A comprehensive characterization of anatomical and molecular risk factors in gastric gastrointestinal stromal tumor.

Abstract

e23522 Background: Gastric gastrointestinal stromal tumors (GISTs) demonstrate a remarkable diversity in clinical behavior. Established risk criteria identify patients prone to recurrence with high sensitivity, but factors that could add specificity are needed. The aim of this study was to give a comprehensive picture of localized, gastric GIST and to investigate prognostic factors in a large population-based series. Methods: Patients with primary gastric GISTs completely resected between 2000 and 2018 were identified in the sarcoma database at Oslo University Hospital. Gastric subsite was divided into the upper, middle and lower thirds. Macroscopic growth pattern was coded as luminal, exophytic or transmural based on imaging and surgical reports. Mutation analysis was performed by Sanger sequencing of selected exons in KIT and PDGFRA and by targeted next-generation sequencing. Results: The cohort comprised 295 patients, representing 98% of patients in the region reported to the Cancer Registry of Norway. Of 292 tumors suitable for anatomical classification, 122 were located in the upper third of the stomach (41.8%), 120 in the middle (41.1%), and 50 in the lower third (17.1%). The number of luminal, exophytic and transmural tumors were 100 (34.1%), 94 (32.1%) and 99 (33.8%), and 2 tumors were not possible to classify. KIT mutations were detected in 183 of 256 tumors (71.5%), PDGFRA mutations in 62 (24.2%), whereas only 11 patients (4.3%) had KIT and PDGFRA wild-type tumors. Transmural tumors were larger, more often located in the upper third, had higher mitotic activity, and more frequently had KIT del557/558 mutations. KIT mutated tumors had a predilection for the upper two thirds and PDGFRA mutated tumors for the lower two thirds. Recurrences were rare among patients with luminal or exophytic tumors, with a 5-year RFS of 96% versus 71% with transmural tumors (HR 8.45; 95% CI 3.69-19.36; P< 0.001). RFS was inferior with transmural tumor growth also among high-risk patients, 46% versus 83% at 5 years ( P= 0.001). Excluding patients with tumor rupture, there was only one recurrence among 24 high-risk patients with luminal or exophytic primaries, of whom 11 did not receive adjuvant therapy. Conclusions: This study provides a comprehensive, population-based description of the anatomical and molecular landscape of gastric GIST, with findings of potential clinical relevance. Transmural tumor growth was a predictor of poor outcome and could supplement established risk factors in selecting patients for adjuvant imatinib treatment.