• Patient must be at least 18 years of age.

• Diagnosis of recurrent or progressive glioblastoma, WHO Grade IV, IDH wild-Type or astrocytoma WHO grade IV.

• Unequivocal evidence of tumor progression by brain MRI scan per RANO criteria. Patients who experience a second disease progression are eligible provided that they have not been previously treated with anti-angiogenic agents including bevacizumab (at the exception of bevacizumab radiation necrotic protocol)

• A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively, within 28 days prior to study enrollment.

• There must be an interval of at least 12 weeks from the completion of radiation therapy to study registration unless there is unequivocal evidence for tumor recurrence per RANO criteria. When the interval is less than 12 weeks but more than 4 weeks from the completion of radiotherapy, the use of perfusion imaging and/or PET scan is allowed to differentiate between unequivocal evidence of tumor recurrence and pseudoprogression.

• Karnofsky performance status (KPS) ≥60%.

• Candidate for MLA based on the size, location, and shape of the recurrent tumor as determined by the performing neurosurgeon. Surgical resection/debulking prior to MLA is allowed per standard of care but is not required.

• Candidate for Optune GIO® therapy.

• Candidate for pembrolizumab.

⁃ Adequate bone marrow and organ function as defined below:

∙ ANC ≥ 1,500/mcL

‣ Platelets ≥ 100,000/mcL

‣ Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L (transfusion is allowed)

‣ Serum creatinine ≤ 1.5 x IULN OR creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine \> 1.5 x IULN

‣ Serum total bilirubin ≤ 1.5 x IULN OR direct bilirubin ≤ IULN for patients with total bilirubin \> 1.5 x IULN

‣ AST (SGOT) ≤ 3 x IULN

‣ ALT (SGPT) ≤ 3 x IULN

⁃ Participants of childbearing age must use effective contraception:

⁃ Women of childbearing potential (WOCBP) must be using a highly effective method of contraception to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy.

‣ WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or oophorectomy) or who is not post-menopausal. Post-menopause is defined as:

⁃ Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or

• For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL.

‣ Males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.

⁃ Ability of the patient to understand and willingness to sign an IRB approved written informed consent document