The role of neoadjuvant imatinib therapy of patients with primary locally advanced GIST

Abstract

Background: Percutaneous biopsy of gastrointestinal tumors is contraindicated; that is why prospective randomized trials of the efficiency of preoperative imatinib therapy have not been conducted. According to the results of the RTOG S-0132/ACRIN 6665, CST1571-BDE43 and other studies, neoadjuvant imatinib therapy increases tumor resectability and improves progression-free and disease-specific survival. The purpose: to estimate efficiency of neoadjuvant imatinib therapy of patients with locally advanced primary GIST. Methods:We have analyzed the treatment results of 86 patients with locally advanced GIST who were treated from January 1st 2002 till 20 January 2016 at the N. N. Blokhin Russian Cancer Centre. The primary tumor was located in the stomach - 32 pts (37.2%), duodenum and small bowel - 37 (43.1%), other (colon, rectum and extraorgan) - 17 pts ( 19.7%). The median follow-up time was 4.9 years. There are 4 groups in the trial: group 1 - 29 patients received only surgical treatment, group 2 - 12 pts - surgical resection with adjuvant imatinib therapy for 1 year; group 3 - 25 pts - adjuvant imatinib therapy for 3 years and group 4 - 17 pts - surgical resection with neoadjuvant and adjuvant imatinib therapy (1 - 3 years). The remaining 3 patiens received surgical resection with adjuvant imatinib therapy for 5 years. Results: Survival analyses showed a significant improvement of RFS and OS in patients who received combined treatment with neoadjuvant and adjuvant imatinib therapy. The 5-year RFS in the first group of patients was 10.8%, in group 2 - 16.7%, in group 3 - 68.4%, and group 4 - 79.8% (p = 0.0001). The 5-year overall survival in these groups was 42.6%, 66.7%, 76.1% and 91.6% ( p = 0,0072), respectively. In the patients with 5-years of adjuvant therapy, diseases progression was not noted. During neoadjuvant therapy disease progression has been registered in two patients. The median time of preoperative imatinib therapy was 11 months (from 3 to 24 months). Neoadjuvant imatinib therapy increased the rate of R0 (14 pts - 82.4%) and organ-sparing (12 pts - 70.6%) resections. Conclusions: The optimal approach in patients with locally advanced GIST is combined surgical treatment with neoadjuvant and adjuvant (at least for 3 years) imatinib therapy.