EPEN-11. ONGOING RESPONSE IN A MULTIPLY RELAPSED METASTATIC POSTERIOR FOSSA EPENDYMOMA A AFTER VORINOSTAT AND CONCOMITANT IRRADIATION

BACKGROUND: Among the nine molecular subgroups of ependymoma identified, posterior fossa ependymoma A (PF-EPN-A) confers the worst prognosis. These tumors often relapse despite aggressive resection and irradiation, resulting in limited therapeutic options. Although the genomic profile of PF-EPN-A does not typically show any recurrent alterations; they demonstrate distinct epigenetic changes which can be targeted with modulators such as histone deacetylase (HDAC) inhibitors. These inhibitors have shown efficacy in pre-clinical studies in both their anticancer and radio-sensitizing properties. CASE: We describe a male diagnosed with a posterior fossa ependymoma at 3 years of age. After initial therapy with resection and focal irradiation, he went on to have a number of recurrences requiring multimodal therapy. Most recently, he developed diffuse intraventricular and leptomeningeal disease not amenable to surgical intervention. Genetic evaluation demonstrated a BCOR mutation and methylation profile was consistent with PF-EPN-A. He received 23.4 Gray craniospinal irradiation with a 30.6 Gray boost to the nodular lesions. Vorinostat was given concomitantly for radio-sensitization in 2 week intervals for a total of 6 weeks. Serial imaging after irradiation revealed decreased tumor burden with almost complete resolution of disease at 15 months. Unfortunately, MRI at 18 months exhibited mild interval growth of 2 lesions. CONCLUSIONS: To our knowledge, this is the first report of a clinical response in a pediatric patient with PF-EPN-A following irradiation administered concomitantly with vorinostat therapy. This response highlights the importance of further studies evaluating this combination therapy and its potential use in this population.