The prognosis of patients with gastrointestinal stromal tumors harboring the KIT exon 11 mutation: a retrospective cohort study.

BACKGROUND: The different pathogenic variant locations of KIT are associated with variable outcomes in patients with gastrointestinal stromal tumors (GISTs). The aim of this study was to investigate the prognosis and optimal duration of adjuvant imatinib treatment in patients with GISTs with the KIT exon 11 mutation. METHODS: Patients who received surgical resection between January 2004 and December 2023 for primary GISTs with the KIT exon 11 mutation were retrospectively reviewed. The association of genotype and imatinib treatment with the prognosis of patients was analyzed. RESULTS: Among the 647 patients included in the study, 155 different mutations were detected, and the most frequently mutated codons were 557-560. The common mutation types were deletion (n=233, 36.0%), substitution (n=222, 34.3%), and insertion-deletion (indel; n=132, 20.4%). GISTs with deletion or indel mutations were associated with more high-risk disease as compared to other mutations (43.0% vs. 31.2%; P=0.002). The median follow-up time was 55 (range, 12-255) months, and the 5-year disease-free survival (DFS) rate of the entire cohort was 83.4%. Adjuvant imatinib treatment significantly improved the DFS compared with surgery only in patients with intermediate-risk disease (5-year DFS rate: 96.4% vs. 91.7%) and high-risk disease (5-year DFS rate: 76.4% vs. 28.6%), respectively. Prolonged duration of adjuvant imatinib treatment was associated with better prognosis for high-risk patients (log-rank P<0.001). After the variables in the Cox model were adjusted, mutation type and adjuvant imatinib treatment were the independent predictors of prognosis. CONCLUSIONS: The deletion and indel mutations of KIT exon 11 may be unfavorable prognostic factors for patients with GIST. Prolongation of adjuvant imatinib treatment to 5 years may provide greater benefit to patients with high-risk GISTs harboring KIT exon 11 mutations.