A Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma

The primary purpose of this study is to investigate whether surgery and re-irradiation will help treat ependymoma that has come back after initial treatment. The combined doses of the first and second courses of radiation are higher than what is usual standard of care. The investigators will study the effects and side effects of surgery and re-irradiation. They will also evaluate and study tumor tissue and blood to learn more about the tumor and how it does or does not respond to treatments and will use magnetic resonance imaging (MRI) and positron emission tomography (PET) scans to see if they can predict tumor response and tumor recurrence. Participants will be followed for up to 5 years following enrollment. Evaluations during radiation therapy will be done weekly while receiving therapy for up to 7 weeks. Other evaluations will be done at enrollment, every 4 months from enrollment through 3 years, and every 6 months during the 4th and 5th year.

Stratification for treatment will be determined when radiation therapy planning is initiated. Patients will be stratified for outcome according to diagnosis and prior therapy. * Stratum 1 (initial pattern of failure is local); disease confined to primary site; age \>12 months at time of enrollment to \< 21 years. Treatment: focal irradiation. * Stratum 2 (initial pattern of failure is metastatic); neuraxis metastatic disease without equivocal evidence of local failure; age \> 36 months at time of enrollment to \< 21 years. Treatment: craniospinal irradiation. * Stratum 3 (Initial pattern of failure is both local and metastatic): neuraxis metastatic disease with unequivocal evidence of local failure; age \> 36 months at time of enrollment to \< 21 years. Treatment: craniospinal irradiation. * Stratum 4 (initial pattern of failure is local): disease confined to primary site, age \>36 months at time of enrollment to \<21 years; tumor shows presence of 1g gain. Treatment: craniospinal irradiation (optional). PRIMARY OBJECTIVE: * To prospectively estimate the progression-free and overall survival distributions for children and young adults with recurrent ependymoma treated with a second course of irradiation while monitoring for excessive central nervous system necrosis. SECONDARY OBJECTIVES: * To explore potential associations of clinical and treatment factors with the incidence and severity of neurological, endocrine and cognitive deficits in children and young adults with ependymoma treated with a second course of irradiation. * Using specific measures of sleep quality, excessive daytime sleepiness, daytime activity, fatigue, symptom distress, and quality of life, explore associations of sleep, fatigue and quality of life with other measures of CNS effects, clinical and treatment factors in children and young adults with ependymoma treated with a second course of irradiation. * To evaluate and explore differences in physical performance and movement in children and young adults with ependymoma treated with a second course of irradiation. * Estimate and compare the response of residual tumor and the incidence and severity of structural, physiological, and vascular effects of normal brain in children and young adults with ependymoma after treatment with a second course of irradiation using specific methods of diffusion, contrast-enhancement, magnetization transfer, vascular and functional neuroimaging, and explore the association between these and other measures of CNS effects and clinical and treatment factors. Determine the time course of gray matter and white matter tract injury and recovery post irradiation and the association between imaging metrics derived from serial quantitative neural imaging and radiation dosimetry as well as neuro-cognitive outcomes. Other Pre-Specified (Exploratory) Objectives: * Estimate the avidity of ependymoma to 18F-fluorodeoxyglucose (FDG) and 11C-methionine positron emission tomography (IND # 104987) prior to radiation therapy and correlate change in avidity 12, 24 and 36 months after a second course of irradiation with tumor progression. * Measure growth factor and cytokine responses in children and young adults with ependymoma after treatment with a second course of irradiation, and explore associations between these and other measures of CNS effects and clinical and treatment factors. Descriptively compare findings for patients treated with an initial course of irradiation. * To conduct a variety of exploratory molecular analyses on tumor samples (and blood where a germline control is required), including but not limited to broad (genome-wide / array-based) or focused (gene-specific) analyses at the DNA, RNA, or protein level and next generation (whole genome, exome, transcriptome) sequencing in an effort to improve the investigators understanding of ependymoma biology, and to explore associations between molecular findings and treatment response and various side effects including vasculopathy, hearing loss, cognitive deficits, and growth hormone deficiency and other measures as appropriate. * To explore the association of chemotherapy given prior to re-irradiation with progression-free survival and overall survival distributions * To compare the progression-free and overall survival distributions for children (age \>3 years) and young adults with recurrent ependymoma and 1g gain treated with a second course of irradiation (focal or craniospinal) while monitoring for excessive central nervous system necrosis.