Chemotherapy and Radiation Therapy for the Treatment of IDH Wildtype Gliomas or Non-histological (Molecular) Glioblastomas

Inclusion Criteria:

• Historical grade II and III gliomas IDH wildtype gliomas by including; diffuseastrocytoma, anaplastic astrocytoma, oligodendroglioma, anaplasticoligodendroglioma, oligoastrocytoma, anaplastic oligoastrocytoma

• IDH wildtype gliomas (molecularly defined high grade glioma or molecularly definedglioblastoma [GBM])

• History & physical exam, and Karnofsky performance status (KFS) of >= 70 within 30days prior to enrollment

• Post-operative magnetic resonance imaging (MRI) with contrast is mandatory andnecessary for radiation therapy (RT) planning

• Thin-slice (< 1.5 mm) three-dimensional (3D) T1 pre and post contrast and axialT2/fluid-attenuated inversion recovery (FLAIR) sequences for planning purposes arehighly encouraged to obtain.

• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 60 days prior toregistration)

• Platelets >= 100,000 cells/mm^3 (within 60 days prior to registration)

• Hemoglobin >= 10.0 g/dl (within 60 days prior to registration) (Note: The use oftransfusion or other intervention to achieve hemoglobin [Hgb] >= 10.0 g/dl isacceptable)

• 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)

Exclusion Criteria:

• Definitive clinical or radiologic evidence of metastatic disease; if applicable

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease freefor a minimum of 3 years. (For example, carcinoma in situ of the breast, oral cavityor cervix are permissible)

• Prior cranial radiotherapy or radiotherapy to the head and neck where potentialfield overlaps would exist

• Prior chemotherapy or radiotherapy for any brain tumor

• Histologic diagnosis of gliosarcoma World Health Organization (WHO grade IV) orpilocytic astrocytoma (WHO grade I)

• Multicentric glioblastoma

• Leptomeningeal disease

• Inability to undergo MRI with and without contrast

• Severe, active co-morbidity defined as follows:

• Unstable angina or congestive heart failure requiring hospitalization within 6months prior to enrollment

• Transmural myocardial infarction within the last 6 months prior toregistration. Evidence of recent myocardial infarction or ischemia by thefindings of S-T elevations of >= 2 mm using the analysis of anelectrocardiogram (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 failurerequiring 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 abdominalfistula, intra-abdominal abscess requiring major surgical procedure, openbiopsy 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 thetime of registration

• Hepatic insufficiency resulting in clinical jaundice and/or coagulationdefects; note, however, that laboratory tests for coagulation parameters arenot required for entry into this protocol

• Chronic obstructive pulmonary disease exacerbation or other respiratory illnessrequiring hospitalization or precluding study therapy at the time ofregistration

• Human immunodeficiency virus (HIV) positive with CD4 count < 200cells/microliter. Acquired immune deficiency syndrome (AIDS) based upon currentCenters for Disease Control and Prevention (CDC) definition; note, however,that HIV testing is not required for entry into this protocol. The need toexclude patients with AIDS from this protocol is because the treatmentsinvolved in this protocol may be significantly immunosuppressive withpotentially fatal outcomes in patients already immunosuppressed

• Any other severe immunocompromised condition

• Active connective tissue disorders, such as lupus or scleroderma that in the opinionof 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 theinvestigator's opinion will prevent administration or completion of protocol therapy