In this research study the investigators are looking at a type of radiation called proton radiation. Proton radiation has been shown to deliver virtually no radiation beyond the area of the tumor, sparing surrounding normal tissue from exposure. This may reduce side effects that patients would normally experience with conventional radiation therapy.

In this research study the investigators are looking to determine if proton radiation with a reduced field size will be as effective in controlling tumor growth as photon therapy, while reducing the treatment-related side effects observed in patients with brain tumors.

Proton radiation will be delivered daily for approximately 6 weeks. Subjects will be assessed weekly for side effects. Each visit will take about 15 minutes.

Subjects will have follow-up visits at 3, 6, 12, 24, 36, 48, 60, 72, and 84 months after their last proton radiation treatment. They will receive a physical exam, MRI, have blood tests (about 4 teaspoons) and answer questionnaires regarding medical history, quality of life, and emotional well-being. Subjects will also receive a neurocognitive exam annually.

Inclusion Criteria:

• Histologically confirmed low-grade gliomas OR Grade III anaplastic glioma with either or both IDH1 mutation or 1p/19q codeletion
• Subject must be indicated for radiation therapy
• Life expectancy greater than 5 years
• Willing to participate in rigorous neurocognitive evaluations at baseline and serially following treatment
• Able to speak and comprehend English
• Recovered from adverse events due to agents administered more than 4 weeks before entering study
• Able to undergo MRI scans

Exclusion Criteria:

• Prior cranial radiation therapy
• Chemotherapy within 4 weeks prior to entering study
• Pregnant or breastfeeding
• Known brain metastases
• Baseline neurocognitive or emotional disorders
• Uncontrolled intercurrent illness
• History of a different malignancy unless disease-free for at least 5 years
• HIV positive on antiretroviral therapy