Treatment of non-resectable and metastatic gastrointestinal stromal tumors: experience with the use of tyrosine kinase inhibitors in a third level hospital in Mexico

Abstract

Background: Stromal tumors of the digestive tract are uncommon malignant diseases, are subclassified as leiomyosarcomas and Gastrointestinal Stromal Tumors (GIST) depending on the molecular expression of tyrosine kinase receptor KIT (CD117). GISTs represent 1% of malignant tumors affecting this anatomical site. Localized tumours diseases are reasonably well controlled by surgical resection and several criteria define the need for adjuvant therapy. In the case of metastatic disease a poor prognosis has been reported with systemic treatment based on chemotherapy. Recently, significant advances have been shown since tyrosine kinase inhibitors (TKIs) were introduced, with median overall survival close to 5 years. Unfortunately in Mexico, even though the therapy has been long used there are no published data of the experience in the treatment of these tumors. Methods: We used an electronic data base to obtain clinical, radiological and histological data of patients diagnosed with GIST and treated in the oncological center of the Mexican Institute of Social Security, patients were subclassified by stage, symptoms at diagnosis as well as the initial and subsequent systemic treatment. Finally we made an analysis for progression free survival and overall survival identifying prognostic factors. Results: We obtained information of 71 patients with metastatic, non-resectable or recurrent GIST, treated with a TKI, we observed a predominant relation for women (60.4%) with median age of 58 years.Stage at diagnosis was predominantly metastatic (46.5%), most frequently affected sites were lung, liver and retroperitoneum. Median progression free survival was 30.6 months and overall survival was 81.3 months.All patients were initially treated with imatinib at a dose of 400 mg per day. Treatment was well-tolerated in most cases. Conclusions: Metastatic GIST evaluated in our center shows a different affection in gender and age, and our population shows a different response to TKIs, compared to those reported in other series with superior overall survival. Poor prognosis is associated with lung affection. Biological studies will be started for the molecular evaluation of these tumors.

Primary Tumor Resection Improves Survival in Patients With Metastatic Gastrointestinal Stromal Tumors: A Preliminary Population-Based Analysis

“…Nevertheless, with the long-term use of IM, most patients will inevitably occur adverse events and secondary resistance to the drug, in part, as a result of secondary molecular alteration (secondary mutations) attributed to high tumor burden ( 11 ). Further to this, given the considerable inter-individual variability, some patients may not respond to IM and experience rapid progression, while the beneficial effects of IM can be maintained indefinitely in the other patients ( 12 ). For these reasons, as a means of assisted treatment, primary tumor resection is attempted for recurrent and metastatic GISTs on the basis of the theory that cytoreduction can minimize the number of tumor cells exposed to IM, thereby reducing the risk of secondary mutations ( 13 ).…”