Background: For patients with LGCA, adjunctive therapies improve the 5-year survival rates by ≈10% over surgery alone. We studied preoperative oxaliplatin/5-FU-based chemotherapy followed by chemoradiation. Methods: Patients with LGCA with baseline eusT2-T3 any N, M0 (M stage by laparoscopy and imaging) were eligible. Patients received ≤4 doses of oxaliplatin and infusional 5-FU q 2 weeks then oxaliplatin and infusional 5-FU with 45 Gy of conformal radiation in 25 fractions. 5-6 weeks after chemoradiation, patients underwent an attempted D2 dissection and were followed. Results: Between Feb. 2004 and Nov. 2010 a total of 58 patients were enrolled. Most patients were men (66%) and had clinical stage IIIA cancer (52%). 14% (95%CI: 6%, 25%) of patients achieved a pathCR. With a median follow-up of 37.4 months, the median survival was 39.4 (95%CI: 27.6, NR) months. The 5-yr OS was 44% and the 5-yr PFS was 42%. 72% of patients proceeded to surgery and 86% of these had an R0 resection. The 5-yr OS for patients who had surgery was 56%. 44.8% of patients experienced grade 3 and/or 4 toxicities (commonly, fatigue, anorexia and insomnia) due to induction chemotherapy. 58.6% experienced grade 3 and/or 4 toxicities due to chemoradiation (commonly, fatigue, myelosuppression, vomiting, and dysphagia). No treatment-related death occurred. Conclusions: The 5-yr OS for all patients treated on this study was 44%. Our data show that if LGCA patients can complete the described therapeutic strategy (i.e., including surgery), their outcome may be excellent. Therefore, we must refine patient selection for future trials based on clinical variables and biomarkers. This will help in identifying patients who are likely to respond to pre-operative treatment versus those who are not. Biomarker studies (with mTOR, Gli-1, Sox9, ALDH-1, and Shh, etc.) are underway and will be presented. Clinical trial information: 2003-0769.