• ≥18 years of age

• Histologically confirmed HGG (WHO grade III or IV, including GBM, astrocytoma, gliosarcoma, H3K27M mutant diffuse midline glioma). Patients with methylated or unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) promoter are eligible, as are IDH WT and mutant patients as long as the treatment plan is for combined XRT/TMZ. The neuropathologic diagnosis of HGG will be made at the respective institution. If any question arises regarding the accuracy of the neuropathologic diagnosis, slides (and pathological blocks, if necessary) will be centrally reviewed

• Planning standard therapy with TMZ and XRT for 6 weeks and adjuvant TMZ for six 28-day cycles.

• Karnofsky Performance Scale (KPS) ≥ 70%

• Adequate organ and marrow function defined as:

⁃ Hgb \> 9 g/dL

⁃ ANC ≥ 1500/µL

⁃ Platelet count ≥ 100,000/µL

⁃ Total bilirubin ≤ 1.5 \* institutional ULN

⁃ AST and ALT ≤ 3 \* institutional ULN OR

⁃ Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 unless data exist supporting safe use at lower values of renal function, but eGFR must be ≥ 30 mL/min/1.73 m2

• Patients with human immunodeficiency virus (HIV) who are on effective antiretroviral therapy are eligible if the viral load was assessed as undetectable within 6 months prior to baseline

• Women: WOCBP must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation

• Men: must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 4 months after completion of LC administration