Prospective Evaluation of Neoadjuvant Imatinib Use in Locally Advanced Gastrointestinal Stromal Tumors: Emphasis on the Optimal Duration of Neoadjuvant Imatinib Use, Safety, and Oncological Outcome

Abstract

Background: Neoadjuvant imatinib therapy has been proposed for routine practice with favorable long-term results for patients with locally advanced gastrointestinal stromal tumors (GISTs). However, clarification of the optimal duration, safety, and oncological outcomes of neoadjuvant imatinib use before surgical intervention remains necessary. Methods: We prospectively analyzed the treatment outcomes of 51 patients with locally advanced, nonmetastatic GISTs treated with neoadjuvant imatinib followed by surgery. The optimal duration was defined as the timepoint when there was a <10% change in the treatment response or a size decrease of less than 5 mm between two consecutive computed tomography scans. Results: Primary tumors were located in the stomach (23/51; 45%), followed by the rectum (17/51; 33%), ileum/jejunum (9/51; 18%), and esophagus (2/51; 4%). The median maximal shrinkage time was 6.1 months, beyond which further treatment may not be beneficial. However, the maximal shrinkage time was 4.3 months for the stomach, 8.6 months for the small bowel and 6.9 months for the rectum. The R0 tumor resection rate in 27 patients after neoadjuvant imatinib and surgery was 81.5%, and 70.4% of resection procedures succeeded in organ preservation. However, 10 of 51 patients (19.6%) had complications following neoadjuvant imatinib use (six from imatinib and four from surgery). Conclusion: Our analysis supports treating GIST patients with neoadjuvant imatinib, which demonstrated favorable long-term results of combined therapy. However, careful monitoring of complications is necessary. The optimal duration of neoadjuvant imatinib use before surgical intervention is, on average, 6.1 months.

Preoperative adjuvant therapy for locally advanced and recurrent/metastatic gastrointestinal stromal tumors: a retrospective study

“…Multidisciplinary team members should cooperate to monitor the response to IM and determine the optimal operation time for those patients. In addition, both 6 months of preoperative IM therapy and surveillance when tumor size shrinkage is detected by consecutive radiographic imaging in metastatic/recurrent GISTs are suggested [15,16], but the survival benefit from an operation following IM therapy cannot be determined. Hence, our study aimed to explore the clinical efficacy and the optimal duration of preoperative IM therapy in patients with locally advanced and recurrent/metastatic GISTs.…”

Preservation of Organ Function in Locally Advanced Non-Metastatic Gastrointestinal Stromal Tumors (GIST) of the Stomach by Neoadjuvant Imatinib Therapy

“…The use of IM in the neoadjuvant setting can play an important role by downsizing the tumor, in this way decreasing the extent of resection (i.e., organ-preserving operation) [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Particularly in cases of gastric GISTs, neoadjuvant IM therapy may also convert surgical procedures from an open to a laparoscopic approach.…”

Preoperative imatinib treatment in patients with locally advanced and metastatic/recurrent gastrointestinal stromal tumors

“…In this study, median duration of preoperative IM is 8.2months (range 3.5–85 months) which is in-line with the previous published reports. [ 16 , 17 , 29 ] The National Comprehensive Cancer Network guidelines and Asian Consensus Guidelines have recommended patients with disease that is responding to IM, should continue IM until reaching best response to IM which defined as no further improvement between 2 successive via CT/MRI scans. [ 30 , 31 ] Concerning mutation analysis, there is an increasing number of studies support that testing for mutations in KIT and PDGFRA when determine treatment strategy especially before beginning preoperative IM to ensure tumor has a mutation type that is likely to respond to IM.…”