This is a prospective, observational clinical trial investigating the morphological and volumetric changes in the brain following cranial Radiation Therapy in pediatric patients with brain or skull base tumors.

Brain injury is a known complication of cranial RT, but little is known about the factors that predispose patients to such injury. The brain is a highly interconnected organ linked through neuronal connections, cellular migration, and vascular supply and is endowed with exquisitely radiosensitive stem cell niches responsible for neuro-regeneration. To date, the effects of brain radiation have been quantified in few brain substructures. The majority of publications on this topic have focused on regions receiving higher doses. Even low dose radiation exposure, however has global implications on brain development and function, and its effects are less well studied. It is increasingly recognized that radiation damage to one brain region can potentially affect brain development more broadly. This has important implications on RT planning and the potential for understanding its long-term effects.

In this protocol, the investigators aim to measure serum inflammatory cytokine levels and other molecular biomarkers at baseline and post-exposure in an exploratory manner to investigate potential associations with the risk of developing volumetric changes in the brain and radiation-induced toxicities.

This study will observe sixty (60) patients under the age of 21 with brain or base of skull tumor. The study team will observe the effect of radiation therapy per the study protocol versus standard of care.

Inclusion Criteria:

• Patient (parent) must give study-specific informed consent on an IRB-approved consent prior to any research related procedures or study treatment. Written assent will be obtained as per Institutional guidelines.
• Patients (Age equal to or less than 35 years old) that are planned to receive photon or proton RT to the brain according to standard of care are eligible to participate.
• Patients that are planned to receive fractionated RT at 1.2-2.0 Gy RBE dose per fraction per standard of care are eligible to participate. If patients are planned to receive an alternative dose/fractionation regimen, then they should be treated according to standard of care and should not be enrolled.
• Zubrod/Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1

Exclusion Criteria:

• Patient cannot undergo MRI without contrast as per standard of care
• Patient and family do not speak English or Spanish
• Patient receiving treatment with non-curative intent
• Patients with an expected 3-year overall survival less than 50%

The study sample size will be 60 patients. This sample size was selected to ensure an adequate distribution of primary tumor diagnoses and dosimetric variation in major brain substructures treated based on tumor location/brain regions treated. The estimated case distribution based on historical data from 2007-2015 will be: Craniopharyngioma 20%, Ependymoma 20%, Low Grade Glioma 20%, Medulloblastoma/PNET 15%, Sarcoma 10%, Other 15%.