Tumour-treating Fields Research Articles

Tumour-treating fields (TTFields): Investigations on the mechanism of action by electromagnetic exposure of cells in telophase/cytokinesis

Tumour-treating fields (TTFields) use alternating electric fields which interfere with dividing cells, thereby reducing tumour growth. Previous reports suggest that electrical forces on cell structure proteins interfered with the chromosome separation during mitosis and induced apoptosis. In the present report we evaluate electromagnetic exposure of cells in telophase/cytokinesis in order to further analyse the mechanism of action on cells. We performed numerical electromagnetic simulations to analyse the field distribution in a cell during different mitotic phases. Based thereon, we developed an electric lumped element model of the mitotic cell. Both the electromagnetic simulation and the lumped element model predict a local increase of the specific absorption rate (SAR) as a measure of the electromagnetically induced power absorption density at the mitotic furrow which may help to explain the anti-proliferative effect. In accordance with other reports, cell culture experiments confirmed that TTFields reduce the proliferation of different glioma cell lines in a field strength- and frequency-dependent manner. Furthermore, we found an additional dependence on the commutation time of the electrical fields. The report gives new insights into TTFields’ anti-proliferative effect on tumours, which could help to improve future TTFields application systems.

Improving survival in molecularly selected glioblastoma

Clinical investigation of novel treatments for glioblastoma has been met with repeated setbacks over the past two decades. Modest, but clinically meaningful, improvement in survival has only been shown for temozolomide 1 Stupp R Mason WP van den Bent MJ et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352: 987-996 Crossref PubMed Scopus (14754) Google Scholar and tumour-treating fields, 2 Stupp R Taillibert S Kanner A et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017; 318: 2306-2316 Crossref PubMed Scopus (1066) Google Scholar whereas many randomised trials assessing drugs targeted to vascular endothelial growth factor, 3 Gilbert MR Dignam JJ Armstrong TS et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014; 370: 699-708 Crossref PubMed Scopus (1854) Google Scholar , 4 Chinot OL Wick W Mason W et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014; 370: 709-722 Crossref PubMed Scopus (1723) Google Scholar integrins, 5 Stupp R Hegi ME Gorlia T et al. Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071–22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2014; 15: 1100-1108 Summary Full Text Full Text PDF PubMed Scopus (669) Google Scholar and epidermal growth factor receptor (EGFR), 6 Weller M Butowski N Tran DD et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 2017; 18: 1373-1385 Summary Full Text Full Text PDF PubMed Scopus (580) Google Scholar showed that such drugs failed to prolong patient survival. Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA–09): a randomised, open-label, phase 3 trialOur results suggest that lomustine-temozolomide chemotherapy might improve survival compared with temozolomide standard therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. The findings should be interpreted with caution, owing to the small size of the trial. Full-Text PDF

A nurse led clinic improves care for patients with Glioblastoma and tumour treating fields

Introduction Poor prognosis and limited access to clinical trials can result in a poor hospital experience for patients diagnosed with Glioblastoma. The role of the clinical nurse specialist (CNS) is pivotal to improving patient experience. TTF (Tumour treating fields) is a novel, non-invasive technique using electrical fields to disrupt cell division, and requires monthly review. Utilisation of a nurse led clinic co-ordinating the TTF patient pathway was examined.

P02.14 Tumour Treating Fields (TTFields) demonstrate variable efficacy on high-grade paediatric brain tumour cell lines in a frequency-dependent manner

P02.14 Tumour Treating Fields (TTFields) demonstrate variable efficacy on high-grade paediatric brain tumour cell lines in a frequency-dependent manner

Use of FET PET in glioblastoma patients undergoing neurooncological treatment including tumour-treating fields: initial experience.

We present our first clinical experience with O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET in patients with high-grade glioma treated with various neurooncological therapies including tumour-treating fields (TTFields) for the differentiation of tumour progression from treatment-related changes. We retrospectively assessed 12 patients (mean age 51 ± 12years, range 33-72years) with high-grade glioma (11 glioblastomas, 1 gliosarcoma) in whom the treatment regimen included TTFields and who had undergone FET PET scans for differentiation of tumour progression from treatment-related changes. Mean and maximum tumour-to-brain ratios (TBRmean, TBRmax) were calculated. The definitive diagnosis (tumour progression or posttherapeutic changes) was confirmed either by histopathology (4 of 12 patients) or on clinical follow-up. In all nine patients with confirmed tumour progression, the corresponding FET PET showed increased uptake (TBRmax 3.5 ± 0.6, TBRmean 2.7 ± 0.7). In one of these nine patients, FET PET was consistent with treatment-related changes, whereas standard MRI showed a newly diagnosed contrast-enhancing lesion. In two patients treated solely with TTFields without any other concurrent neurooncological therapy, serial FET PET revealed a decrease in metabolic activity over a follow-up of 6months or no FET uptake without any signs of tumour progression or residual tumour on conventional MRI. FET PET may add valuable information in monitoring therapy in individual patients with high-grade glioma undergoing neurooncological treatment including TTFields.

Biological effect of an alternating electric field on cell proliferation and synergistic antimitotic effect in combination with ionizing radiation.

Alternating electric fields at an intermediate frequency (100~300 kHz), referred to as tumour-treating fields (TTF), are believed to interrupt the process of mitosis via apoptosis and to act as an inhibitor of cell proliferation. Although the existence of an antimitotic effect of TTF is widely known, the proposed apoptotic mechanism of TTF on cell function and the efficacy of TTF are controversial issues among medical experts. To resolve these controversial issues, a better understanding of the underlying molecular mechanisms of TTF on cell function and the differences between the effects of TTF alone and in combination with other treatment techniques is essential. Here, we report experimental evidence of TTF-induced apoptosis and the synergistic antimitotic effect of TTF in combination with ionizing radiation (IR). For these experiments, two human Glioblastoma multiforme (GBM) cells (U373 and U87) were treated either with TTF alone or with TTF followed by ionizing radiation (IR). Cell apoptosis, DNA damage, and mitotic abnormalities were quantified after the application of TTF, and their percentages were markedly increased when TTF was combined with IR. Our experimental results also suggested that TTF combined with IR synergistically suppressed both cell migration and invasion, based on the inhibition of MMP-9 and vimentin.