Temperature control in TTFields therapy of GBM: impact on the duty cycle and tissue temperature

Gentilal, Nichal; Salvador, Ricardo; Miranda, Pedro C.

doi:10.1088/1361-6560/ab5323

Cited by 16 publications

(11 citation statements)

References 45 publications

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“…It is worth noting that there was an observed heating of the phantom during the water phantom measurements that appear to be consistent with Joule heating. In a clinical study, 10% to 17% of patients felt a heat sensation, 27 indicating that hyperthermia could potentially be another synergistic effect of the simultaneous therapies, [27][28][29][30] although this was superficial heating and presumed not to be heating of the deep tissue. This phenomenon is being studied in greater detail in our upcoming work, which will also account for inherent temperature regulation within a patient.…”

Section: Discussionmentioning

confidence: 99%

Targeting Accuracy Considerations for Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy

Biswas

Kapitanova

Divekar³

et al. 2021

Technol Cancer Res Treat

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Purpose: Tumor treating fields (TTFields) is a novel antimitotic treatment that was first proven effective for glioblastoma multiforme, now with trials for several extracranial indications underway. Several studies focused on concurrent TTFields therapy with radiation in the same time period, but were not given simultaneously. This study evaluates the targeting accuracy of simultaneous radiation therapy while TTFields arrays are in place and powered on, ensuring that radiation does not interfere with TTFields and TTFields does not interfere with radiation. This is one of several options to enable TTFields to begin several weeks sooner, and opens potential for synergistic effects of combined therapy. Methods: TTFields arrays were attached to a warm saline water bath and salt was added until the TTFields generator reached the maximal 2000 mA peak-to-peak current. A ball cube phantom containing 2 orthogonal films surrounded by fiducials was placed in the water phantom, CT scanned, and a radiation treatment plan with 58 isocentric beams was created using a 3 cm circular collimator. Fiducial tracking was used to deliver radiation, the films were scanned, and end-to-end targeting error was measured with vendor-supplied software. In addition, radiation effects on electric fields generated by the TTFields system were assessed by examining logfiles generated from the field generator. Results: With TTFields arrays in place and powered on, the robotic radiosurgery system achieved a final targeting result of 0.47 mm, which was well within the submillimeter specification. No discernible effects on TTFields current output beyond 0.3% were observed in the logfiles when the radiation beam pulsed on and off. Conclusion: A robotic radiosurgery system was used to verify that radiation targeting was not adversely affected when the TTFields arrays were in place and the TTFields delivery device was powered on. In addition, this study verified that radiation delivered simultaneously with TTFields did not interfere with the generation of the electric fields.

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Section: Discussionmentioning

confidence: 99%

Targeting Accuracy Considerations for Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy

Biswas

Kapitanova

Divekar³

et al. 2021

Technol Cancer Res Treat

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“…The values assigned to each tissue and material were chosen after an extensive literature review. Additional details about these values and how the studies were performed can be found in [31].…”

Section: Simulations' Conditionsmentioning

confidence: 99%

“…In our first work [31], we predicted the thermal impact of TTFields and quantified the duty cycle of Optune. We defined the latter as the time that each configuration is on divided by the maximum time it could be delivering the fields and assumed that there was a complete current shutdown whenever the average temperature of any transducer reached a cutoff temperature.…”

Section: Duty Cycle and Effective Electric Field At The Tumormentioning

confidence: 99%

“…Additionally, because we only simulated the first 6 min of therapy, we assumed that the temperature at the last time step would remain the same to calculate the CEM 43 C for a typical treatment day (18 h). This approach is feasible because the temperature in each tissue had practically reached a steady-state distribution [31].…”

Section: Prediction Of the Thermal Impactmentioning

confidence: 99%

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A Thermal Study of Tumor-Treating Fields for Glioblastoma Therapy

Gentilal

Salvador²,

Miranda

2020

Brain and Human Body Modeling 2020

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Tumor-treating fields (TTFields) is an antimitotic cancer treatment technique used for glioblastoma multiforme (GBM) and malignant pleural mesothelioma. Although the frequency used is not as high as in hyperthermia, temperature increases due to the Joule effect might be meaningful given the necessary time that these fields should be applied for. Post hoc analysis of the EF-11 clinical trial showed higher median overall survival in patients whose compliance was at least 18 h per day. To quantify these temperature increases and predict the thermal impact of TTFields delivery to the head, we used a realistic model created from MR images segmented in five tissues: scalp, skull, CSF, gray matter (GM), and white matter (WM). Through COMSOL Multiphysics, we solved Laplace’s equation for the electric field and Pennes’ equation for the temperature distribution. To mimic the therapy as realistically as possible, we also considered complete current shutdown whenever any transducer reached 41 °C to allow transducers and tissues’ temperature to decrease. Our results indicate an intermittent operation of Optune due to this necessary current shutdown. Localized temperature increases were seen, especially underneath the regions where the transducers were placed. Maximum temperature values were around 41.5 °C on the scalp and 38 °C on the brain. According to the literature, significant thermal impact is only predicted for the brain where the rise in temperature may lead to an increased BBB permeability and variation in the blood flow and neurotransmitter concentration. Additionally, our results showed that if the injected current is reduced by around 25% compared to Optune’s standard way of operating, then uninterrupted treatment might be attainable. These predictions might be used to improve TTFields delivery in real patients and to increase awareness regarding possible thermal effects not yet reported elsewhere.

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“…The temperature variations that occur during TTFields therapy were first investigated by Gentilal et al ( 2019 ) through in-silico studies. In that work, it was seen that, in each tissue, the temperature increased mainly underneath the regions where the arrays were placed, and they were very superficial.…”

Section: Introductionmentioning

confidence: 99%

Temperature and Impedance Variations During Tumor Treating Fields (TTFields) Treatment

Gentilal

Abend²,

Naveh³

et al. 2022

Front. Hum. Neurosci.

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Tumor Treating Fields (TTFields) is an FDA-approved cancer treatment technique used for glioblastoma multiforme (GBM). It consists in the application of alternating (100–500 kHz) and low-intensity (1–3 V/cm) electric fields (EFs) to interfere with the mitotic process of tumoral cells. In patients, these fields are applied via transducer arrays strategically positioned on the scalp using the NovoTAL™ system. It is recommended that the patient stays under the application of these fields for as long as possible. Inevitably, the temperature of the scalp increases because of the Joule effect, and it will remain above basal values for most part of the day. Furthermore, it is also known that the impedance of the head changes throughout treatment and that it might also play a role in the temperature variations. The goals of this work were to investigate how to realistically account for these increases and to quantify their impact in the choice of optimal arrays positions using a realistic head model with arrays positions obtained through NovoTAL™. We also studied the impedance variations based on the log files of patients who participated in the EF-14 clinical trial. Our computational results indicated that the layouts in which the arrays were very close to each other led to the appearance of a temperature hotspot that limited how much current could be injected which could consequently reduce treatment efficacy. Based on these data, we suggest that the arrays should be placed at least 1 cm apart from each other. The analysis of the impedance showed that the variations seen during treatment could be explained by three main factors: slow and long-term variations, array placement, and circadian rhythm. Our work indicates that both the temperature and impedance variations should be accounted for to improve the accuracy of computational results when investigating TTFields.

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Temperature control in TTFields therapy of GBM: impact on the duty cycle and tissue temperature

Cited by 16 publications

References 45 publications

Targeting Accuracy Considerations for Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy

Targeting Accuracy Considerations for Simultaneous Tumor Treating Fields Antimitotic Therapy During Robotic Hypofractionated Radiation Therapy

A Thermal Study of Tumor-Treating Fields for Glioblastoma Therapy

Temperature and Impedance Variations During Tumor Treating Fields (TTFields) Treatment

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