8 months) at 7.6-11.8 months. This is likely explained by the propensity of pancreatic cancer to microscopically disseminate early (31), rendering local salvage therapy ineffective for prolonging survival due to subsequent

emergence of occult distant metastases. Notably, however, two patients in our series who received a pancreatic tumor cell PR-171 mw vaccine with ipilimumab prior to local recurrence/progression demonstrated extended survival after SBRT. While we cannot confirm the Inhibitors,research,lifescience,medical role of SBRT in prolonging survival in these cases, it is possible that these patients manifested an improved immune response to their tumors following SBRT, similar to the abscopal effect recently reported for patients with melanoma (32,33). In order to prevent administration of futile local therapy, one strategy is to give chemotherapy for 2-6 months and reassess for metastases before administering re-irradiation with SBRT (30). While this selection approach is preferable, Inhibitors,research,lifescience,medical some patients with acute local symptoms may require a more rapid decision regarding local therapy. Our data indicate that SBRT is

more effective in prolonging survival for patients who develop isolated local recurrence/progression ≥9 Inhibitors,research,lifescience,medical months after surgical resection or definitive CRT. Therefore, in patients for whom a 2-6 month course of chemotherapy is not feasible due to acute symptoms or inability to tolerate further systemic therapy, the decision to give salvage SBRT without induction chemotherapy could be based on the interval between surgery or definitive Inhibitors,research,lifescience,medical CRT and local recurrence/progression. Those recurring/progressing after a prolonged time interval (≥9 months) would be more likely to benefit from SBRT, while those recurring/progressing

within 9 months would be better served by palliative measures directed at symptom relief (e.g., nerve block, stenting, surgical bypass) with or without salvage chemotherapy. In conclusion, re-irradiation with hypofractionated SBRT appears to be a safe and reasonable option for palliation of isolated local recurrence or progression of pancreatic adenocarcinoma Inhibitors,research,lifescience,medical following previous conventional CRT. Conclusions regarding efficacy are strongly limited by the small number of patients, retrospective study design, and patient heterogeneity. However, our study suggests that a group of patients who locally recur or progress greater than 9 months from surgery or definitive CRT may have a better prognosis regarding long-term survival and may therefore benefit most Physiological Reviews from re-irradiation with SBRT given their higher likelihood of living long enough to experience morbidity from eventual local progression. Given the limited data currently available regarding the use of SBRT for salvage treatment of isolated local recurrence or progression of pancreatic adenocarcinoma following previous radiotherapy, these findings may inform clinical decision making and future trial design for this unique patient population.