Surgery and Second-Course Radiation Therapy in Treating Younger Patients with Recurrent Ependymoma

PRIMARY OBJECTIVE:

I. 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:

I. 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.

II. 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 central nervous system (CNS) effects, clinical and treatment factors in children and young adults with ependymoma treated with a second course of irradiation.

III. To evaluate and explore differences in physical performance and movement in children and young adults with ependymoma treated with a second course of irradiation.

IV. 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.

EXPLORATORY OBJECTIVES:

I. Estimate the avidity of ependymoma to 18F-fluorodeoxyglucose (FDG) and 11C-methionine positron emission tomography prior to radiation therapy and correlate change in avidity 12, 24 and 36 months after a second course of irradiation with tumor progression.

II. 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.

III. 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 deoxyribonucleic acid (DNA), ribonucleic acid (RNA), or protein level and next generation (whole genome, exome, transcriptome) sequencing in an effort to improve our 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.

IV. To explore the association of chemotherapy given prior to re-irradiation with progression free survival and overall survival distributions.

V. To compare the progression-free and overall survival distributions for children (age > 3 years) and young adults with recurrent ependymoma and 1q gain treated with a second course of irradiation (focal or craniospinal) while monitoring for excessive central nervous system necrosis.

OUTLINE:

Patients undergo surgery. Within approximately 12 weeks, patients undergo either focal irradiation or craniospinal irradiation over 20 minutes-1 hour 5 days per week for approximately 6-7 weeks.

After completion of study treatment, patients are followed up every 4 months for 3 years and then every 6 months for 2 years.