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

Overview

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.

Protocol

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).

1. 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:
   1. 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.
   2. Use a charged battery to power the electric field generator or "Device", which in turn delivers the electric fields to the transducer arrays.
   3. Plug the battery in through its connecter to a socket labeled "DC IN" on the front panel of the device. Ensure that the arrows on the battery connector are facing up towards the "DC IN" sign while plugging in the connector.
   4. Turn on the power button after the battery is plugged into the device.
   5. 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 "N1") on the connection cable box (see Figure 1).
   6. Connect the coiled connection cable to the box on one end and the device to the other end.
   7. Connect the battery to the device to provide the necessary power for the device to generate alternating electric fields.
   8. Connect the device to the connection cable and box using the color-coded sockets that match color coded cables attached to the transducer arrays.
2. Applying the transducer arrays to the scalp
   1. 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.
   2. 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' magnetic resonance imaging (MRI) to generate the optimal electric field intensity at the site of the tumor to achieve maximal results.
   3. 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.
   4. Snap the plugs into the connector.
   5. 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).
   6. Plug the array cables into the color-matched connection cable and box as mentioned above (see section 1.1).
   7. Turn on the power switch on the device once the arrays are in place and the system is fully connected.
   8. 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'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.

Representative Results

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.

Materials

Name	Company	Catalog Number	Comments
NovoTTF-100A System	Novocure Limited		Portsmouth, NH
Bevacizumab (Avastin)	Genetech Corporation		South San Francisco, USA