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Context Primary resectability is expected in up to 20% of pancreatic cancer patients. While most patients relapse with distant metastases, approximately 30% of patients show isolated local recurrence without evidence of distant metastases. Objective The present analysis investigates the efficacy of chemoradiotherapy in this particular patient group.. Design Retrospective study. Patients Eighteen consecutive pancreatic cancer patients presenting with isolated locoregional recurrence after surgical resection. The median interval between primary surgery and diagnosis of local recurrence was 10.4 months (range: 2.0-19.3 months). Interventions Patients received 3-D conformal radiation with 45 Gy in 25 fractions of 1.8 Gy/day. Simultaneous chemotherapy was employed either with continuous 5-FU infusion, partly in combination with gemcitabine, or with gemcitabine and cisplatin. Sequential chemotherapy with gemcitabine and cisplatin was given to some patients before and after the chemoradiotherapy. Results In 17 of the 18 patients included, radiotherapy was employed at the intended dose. While WHO grade 3-4 gastrointestinal toxicity was not reported, hematotoxicity was more pronounced. Grades 3 and 4 leukocytopenia occurred in 4 patients (22.2%) and 1 (5.6%) patient, respectively, and grades 3 and 4 thrombocytopenia occurred in 4 patients (22.2%) and 1 patient(5.6%), respectively. Six (37.5%) complete remissions, 6 (37.5%) partial remissions, and 4 (25.0%) stable diseases were noted in 16 evaluable patients. Median progression-free survival calculated from the start of the chemoradiotherapy was 14.7 months (range: 8.4-21.0 months) . Seven (28.9%) patients had another local relapse, while 11 (61.1%) patients developed distant metastases. Median overall survival from the start of the chemoradiotherapy was 17.5 months (95% CI: 15.6-19.4 months) and median survival from the initial diagnosis was 27.2 months (95% CI: 23.9-30.6 months). Conclusion The data provide a first indication that chemoradiotherapy is feasible and may be an effective treatment option in those patients who present with local metastasis after primary surgery for pancreatic cancer.