The effects of alternating electric fields in glioblastoma: current evidence on therapeutic mechanisms and clinical outcomes

Abstract

<jats:p>Glioblastoma is both the most common and most lethal primary CNS malignancy in adults, accounting for 45.6% of all malignant CNS tumors, with a 5-year survival rate of only 5.0%, despite the utilization of multimodal therapy including resection, chemotherapy, and radiation. Currently available treatment options for glioblastoma often remain limited, offering brief periods of improved survival, but with substantial side effects. As such, improvements in current treatment strategies or, more likely, the implementation of novel strategies altogether are warranted. In this topic review, the authors provide a comprehensive review on the potential of alternating electric fields (AEFs) in the treatment of glioblastoma. Alternating electric fields—also known as tumor-treating fields (TTFs)—represent an entirely original therapeutic modality with preliminary studies suggesting comparable, and at times improved, efficacy to standard chemotherapeutic agents in the treatment of recurrent glioblastoma. A recent multicenter, Phase III, randomized clinical trial comparing NovoTTF-100A monotherapy to physician's best choice chemotherapy in patients with recurrent glioblastoma revealed that AEFs have similar efficacy to standard chemotherapeutic agents with a more favorable side-effects profile and improved quality of life. In particular, AEFs were shown to have limited systemic adverse effects, with the most common side effect being contact dermatitis on the scalp at the sites of transducer placement. This study prompted FDA approval of the NovoTTF-100A system in April 2011 as a standalone therapy for treatment of recurrent glioblastoma refractory to surgical and radiation treatment. In addition to discussing the available clinical evidence regarding the utilization of AEFs in glioblastoma, this article provides essential information regarding the supposed therapeutic mechanism as well as modes of potential tumor resistance to such novel therapy, delineating future perspectives regarding basic science research on the issue.</jats:p>

Blood-brain barrier, cytotoxic chemotherapies and glioblastoma

“…The Novocure device delivers "tumor-treating fields" (TTF) to the brain, and was shown to induce tumor cells death in preclinics and to increase survival of newly diagnosed GBM patients (NCT00916409) [120]. The mechanism of tumor cells death remains unclear, but it is at least partly due to interaction of TTF with the cytoskeleton.…”

“…Electroporation was proposed to explain the synergic effect of TTF and chemotherapy observed in some patients [120].…”

Tumor treating fields for glioblastoma: Review

“…Potential tumor resistance is a really important topic needed to be researched for these Who Grad 4 dismal tumors [16].…”

Numeric Investigation of Brain Tumor Influence on the Current Distributions During Transcranial Direct Current Stimulation

“…Meanwhile, several electrical based therapies were reported as novel treatments for tumors and they could provide useful comparison information for the initiative applications of tDCS on brain tumors [13][14][15]. The innovative tumor treatments include electrochemotherapy (EChT), tumor-treating fields (TTFs) and low level direct current therapy (DCT).…”