H. M. Dohnalek1,2,3, R. Acree1,2,3, D. Bihm1,2,3, K. Pulice1,2,3, H. Quadri1,2,3, N. G. Haddad1,2,3, L. B. Johnson1,2,3, J. Marshall1,2,3, W. Al-Refaie1,2,3 1Georgetown University Medical Center,Surgery,Washington, DC, USA 2MedStar Georgetown University Hospital,Surgery,Washington, DC, USA 3MedStar Georgetown Surgical Outcomes Research Center,Washington, DC, USA
Introduction: While surgery remains the cornerstone treatment for Gastrointestinal stromal tumors (GIST), imatinib meselate has emerged as an effective targeted tyrosine kinase inhibitor in the adjuvant and advanced/ metastatic settings. Several clinically significant exonal mutations have been discovered in KIT and PDGFRA. Exonal mutational analysis (EMA) can identify such mutations and thus informs a patient’s prognosis and subsequent treatment strategies. Indeed, the National Comprehensive Cancer Network has recommended that patients undergo EMA following resection of high risk tumors (defined as per the Meittinen and Lasota criteria) or prior to initiation of TKI therapy in advanced or metastatic tumors. However, the use of EMA within a comprehensive cancer center remains unknown. We hypothesize that use of exonal mutation analysis at our comprehensive cancer center is similar to that of published rates of 17.7% (Bischof et al. 2014).
Methods: An IRB-approved retrospective cohort study was performed on 59 patients who underwent surgical resection of pathologically-confirmed, biobanked and c-KIT positive GIST from 2006 through 2015. Patient’s electronic health records were accessed and information was then stored in a RedCap cloud-based database. To ensure data collection accuracy, two quality assurance evaluations of a 10% random selection of patients were performed. The NCCN guidelines based on the Meittinen and Lasota criteria for GIST risk stratification were used.
Results: The most frequent location of GIST within our cohort was in the stomach (71.1%), followed by small bowel (20.3%), pancreas and biliary tract (6.8%) and large bowel (1.7%). Only 15% of our cohort were classified as high-risk tumors and 5% had metastatic or locally advanced tumors. Of our entire cohort of 59 patients, 15% underwent EMA. Only one third of high-risk and metastatic patients underwent EMA. The overall exonal mutational distributions were KIT exon 11 mutations in 78% and PDGFRA exon 18 mutations in 22%. Overall, the use of EMA has shown an increasing trend during the study period [Figure].
Conclusion: This hypothesis-generating exploratory study demonstrates uptake of EMA after resection of high-risk or advanced/metastatic GIST is relatively comparable to published rates. However, these rates are lower than guideline-recommended care. As personalized medicine becomes more common, further studies are needed to uncover reasons behind this low uptake while investigating its impact on outcomes and cost of care.
