Optune for Children With High-Grade Glioma or Ependymoma, and Optune With Radiation Therapy for Children With DIPG

Inclusion Criteria: * Age: at the time of enrollment Stratum 1: ≥ 5 years but ≤ 21 Stratum 2: ≥ 3 years but ≤ 21 * Diagnosis: Stratum 1: Patients must have a histologically confirmed diagnosis of supratentorial high-grade glioma or supratentorial ependymoma that is recurrent, progressive or refractory. Stratum 2: Patients with newly diagnosed DIPG * Patients with a typical DIPG on MR imaging, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation. * Note: Patients with typical DIPG who undergo a biopsy are eligible provided the tumor is a diffuse glioma WHO Grade II-IV with OR without H3 K27M mutation. * Patients with pontine lesions that do not meet these MR imaging criteria will be eligible if there is histologic confirmation diffuse glioma WHO Grade II-IV with H3 K27M-mutation. * Disease Status: Patients must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two planes Stratum 1: * This disease must be located primarily in the supratentorial region * Patients with significant disease that is metastatic outside of the supratentorial region are ineligible Stratum 2: * This disease must be located primarily in the pons * Prior Therapy: Stratum 1: Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. Stratum 2: Patients may not have had any prior antitumor therapy except surgery and/or steroids. • Myelosuppressive Chemotherapy: Patients must have received last dose of known myelosuppressive chemotherapy \>21 days prior to enrollment; \>42 days if nitrosourea. * Biologic Agent: Biologic agent must have recovered from any acute toxicity potentially related to the agent and received their last dose of the biologic agent \> 7 days prior to study enrollment. \- For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. * Immunomodulatory treatment: Patient must have received the last dose \>21 days prior to enrollment. \- Monoclonal antibody treatment and agents with known prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment. Radiation: * Stratum 1: Patients must have had their last fraction of: \- Craniospinal irradiation (\>24Gy) or total body irradiation or radiation to ≥ 50% of pelvis ≥ 42 days prior to enrollment * Focal irradiation ≥ 14 days prior to enrollment * Local palliative irradiation (small port) ≥ 14 days * Stratum 2: Patients must not have received any radiotherapy prior to enrollment. If clinically indicated, enrolled patients may receive up to 5 fractions of radiotherapy prior to starting Optune therapy. * Surgery: o Stratum 1: Optune device application start date must be at least 4 weeks (28 days) from CNS surgical procedure. Excluding VP shunts, Endoscopic Third Ventriculostomy (ETV) for which treatment could start 10 days post procedure. Non-CNS surgical procedures such as but not limited to central venous catheter insertion at the discretion of treating physician and study chair. o Stratum 2: Radiation therapy and Optune device application start date must be at least 5 days after the date of a tumor biopsy if obtained. * Inclusion of Women and Minorities: Both males and females of all races and ethnic groups are eligible for this study. * Neurologic Status: * Stratum 1: Patients with neurological deficits should be stable for a minimum of 1 week prior to enrollment. * Stratum 2: Stable neurologic deficits are not an eligibility criterion for Stratum 2. Performance Status: Stratum 1: Karnofsky Performance Scale (KPS for \> 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within two weeks of enrollment must be ≥ 60. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. There are no performance status requirements for Stratum 2 patients. • Organ Function: Stratum 1 patients must have organ and marrow function as defined below: Absolute neutrophil count ≥ 1.0 X 109/L; Platelets ≥ 100 X 109/L (transfusion independent); Hemoglobin ≥8g/dl (may receive transfusions); Total bilirubin ≤1.5 times institutional upper limit of normal (ULN); ALT(SGPT) ≤3 times institutional upper limit of normal; AST(SGOT) ≤3 times institutional upper limit of normal; Albumin ≥2 g/dl. Serum creatinine based on age/gender as noted below. Patients that do not meet the criteria below but have a 24 hour Creatinine Clearance or GFR (radioisotope or iothalamate) ≥ 70 ml/min/1.73 m2 are eligible. Age Maximum Serum Creatinine (mg/dL) 3 to \< 6 years 0.8 (Male) 0.8 (Female); 6 to \< 10 years 1 (Male) 1 (Female); 10 to \< 13 years 1.2 (Male) 1.2 (Female); 13 to \< 16 years 1.5 (Male) 1.4 (Female); * 16 years 1.7 (Male) 1.4 (Female). * Stratum 2: Patients must have adequate organ and marrow function as defined below: o Absolute neutrophil count ≥ 1.0 X 109/L o Platelets ≥ 100 X 109/L (transfusion independent) o Hemoglobin ≥8g/dl (may receive transfusions) * Head circumference: Patients must have minimum head circumference of 44 cm. * Compliance in Optune Device Usage: * Stratum 1: Patients must be willing to use the Optune device ≥18 hours/day for at least 23 days in a 28-day cycle, and keep head shaved throughout treatment. * Stratum 2: During concurrent Optune therapy and RT, patients must be willing to use the Optune device ≥18 hours/day for at least 40 of the 49 days of the duration of the feasibility period. During subsequent cycles of Optune therapy alone, patients must be willing to use the Optune device ≥18 hours/day for at least 23 days in a 28-day cycle. During concurrent Optune therapy and RT and Optune therapy alone, patients must be willing to keep their head shaved throughout treatment. * Pregnancy Status: Female patients of childbearing potential must have a negative serum or urine pregnancy test. * Pregnancy Prevention: Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study. * Informed Consent: The patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document according to institutional guidelines. * Steroids: o Stratum 1: If patient is on corticosteroids, the dose must be stable or decreasing for at least 5 days prior to enrollment. * Stratum 2: There are no eligibility requirements for corticosteroid dosing for Stratum 2. Exclusion Criteria: * Systemic Illness: Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results. * Other Malignancy: Patients with a history of any other malignancy. * Concurrent Therapy: Patients who are receiving any other anticancer or investigational drug therapy are not eligible. * Inability to Participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits or obtain follow-up studies required to assess toxicity to therapy or to adhere to device usage plan, other study procedures, and study restrictions. * Stratum 1 Tumor Location: Patients with primarily infra-tentorial or spinal cord tumor are not eligible. * Tumor Dissemination: Patients for who clinical suspicion is present of metastatic disease in the CSF or Spine must have MRI of Spine and CSF obtained (Lumbar puncture or through ommaya, EVD or Shunt) with negative cytology. Patients with CSF that is positive for tumor cells or metastatic disease found on MRI are ineligible. * Skull Defects: Patients with major skull defects (such as missing bone without replacement) are not eligible. * Neurological Disorder: Patients with active implanted electronic devices in the brain or spinal cord such as programmable VP shunts, deep brain stimulators, vagus nerve stimulators, are not eligible. * Cardiac Disorder: Patients with pacemaker, defibrillator, or documented significant arrhythmia, are not allowed. * Intracranial Objects: Patients with foreign body intracranially, such as bullet fragments, are not allowed, with the exception of VP-shunts (non-programmable) and Ommaya catheters. * Allergy: Patients with history of hypersensitivity to conductive hydrogel are not eligible.