HSV-tk + Valacyclovir + SBRT + Chemotherapy for Recurrent GBM

Inclusion Criteria: * All patients must have biopsy proven recurrent anaplastic astrocytoma or glioblastoma multiforme without evidence of multifocal tumor or brainstem involvement. Multifocal disease does not exist if enhancing areas are connected by abnormal T2 FLAIR on the MRI scan. * Radiographic evidence of recurrence/progression by iRANO criteria * ≥ 3 weeks since any major surgery, completion of RT, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy). * Life expectancy ≥ 12 weeks. * Patient can receive second treatment of HSV-tk after 6 months * Patients should have the following characteristics: recurrent glioblastoma or AA demonstrated by biopsy or imaging study, ECOG performance status of 0-1, has had prior surgery and radiotherapy /chemotherapy for the glioblastoma. * Patients with leptomeningeal disease may be considered for enrollment into the study. * No evidence of other active malignancy (except squamous or basal cell skin cancers). * Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks of the study by the investigator (or his/her designee) with the aid of written information. * Willing to provide biopsies as required by the study. * WOCBP must have a negative serum pregnancy test within 7 days prior to the administration of the first study treatment. Women must not be lactating. * WOCBP a…