Dose-Escalated Photon IMRT or Proton Beam Radiation Therapy Versus Standard-Dose Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma

Prior treatment

• Prior chemotherapy or radiosensitizers for cancers of the head and neck region; note that prior chemotherapy for a different cancer is allowable (except temozolomide)
• Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted
• Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields
• Patients treated on any other therapeutic clinical protocols within 30 days prior to step 2 registration
• Postoperative tumor plus surgical bed size exceeds 5 cm in maximum diameter

Other illness

• 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 all permissible)
• Recurrent or multifocal malignant gliomas
• Any site of distant disease (for example, drop metastases from the GBM tumor site)

Lab values

• Severe, active co-morbidity, defined as follows:
  • Unstable angina at step 2 registration
  • Transmural myocardial infarction within the last 6 months prior to step 2 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 step 2 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 step 2 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 step 2 registration, with the exception of the craniotomy for surgical resection
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of step 2 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 step 2 registration
  • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol; the need to exclude patients with AIDS from this protocol is because the treatments involved in this protocol may be significantly immunosuppressive with potentially fatal outcomes in patients already immunosuppressed
  • 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 (ie, 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

Other

• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
• Inability to undergo MRI (e.g., due to safety reasons, such as presence of a pacemaker, or severe claustrophobia)

• PRIOR TO STEP 1 REGISTRATION
• A diagnostic contrast-enhanced MRI (no other scan type allowed) of the brain must be performed postoperatively; the residual enhancing tumor and/or resection cavity must have a maximal diameter of 5 cm or less; the tumor diameter will be the greatest diameter as measured on the contrast-enhanced postoperative MRI and will include residual disease and/or the postoperative surgical cavity as appropriate
  • The postoperative brain MRI should be obtained within 72 hours of resection; if it is not obtained within 72 hours post-resection, then an MRI obtained 2 weeks or longer after surgery is required and can be utilized to ensure maximal diameter of residual tumor and/or resection cavity is 5 cm or less
  • For cases where a gross total resection of enhancing tumor is performed, but postoperative surgical cavity is NOT identifiable, the patient will be excluded from the trial
• Tumor tissue must be available for submission for central pathology review
  • Timing requirements:
  • If MGMT has been assessed locally by LabCorps or MD Anderson Cancer Center Molecular Diagnostics Lab (MDACC-MDL):
  • Tissue for central pathology review and central MGMT assessment and the official LabCorps or MDACC-MDL MGMT result must be received by the NRG Oncology Biospecimen Bank on or before postoperative calendar day 40
  • The site's local MGMT report from LabCorp or MDACC-MDL will then be used to stratify the patient; a post-stratification MGMT central review will be performed, but step 2 registration and protocol treatment can proceed without central review of MGMT
  • Patients whose tissue for central pathology review and official LabCorps or MDACC-MDL MGMT result cannot be received by NRG Oncology Biospecimen Bank on or before 40 calendar days after surgery may NOT enroll on this trial, as central pathology review and stratification will not be complete in time for the patient to start treatment within 49 calendar days following surgery
  • If MGMT has not been assessed locally by LabCorps or MDACC-MDL:
  • Tissue for central pathology review and central MGMT assessment must be received by the NRG Oncology Biospecimen Bank on or before postoperative calendar day 30
  • Central MGMT analysis will be performed at MDACC-MDL and used for patient stratification; results will be conveyed to NRG Oncology within 10 business days of receipt of the tissue
  • Patients who have not had local MGMT assessment by LabCorps or MDACC-MDL and whose tissue for central pathology review cannot be received by NRG Oncology Biospecimen Bank on or before 30 calendar days after surgery may NOT enroll on this trial, as central pathology review and stratification will not be complete in time for the patient to start treatment within 49 calendar days following surgery
  • Tissue Requirements:
  • Patients must have at least 1 block of tumor tissue; submission of 2 blocks is strongly encouraged to maximize the chances of eligibility; in total, at least 1 cubic centimeter of tissue composed primarily of tumor must be present
  • Submission of an accompanying hematoxylin and eosin H\&E slide(s) is MANDATORY
  • Diagnosis must be made by surgical excision, either partial or complete; stereotactic biopsy and cavitronic ultrasonic surgical (CUSA) techniques are not allowed
• The tumor must be located in the supratentorial compartment only (any component involving the brain stem or cerebellum is not allowed)
• Patients must provide study-specific informed consent prior to step 1 registration
• PRIOR TO STEP 2 REGISTRATION
• Histologically proven diagnosis of glioblastoma (World Health Organization \[WHO\] grade IV) confirmed by central review prior to step 2 registration
• Tumor tissue that is determined by central pathology review prior to step 2 registration to be of sufficient quantity for central analysis of MGMT status
• History/physical examination within 28 days prior to step 2 registration
• The patient must have recovered from effects of surgery, postoperative infection, and other complications within 28 days prior to step 2 registration
• Documentation of steroid doses within 28 days prior to step 2 registration
• Karnofsky performance status \>= 70 within 28 days prior to step 2 registration
• Age \>= 18
• Complete blood count (CBC)/differential obtained within 28 days prior to step 2 registration
• Absolute neutrophil count (ANC) \>= 1,500 cells/mm\^3 (obtained within 28 days prior to step 2 registration)
• Platelets \>= 100,000 cells/mm\^3 (obtained within 28 days prior to step 2 registration)
• Hemoglobin \>= 10.0 g/dl (obtained within 28 days prior to step 2 registration) (note: the use of transfusion or other intervention to achieve hemoglobin \[Hgb\] \>= 10.0 g/dl is acceptable)
• Bilirubin =\< 1.5 upper limit of normal (ULN) (within 28 days prior to step 2 registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (within 28 days prior to step 2 registration)
• Negative serum pregnancy test obtained for females of child-bearing potential within 28 days prior to step 2 registration
• As of Amendment 2, if the registering site is a photon center (registering patients to group I), the patient must agree to participate in the advanced imaging sub-study