Phase III Intergroup Study of Radiotherapy With Concomitant and Adjuvant Temozolomide Versus Radiotherapy With Adjuvant PCV Chemotherapy in Patients With 1p/19q Co-deleted Anaplastic Glioma or Low Grade Glioma

• United States (US) and Canadian sites:

• \* This review is mandatory prior to registration to confirm eligibility; patients must be willing to submit tissue samples for mandatory central pathology review submission; it should be initiated as soon after surgery as possible

• Tissue must have been determined to have local 1p/9q co-deletion and IDH mutation prior to submission for central path review

‣ Tumor tissue must show co-deletion of chromosomes 1p and 19q; for eligibility, the 1p/19q analysis results will be accepted from the local site, as determined by either a locally available or reference laboratory (for US, must be Clinical Laboratory Improvement Act \[CLIA\] certified); acceptable methods for determination of 1p/19q loss include fluorescent in-situ hybridization (FISH), by genomic sequencing or methylomic analyses; US and Canadian sites must send a copy of the official report to the pathology coordinator and quality assurance specialist (QAS)

⁃ Tumor must also show evidence of IDH mutation by immunohistochemistry or genomic analyses; this should be performed at the local site (US: performed in a CLIA certified laboratory); the site must send a copy of the official report to the pathology coordinator and QAS

• Newly diagnosed and =\< 3 months from surgical diagnosis; patients are also eligible if they have had a prior surgical procedure \> 3 months earlier for low grade glioma, as long as the patient has not received prior radiation or prior chemotherapy

• Histological evidence of World Health Organization (WHO) grade III anaplastic glioma or WHO grade II low grade glioma with locally diagnosed combined 1p/19q loss and the presence of an either IDH1 or IDH2, both as established by a local or referenced laboratory qualified for the study

• \* Note: mixed gliomas are eligible, regardless of the degree of astrocytic or oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q

• Patients with codeleted low grade gliomas must also be considered high risk by exhibiting one or more of the following characteristics:

‣ Age \>= 40 and any surgical therapy

⁃ Age \< 40 with prior and subtotal resection or biopsy (i.e., anything less than gross total resection)

⁃ Documented growth following prior surgery (NOTE: patients with prior surgery cannot have received prior radiation, chemotherapy or targeted therapy)

⁃ Intractable seizures

• Surgery (partial or gross total resection or biopsy) must be performed \>= 2 weeks prior to registration; patient must have recovered adequately from the effects of surgery

• Absolute neutrophil count (ANC) \>= 1,500/mm\^3 obtained =\< 21 days prior to registration

• Platelet (PLTs) count \>= 100,000/mm\^3 obtained =\< 21 days prior to registration

• Hemoglobin (Hgb) \> 9.0 g/dL obtained =\< 21 days prior to registration

• Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) obtained =\< 21 days prior to registration

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 3 x ULN obtained =\< 21 days prior to registration

• Creatinine =\< 1.5 x ULN obtained =\< 21 days prior to registration

• Negative serum or urine pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only

• Willingness and ability to personally complete neurocognitive testing (without assistance) and willingness to complete the QOL testing, (either personally or with assistance)

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2

• Written informed consent

• Willingness to return to enrolling institution for follow-up during the active monitoring phase (that is, the active treatment and observation portion) of the study); patients who have been formally transferred to another active and approved site participating in this study would not need to return to the enrolling institution for this purpose

• Willingness to allow the provision of tissue samples for correlative research, as long as adequate tissues are available; patients will not be excluded from participation in the study, if they are willing to allow provision of tissues for the correlative research, but there are insufficient quantities of tissue for the correlative analyses (e.g., a patient otherwise eligible and willing who had biopsy only) Willingness to allow the provision of blood samples for correlative research; patients are not excluded from participation in the study, if they are willing to provide the mandatory biospecimens for translational/correlative research, but for logistical reasons the specimens(s) were not obtainable or if the volume collected was insufficient