Proton Beam or Intensity-Modulated Radiation Therapy in Preserving Brain Function in Patients with IDH Mutant Grade II or III Glioma

Inclusion Criteria

• PRIOR TO STEP 1 REGISTRATION
• Tumor tissue must be available for submission for central pathology review
• Grade II and III gliomas IDH mutant gliomas including; diffuse astrocytoma, anaplastic astrocytoma, oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma, anaplastic oligoastrocytoma
• Documentation from the enrolling site confirming the presence of IDH mutation and 1p/19q status; the provided information must document assays performed in clinical laboratory improvement amendments (CLIA)-approved laboratories and be uploaded prior to Step 2 registration
• Age >= 18
• The trial is open to both genders
• Only English or French speaking patients are eligible to participate as the cognitive assessments are only available in these languages
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
• History and physical exam, and Karnofsky performance status of >= 70 within 30 days prior to registration
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 60 days prior to registration)
• Platelets >= 100,000 cells/mm^3 (within 60 days prior to registration)
• Hemoglobin >= 10.0 g/dl (Note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl is acceptable) (within 60 days prior to registration)
• Bilirubin =< 1.5 upper limit of normal (ULN) (within 60 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (within 60 days prior to registration)
• Blood urea nitrogen (BUN) < 30 mg/dl (within 60 days prior to registration)
• Serum creatinine < 1.5 mg/dl (within 60 days prior to registration)
• Pre-operative MRI imaging of the brain available for radiation planning
• Post-operative MRI imaging with contrast is mandatory obtained for radiation therapy planning; enrolling sites are not mandated although highly encouraged to obtain thin-slice (< 1.5 mm) 3 dimensional (D) pre and post contrast and axial T2/FLAIR sequences for planning purposes
• Patients must be able to swallow capsules
• PRIOR TO STEP 2 REGISTRATION
• Histologically proven diagnosis of supratentorial, World Health Organization (WHO) grade II or III astrocytoma, oligodendroglioma or oligoastrocytoma, with IDH mutation confirmed by central review
• The following baseline neurocognitive assessments must be completed and uploaded prior to Step 2 registration: HVLT-R (recall, delayed recall, and recognition), TMT Parts A and B, and COWA; the neurocognitive assessment will be uploaded into a folder in the NRG Medidata RAVE System for central evaluation; once the upload and scoring of the tools are complete, a notification will be sent within 3 business days to the Research Associate (RA) to proceed to Step 2; in order for the patient to be eligible, at least 5 of the 6 neurocognitive assessments must be able to be scored (i.e. free of any errors)
• Completion of all items on the following baseline quality of life forms: MDASI-BT, LASA QOL, WPAI-GH and Employment Questionnaire; these quality of life forms will be required and data entered at step 2 registration
• Financial clearance for proton therapy treatment prior step 2 registration
• Women of childbearing age must have a negative serum pregnancy test within 14 days prior to step 2 registration

Exclusion Criteria

• Definitive clinical or radiologic evidence of metastatic disease; if applicable
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity or cervix are permissible)
• Prior cranial radiotherapy or radiotherapy to the head and neck where potential field overlaps would exist
• Prior chemotherapy or radiotherapy for any brain tumor
• Histologic diagnosis of glioblastoma (WHO grade IV) or pilocytic astrocytoma (WHO grade I)
• Definitive evidence of multifocal disease
• Planned use of cytotoxic chemotherapy during radiation (only adjuvant temozolomide therapy will be used on this protocol)
• Patients with infra-tentorial tumors are not eligible
• Prior history of neurologic or psychiatric disease believed to impact cognitive function
• The use of memantine during or following radiation is NOT allowed
• Severe, active co-morbidity defined as follows: * Unstable angina or congestive heart failure requiring hospitalization within 6 months prior to enrollment * Transmural myocardial infarction within the last 6 months prior to registration; evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of >= 2 mm using the analysis of an electrocardiogram (EKG) performed within 28 days prior to registration (Note: EKG to be performed only if clinical suspicion of cardiac issue) * New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration * Serious and inadequately controlled arrhythmia at step 2 registration * Serious or non-healing wound, ulcer or bone fracture or history of abdominal fistula, intra-abdominal abscess requiring major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for surgical resection * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration * Human immunodeficiency virus (HIV) positive with CD4 count < 200 cells/microliter; acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that HIV testing is not required for entry into this protocol * Any other severe immunocompromised condition * Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity * End-stage renal disease (i.e., on dialysis or dialysis has been recommended) * Any other major medical illnesses or psychiatric treatments that in the investigator’s opinion will prevent administration or completion of protocol therapy
• Inability to undergo MRI with and without contrast (e.g. claustrophobia, non-MRI compatible implant or foreign body, gadolinium allergy or renal dysfunction preventing the patient from receiving gadolinium- institutional guidelines should be used to determine if patients are at risk for renal dysfunction); note that patients with severe claustrophobia are permitted on this study if they are willing and able to undergo MRI with adequate sedation or anesthesia
• Patients known to have hypersensitivity to dacarbazine (DTIC) are not eligible