12 Background: Pancreatic adenocarcinoma is among the most lethal of human cancers. Data on overall survival rates of patients treated in the community hospital setting are limited. The purpose of this retrospective data collection study was to assess the CA19-9 change during the neo-adjuvant treatment of locally advanced pancreatic cancer patients and whether this test predicts the overall survival (OS). This study was conducted within a high volume community hospital setting. Methods: Eligibility included cytological or histological evidence of locally advanced, unresectable, and borderline resectable adenocarcinoma of the pancreas, not amenable for surgical resection. Resectability was determined with EUS and CT scan/MRI and was discussed in the multi-disciplinary conference. Patients diagnosed before July 2009 were treated with continuous 5-FU 200mg/m2 for 5 weeks with radiation of 1.8 Gy per daily fraction, for a total dose of 50.4 Gy over 5.5 weeks. Patients diagnosed after July 2009 received gemcitabine 400mg/m2 intravenously (over 60 minutes) beginning on the first day of radiation therapy (before radiation), then weekly thereafter during radiation. Results: Data were abstracted on 64 patients (40 deceased; 24 alive) diagnosed between 6/2005 and 4/2011. The median age was 68 years (range 41-87), and 52% were male. The majority of patients (97%) were diagnosed by endoscopic ultrasound (EUS) with biopsy. At diagnosis, 56 (88%) patients were locally advanced unresectable (without metastasis) or borderline resectable; 49 of these had neoadjuvant treatment, and 13 were later resected. Median OS for all 64 patients was 45.4 weeks (95% CI: 29.6-61.3), with no significant differences in OS by sex of patient (p = 0.210) or smoking history (p = 0.625). Twenty-two patients (34%) had >75% decreases in CA19-9 from baseline; median OS was 89.4 weeks in this group compared to 41.3 weeks in patients with changes in CA19-9 <75% (p = 0.025). Conclusions: This trial demonstrates improved overall survival in patients with locally advanced pancreatic cancer, who had significant decrease in CA19-9 (>75% decreases in CA19-9 from baseline) in response to neo-adjuvant chemotherapy and radiation.