(P 179) PRIMARY MANAGEMENT OF LOCALIZED GASTROINTESTINAL STROMAL TUMORS WITH IMATINIB MONOTHERAPY: AN ALTERNATIVE TO RESECTION FOR PATIENTS PRECLUDED FROM SURGERY

Objective: Surgical resection is the primary approach to management of localized gastrointestinal stromal tumors (GIST) with high-risk EUS or biopsy features. However, not all patients are surgical candidates due to underlying medical co-morbidities. Our goal was to better understand the role and efficacy of imatinib therapy in a patient population with resectable disease precluded from standard of care surgical intervention.

Methods: Adult patients diagnosed with GIST at Northwestern Medicine from 2014 to 2023 who had a pathology confirmed diagnosis prior to initiation of therapy were included. Of the 400 patients who met these criteria, there were 12 cases identified of localized GIST treated with imatinib monotherapy in lieu of their medical co-morbidities precluding them from surgery. All patients who had undergone surgical resection of their tumor were excluded. All patients with a diagnosis of metastatic GIST were excluded. GIST disease characteristics, treatment type, co-morbidities, and patient demographics were assessed at time of diagnosis. Descriptive statistics were used to characterize the patient population. Progression free survival (PFS) and overall survival (OS) were calculated using GraphPad Prism per the last documented follow-up within the Northwestern Medicine Health System.

Results: Twelve GIST patients met inclusion criteria with a median age of 78.5 (range 69-86) and seven patients (58%) were male. Regarding primary site, nine of the tumors were gastric, two were duodenal, and one was esophageal. While our current practice is to perform mutation testing for all GIST patients at the time of diagnosis, only five patients had genomics available: four had KIT mutations and one was putatively wild type with no evident mutations on sequencing. Amongst the KIT mutated tumors, exon 11 was mutated in three tumors and exon 17 in one tumor (Table 1).

Two patients were initially followed with surveillance alone, but started imatinib after tumor progression on interval imaging at four months and four years post-diagnosis respectively. The remaining patients immediately started imatinib as they had sufficiently high-risk features to qualify for resection had their co-morbidities not precluded them from surgery. The most common co-morbidities included cardiac disease, obesity, lung disease, substance use disorder, and concomitant malignancy. All patients received imatinib monotherapy as their only treatment modality. The median time on imatinib was 15 months. Three patients experienced significant enough adverse events (fatigue, LE edema, and diarrhea respectively) that they elected to discontinue treatment (Table 2). With a median follow-up of 34.5 months, the one-year progression free survival and overall survival were 90% and 90% The three-year progression free survival and overall survival were also 90% and 90%. Two patients progressed on imatinib with interval enlargement of the tumor on imaging at fifty-four months while off imatinib (Table 2, Case 2) and at eight months while on imatinib (Table 2, Case 10). Of note, the one patient who passed prior to the three-year endpoint had a concurrent diagnosis of Stage IV triple-negative breast cancer; her GIST was stable in size throughout her treatment course.

Conclusion: In patients with locally resectable GIST precluded from surgical intervention due to medical co-morbidities, imatinib offers an alternative option as a well-tolerated targeted therapy with robust survival data. This cohort includes patients from varied demographic backgrounds and primary tumor sites including the stomach, duodenum, and esophagus. Our findings offer another treatment option for patients with localized GIST who are ineligible for the current standard of care surgical resection and advocate for future research to better characterize novel applications of existing targeted therapies.