Integrating Anatomical, Molecular and Clinical Risk Factors in Gastrointestinal Stromal Tumor of the Stomach

Abstract

Background Adjuvant imatinib for 3 years is recommended to patients with high-risk gastrointestinal stromal tumor (GIST). Risk stratification is inaccurate, and risk assessments are further complicated by the increased use of neoadjuvant treatment. Anatomical criteria for prognostication have not been investigated. Methods Clinical, molecular, and anatomical variables were retrospectively studied in a population-based cohort of 295 patients with gastric GIST resected between 2000 and 2018. Gastric subsite was divided into the upper, middle, and lower thirds. Growth pattern was classified as luminal, exophytic, or transmural based on imaging and surgical reports. Results Of 113 tumors in the upper third of the stomach, 103 (91.2%) were KIT mutated, 7 (6.2%) were PDGFRA mutated, and 104 (92.0%) harbored genotypes sensitive to imatinib. Transmural tumors were strongly associated with a high mitotic index. Five-year recurrence-free survival (RFS) was 71% for patients with transmural tumors versus 96% with luminal or exophytic tumors (hazard ratio [HR] 8.45, 95% confidence interval [CI] 3.69–19.36; p < 0.001), and, in high-risk patients, 5-year RFS was 46% for patients with transmural tumors versus 83% with luminal or exophytic tumors (HR 4.47, 95% CI 1.71–11.66; p = 0.001). Among 134 patients with tumors > 5 cm, there were 29 recurrences. Only five patients with exophytic or luminal tumors had recurrent disease, of whom four had tumor rupture. Five-year RFS for patients with exophytic/luminal tumors >5 cm without rupture was 98%. Conclusions In the upper third, over 90% of tumors were sensitive to imatinib. Patients with exophytic or luminal tumors without rupture, irrespective of size, had an excellent prognosis and may not benefit from adjuvant therapy.

PDGRFA-mutant gastrointestinal stromal tumours (GISTs) in Eastern England: clinicopathological features and outcomes of 50 patients diagnosed between 2008-2021

“…All GISTs in our cohort presented in the stomach, majority of PDGRFA-mutant GISTs occur within the gastric body (72%) and antrum (28%). This adds to the findings of a recent study which found that different driver mutations influenced primary GIST location: PDGRA-mutant tumours (n=7) being found in the lower two-thirds whilst KIT-mutant tumours (n=103) were mostly located in the upper-third 19 . One patient in our cohort was diagnosed with metastatic peritoneal disease without a located primary despite extensive radiological and endoscopic investigation.…”

ASO Author Reflections: How to Identify Patients at Genuinely High Risk of Recurrence from Localized Gastrointestinal Stromal Tumor of the Stomach?

“…In this study, few recurrences were detected among patients with luminal or exophytic tumors, and without rupture, their prognosis was excellent irrespective of tumor size. 5 These patients may not benefit from adjuvant imatinib. By contrast, a transmural growth pattern was a predictor of poor outcome and associated with increased mitotic activity.…”

Cytogenetic and molecular analyses of 291 gastrointestinal stromal tumors: site-specific cytogenetic evolution as evidence of pathogenetic heterogeneity

“…Exons 9, 11, 13, and 17 of KIT and exons 12, 14, and 18 of PDGFRA were analyzed by Sanger sequencing and categorized as described previously [ 29 ]. Tumors not analyzed in clinical routine were analyzed using AmpliSeq for Illumina Cancer Hotspot Panel version 2 as previously described [ 30 ]. The scoring was based on the sequence NM_000222.2 for KIT and NM_006206.4 for PDGFRA on the Human GRCh37/hg19 assembly [ 31 ].…”