A Feasibility Study Examining the Use of Non-Invasive Focused Ultrasound (FUS) With Oral Etoposide Administration in Children With Progressive Diffuse Midline Glioma (DMG)

Inclusion Criteria: * Ages 4 - 21 years * Radiological diagnosis of Diffuse Midline Glioma with tumor involving the pons (intrinsic, pontine based infiltrative lesion; hypointense on T1 weighted images (T1WIs) and hyperintense in T2 sequences, with mass effect on the adjacent structures and occupying at least 50% of the pons), thalami, and/or histological confirmation of H3K27M mutation of pontine or thalamic glioma. Subjects must have evidence of clinical and/or radiographic progression of disease. * Lansky performance status score of at least 60 for subjects 16 years of age or younger. * Karnofsky performance status of at least 60 for subjects greater than 16 years of age * Organ Function: * Adequate hematologic function defined as: * Peripheral absolute neutrophil count ≥ 1,500/µL * Platelet count ≥ 100,000/µL * Partial thromboplastin time (PTT) and activated partial thromboplastin time (APTT): within normal institutional limits * Adequate renal function defined as: * Potassium and magnesium levels within institutional limits * Serum creatinine below the institutional upper limit of normal (ULN) for age and gender, or creatinine clearance: ≥ 60 mL/min/1.73m2 * Adequate hepatic function defined as: * Total bilirubin below the institutional ULN for age * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × institutional ULN * Prior Therapy: * Subjects must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. * Cytotoxic chemotherapy or anti-cancer agents known to be myelosuppressive: at least 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy. * Anti-cancer agents not known to be myelosuppressive: at least 7 days must have elapsed from last dose of agent. * Antibodies: at least 21 days must have elapsed from infusion of last dose of antibody. * Interleukins, interferons, and cytokines: at least 21 days must have elapsed since the completion of interleukins, interferon, or cytokines. * Stem cell infusions: at least 42 days must have elapsed after completion of an autologous stem cell infusion, and at least 84 days must have elapsed after completion of an allogeneic stem cell infusion. * Cellular therapy: at least 42 days must have elapsed since the completion of any type of cellular therapy * Radiotherapy (XRT): at least 1 month must have elapsed after local XRT. * Subjects must be on a stable or decreasing dose of steroids, as well as stable dose of anti-seizure medication for at least 1 week. * Subject able to give consent Exclusion Criteria: * Subjects that have previously received etoposide therapy * Subjects unable to tolerate study procedures and/or anesthesia based on the opinion of the principal investigator * Uncontrolled seizure disorder * Pregnancy or Breast-Feeding: pregnant or breast-feeding women will not be entered on this study, since there is yet no available information regarding human fetal or teratogenic toxicities; a pregnancy test must be obtained in girls who are post-menarchal. Males with female partners of reproductive potential or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control- including a medically accepted barrier method of contraception (e.g., a male or female condom) for the entire period in which they are receiving protocol therapy and for at least 1 month following their last study treatment requirement. Abstinence is an acceptable method of birth control. Women of childbearing potential will be provided a routine quantitative beta-human chorionic gonadotropin (B-hCG) test during the pre-study phase, prior to enrollment and each cycle. * Concomitant medications: subjects who are currently receiving another investigational drug or other anti-cancer agents are not eligible. * Screening EKG with a QTc \> 450 msec. * Subjects with evidence of active systemic infection * Subjects with a documented allergy to compounds of similar chemical or biologic composition to etoposide or gadolinium compounds * Subjects with implanted metallic or electrical devices * Subjects with uncontrollable hypertension * Subjects with a documented bleeding disorder * Subjects with history of structural cardiac anomalies or arrhythmias * Subjects with history of unprovoked stroke or signs of stroke in the area of FUS target * Subjects with SARS-CoV-2 infection requiring hospitalization in the past month and requires anticoagulation as per the Columbia University Irving Medical Center (CUIMC) institutional "Anticoagulation for COVID-19 Positive Pediatric Inpatients" guidelines (See Appendix B) * Subjects with coagulopathy or under anticoagulant therapy. * Subjects with signs of impending herniation or an acute or previous intratumoral hemorrhage * Subjects with spinal cord diffuse midline glioma * Subjects receiving a drug where CNS toxicity is reasonably suspected