Outcomes
toxicity, tumor, renal, hepatic, cardiac, and metabolic
ADVERSE EVENT, TUMOR
Since the main aim of this study was to evaluate the safety of suicide gene therapy, a data and safety monitoring board (DSMB), including different experts in relevant fields was established. Each patient was followed up for 24 months after the suicide gene therapy and the overall study duration was 26 months. The primary outcome measure of the present study was the safety profile of suicide gene therapy using allogeneic HSV-TK carrying ADSCs in patients with recurrent GBM, which was defined as the absence of dose-limiting toxicity (DLT). During this investigation, AEs were monitored and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4. DLT was defined as any grade III or more non-hematological or grade IV or more hematological AEs associated with study intervention according to the DSMB decision and occurring within 4 weeks following the stereotactic cell injection. Based on the 3 + 3 design of the study, the maximum tolerated dose (MTD) was defined as the highest dose at which no more than 0/3 or 1/6 patients experienced a DLT. If one DLT was observed in any cohort, three more patients were recruited to that dosing cohort. Safety monitoring was performed using serial physical examinations, electrocardiography, and complete laboratory investigations, including serum biochemistry, hematological, coagulation, renal, hepatic, cardiac, and metabolic profiles. In addition to baseline, all the aforementioned assessments were performed on a daily basis during the first 17 days after the surgery and monthly afterward until 3 months postoperatively. Further, all patients were informed about all the potential treatment-related AEs before discharge, and also weekly contacted through regular telephone calls. As part of safety evaluation and potential early effects of suicide gene therapy, MR imaging was also performed at baseline, 3-day (before prodrug administration and after cell injection), and 17-day (before discharge) after the injection.In addition, potential effects of suicide gene therapy using HSV-TK-carrying ADSCs on the tumor were investigated. Secondary outcome measures for potential efficacy assessment included CET and fluid-attenuated inversion recovery (FLAIR) volumes, progression-free survival (PFS), and overall survival (OS). Quantitative volumetric analysis of changes in CET and FLAIR volumes following the study intervention and over time was performed using semi-automated segmentation method. Moreover, tumor response and progression was evaluated based on Response Assessment in Neuro-Oncology (RANO) response criteria in the present study [