Investigating the Connection Between Tumor-Treating Fields Distribution in the Brain and Glioblastoma Patient Outcomes. A Simulation-Based Study Utilizing a Novel Model Creation Technique

Urman, Noa; Levy, Shay; Frenkel, Avital; Manzur, Doron; Hershkovich, Hadas Sara; Naveh, Ariel; Yesharim, Ofir; Wenger, Cornelia; Lavy-Shahaf, Gitit; Kirson, Eilon D.; Bomzon, Zéev

doi:10.1007/978-3-030-21293-3_7

Cited by 5 publications

(7 citation statements)

References 24 publications

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“…Following the phase 3 EF‐14 trial, Urman et al. [ 160 ] used computational modelling to correlate the PFS and overall (OS) survival of 119 patients to the relative field distributions. Their models show that when at least 95% (E95) of the combined volume of the gross tumour volume and proximal boundary zone achieved E ≥ 1.3 V cm −1 , PFS was 11.9 months and OS was 33 months compared to PFS 7.5 months and OS 21.9 months for E ≤ 1.3 V cm −1 .…”

Section: Tumour‐treating Fieldsmentioning

confidence: 99%

Electrotherapies for Glioblastoma

et al. 2021

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Non-thermal, intermediate frequency (100-500 kHz) electrotherapies present a unique therapeutic strategy to treat malignant neoplasms. Here, pulsed electric fields (PEFs) which induce reversible or irreversible electroporation (IRE) and tumour-treating fields (TTFs) are reviewed highlighting the foundations, advances, and considerations of each method when applied to glioblastoma (GBM). Several biological aspects of GBM that contribute to treatment complexity (heterogeneity, recurrence, resistance, and blood-brain barrier(BBB)) and electrophysiological traits which are suggested to promote glioma progression are described. Particularly, the biological responses at the cellular and molecular level to specific parameters of the electrical stimuli are discussed offering ways to compare these parameters despite the lack of a universally adopted physical description. Reviewing the literature, a disconnect is found between electrotherapy techniques and how they target the biological complexities of GBM that make treatment difficult in the first place. An attempt is made to bridge the interdisciplinary gap by mapping biological characteristics to different methods of electrotherapy, suggesting important future research topics and directions in both understanding and treating GBM. To the authors' knowledge, this is the first paper that attempts an in-tandem assessment of the biological effects of different aspects of intermediate frequency electrotherapy methods, thus offering possible strategies toward GBM treatment.

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Section: Tumour‐treating Fieldsmentioning

confidence: 99%

Electrotherapies for Glioblastoma

et al. 2021

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“…In order to estimate field intensity distributions within the lesions, numerical simulations were performed using finite element method calculations and a realistic head model created as previously described (9,10). Briefly, tumor tissues were segmented manually using a T1 contrast MRI of the patient.…”

Section: Calculation Of Ttfields Intensitymentioning

confidence: 99%

“…Tumor-treating fields therapy was used together with maintenance TMZ for six TMZ cycles and was continued as a monotherapy for additional 14 months. The placement of the transducer arrays, through which TTFields are applied, was calculated using the NovoTAL TM methodology (9,10). Despite the deep location of the lesion, numeric simulations (Figure 4) demonstrated that the field intensity delivered to the lesion was above therapeutic levels (>1 V/cm).…”

Section: Ttfieldsmentioning

confidence: 99%

Case Report of Complete Radiological Response of a Thalamic Glioblastoma After Treatment With Proton Therapy Followed by Temozolomide and Tumor-Treating Fields

et al. 2020

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Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. We present a case of a 42-year-old male patient presenting with headache and vomiting. Imaging demonstrated obstructive hydrocephalus and a ring-enhancing lesion in the right posterior thalamus. After endoscopic third ventriculostomy and stereotactic biopsy, the histopathologic diagnosis of a malignant glioma was confirmed by DNA methylation array as GBM isocitrate dehydrogenase wild type. The patient was treated with combined treatment of chemoradiation with temozolomide (TMZ) including proton boost, TMZ maintenance, and tumor-treating fields. In this case report, complete radiological response was observed 1 year after the end of radiation therapy.

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“…A total of N ¼ 340 patients who received TTFields as part of the EF-14 trial were included in the study. Realistic head models of the patients were derived from T1-contrast-enhanced images captured at baseline using a previously described method [24]. The transducer array layout on each patient was obtained from EF-14 records, and average usage and average electrical current delivered to the patient during the first 6 months of treatment were derived from log files of the TTFields devices used by patients.…”

Section: An Outline For Ttfields Dosimetry and Treatmentmentioning

confidence: 99%

“…In order to properly perform numerical simulations of TTFields delivery, it is necessary to create accurate computational models that are patient-specific [11,12,[24][25][26]. This involves creating a 3D volume representing the patient, in which dielectric properties (primarily conductivity) are assigned to each voxel.…”

Section: Patient-specific Model Creationmentioning

confidence: 99%

Tumor-Treating Fields at EMBC 2019: A Roadmap to Developing a Framework for TTFields Dosimetry and Treatment Planning

Bomzon¹,

Wenger²,

Proescholdt

et al. 2020

Brain and Human Body Modeling 2020

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Tumor Treating Fields (TTFields) are electric fields known to exert an anti-mitotic effect on cancerous tumors. TTFields have been approved for the treatment of glioblastoma and malignant pleural mesothelioma. Recent studies have shown a correlation between TTFields doses delivered to the tumor bed and patient survival. These findings suggest that patient outcome could be significantly improved with rigorous treatment planning, in which numerical simulations are used to plan treatment in order to optimize delivery of TTFields to the tumor bed.Performing such adaptive planning in a practical and meaningful manner requires a rigorous and scientifically proven framework defining TTFields dose and showing how dose distribution influences disease progression in different malignancies (TTFields dosimetry). At EMBC 2019, several talks discussing key components related to TTFields dosimetry and treatment planning were presented. Here we provide a short overview of this work and discuss how it sets the foundations for the emerging field of TTFields dosimetry and treatment planning.

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Investigating the Connection Between Tumor-Treating Fields Distribution in the Brain and Glioblastoma Patient Outcomes. A Simulation-Based Study Utilizing a Novel Model Creation Technique

Cited by 5 publications

References 24 publications

Electrotherapies for Glioblastoma

Electrotherapies for Glioblastoma

Case Report of Complete Radiological Response of a Thalamic Glioblastoma After Treatment With Proton Therapy Followed by Temozolomide and Tumor-Treating Fields

Tumor-Treating Fields at EMBC 2019: A Roadmap to Developing a Framework for TTFields Dosimetry and Treatment Planning

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