What is the Role of Tumor-treating Fields in Newly Diagnosed Glioblastoma?

Abstract

Alternating electrical fields can disrupt mitosis leading to apoptosis of rapidly dividing cancer cells. The device that utilizes this mechanism is known as tumor-treating fields (TTFields). TTFields can be applied by ceramic transducer arrays on a shaved scalp to deliver the alternating electric activity to patients with glioblastoma (GBM). It has FDA approval for use in both recurrent and newly diagnosed GBM. The objective is to critically appraise the current evidence for the use of TTFields as adjunctive treatment to newly diagnosed GBM. The objective was addressed through the development of a structured, critically appraised topic. We incorporated a clinical scenario, background information, a structured question, literature search strategy, evidence summary, clinical bottom lines, and expert discussion. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of neurooncology. A randomized controlled trial was selected for critical appraisal. Patients with newly diagnosed GBM completing standard radiation and chemotherapy with temozolomide (TMZ) were subsequently randomized to receive maintenance TMZ with TTFields, or TMZ alone. With the addition of TTFields, median progression-free survival was 6.7 months compared with 4 months without the addition of TTFields (95% confidence interval, 0.52-0.76; P<0.001) and overall survival was 20.9 months compared with 16.0 months without the addition of TTFields (95% confidence interval, 0.53-0.76; P<0.001). TTFields may increase both progression-free and overall survival in patients receiving standard chemoradiation therapy for GBM.

Tumor Treating Fields (TTFields) Reversibly Permeabilize the Blood–Brain Barrier In Vitro and In Vivo

“…Tumor Treating Fields (TTFields) are low-intensity (1–3 V/cm), intermediate-frequency (100–300 kHz), alternating electric fields delivered loco-regionally via arrays placed on the skin, with known antimitotic effects on cancer cells. TTFields are frequency tuned per indication (e.g., 150 kHz for breast, pancreatic, and non-small cell lung cancer [ 21 , 22 , 23 ]), and they are approved as therapy for glioblastoma (GBM) patients when applied at 200 kHz [ 23 , 24 , 25 , 26 , 27 ]. The addition of TTFields (200 kHz) to maintenance temozolomide (TMZ) chemotherapy resulted in statistically significant improvements in progression-free and overall survival relative to TMZ alone in a randomized Phase III clinical trial [ 28 ].…”

Tumor Cell Infiltration into the Brain in Glioblastoma: From Mechanisms to Clinical Perspectives

“…While TTFs affect the cell division, the nondividing cells remain undisturbed, which makes TTFs a cancer-specific application [ 195 ]. The combination of TTFs with the conventional chemotherapy and radiotherapy has proven to be highly efficacious without severe side effects [ 192 , 196 , 197 ]. Since TTFs are a regional therapy with the delivery of the electric fields to a limited location, this option has been a promising one for glioma treatment, considering the diffuse infiltrative, but almost never metastasizing, nature of gliomas [ 198 ].…”

Exploring the efficacy of tumor electric field therapy against glioblastoma: An in vivo and in vitro study

“…It has been reported previously that TTFields inhibit tumor cell proliferation, [28][29][30] promote apoptosis, [31][32][33] and increase CD8 + T-cell infiltration in the tumor. 14 To determine whether TEFT suppresses glioblastoma growth by similar mechanisms, we performed immunohistochemical staining on tumor specimens (Figure 6A).…”