e15037 Background: Small-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. Activating KRAS and/or BRAF mutations… Click to show full abstract
e15037 Background: Small-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. Activating KRAS and/or BRAF mutations have been identified as predictors of resistance to anti-epidermal growth factor receptor (EGFR) The aim of this study was to perform a comprehensive immunohistochemical.analysis of KRAS, NRAS, V600E BRAF mutations and microsatellite instability using a cohort of surgically resected cases in our institution. Methods: A total of 17 patients (10 males and 7 females; mean age, 56.2 years old; range, 45-75 years old) received chemotherapy due to non-curative tumor resection, unresectable tumor or post-operative recurrence. Twelve patents received fluoropirimidine and oxaliplatin based first line chemotherapy. Molecular targeted agents were administered to 15 patients, for whom it was their first- or second-line therapy. Results: KRAS mutations were found in 7 cases (41%), out of which 5 (29%) were in exons 12/13. BRAFV600E mutation was observed in 1/17 pt. Microsatellite instability was identified in 3/17pt (MSI; 18%), mainly related to a loss of expression of MLH1 protein. Univariate analysis revealed a PS of 0 (P=0.0226) and treatment with platinum-based chemotherapy (P=0.0047) were significant factors for an improved prognosis. Among the 12 patients who received oxaliplatin-based chemotherapy as a first-line chemotherapy, a PS of 0 (P=0.0255) and treatment with anti-EGFR agents (P=0.0127) were significant positive prognostic factors. Toxicities due to the molecular targeted agents were not experienced. The median overall survival time was 14.3 months (range, 3-52 months), the median DFS was 14.2 months and the median OS was 32 months. Conclusions: To date, there is no standard chemotherapy regimen for advanced SBAs and little is known about their molecular characteristics. The results of the present study indicate that oxaliplatin based chemotherapy containing molecular targeted agents is a well-tolerated and effective treatment option for SBA. A better understanding of disease biology may help to identify therapeutic targets and advance precision medicine.
               
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