Mathematical Model-Adapted Radiation In Glioblastoma

Inclusion Criteria:

* Participants must have recurrent glioblastoma (WHO Grade IV), as defined on brain imaging with CT or MRI, after prior receipt of definitive therapy including neurosurgical biopsy or resection and radiation therapy with or without systemic therapy.
* Participants must be deemed appropriate candidates for re-irradiation
* Histopathologic confirmation of disease as part of routine clinical care is required either at the time of initial diagnosis and/or at the time of recurrent disease. There is no requirement for central pathologic review.
* Age ≥ 18 years at the time of enrollment
* Karnofsky Performance Status (KPS) of at least 70
* Exclusion Criteria
* Participants who have received more than one prior course of radiotherapy to the local site of progressive disease
* Participants who have received prior radiotherapy to the local site of progressive disease within \< 3 months of the anticipated start of re-irradiation
* Participants with recurrent tumor extensively abutting or involving the optic structures or brainstem, as assessed by the treating radiation oncologist
* Participants without a definable tumor cavity on MRI or CT obtained at study enrollment
* Participants receiving concurrent cytotoxic chemotherapy (i.e. temozolomide, CCNU, vincristine, procarbazine) or concurrent immunotherapy (i.e. pembrolizumab, nivolumab); however, participants may receive sequential chemotherapy before or after radiation without limitation. Participants may receive concurrent corticosteroid and/or anti-angiogenic therapy (i.e. bevacizumab) if clinically indicated.