• Subject is 18 years or older and has signed and dated the trial informed consent form (ICF)

• Life expectancy ≥ 12 weeks

• Subject is willing and able to comply with the trial testing, procedures, and follow-up schedule

• History of a histologically confirmed diagnosis of glioblastoma per 2021 WHO criteria

• Have radiographic evidence of tumor progression/recurrence with measurable disease (≥ 1 cm to ≤ 5cm bidirectional diameters) by contrast-enhancement on MRI, according to RANO criteria

• Prior surgery and treatment with combination of radiotherapy and chemotherapy ± Tumor Treating Fields (Optune®)

• Prior cranial radiation dose \< 66 Gy

• WHO performance status ≤ 2

• The interval since completion of cranial radiotherapy must be \> 6 months, unless there is tissue confirmation of tumor recurrence/progression outside the previous radiation treatment field, in which case the interval since completion of cranial radiation must be at least 12 weeks

⁃ Interval since last systemic therapy until presumed date of intervention ≥ 1 cycle or ≥ 2 biological half-lives, i.e.

∙ ≥ 4 weeks since last dose of temozolomide

‣ ≥ 6 weeks since last dose of lomustine or other nitrosourea

‣ ≥ 2 weeks since last dose of a small molecule targeted agent (Tyrosine Kinase Inhibitor or similar)

‣ ≥ 6 weeks from last dose of last intravenous bevacizumab infusion, or other antibody-based VEGF therapy

⁃ If receiving steroids, patient should be on a stable or decreasing dose equivalent to dexamethasone ≤ 6 mg/d, for at least 7 days prior to registration

⁃ Have adequate organ and bone marrow function within 14 days prior to registration, as defined below:

∙ INR ≤ 1.2 (in absence of anticoagulation)

‣ Platelets ≥ 100,000/L

‣ Creatinine ≤1.5 mg/dL

‣ Absolute Neutrophil Count ≥1.5 x 10\^9/L

‣ Hemoglobin ≥9.0 g/dL

⁃ Have a negative pregnancy test within 14 days prior to registration on study (for FOCBP, female of child-bearing potential)

⁃ Subject is a male or non-pregnant female. If female of child-bearing potential, and if sexually active must be using, or agree to use, a medically acceptable method of birth control as confirmed by the investigator

⁃ Angiographic Mapping Inclusion Criteria:

∙ Accessible neurovascular anatomy that allows for safe microcatheter placement (up to two locations) to infuse TheraSphere GBM to treat all of the T1 enhancing component of target lesion confirmed by neuro-interventional team.

‣ Total treatment volume is ≤ 150cc as determined by multidisciplinary team.

⁃ Additional Inclusion Criteria:

∙ Group A: perfused volume encompasses the non-dominant hemisphere and non-eloquent regions of the brain

‣ Group B: perfused volume encompasses the non-dominant hemisphere and eloquent regions of the brain

‣ Group C: perfused volume encompasses the dominant hemisphere and non-eloquent regions of the brain

‣ Group D: perfused volume encompasses the dominant hemisphere and eloquent regions of the brain