Abstract 2410: Recurrent pediatric ependymomas exhibit increased tumorigenicity in mouse brains of patient-derived xenograft models

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA Ependymoma is the third most common malignant pediatric brain tumor, accounting for ∼10% all intracranial tumors in children. Current standard treatment for ependymoma patients include maximally safe surgical resection followed by radiation therapy. The degree of gross total resection remains the best prognostic factor, although more molecular characterization has been completed in recent years demonstrating several subgroups of ependymoma that can more accurately predict clinical outcome. 5-year event free survival is 40-85% and varies depending on the extent of surgical resection, tumor grade, and other prognostic factors. Prognosis is even more dismal in those patients with recurrent ependymomas which occurs in nearly half of the patients, and there are no known curative options to offer these patients other than palliative re-irradiation and additional surgeries. Chemotherapies and molecular targeted therapies have not been proven to increase survival outcomes. Therefore, it is imperative to learn more about the biology of recurrent diseases and identify the cellular driver of ependymoma recurrence, as well as understanding the mechanisms of therapy resistance. We hypothesize that ependymoma recurrence is driven by a subpopulation of therapy-resistant tumors cells with enhanced tumorigenicity in SCID mice. Between the years of 2005 to present, we have collected a total of 77 pediatric ependymoma patient tumor samples from across the country. Of those, we identified 9 patients with recurrent ependymomas in which we have collected tumor samples from each recurrence. The median age of these patients is 6 years old (ranges from 2 - 10 years) and has a 2:1 male to female ratio. The median time to first recurrence is 35 months (ranges from 9 - 61 months). 5 patients had one recurrence, 2 patients had two recurrences, 1 patient had 3 recurrences, and 1 patient had more than 5 recurrences and we have tumor tissues from this particular patient over the span of 6-year period. To study the tumorigenicity of these brain tumors at the different clinical stages, whether at diagnosis, first recurrence, second recurrence, or beyond, we directly implanted tumor cells (10,000 cells/mouse) from all 9 patients into the matched locations in the brains of SCID mice (e.g., human cerebral tumors to mouse cerebrum, human cerebellar tumors to mouse cerebellum). In 3 of the 9 models, tumor formation was confirmed in mouse brains from the latest recurrent patient tumor, while samples from the same patient from earlier stages either did not form tumors in mouse brains or are currently pending. Tumor formation in the remaining models are still pending. In conclusion, our preliminary findings demonstrate progressive enhancement of tumorigenicity during ependymoma recurrence. This has become a very unique and extremely valuable platform to study brain tumor recurrence. Citation Format: Sibo Zhao, Huiyuan Zhang, Laszlo Perlaky, Adekunle Adesina, Ching Lau, Donald W. Parsons, Murali Chintagumpala, Xiao-Nan Li. Recurrent pediatric ependymomas exhibit increased tumorigenicity in mouse brains of patient-derived xenograft models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2410.