Standard Chemotherapy vs. Chemotherapy Guided by Cancer Stem Cell Test in Recurrent Glioblastoma

Inclusion Criteria: 1. Men and Women and members of all ethnic groups who are at least 18 years old at the time of enrollment are eligible for this trial; 2. Informed consent obtained and signed; 3. Willing and able to commit to study procedures including long-term follow-up visit(s); 4. Histopathologically confirmed 2016-WHO grade III recurrent glioma, and grade IV recurrent glioblastoma (GBM), inclusive of Gliosarcoma 5. In all cases, the diagnosis must be confirmed by a pathologist. 6. Recurrent surgically resectable tumor and/or biopsy; 7. Participants who have undergone surgical resection should have received an MRI or a scan after surgery in order to visualize residual tumor. If not, the operative report must be available; 8. Prior to surgery there was imaging evidence of measurable progressive disease (PD); 9. Start of radiotherapy, if indicated, must occur at least 2 weeks after surgery and/or biopsy; 10. Estimated survival of at least 3 months; 11. Hgb \> 9 gm; absolute neutrophil count (ANC) \> 1500/μl; platelets \> 100,000; Creatinine \< 1.5 times the upper limit of laboratory normal value; Bilirubin \< 2 times the upper limit of laboratory normal value; serum glutamate pyruvate transaminase (SGPT) or serum glutamate oxaloacetate transaminase (SGOT) \< 3 times the upper limit of laboratory normal value; 12. If indicated radiation therapy and chemotherapy must start within 8 weeks of tumor resection or biopsy. 13. Bevacizumab (Avastin) is allowed. If indicated it should be initiated at least 4 weeks post craniotomy or biopsy if the wound has healed well without any drainage or cellulitis; 14. The use of herbal preparation or tetrahydrocannabinol/cannabidiol is strongly discouraged, but not contraindicated; Exclusion Criteria: 1. Subjects with newly diagnosed GBM 2. Pregnant women or nursing mothers cannot participate in the study. Women of childbearing age must have a negative pregnancy test within 72 hours prior to study entry. Women of childbearing potential must practice medically approved contraceptive precautions; 3. Abnormal hematological results at inclusion with: Neutrophils \< 1,500/mm3; Blood-platelets \< 100,000/mm3 4. Severe or chronic renal insufficiency (creatinine clearance ≤ 30 ml/min); 5. Patient unable to follow procedures, visits, examinations described in the study; 6. Any usual formal indication against imaging examinations (important claustrophobia, pacemaker); 7. History of another malignancy in the previous 2 years, with a disease-free interval of \< 2 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer, any time prior to screening, are eligible; 8. OPTUNE device is not permitted in the study; 9. Patients cannot participate to any clinical trials utilizing a liquid biomarker or imaging studies that impact the overall survival.