. Among the pathologic factors, necrosis extent, mitotic count, and cellularity showed potential association with both PFS and OS (p<0.25). Considering the correlation between these individual pathologic factors, a pathologic index combining these factors (high mitotic count or high cellularity without total necrosis of the resected tumor vs. total necrosis of the resected tumor or low mitotic count with low to intermediate cellularity) was used for further analysis. In the multivariate analysis including potential prognostic factors, presence of extra-liver metastasis (HR for PFS and OS; 4.1 and 28.4, respectively), primary genotype other than KIT exon 11 mutation (HR for PFS and OS; 7.9 and 11.0, respectively), and high mitotic count (>5/50 HPF) or high cellularity without total necrosis of the resected tumor (HR for PFS and OS; 2.76 and 8.21, respectively) were independently associated with both poor PFS and OS (p<0.05). Our study confirms that long-term survival can be achieved in advanced GIST pts receiving residual lesion surgery following disease control with IM. In addition to the metastatic sites and primary genotype, pathologic index composed of necrosis extent, mitotic count, and cellularity may improve the risk stratification of these pts.