In our patterns of failure analysis, we found that the majority of treatment failures in both groups occurred at distant sites. The proportion of patients with a component of distant metastasis in the RT (+) group was 92% (46 of 50) and it was 91% (10 of

11) in the RT (-) group. The need for more effective chemotherapy is suggested by the high rate of distant metastasis in the RT (+) and RT (-) groups as shown Inhibitors,research,lifescience,medical in Table 2. Over the last 10 years, gemcitabine alone and in combination has evolved as a standard of chemotherapy in LAPC (30,31). In more recent phase I/II studies, concurrent gemcitabine with radiation has shown promise in the treatment of locally advanced unresectable disease with manageable toxicity (32-40). In some of these trials, radiation targets included elective coverage of draining lymphatics, resulting in large treatment the site volumes that may have contributed to the increased toxicity that was described. Conformal radiation fields Inhibitors,research,lifescience,medical combined with newer systemic agents may help to reduce toxicity of treatment. More recently, biologic agents such as erlotinib have

been tested in combination with gemcitabine, with varying success (7,14,41). There is a Inhibitors,research,lifescience,medical need for clinical trials using newer systemic agents and molecular targets to evaluate their efficacy in reducing the incidence of distant metastases. Our study is limited by its retrospective nature, small sample size, and lack of data regarding quality of life. Many of the cited studies Inhibitors,research,lifescience,medical in this patient population have not incorporated assessments of quality of life, improvement in performance status, and palliation of symptoms (4-6,9,10). These endpoints are important to consider in patients with limited survival and marginal performance status who are at increased risk for toxicity from chemoradiation. In 2002, a study in Japan looked at combined-modality therapy versus best supportive care and found that locally advanced patients who underwent treatment Inhibitors,research,lifescience,medical derived benefit in quality of life as measured by a maintained performance status (42). An attractive inhibitor Tubacin strategy to facilitate

patient selection for CRT is through a trial of upfront systemic Entinostat therapy followed by re-assessment. Radiotherapy may offer a survival benefit in patients with disease that proves to be localized after a period of time. Many patients will progress during induction chemotherapy and may be spared the added toxicity of combined-modality therapy. In a study by The Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR) LAP07, 181 patients were reviewed who were treated with 5-fluorouracil (5-FU) or gemcitabine-based chemotherapy for four months. Those without evidence of disease progression were given additional chemotherapy or chemoradiation. Overall survival was improved in patients who went on to receive chemoradiation (43).