State of the Art in the Treatment of Gastrointestinal Stromal Tumors

Abstract

Background: Gastrointestinal stromal tumors (GISTs) are the most frequently diagnosed mesenchymal neoplasms of the gastrointestinal tract. Despite their biological and clinical heterogeneity, the majority of these tumors are positive for the receptor tyrosine kinase KIT and are driven by KIT- or platelet-derived growth factor receptor alpha (PDGFRA)-activating mutations. There are still uncertainties regarding their clinical and molecular characterization and the optimal treatment regimens, making it difficult to establish a universal treatment algorithm for these tumors. Summary: From a clinical perspective, the main difference between GISTs and other gastrointestinal neoplasms is that the benign or malignant behavior of GISTs cannot be predicted from histopathology, but instead relies on empirically established scoring systems. Clinical data suggest that malignant potential may be an inherent quality of some GISTs rather than a feature acquired by the tumor during disease progression. Thus, some patients may require prolonged anti-tumor treatment even after complete surgical removal of the tumor. Key Message: Although GISTs are the most frequently occurring mesenchymal neoplasms in the gastrointestinal tract, no universal treatment algorithms exist. This paper reviews the current evidence that guides the management of GISTs. Practical Implications: The management of localized GISTs involves the use of surgical resection, with the inclusion of preoperative tyrosine kinase inhibitor treatment for locally advanced, primarily unresectable tumors and for resectable cases requiring extensive surgery. Imatinib is also indicated as adjuvant therapy after complete surgical removal of GISTs with a high estimated risk of recurrence unless specific mutations conferring imatinib resistance are present. The optimal duration of adjuvant treatment is still controversial. For patients with metastatic imatinib-sensitive GISTs, imatinib constitutes the first-line standard treatment. Molecular characterization of the tumor (with respect to the PDGFRA and KIT genes) is mandatory prior to imatinib therapy. Sunitinib and regorafenib are established as alternative treatments for patients demonstrating generalized disease progression on imatinib. New tyrosine kinase inhibitors such as ponatinib and crenolanib as well as drugs targeting alternative pathways are currently under investigation. Surgery and locally ablative treatments may be indicated in some metastatic patients.

5 years Experience in the Treatment of GIST Tumors in the Virgen Macarena University Hospital

“…Given our descriptive study of cases treated surgically, we will only establish a comparison in relation to said data. We agree with the literature in which the gold standard for the surgical approach of GIST tumors is still open surgery, since the conditions for a minimally invasive approach are restrictive [2,16] on laparoscopic treatment in gastric GIST. Thus, 80% of our patients were operated on in such a way.…”

“…From a clinical point of view, GISTs are extremely heterogeneous, being impossible to predict a benign or malignant character from their histopathology. The spectrum of behavior ranges from GIST that remain dormant throughout life without requiring any treatment, to GIST multifocal of rapid dissemination that require intense multidisciplinary treatment, being in many cases resistant to it [2].…”

“…GISTs have been considered as rare tumors, mainly due to their incorrect classification. Nowadays, they are the most frequent gastrointestinal tumors, once it was known that many of the neoplasms that under the optical microscope corresponded to muscle or nervous tumors, were actually GISTs [2].…”

“…For therapeutic planning, endoscopic study is complemented with imaging studies in all patients. This will include CT with contrast and MRI, both used to evaluate the extent of the primary tumor in relation to adjacent organs, as well as the detection of possible metastases [2]. When it comes to staging GIST in a preoperative study, PET offers many advantages, being able to show early metastases and demonstrating tumor metabolic activity.…”

Multifocal gastrointestinal stromal tumor: A case report with CT, surgical, and histopathologic correlation

“…In our case, surgical treatment with explorative laparotomy was essential to aid in the diagnosis of the large multinodular tumor found on the right iliac fossa at 150 cm from the ileocecal valve and in the diagnosis of the nodule on the left iliac fossa that was misinterpreted as a nodule of carcinomatosis on the CT. A risk classification was proposed by the Armed Forces Institute of Pathology for tumor recurrences and includes 3 clinical factors: the anatomic location (small intestinal GISTs are more aggressive than gastric GISTs of equal size), the tumor size, and the mitotic rate [20]. In the absence of high-risk features, small lesions with less than 2 cm in diameter may be followed up by annual endoscopic ultrasound or imaging and biopsied or excised if they continue to grow [20], [21]. Adjuvant therapy with Imatinib is the standard treatment for GISTs with a significant risk of relapse, in cases of unresectable and metastatic disease [21], [22].…”