Neoadjuvant imatinib and organ preservation in locally advanced gastrointestinal stromal tumors (GIST).

10550 Background: We assessed the outcome of patients with locally advanced gastrointestinal stromal tumors (GIST) undergoing preoperative therapy with imatinib. METHODS 36 patients with biopsy proven GIST (23 f, 13 m, median age 58 (27-85) yrs, 31 primary tumors, 5 local recurrences) of the esophagus/EGJ (n=5), stomach (n=17), duodenum (n=2), small bowel (n=3), or rectum (n=9) were treated with imatinib 400mg/d for 6 mos. preop. Six pts had been found unresectable at exploratory lap. and no pt. had signs of metastases on CT/MRI and/or FDG-PET. Average tumor size was 10.5 cm (4-28 cm). According to Consensus two tumors were low risk, 11 intermediate, and 23 were high risk for aggressive behaviour. 33 pts were symptomatic. Extent of surgery, local outcome, morbidity and response to therapy were analyzed; median follow-up is 22 mos. RESULTS Median treatment duration was 11 mos. (range 2-31 mos). Successful dose adjustment for exon 9 mutation to 800 mg imatinib/d was used in two pts. 33 pts. completed the treatment schedule, two died from unrelated disease, another one had to be operated for tumor rupture. Of the remaining 33, median tumor size shrank to 55 mm. Two elderly patients refused surgery and continued with the drug; one pt. was found still unresectable. Complete tumor removal was possible in 28 pts without operative mortality, but two pts showed previously undetected peritoneal spread (R2 resection). Histologically, one pCR and 11 near CR/good PRs were found. The extent of resection found 5 of 6 inoperable pts now resectable and in 21/25 pts a less extensive procedure could be performed in comparison to recommendations by previous tumor boards (segmental gastric resection for gastrectomy, avoidance of pancreatectomy, transanal resection instead of colo-anal anastomosis). Two local recurrences were detected at 31 and 44 mos. postop. CONCLUSIONS Locoregionally advanced GIST can be treated successfully with upfront imatinib at 400mg/ (800 mg in exon 9 mutation). Substantial tumor shrinkage facilitates radical but conservative surgery and results in organ-preservation in the overwhelming majority of patients. PET monitoring proved very helpful and added to CT/MRI evaluation. Long-term results on survival and metastatic spread have to be awaited. [Table: see text].