Researchers described the clinicopathologic aspects of wild-type gastrointestinal stromal tumors (GISTs) and identified important factors that influenced overall survival such as male gender, middle age, and the 3 primary tumor sites that include the stomach (57%), small intestine (35.2%), and colon (3.3%), as published in Science Reports.

Khan et al evaluated a large national cohort of patients (244 in total) with wild-type GISTs harboring the wild-type KIT proto-oncogene and the platelet-derived growth factor receptor A (PDGFRA) gene. They assessed patient demographics, clinicopathologic features, treatment patterns, and outcomes to provide a more complete understanding upon which to base management recommendations for this rare tumor.

The study analysis found that most patients were males, with a median age of 59 years old, and caucasian. The most frequent location of primary tumors was in the stomach, although about a third originated from the small intestine. Colorectal or esophageal primaries were rare, and most tumors were greater than 5 cm in maximum dimension yet had 5 or fewer mitoses per 50 high-powered fields (HPF). Multifocality (17%), lymph node dissemination (7%), and synchronous metastatic disease at diagnosis (14%) were relatively uncommon.


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The majority of the patients underwent surgical resection, which largely achieved negative tumor margins. When evaluating gastric or small intestinal primaries, the latter and >5 mitoses per 50 HPF were independently associated with decreased overall survival.

“This study adds to the growing global literature on [wild-type] GIST disease to further dispel the misconception that patients with [wild-type] GIST are predominantly pediatric aged, female, and limited to the stomach,” the authors said. “The importance of accurate and complete molecular characterization of GISTs among patients across the age spectrum is important to identify and most appropriately treat patients with wild-type KIT and PDGFRA GIST.”

GISTs are rare mesenchymal neoplasms of the gastrointestinal tract; those that arise from the bowel wall typically present as subepithelial neoplasms in the stomach and small intestine. The vast majority of GISTs harbor mutations in either the KIT proto-oncogene (80%) or PDGFRA (15%) receptor tyrosine kinases.

Nonetheless, up to 10% of these tumors are found to have nonmutated KIT and PDGFRA and are therefore called wild-type GISTs. Unlike KIT/PDGFRA mutation-driven GISTs, the wild-type often does not respond to targeted therapy with the first-generation tyrosine kinase inhibitor (TKI) imatinib. Only limited clinical benefit has been observed with the newer-generation TKIs sunitinib and regorafenib.

Reference

Khan T, Verbus E, Rossi A, et al. Patient demographics, clinicopathologic features, and outcomes in wild-type gastrointestinal stromal tumor: a national cohort analysis. Sci Rep. Published online April 6, 2022. doi:10.1038/s41598-022-09745-1