The Children’s Oncology Group ACNS0121 trial was designed to observe patients with WHO grade II, supratentorial ependymoma (EP) after microscopically complete (GTR1) resection (stratum 1), administer chemotherapy with optional second surgery prior to conformal radiation therapy (CRT) for patients with subtotal (STR) resection at the time of protocol enrollment (stratum 2) and immediate post-operative CRT for patients after near-total (NTR defined as <5 mm residual thickness) or macroscopic gross-total (GTR2) resection (stratum 3) and WHO grade III, supratentorial or any grade, infratentorial after GTR1 (stratum 4).