Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract. While surgical resection remains standard for localized disease, the low risk of lymph node spread makes organ-preserving endoscopic resection a viable alternative. Neoadjuvant imatinib further enhances this approach by shrinking tumors, reducing bleeding risk, and enabling safe en-bloc endoscopic removal in anatomically challenging locations

Retrospective analysis of prospectively maintained database of 5 patients with large GISTs undergoing neoadjuvant imatinib followed by endoscopic resection. Assessed for demographics, tumor characteristics, imatinib response, resection/closure techniques; outcomes including histology with chemotherapy related changes and residual viable tumor, margins, complications, length of stay and follow-up.

5 patients with anatomically difficult location - 2 rectal (involving internal anal sphincter and abutting the external anal sphincter), 2 duodenal (1- D3, 1- D1-D2 junction), 1 - exophytic gastric lesion. Mean baseline tumor size (mm) - 38 [SD 9.30]. Layer of origin on EUS - all arising from muscularis propria (MP) and 1 involving the gastric serosa. Clinical presentation – G.I bleed - 3 (ulcerated lesions), abdominal pain - 1 and dyspepsia - 1. Tumor grade 4 - low grade (Mitotic index < 2/50 hpf), 1 - high grade (> 5/50 hpf).

Neoadjuvant imatinib (400-800 mg OD) for 13 -24 weeks. 3 patients tolerated Imatinib well. 2- diarrhoea – managed symptomatically. None of the ulcerated lesions had bleeding episodes while on imatinib and achieved a mean size reduction- 54% i.e 20.6 mm(SD-4.66) on CECT.

Resection modalities  EFTR-3,  STER-1,  ETSSD-1 (endoscopic tunneling and subserosal dissection). Primary closure techniques used: 2 - endoscopic suturing, 2 - endoclips and 1 -  endoclips + intraluminal EVT.

Mean total procedure time - 191 min [SD30.33]. Enbloc resection achieved in all, no complications, with mean length of hospital stay 7 days. R0 resection with treatment related changes on HPE. Adjuvant Imatinib continued in all.

 Follow up PET scan at most recent follow up- negative for recurrence/metastasis. Rectal lesions resected - no stool incontinence on follow-up. Median follow up 22 months and maximum 38 months. 

Neoadjuvant imatinib substantially downsizes large non-metastatic GISTs and enhances tissue planes, enabling safe, effective, organ-preserving en-bloc endoscopic resection even in anatomically challenging locations where surgery would otherwise require morbid surgeries. This strategy achieves high R0 rates, preventing morbidity, suggesting that neoadjuvant imatinib may serve as a viable alternative to radical surgery for selected large localised GISTs amenable to endoscopic resection. Prospective studies are needed to validate and expand its use beyond expert centers.