e17042 Background: Historical outcomes in ATC have been highly discouraging. However, in response to aggressive first-line therapy combining intensity modulated radiation therapy (IMRT) and multiagent chemotherapy, we had previously observed apparently improved outcomes; we now update our experience. Methods: From January 1, 2003 to January 31, 2013 all newly diagnosed ATC patients seen at Mayo Clinic Rochester were offered aggressive therapy, individualized based upon patient conditions and preferences. Of 40 treated patients, 9 (22.5%), 20 (50%), and 11 (27.5%) had stage IVA, IVB, or IVC ATC respectively. Mean age was 66 years (range, 37-89); half were women. Twenty three patients underwent primary surgery [8 IVA (88.8%), 14 IVB (70%) and 1 IVC (9%)]. Complete (R0) resection was achieved in only 2 IVA (22.2%) and 3 IVB (15%) patients. Twenty-six patients (65%) received definitive intention chemo-radiation therapy: 8 IVA, 17 IVB, and 1 IVC, most receiving doxorubicin + docetaxel + IMRT. Results: Kaplan-Meier median and 1-year overall survival (OS) for the 40 patients combined were 10.1 months (95% CI: 3.9-55) and 48% - compared to 3 months and 20% observed among 134 analogous patients treated at our center over a preceding 50 year period. Median survival for stages IVA, IVB and IVC patients were 61.5 (95% CI: 55-67.9), 5.1 (95% CI: 3.5-22.1), and 2.8 months (95% CI: 0.8-29.6) respectively (p<0.001). One year OS was 100, 33 and 34% for stage IVA, IVB and IVC patients respectively. For IVA patients, Kaplan-Meier survival was 100% at 4 years. There were no treatment-related deaths. Stage at diagnosis, total doses and number of fractions of radiation therapy administered, and response to treatment were each significantly positively associated with OS by univariate analysis. Conclusions: Concordant with a practice change offering more aggressive combined-modality therapy, we observed improved outcomes in ATC. Further multi-center, randomized controlled trials are needed to define optimal treatments for this rare cancer, but continued efforts to pursue aggressive primary combined-modality therapeutic approaches in ATC appear justified.