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PURPOSE Effective preoperative regimens and biomarkers for pancreatic ductal adenocarcinoma (PDAC) are lacking. We prospectively evaluated fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX)-based treatment and imaging-based biomarkers for borderline resectable PDAC. METHODS Eligible patients had treatment-naïve, histology-confirmed PDAC and one or more high-risk features: mesenteric vessel involvement, CA 19-9 level of 500 mg/dL or greater, and indeterminate metastatic lesions. Patients received modified FOLFIRINOX and chemoradiation before anticipated pancreatectomy. Tumors were classified on baseline computed tomography as high delta (well-defined interface with parenchyma) or low delta (ill-defined interface). We designated computed tomography interface response after therapy as type I (remained or became well defined) or type II (became ill defined). The study had 80% power to differentiate a 60% from 40% resection rate (α = .10). Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and subgroups were compared using log-rank tests. RESULTS Thirty-three patients initiated therapy; 45% underwent pancreatectomy. The median OS was 24 months (95% CI, 16.2 to 29.6 months). For patients who did and did not undergo pancreatectomy, the median OS was 42 months (95% CI, 17.7 months to not estimable) and 14 months (95% CI, 9.0 to 24.8 months), respectively. Patients with high-delta tumors had lower 3-year PFS (4% v 40%) and 3-year OS rates (20% v 60%) than those with low-delta tumors (both P < .05). Patients with type II interface responses had lower 3-year PFS (0% v 29%) and 3-year OS rates (16% v 47%) than those with type I responses (both P < .001). CONCLUSION Preoperative FOLFIRINOX followed by chemoradiation for high-risk borderline resectable PDAC was associated with a resection rate of 45% and median OS of approximately 2 years. Our imaging-based biomarker validation indicates that personalized treatment may be achieved using these biomarkers at baseline and post-treatment.

e15773 Background: Recent studies showed that gut microbial dysbiosis can affect carcinogenesis and tumor responses to therapies. Antibiotics, key pharmacologic agents that modulate microbiota diversity and bacterial strains, can lead to dysbiosis. Recent studies have postulated a tumor promoting effect for some pancreatic ductal adenocarcinoma (PDAC)-associated gut bacteria. However, the effects of antibiotic use on PDAC patients outcome is yet to be discovered. Methods: We examined a total of 342 patients who were diagnosed with PDAC between 2003-2015 and underwent primary tumor resection. Antibiotic exposure was defined as the use of antibiotics for ≥7 days between diagnosis and surgery. We collected data on patient demographics, presurgical antibiotic use, duration, type and reason, disease and therapy characteristics, and prognostic parameters. We analyzed and compared the objective responses, progression free survival (PFS) and overall survival (OS). Results: From a total 342 patients with resected PDAC, 147 patients (43%) used antibiotics for ≥7 days duration during the presurgical period. The most frequently used antibiotics were quinolones (80.4%), beta-lactams (38.2%), nitroimidazoles (23%), glycopeptides (15.3%), tetracyclines (8.6%), and macrolides (6.7%). The median OS for patients with antibiotic use was 1007 vs. 940 days for those without antibiotic use (p = 0.57). The median PFS was 374 for patients with antibiotic use and 313 days for those without antibiotic use (p = 0.51). The effect of individual antibiotics was examined and statistical analysis was done for possible confounding factors including disease stage, treatment type, and the reason for antibiotic use. Tetracyclines use was found to be significantly associated with worse survival on resected PDAC patients and was not affected by confounding factors such as skin infections. The median OS of patients who had tetracycline for ≥7 days was 687 vs. 1004 days for those not exposed to this antibiotic (HR 1.836; p = 0.015). Although not statistically significant, PFS was shorter with tetracycline use. Conclusions: We conducted the first retrospective, single-center cohort study on resected PDAC patients examining the potential influence of antibiotic use on survival. Tetracycline use in resectable PDAC patients is associated with clinically significant decreased PFS and statistically significant worse OS. Further multicenter studies with larger population would be necessary to confirm these findings that could help clinical practice for infectious treatment in PDAC patients.

369 Background: Chemotherapy is widely used as a component of treatment of localized pancreatic ductal adenocarcinoma (PDAC). Pre-operative chemotherapy is associated with early treatment of micro-metastases and guaranteed delivery of all components of multimodality therapy. For locally advanced (LA) PDAC, induction chemotherapy is standard of care. We evaluated the use of gemcitabine and nab-paclitaxel (Gem/nab-P) as first-line therapy in localized PDAC. Methods: Records of pts with localized PDAC who initiated Gem/nab-P at a single institution from 2013-2015 were retrospectively reviewed. Clinicopathologic features, dose and outcomes were evaluated. Pts were staged using our previously published criteria: potentially resectable (PR), borderline type A (BR-A) (anatomy amenable to vascular resection), BR-B (biology suspicious for metastatic disease including high CA19-9), BR-C (co-morbidities requiring medical optimization), and LA. Co-morbidities were classified using adult comorbidity evaluation-27 score. Overall survival (OS) was analyzed using Kaplan Meier method. Results:99 pts [M/F: 50/49; median age: 70 yrs (range 30-85); PR/BR/LA: 45/14/40] were treated with Gem/nab-P. Clinical staging showed PR+BR-A/BR-B+C: 20/39. BR-B+C included one or more of the following factors: age ≥80 yrs [13%], ECOG PS ≥2 [13%], moderate/severe co-morbidities [55%], CA19-9≥1000 [28%], suspicion for metastatic disease [21%]. Majority of pts received biweekly Gem/nab-P dosing [standard/biweekly/other: 10/80/9] with minimal grade 4 toxicity. 45/99 pts received chemoradiation after Gem/nab-P [30Gy/50.4Gy: 15/30]. 12/20 (60%) PR+BR-A, 2/39 (5%) BR-B+C and 1/40 (3%) LA pts underwent pancreatectomy. 13/15 resected pts received adjuvant chemotherapy. At median follow-up of 26 mo, median OS was 18 (95% CI: 15.6-20.5) mo for all, 17 (95% CI: 14.6-19.5) mo for unresected and not reached for resected pts (p = 0.03). Conclusions: A significant number of pts with resectable PDAC albeit aggressive biology (BR-B) and/or medically inoperable disease (BR-C) received first-line Gem/nab-P; resection rates were lower compared to PR/BR-A pts. Biweekly dosing is being used in localized PDAC and is well tolerated.