Outcomes for young children with molecularly defined ependymoma treated on the multi-institutional SJYC07 clinical trial

Abstract

Background: Retrospective reports of poor outcomes of ependymoma (EPN) subgroups, posterior fossa A (PF-EPN-A) and supratentorial C11orf95-RELA (ST-EPN-RELA), need confirmation in prospective trials. Methods: Fifty-four children (median age 1.6 y, range 0.4-3.1) with newly diagnosed EPN (WHO grade II/ III) were treated (2008-2016) with maximal safe surgical resection + chemotherapy (high-dose methotrexate, vincristine, cisplatin and cyclophosphamide), consolidation using focal conformal radiation therapy (RT) to 54Gy (M0) or additional cyclophosphamide/topotecan with no RT (M+) and 6 months of oral maintenance chemotherapy. DNA methylation was performed using Infinium MethylationEPIC BeadChip and profiled on the DKFZ MN2.0 classifier. Fluorescent in-situ hybridization was used to determine tumor 1q status. Results: No participant had imaging evidence of metastatic disease at diagnosis (M0 = 40, M1 = 1, CSF not obtained = 13). At a median follow-up of 3.6 y (range, 1.0-9.3), 49 patients (91%) were alive with a 4-y PFS = 77.0%±7.5% and OS = 91.3%±5.2%. There was no significant difference in outcomes by subgroup [4-y PFS: PF-EPN-A (n = 42), 74.3%±8.2%; ST-EPN-RELA (n = 8), 80%±20.7%; ST-EPN-YAP (n = 4), 100%, p = 0.42]. Five patients with PF-EPN-A had 1q gain but no difference in outcome (p = 0.59 for OS and p = 0.15 for PFS). For 6 patients with subtotal resection (STR) prior to RT, outcome was inferior to those of the 48 with gross-total or near-total resection (4-y PFS = 27.8%±16.7% vs 81.7% ±7.3%, p = 0.047). Fourteen patients experienced progression at a median time of 28 mos (range, 1.7m-7.3 y). Recurrence was distant (n = 7), local (n = 6), or combined (n = 1), 3/14 recurred at 6 (n = 2) and 7 years post diagnosis. Conclusions: In a uniformly treated, prospective EPN cohort, we found no significant difference in PFS or OS by molecular subgroup; however, the number of ST-EPNRELA was small. In our data, 1q was not associated with outcome in PF-EPN-A, though only 5 subjects had 1q gain. Patients with STR prior to RT had inferior outcomes. Close surveillance and follow-up beyond 5 years is warranted due to risk of metastasis and late progression.L6259763632019-01-22 <br />