The use of neoadjuvant imatinib (Gleevec®) may help reduce the risk of gastrointestinal stromal tumors (GISTs) requiring more extensive surgery, according to a long-term retrospective study published in the International Journal of Cancer.
During the study, patients with large tumors or those located in areas where the primary operation was not feasible or had a high risk of morbidity were identified to receive neoadjuvant imatinib prior to resection surgery. Some of the difficult-to-operate locations included those near the gastroesophageal junction, ligament of Treitz, or the lower portion of the rectum.
A tumor size reduction of ≥30% was observed in 54% of patients. The mean tumor size at diagnosis was 10.5 cm (range, 2-27 cm) which decreased to a mean of 7.6 cm (range, 1.3-30 cm) after neoadjuvant imatinib.
The effectiveness of imatinib treatment appeared to be dependent on the mutational status of the GIST with 65% (n=33) of patients with c-KIT exon 11 mutations experiencing ≥30% reduction in size compared to 1 out of 3 patients with c-KIT exon 9 mutations and 1 out of 5 with platelet-derived growth factor-alpha (PDGFRA) mutations.
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After resection surgery, 94% of tumors had R0-resections. Local relapse occurred in 8% of patients and 19% developed distant metastasis (3 of which had a previous local relapse). The median event-free survival was 89.23 months and the overall survival was 166.74 months.
Only 4 out of 10 patients with tumors near the gastroesophageal junction and none of the 29 patients with tumors of the stomach underwent gastrectomy. Pancreaticoduodenectomy (Whipple procedure) was performed in only 3 out of 30 patients with small intestine tumors. Despite neoadjuvant imatinib, 7 out of 12 patients with rectal tumors required rectum amputation.
“Although the benefit of neoadjuvant imatinib on the risk of relapse or long-time survival for patients with high-risk GISTs remains to be established, it seems clear that this approach is feasible, with low toxicity and increases the chance of radical and organ-preserving surgery,” the authors concluded.
A total of 84 patients were included in the 20-year retrospective study. The most common tumor locations were the small intestine (n=30; 36%) and the stomach (n=29; 35%) followed by the rectum (n=12; 14%) and the gastroesophageal junction (n=10; 12%).
Renberg S, Zhang Y, Karlsson F, et al. The role of neoadjuvant imatinib in gastrointestinal stromal tumor (GIST) patients – 20 years of experience from a tertial referral center. Int J Cancer. Published online April 27, 2022. doi:10.1002/ijc.34052