IMPORTANCE Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor.OBJECTIVE To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system. MAIN OUTCOMES AND MEASURESProgression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group. RESULTSOf the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P < .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P < .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone. CONCLUSIONS AND RELEVANCEIn the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00916409

clinicaltrials.gov Identifier: NCT00916409.

Direct in situ introduction of exogenous genes into proliferating tumors could provide an effective therapeutic approach for treatment of localized tumors. Rats with a cerebral glioma were given an intratumoral stereotaxic injection of murine fibroblasts that were producing a retroviral vector in which the herpes simplex thymidine kinase (HS-tk) gene had been inserted. After 5 days during which the HS-tk retroviral vectors that were produced in situ transduced the neighboring proliferating glioma cells, the rats were treated with the anti-herpes drug ganciclovir. Gliomas in the ganciclovir- and vector-treated rats regressed completely both macroscopically and microscopically. This technique exploits what was previously considered to be a disadvantage of retroviral vectors--that is, their inability to transfer genes into nondividing cells. Instead, this feature of retroviruses is used to target gene delivery to dividing tumor cells and to spare nondividing neural tissue.