Analysis of Prognostic Factors Impacting Oncologic Outcomes After Neoadjuvant Tyrosine Kinase Inhibitor Therapy for Gastrointestinal Stromal Tumors

Abstract

Background Management of gastrointestinal stromal tumors (GISTs) has been transformed with tyrosine kinase inhibitors (TKIs). While data on optimal duration of adjuvant imatinib remains elusive, guidelines for administration of neoadjuvant TKIs remain unknown. Methods Under an institutional review board-approved protocol, patients at our institution with a diagnosis of GIST treated with neoadjuvant TKIs and surgical resection were identified. Clinical and pathologic characteristics were obtained from medical records. Results Ninety-three patients underwent surgical resection after neoadjuvant TKI therapy; 41 had primary and 52 had recurrent/metastatic GIST. Median follow-up was 2.4 years. Median duration of neoadjuvant therapy was 315 (range 3–1,611) days for primary and 537 (range 4–3,257) days for recurrent/metastatic GIST (p = 0.001). Two-year, recurrence-free survival (RFS) was 85 and 44 % for primary and recurrent/metastatic disease, respectively, whereas 2-year overall survival (OS) was 97 % for primary and 73 % for recurrent/metastatic GIST. For primary GIST, duration of neoadjuvant therapy >365 days (p = 0.02) was associated with higher risk of recurrence on univariate analysis, whereas none of the clinicopathologic factors impacted OS. For recurrent/metastatic disease, disease progression was associated with a shorter OS (p = 0.001), but no factors were found to impact RFS. Lastly, when examining all patients, KIT mutations (p = 0.03) and multivisceral resection (p = 0.011) predicted shorter RFS. Conclusions Neoadjuvant TKIs can be effectively used for the treatment of primary and recurrent/metastatic GIST. While duration of neoadjuvant therapy, KIT mutation status, and the need for multivisceral resection can help to predict higher risk for recurrence, progression on neoadjuvant TKIs can aid in selection of patients with recurrent/metastatic disease for surgical resection.

Clinicopathological and Prognostic Features of Surgical Management in Duodenal Gastrointestinal Stromal Tumors

“…Studies indicate that the optimum duration of imatinib treatment ranges from 4 to 12 months [39, 40]. While 2 studies show that the duration of neoadjuvant therapy beyond 10 and 12 months will have bad outcomes considering the chances of tumor progression during long treatments [41, 42], a phase II study proved that promising duration is 6–9 months for large gastric GIST with high R0 resection rate and acceptable toxicity [35]. Consequently, extensive studies on GIST must thus shed further light on doses and duration of neoadjuvant therapy.…”

Neoadjuvant Imatinib in Locally Advanced Gastrointestinal stromal Tumours, Will Kit Mutation Analysis Be a Pathfinder?

“…This is in contrast to most studies where locally advanced and metastatic [7,11,14,15,19] as part of subset analysis. The most comprehensive information on locally advanced GIST comes from the EORTC-STBSG retrospective experience [8] of 161 patients, which clearly specified the safety and suggested duration of neoadjuvant IM prior to surgery.…”

“…While the duration of adjuvant IM in high risk GIST has been standardized to 3 years based on the SSGXVIII/AIO trial [20], there is no such defined duration for neoadjuvant IM. Eighty-three percent of patients in the EORTC-STBSG underwent R0 resection after a median of 40 weeks (approximately 9 months) of neoadjuvant IM, and 64 % of patients underwent surgery after 6 months of IM in the APOLLON trial [9], with two studies showing that neoadjuvant IM beyond 10 and 12 months, respectively, predicted for adverse outcomes [11,15]. The median duration of neoadjuvant IM 400 mg was 6 months in our study, following which 33 patients (73.3 %) were candidates for surgery, of which 27 patients (60 %) actually underwent surgery.…”

“…RR and surgery based on c-kit exon status (Tables 2 and 3) For the purpose of evaluating differences between c-kit mutants, patients were divided into three non-mutually exclusive categories-exon 11 mutants, non-exon 11 mutants and WT kit as used by Bednarski et al [15]. Twenty-nine patients (64.4 %) had response to IM 400 mg per day, with disease control rate in 38 patients (84.4 %).…”

Gastrointestinal stromal tumor of the esophagus: current issues of diagnosis, surgery and drug therapy

“…Concerning the duration of preoperative administration of imatinib, it has been reported to range from a few days to more than 1 year (13,(47)(48)(49). The optimal duration of preoperative imatinib is considered to be as long as 6 to 12 months to obtain a maximal response prior to surgery (3).…”