Inclusion Criteria:

• Willing to return to enrolling institution for follow-up during the active monitoring phase of the study.

• Caregiver able to complete questionnaires by themselves or with assistance.

• Patient or caregiver willing and able to provide written informed consent.

• Primary language of English or Spanish for patients and their caregiver.

• Negative urine pregnancy test completed ≤7 days prior to registration, for women of childbearing potential only.

• Able to undergo MRI Brain.

• Radiologic appearance of diffuse midline glioma of the pons, including diffuse infiltration of ≥50% of the pons on MRI, with or without extension to the midbrain and/or medulla oblongata with at least 1 of the 3 brainstem symptoms (cranial nerve deficit, long tract sign, or cerebellar sign).

• If all features of this clinicoradiologic criteria are met, then patients can continue on protocol with or without a biopsy.

• If all features of this clinicoradiologic criteria is not met, patients must receive a brainstem lesion biopsy to be treated on protocol. If this cannot be completed, patients will be withdrawn from the study.

• If biopsy has already been completed at an outside institution, pathology must be reviewed at Mayo Clinic for trial enrollment.

Exclusion Criteria:

• Any patient who has received previous radiation to the brain.

• Any patient who has received previous chemotherapy.

• Any patient with a diagnosis of neurofibromatosis type 1 or 2 (NF1 or NF2).

• Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:

  • Pregnant women;

  • Nursing women;

  • Women of childbearing potential who are unwilling to employ adequate contraception.

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Other active malignancy ≤ 5 years prior to registration.

  • EXCEPTIONS: Non-melanotic skin cancer, breast cancer, prostate cancer, well-differentiated thyroid cancer, carcinoma-in-situ of the cervix.

  • NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer.

• Patients > 16 years with an ECOG score ≥ 4 and patients ≤ 16 years with a Lansky play scale ≤ 20.