Insights from Computer Modeling: Analysis of Physical Characteristics of Glioblastoma in Patients Treated with Tumor-Treating Fields

Abstract

Tumor-treating fields (TTFields) are intermediate frequency electric fields at 200 kHz (kHz or 10 3 Hz) that have anti-tumor activity. In a pivotal phase III clinical trial for newly diagnosed glioblastoma patients, the addition of TTFields to maintenance temozolomide, which was administered after initial radiotherapy and concurrent daily temozolomide, was found to improve both progression-free survival and overall survival when compared to those who only received maintenance temozolomide [1, 2]. This positive trial result led the US FDA to approve the use of TTFields for these patients and the incorporation of this therapy into the National Comprehensive Cancer Network (NCCN) guidelines for malignant gliomas [3].

Guidelines for Burr Hole Surgery in Combination With Tumor Treating Fields for Glioblastoma: A Computational Study on Dose Optimization and Array Layout Planning

“…The “dose” of TTFields was calculated as the field intensity, i.e., the Euclidean norm of the field vector, in concordance with many previous studies (Miranda et al, 2014 ; Wenger et al, 2015a , b ; Korshoej et al, 2017 , 2018 ; Lok et al, 2019 , 2020 ). It is well-described that other factors, such as treatment exposure time, frequency, and field orientation are also important determinants of effective TTFields dose (Kirson et al, 2004 ; Korshoej and Thielscher, 2018a ; Toms et al, 2019 ), however, given the rationale of skull remodeling surgery, we only considered field intensity, which was the modified parameter.…”

Tumor treating fields suppress tumor cell growth and neurologic decline in models of spinal metastases

“…While the applicability of TTFields has been explored with both preclinical experiments and simulation studies across various tumors (31,32,(40)(41)(42)(43), the greatest clinical advances have been in glioblastoma (20,21) and malignant pleural mesothelioma (19) for which use of TTFields has been FDA approved. With those encouraging results, further studies are underway investigating TTFields in other solid organ carcinomas (e.g., pulmonary, hepatic, ovarian, pancreatic, and gastric).…”

“…The conductivity of tissue is inversely proportional to the retention of the electrical field (40). In order to apply this concept to spinal metastases, we leveraged the understanding of TTFields distribution for the treatment of glioblastoma, in which the electrical properties of the tissue layers overlying the parenchymal tumor influence the intensity of TTFields at the target tumor.…”

“…Simulation studies demonstrate increased intensity of electrical fields inside brain tumors when strategic bone resections are performed to mitigate against the attenuation of TTFields intensity caused by the skull (31,44). Second, the brain is surrounded by cerebrospinal fluid, which is more conductive than the underlying gray matter, thereby creating a shunt effect that decreases the deposition of TTFields intensity into the brain parenchyma and intraparenchymal tumor (40).…”

Ion channels as molecular targets of glioblastoma electrotherapy

“…For glioblastoma, alternating electric fields with a frequency of 200 kHz are applied capacitively via ceramic electrode arrays placed onto the shaved scalp of the patient. Modeling the field intensity with due consideration of pre-specified conductivity and relative permittivity of skin, skull and brain tissues has predicted electric field strengths in the range of 1-3 V/cm in the brain tumor (Lok et al, 2019). Table 1 gives an overview of all completed clinical trials of TTFields applications in different cancer entities as of December 12 th , 2022.…”