This phase II trial studies how well dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) works in measuring relative cerebral blood volume (rCBV) for early response to bevacizumab in patients with glioblastoma that has come back. DSC-MRI may help evaluate changes in the blood vessels within the cancer to determine a patient?s response to treatment.

PRIMARY OBJECTIVES:

I. To determine whether binary changes (increase versus [vs.] decrease) in rCBV within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with overall survival (OS).

SECONDARY OBJECTIVES:

I. To determine whether the baseline pre-treatment rCBV measure alone is associated with OS.

II. To determine whether binary changes (increase vs. decrease) in rCBV within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with progression-free survival (PFS).

III. To determine whether changes in rCBV as a continuous variable within enhancing tumor from baseline to 2 weeks after initiation of anti-angiogenic therapy is associated with OS or PFS.

IV. To determine the association between rCBV and OS when adjusting for the changes in enhancing tumor volume.

V. To determine whether baseline cerebral blood flow (CBF) or change in CBF is associated with OS or PFS.

OUTLINE:

Patients undergo DSC-MRI within 3 days before bevacizumab initiation and at day 15.

After completion of study intervention, patients are followed up every 3 months for 1 year and then every 6 months for up to 4 years.

Inclusion Criteria:

• Histologically proven intracranial glioblastoma or gliosarcoma at initial surgery

  • Patients will be eligible if the original histology was low-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made (high-grade transformation)

• Karnofsky performance status >= 70

• Women must not be pregnant or breast-feeding

• Progression of disease assessed by local site using Revised Assessment in Neuro-Oncology (RANO) criteria, with plan to give whole-dose bevacizumab therapeutically, either as single therapy or in conjunction with other chemotherapeutic regimens; patients getting bevacizumab to support additional radiation therapy or immunotherapy, or primarily for reduction of edema rather than for tumor treatment, are excluded; this must be the patient?s initial recurrence

• Patient must not have been treated previously with immunotherapies (vaccines, checkpoint inhibitors, T-cells)

• Intratumoral hemorrhage (acute, subacute, or chronic) as seen on hemosiderin-sensitive (gradient-echo) MRI may preclude patient inclusion because of anticipated limited evaluation due to magnetic susceptibility artifact on the heavily T2-weighted DSC-MRI images; if the region of enhancing tumor not affected by blooming artifact on the hemosiderin-sensitive images does not meet the 10 x 10 x 10 mm ?measurable enhancement? threshold specified elsewhere, the patient is ineligible

• Progressive enhancement (> 25% increase in contrast enhancing volume compared to nadir) on MRI within 14 days of registration, >= 42 days since completion of radiation/temozolomide therapy, and >= 28 days since surgical resection or cytotoxic chemotherapy; measurable enhancement is defined as two perpendicular in-plane diameters of at least 10 mm and at least 10 mm in the 3rd orthogonal direction

• Patients must be able to tolerate brain MRI scans with dynamic intravenous gadolinium-based contrast agent injections

  • Ability to withstand 22 gauge intravenous (IV) placement

  • No history of untreatable claustrophobia

  • No magnetic resonance (MR) incompatible implants/devices or metallic foreign bodies

  • No contraindication to intravenous contrast administration

    • Adequate organ function, including adequate renal function defined as estimated glomerular filtration rate (eGFR) >= 40 mL/min/1.73 m^2 as calculated per institution standard of care, and meeting local site requirements for intravenous administration of gadolinium-based MRI contrast agents

  • No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance

  • Weight compatible with limits imposed by the MRI scanner table

• Patient must be scheduled to receive treatment with a standard dose regimen of bevacizumab (bevacizumab infusion on days 1 and 15 of a 28-day treatment cycle); patient can be treated with bevacizumab alone or in combination with other chemotherapies Exclusion Criteria: (see Inclusion Criteria)