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All procedures involving human participants have been performed in compliance with the institutional, national, and international guidelines for human welfare and have been reviewed by the local institutional review board.
1. Application of the TTF System
NOTE: The system consists of the following components: an electric field generator (the Device), a connection cable and box, a portable battery(s), a charger for portable batteries, a plug-in power supply, and a set of Transducer arrays (4) (Figure 1).
<ol>
	<li>Assembling the system 
	NOTE: For the electric field generator to deliver the electric fields to the tumor mass, the components must be interconnected in the following manner:
	<ol>
		<li>Charge the battery(s) using the battery charger by connecting its power cord to a standard wall outlet and switch on the power button on the back of the charger. 
		NOTE: A battery rack can hold up to 3 batteries at a time.</li>
		<li>Use a charged battery to power the electric field generator or &#34;Device&#34;, which in turn delivers the electric fields to the transducer arrays.</li>
		<li>Plug the battery in through its connecter to a socket labeled &#34;DC IN&#34;&#160;on the front panel of the device. Ensure that the arrows on the battery connector are facing up towards the &#34;DC IN&#34;&#160;sign while plugging in the connector.</li>
		<li>Turn on the power button after the battery is plugged into the device.</li>
		<li>Connect each of the four transducer array connectors, using the color-coded plugs, to the matching color-coded socket on the connection cable box. 
		NOTE: For example, the transducer array connector with the red ring is plugged into the red socket (labeled &#34;N1&#34;) on the connection cable box (see Figure 1).</li>
		<li>Connect the coiled connection cable to the box on one end and the device to the other end.</li>
		<li>Connect the battery to the device to provide the necessary power for the device to generate alternating electric fields.</li>
		<li>Connect the device to the connection cable and box using the color-coded sockets that match color coded cables attached to the transducer arrays.</li>
	</ol>
	</li>
	<li>Applying the transducer arrays to the scalp
	<ol>
		<li>Prepare the patients head for array application. Shave the entire scalp using an electric shaver. Ensure no stubble remains and wipe the scalp with 70% medical-grade alcohol. 
		NOTE: An over-the-counter hydrocortisone (steroid) cream may be used if the scalp is irritated.</li>
		<li>Lay out the transducer arrays according to a pre-determined specific array layout on a patients clean and shaven scalp. 
		NOTE: The array layout is calculated using special software that utilizes head and tumor measurements from the patients&#39;&#160;magnetic resonance imaging (MRI) to generate the optimal electric field intensity at the site of the tumor to achieve maximal results.</li>
		<li>Peel off the envelopes and remove the arrays, then apply to the scalp according to specific array layout color scheme. 
		NOTE: The transducer array locations and colors are as follows: front (blue), back (red), right (yellow), left (white) according to where they are placed on the scalp. 
		NOTE: Transducer arrays are supplied in clear sterile envelopes.</li>
		<li>Snap the plugs into the connector.</li>
		<li>Place the color-coded plugs on the transducer array connectors of the four transducer arrays. 
		NOTE: These colors match the color coding of the transducer array placement diagram that has been generated for each patient with the help of special software (step 1.2.2).</li>
		<li>Plug the array cables into the color-matched connection cable and box as mentioned above (see section 1.1).</li>
		<li>Turn on the power switch on the device once the arrays are in place and the system is fully connected.</li>
		<li>Switch on the TTF Field button and the system is now ready for electric field delivery. 
		NOTE: There is no standard duration for continuation of TTF Therapy, however, in the author&#39;s opinion TTF Therapy can be continued until the time of clinical and/or radiographic progression of the disease or development of unacceptable toxicity. To achieve an optimal response, TTF Therapy should be used on a continuous basis for a minimum of 18 hr a day. Treatment duration of less than 18 hr per day has been associated with suboptimal response. A monthly compliance log can be downloaded from the device software by a Novocure technician.</li>
	</ol>
	</li>
</ol>

<table><tbody><tr><td>NovoTTF-100A System</td><td>Novocure Limited</td><td></td><td>Portsmouth, NH</td></tr><tr><td>Bevacizumab (Avastin)</td><td>Genetech Corporation</td><td></td><td>South San Francisco, USA</td></tr></tbody></table>

tumor treating fields application in human brain tumor models: a non-invasive technique to deliver alternating electric fields to human brain for treating brain tumor

Source: Omar, A. I. <a href="https://www.jove.com/v/51638/tumor-treating-field-therapy-combination-with-bevacizumab-for">Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma.</a> J. Vis. Exp. (2014)
This video demonstrates the application of Tumor Treating Fields or TTFields in human brain tumor models. This non-invasive technique delivers low-intensity alternating electric fields directly to the brain, resulting in inhibition of cell division and subsequent apoptosis.

<img alt="Figure 1" src="/files/ftp_upload/20627/20627_Figure1.jpg" /> 
Figure 1: The NovoTTF-100A System components and assembly. (A) The transducer arrays are shown as they are applied to the scalp (1) with the array cables connected to the color-coded sockets on the connection cable and box (2). The box in turn is connected to the electric field generator with the battery as the power supply (3). (B) Transducer arrays showing ceramic discs and connector.

Tumor Treating Fields Application in Human Brain Tumor Models: A Non-invasive Technique to Deliver Alternating Electric Fields to Human Brain for Treating Brain Tumor

Source: Omar, A. I. Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma. J. Vis. Exp. (2014)
This ...

Tumor Treating Fields or TTFields is a non-invasive therapy that uses low-intensity alternating electric fields to disrupt cancer cell division.
To simulate the delivery of TTFields to a brain tumor patient, first, shave the patient&#39;s entire scalp and sterilize it to prepare for TTFields-Transducer arrays placement.
Then, using the patient&#39;s MRI measurements, configure the transducer arrays placement.
Secure the arrays over the predetermined positions on the scalp with adhesive bandages.
Next, connect the color-coded cables attached to the transducer arrays to the matching color-coded sockets on the connection cable box.
Additionally, connect the cable box assembly to the battery-powered TTFields generator, which would deliver electric fields to the transducer arrays.
Now, switch on the power to apply optimal electric field intensity at the tumor site for the desired duration.
In a dividing cancer cell, exposure to low-intensity, intermediate frequency alternating electric fields causes the electrically charged proteins such as tubulin and septin to align in the direction of the applied field.
This alignment disrupts microtubule spindle formation and localization of septin fibers, which are the key mitotic processes.
As a result, mitosis is inhibited, ultimately leading to cell death.

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Research

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Cancer Research

Cancers of the Nervous System

In vivo studies

1.2K Views. Source: Omar, A. I. Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma. J. Vis. Exp. (2014) This video demonstrates the application of Tumor Treating Fields or TTFields in human brain tumor models. This non-invasive technique delivers low-intensity alternating electric fields directly to the brain, resulting in inhibition of cell division and subsequent apoptosis. 

Video: Tumor Treating Fields Application in Human Brain Tumor Models: A Non-invasive Technique to Deliver Alternating Electric Fields to Human Brain for Treating Brain Tumor - Concept

Determining the Optimal Inhibitory Frequency for Cancerous Cells Using Tumor Treating Fields (TTFields)

Tumor Treating Fields (TTFields) are an effective treatment modality delivered via the continuous, noninvasive application of low-intensity (1-3 V/cm), alternating electric fields in the frequency range of several hundred kHz. The study of TTFields in tissue culture is carried out using the TTFields in vitro application system, which allows for the application of electric fields of varying frequencies and intensities to ceramic Petri dishes with a high dielectric constant (&#400; &#62; 5,000). Cancerous cell lines plated on coverslips at the bottom of the ceramic Petri dishes are subjected to TTFields delivered in two orthogonal directions at various frequencies to facilitate treatment outcome tests, such as cell counts and clonogenic assays. The results presented in this report demonstrate that the optimal frequency of the TTFields with respect to both cell counts and clonogenic assays is 200 kHz for both ovarian and glioma cells.

Determining the Optimal Inhibitory Frequency for Cancerous Cells Using Tumor Treating Fields TTFields

Tumor Treating Fields (TTFields) are an effective anti-tumor treatment modality delivered via the continuous, noninvasive application of low-intensity, intermediate-frequency, alternating electric fields. TTFields application to cell lines using a TTFields in vitro application system allows for the determination of the optimal frequency that leads to the highest reduction in cell counts.

Tumor Treating Fields (TTFields) are an effective treatment modality delivered via the continuous, noninvasive application of low-intensity (1-3 V/cm), ...

JoVE Journal

The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma

Glioblastoma is the most common and lethal form of brain cancer, with a median survival of 15 months after diagnosis and a 5 year survival rate of only 5% with current standard of care. Tumors often recur within 9 months following initial surgery, radiation and chemotherapy, at which point treatment options become limited. This highlights the pressing need for the development of better therapeutics to prolong survival and increase the quality of life for these patients.
Tumor Treating Fields (TTFields) therapy was developed to take advantage of the effect of low frequency alternating electrical fields on cells for cancer therapy. TTFields have been demonstrated to disrupt cells during mitosis and slow tumor growth. There is also growing evidence that they act through stimulating immune responses within exposed tumors. The advantages of TTFields therapy include its noninvasive approach and increased quality of life compared to other treatment modalities such as cytotoxic chemotherapies. The Food and Drug Administration approved TTFields therapy for the treatment of recurrent glioblastoma in 2011 and for newly diagnosed glioblastoma in 2015. We report on the effects of TTFields during mitosis, the results of electric fields modeling, and proper transducer array placement. Our protocol outlines the clinical application of TTFields on a patient post-surgery, using the second-generation device.

Glioblastoma is the most common and aggressive primary brain malignancy in adults, with most tumors recurring after initial treatment. Tumor Treating Fields (TTFields) therapy is the newest treatment modality for glioblastoma. Here, we describe the proper application of TTFields-transducer arrays on patients and discuss theory and aspects of treatment.

Glioblastoma is the most common and lethal form of brain cancer, with a median survival of 15 months after diagnosis and a 5 year survival rate of only 5% ...

Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy

The prognosis of patients with metastatic cancers has improved in the past decades due to effective chemotherapy and oligometastatic surgery. For inoperable patients, local ablation therapies, such as stereotactic body radiotherapy (SBRT), can provide effective local tumor control with minimal toxicity. Because of its high precision and accuracy, SBRT delivers a higher radiation dose per fraction, is more effective, and targets smaller irradiation volumes than does conventional radiotherapy. In addition, steep dose gradients from target lesions to surrounding normal tissues are achieved using SBRT; thus, SBRT provides more effective tumor control and exhibits fewer side effects than conventional radiotherapy. The use of SBRT is prevalent for treating intracranial lesions (known as stereotactic radiosurgery); however, it is now also used for treating spinal and adrenal metastases. Because of advancements in image-guided assistance and respiratory motion management, several studies have investigated the use of SBRT for treating lung or liver tumors, which move as a patient breathes. The results of these studies have suggested that SBRT favorably controls tumors in the case of moving lesions.
Four-dimensional computed tomography (4D-CT) with an abdominal compressor (AC) is clinically convenient for effective respiratory motion management. Because this method is noninvasive and allows free breathing, its use reduces complications. Furthermore, patients consider this method convenient. Moreover, it is considered more efficient than other methods of respiratory motion management by physicians and therapists. The use of 4D-CT with an AC for treating pulmonary lesions has also been widely investigated, and the technique is gaining acceptance for treating hepatic lesions. However, the protocols for using 4D-CT with an AC for treating hepatic lesions are different from those used for treating pulmonary lesions. In this article, we describe a new protocol for SBRT with 4D-CT and an AC for treating liver metastases.

Stereotactic body radiotherapy (SBRT) requires rigorous accuracy and precision for delivering high radiation doses per fraction to small treatment volumes to improve tumor control and simultaneously reduce toxicity. Herein, we present a noninvasive and clinically convenient respiratory motion management protocol for SBRT for liver metastases.

Tumor Treating Fields Application in Human Brain Tumor Models: A Non-invasive Technique to Deliver Alternating Electric Fields to Human Brain for Treating Brain Tumor

Transcript

Tumor Treating Fields Application in Human Brain Tumor Models: A Non-invasive Technique to Deliver Alternating Electric Fields to Human Brain for Treating Brain Tumor

Determining the Optimal Inhibitory Frequency for Cancerous Cells Using Tumor Treating Fields (TTFields)

The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma

Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy