Outcome of 1000 Patients With Gastrointestinal Stromal Tumor (GIST) Treated by Surgery in the Pre- and Post-imatinib Eras

Abstract

Objective-To characterize the results of surgery for GIST in the pre-and post-imatinib eras at a single-institution and identify current prognostic clinicopathologic factors.Summary Background Data-Imatinib has radically changed the management of GIST, yet the magnitude of impact on outcome across the spectrum of GIST presentation and relevance of historical prognostic factors are not well defined.Methods-We retrospectively analyzed 1,000 patients who underwent surgery for GIST at our institution from 1982-2016. Patients were stratified by presentation status as primary tumor only (PRIM), primary with synchronous metastasis (PRIM+MET), or metachronous recurrence/ metastases (MET), as well as imatinib era (before and after it became available). Cox proportional hazard models and Kaplan Meier methods were used to model and estimate overall and recurrence-free survival (OS, RFS).Results-OS was longer in the imatinib era compared to the pre-imatinib era in each presentation group, including in Miettinen high risk primary tumors. Among PRIM patients from the pre-imatinib era, tumor site, size, and mitotic rate were independently associated with OS and RFS on multivariate analysis. PRIM patients in the imatinib era who received imatinib (neoadjuvant and/or adjuvant) had higher risk tumors, but after adjusting for treatment, only size >10cm remained independently prognostic of RFS (HR 3.85, p<0.0001) and OS (HR 3.37, p=0.001).

Thymoquinone chemosensitizes human colorectal cancer cells to imatinib via uptake/efflux genes modulation

“…Imatinib (IM), a 2‐phenyl amino pyrimidine derivative, is a potential tyrosine kinase inhibitor (TKI) and has been being used for the treatment of many malignancies 4 . Imatinib was referred to as the magical bullet because it revolutionized the curing of cancers that are addicted to one of its target kinases 5 .…”

“…cytotoxicity, imatinib, thymoquinone, uptake/efflux ratio treatment of many malignancies. 4 Imatinib was referred to as the magical bullet because it revolutionized the curing of cancers that are addicted to one of its target kinases. 5 Imatinib was approved by the Food and Drug Administration (FDA) in 2001 for Philadelphia chromosome-positive chronic myelogenous leukaemia as a first-line treatment.…”

Nationwide evaluation of mutation-tailored treatment of gastrointestinal stromal tumors in daily clinical practice

“…Prognosis varies greatly depending on the malignant potential of the tumor, defined by tumor size, tumor location, the mitotic rate and presence of tumor rupture during surgery [7,8]. While most GISTs are primarily treated with surgery [9], the tyrosine kinase inhibitor (TKI) imatinib has proven to be effective in prolonging survival of patients with a high risk of recurrence after surgery and cases with locally advanced, unresectable and/or metastatic disease [10][11][12][13][14]. However, sensitivity to imatinib therapy depends on the type of initial KIT/PDGFRA mutation [15][16][17].…”

Therapeutic Potential of PI3K/AKT/mTOR Pathway in Gastrointestinal Stromal Tumors: Rationale and Progress

“…Therefore, the National Institutes of Health (NIH) risk classification criteria are mainly used to evaluate imatinib adjuvant treatment. Moreover, the poor prognosis of GIST patients is commonly associated with large tumor volume, tumor ulceration, necrosis, high mitotic activity, tumor location outside the GI tract, infiltration and metastasis [ 34 , 35 ]. The biological behavior of GISTs can considerably differ, so better methods for accurate prediction of the clinical course are required.…”

“…Although GIST patients have obviously benefitted from imatinib, with longer survival than those without treatment [ 34 , 36 , 37 ], drug resistance may be a serious problem. Primary resistance to imatinib in GISTs is closely related with gene mutation types [ 38 ].…”