TW202216238A - Delivering tumor treating fields (ttfields) to the neck - Google Patents

Abstract

Tumor Treating Fields (TTFields) can be used to treat tumors (and/or prevent metastases) in or near a person's neck by affixing a first transducer array (i.e., a set of electrode elements) to the person's head and affixing a second transducer array to the person's chest. Subsequently, an AC voltage at a desired frequency (e.g., 100-300 kHz) is applied between the first transducer array and the second transducer array. This induces an electric field that is strong enough to be effective (e.g., greater than 1 V/cm) in most of the person's neck. In some embodiments, the center of the first transducer array is positioned on the vertex of the head or on an upper surface of the person's head. In some embodiments, the second set of electrode elements is positioned immediately below the base of the neck.

Description

Delivery of tumor treatment fields (TTFIELDS) to the neck

This application relates to methods for delivering Tumor Treating Fields (TTFIELDS) to the neck.

TTFields are low-intensity (eg, 1 to 4 V/cm) alternating electric fields in the mid-frequency range (eg, 100 to 300 kHz) that can be used to treat tumors, as incorporated herein by reference in its entirety, U.S. No. 7,565,205 described in the patent. TTFields therapy is an approved monotherapy for recurrent glioblastoma (GBM) and an approved combination therapy in combination with chemotherapy for newly diagnosed GBM patients. TTFields may also be used to treat tumors in other parts of an individual's body (eg, lung, ovary, pancreas). TTFields are non-invasively induced into the region of interest by sensor arrays (ie, arrays of capacitively coupled electrode elements) that are placed directly on the patient's body (eg, using the Novocure Optune™ system), and An AC voltage is applied between the sensor arrays.

In the case of GBM, a conventional method of positioning sensor arrays is to position a first pair of sensor arrays on the front and back sides of the head, and a second pair of sensor arrays on the right and left sides of the head. In the case of mesothelioma, a conventional method for positioning sensor arrays is to position a first pair of sensor arrays on the front and back sides of the body, and a second pair of sensor arrays on the right and left sides of the body. The AC voltage generator applies an AC voltage (eg, 200 kHz in the case of GBM, or 150 kHz in the case of mesothelioma) between the first pair of sensor arrays for a first time interval (eg, one second), which An electric field is generated with field lines that generally run in the front-to-rear direction. The AC voltage generator then applies an AC voltage of the same frequency between the second pair of sensor arrays for a second time interval (eg, one second), which produces an electric field having field lines that generally run in the left-right direction. The system then repeats this two-step sequence for the duration of the treatment.

One aspect of the present invention pertains to a first method of treating a tumor in or near the neck of a subject or preventing metastasis. The first method includes: attaching a first set of electrode elements having a first center of mass to the head of the individual, wherein the first center of mass is positioned on the head of the individual; attaching a second set of electrode elements to the chest of the individual; and applying an alternating voltage between the first set of electrode elements and the second set of electrode elements. The applying is performed after attaching the first set of electrode elements and the second set of electrode elements.

In some cases of the first method, the electrode elements in the first set of electrode elements and the second set of electrode elements are capacitively coupled. In some cases of the first method, the alternating voltage applied between the first set of electrode elements and the second set of electrode elements has a frequency between 100 kHz and 300 kHz. In some cases of the first method, the first set of electrode elements includes a plurality of electrode elements wired in parallel, and wherein the second set of electrode elements includes a plurality of electrode elements wired in parallel. In some cases of the first method, the first center of mass is positioned overhead. In some instances of the first method, the first center of mass is positioned on the upper surface of the individual's head. In some cases of the first method, the second set of electrode elements is positioned immediately below the root of the neck.

Another aspect of the invention relates to a second method of planning the positioning of a first set of electrode elements and a second set of electrode elements on the body of an individual. The second method comprises: obtaining a 3D model of the electrical conductivity or resistivity of an anatomical volume within the individual's body located in or near the neck of the individual at a given frequency; and identifying the target tissue in the anatomy position within the volume. The second method also includes: the 3D model of the conductivity or the resistivity based on respective ones of the plurality of layouts of the first set of electrode elements and the second set of electrode elements, and the identified location of the target tissue , analyzing the electric field associated with the plurality of layouts; and selecting one of the plurality of layouts based on a result of the analysis. The first set of electrode elements has a first center of mass. In each of the plurality of layouts, (a) the first set of electrode elements is positioned on the individual's head, wherein the first centroid is positioned on the individual's head, and (b) the A second set of electrode elements is positioned on the individual's chest.

In some cases of the second method, the first center of mass is positioned overhead. In some instances of the second method, the first centroid is positioned on the upper surface of the individual's head. In some instances of the second method, the second set of electrode elements is positioned immediately below the root of the neck. In some cases of the second method, the given frequency is between 100 and 300 kHz. In some cases of the second method, the 3D model of the conductivity or the resistivity is a 3D model of the conductivity.

Some aspects of the second method further include the steps of: attaching the first set of electrode elements and the second set of electrode elements to the individual's body at locations corresponding to the selected layout; and after the attaching step An electrical signal is applied between the first set of electrode elements and the second set of electrode elements to impose an electric field in the target tissue.

Another aspect of the invention pertains to a third method of treating a tumor in or near the neck of a subject or preventing metastasis. The third method includes: attaching a first set of electrode elements to the back of the neck of the individual; attaching a second set of electrode elements to the chest of the individual; and between the first set of electrode elements and the second electrode An alternating voltage is applied between sets of components. The applying is performed after attaching the first set of electrode elements and the second set of electrode elements.

In some cases of the third method, the electrode elements in the first set of electrode elements and the second set of electrode elements are capacitively coupled. In some cases of the third method, the alternating voltage applied between the first set of electrode elements and the second set of electrode elements has a frequency between 100 kHz and 300 kHz. In some cases of the third method, the first set of electrode elements includes a plurality of electrode elements wired in parallel, and wherein the second set of electrode elements includes a plurality of electrode elements wired in parallel. In some instances of the third method, the second set of electrode elements is positioned immediately below the root of the neck.

This application describes a variety of sensor array layouts and can be used to treat cancer in the region of interest (ROI) depicted in FIGS. 1A and 1B . This ROI is around the larynx and includes all tissues except the spine, intervertebral discs, and internal air.

In the case of treating brain tumors, one practical approach is to locate one pair of sensor arrays on the anterior and posterior sides of the head and another pair on the left and right sides of the head. However, in the case of treating tumors in the neck, positioning the sensor array on all four sides of the neck can cause discomfort and limit patient movement. The sensor array layout described in this application provides improved comfort and range of motion over conventional four-sided methods.

Preclinical experiments have shown that for TTFields to be therapeutically effective, the field strength should exceed a threshold value of approximately 1 V/cm. But in the case of treating cancers in the ROIs depicted in Figures 1A and 1B (eg, upper neck cancers, such as head and neck squamous cell carcinoma (SCC) and some cases of esophageal SCC and adenocarcinoma), used to locate the sensor Many layouts of arrays do not provide desired levels of field strength.

2A and 2B depict an example of a layout of a pair of sensor arrays that provides a sufficiently high field strength in a region of interest. In this layout, a sensor array comprising 13 circular electrode elements (hereinafter referred to as discs) is positioned so that its center of mass is on the top of the individual's head and the upper surface of the head, and comprises between 13 discs Another sensor array is positioned on the upper chest and oriented vertically. Grayscale plots of the resulting field strength for this layout are depicted in Figures 2C and 2D. (Figure 8 depicts the scale of all grayscale maps in this application.) For this layout, the average intensity is 3.4 V/cm, the median field intensity is 3.41 V/cm, and 99.27% of the region of interest has about 1 V /cm strength.

3A and 3B depict an example of another layout of a pair of sensor arrays that provides a sufficiently high field strength in a region of interest. In this arrangement, one sensor array comprising 13 circular discs is positioned on the upper back of the individual's head, and another sensor array comprising 13 discs is positioned on the upper chest and oriented vertically. Grayscale plots of the resulting field strength for this layout are depicted in Figures 3C and 3D. For this layout, the average intensity was 3.22 V/cm, the median field intensity was 3.25 V/cm, and 99.07% of the region of interest had an intensity of about 1 V/cm.

4A and 4B depict an example of another layout of a pair of sensor arrays that provides a sufficiently high field strength in the region of interest. In this arrangement, one sensor array comprising 13 circular discs is positioned on the back of the individual's neck, and another sensor array comprising 13 discs is positioned on the upper chest and oriented vertically. Grayscale plots of the resulting field strength for this layout are depicted in Figures 4C and 4D. For this layout, the average intensity was 1.47 V/cm, the median field intensity was 1.39 V/cm, and 73.22% of the region of interest had an intensity of about 1 V/cm. It is worth noting that the results of this layout are not as good as the layouts depicted in Figures 2 and 3 .

5A depicts an example of another layout of a pair of sensor arrays that provides a sufficiently high field strength in the region of interest. In this layout, one sensor array comprising 9 circular discs is positioned on the top front side of the individual's head, and another sensor array comprising 9 discs is positioned on the upper chest and oriented horizontally. Grayscale plots of the resulting field strength for this layout are depicted in Figures 5B and 5C. For this layout, the average intensity was 2.55 V/cm, the median field intensity was 2.55 V/cm, and 98.79% of the region of interest had an intensity of about 1 V/cm.

Compared to the layouts described above, other layouts do not provide sufficiently high field strengths in the region of interest. For example, in the Figure 6A layout, one sensor array comprising 9 circular discs is positioned on the left side of the individual's neck, and another sensor array comprising 9 discs is positioned at shoulder level on the individual's spinal deviation. right. Grayscale plots of the resulting field strength for this layout are depicted in Figures 6B and 6C. For this layout, the average intensity was 1.83 V/cm, the median field intensity was 1.32 V/cm, and 64.83% of the region of interest had an intensity of about 1 V/cm. It should be noted that even though these numerical results do not appear to be bad, these numerical results are misleading because most of the energy is dissipated on the skin, as clearly seen in Figures 6B and 6C.

In the Figure 7A arrangement, one sensor array comprising 9 circular discs is positioned on the right side of the subject's neck, and another sensor array comprising 9 discs is positioned on the left side of the subject's spine at shoulder level. Grayscale plots of the resulting field strength for this layout are depicted in Figures 7B and 7C. For this layout, the average intensity was 1.67 V/cm, the median field intensity was 1.21 V/cm, and 60.10% of the region of interest had an intensity of about 1 V/cm. Again, even though these numerical results do not appear to be bad, these numerical results are misleading because most of the energy is dissipated on the skin, as clearly seen in Figures 7B and 7C.

It should be noted that all field strengths depicted and described herein were generated by ZMT (Zürich) running simulations at 150 kHz using the DUKE model. The simulated layout uses a sensor array of 9 disks or 13 disks. The simulation of 9 platters was normalized to 1 A current, and the simulation of 13 platters was normalized to 1.3 A current. The results showed that placing one sensor array on the upper scalp and the other on the upper chest delivered no less than 1.47 V/cm and up to 3.4 V/cm to the area of interest. This result holds when using a 9-disk array or a 13-disk array. And as the upper array moves down, the field strength decreases. This situation is particularly pronounced in the embodiment of FIG. 4 , where the field strength is reduced to less than half of the embodiment of FIG. 2 .

When the sensor array is positioned as described above, the sensor array can use the same configuration for other anatomical locations. An example of a known sensor array is the sensor array used with the Novocure Optune® system. These sensor arrays have flexible backings configured to attach to the body of an individual. Suitable materials for flexible backings include cloth, foam, and soft plastics (eg, similar to corresponding materials used for bandages). A plurality of capacitively coupled electrode elements are positioned on the inner side of the flexible backing, and each of the capacitively coupled electrode elements has an inwardly facing conductive plate with a dielectric layer disposed thereon. Optionally, a temperature sensor, such as a thermistor, may be positioned under each of the electrode elements in a manner similar to conventional arrangements used in the Novocure Optune® system.

A set of conductors is connected to the conductive plates of each of the plurality of capacitively coupled electrode elements. The conductors may be implemented using, for example, discrete wiring or using traces on a flexible circuit. The adhesive layer is configured to hold the portion of the flexible backing covered by any of the electrode elements against the body of the individual.

In the embodiments depicted in Figures 2-5, each sensor array is configured as an array of 9 or 13 individual electrode element disks, and the center of mass of the array coincides with the center of the center disk. However, in alternative embodiments, each sensor array may include a different number (eg, between 4 and 24) of electrode elements. For example, a given sensor array may be configured as a 2x2 array of individual electrode element disks. In this case, the centroid may be in the area between all four platters. In other alternative embodiments, a given set of electrode elements may include only a single electrode element (which may be of any suitable shape, including but not limited to circular and rectangular). In this case, the center of mass will coincide with the center of that single electrode element. It should also be noted that in the embodiments described herein, the upper and lower sensor arrays each use the same number of platters. However, in alternate embodiments, the number of disks on the upper and lower sensor arrays may be different (eg, 9 disks on the upper array and 13 disks on the lower array).

Alternative configurations of sensor arrays may also be used, including, for example, sensor arrays using ceramic elements that are not disc-shaped, and sensor arrays using non-ceramic dielectric materials positioned over a plurality of flat conductors. Examples of the latter include polymer films disposed over pads on printed circuit boards or over flat metal sheets. Sensor arrays using electrode elements other than capacitively coupled can also be used. In this case, each element in the sensor array would be implemented using an area of conductive material configured to be placed against the body of the individual, with no insulating dielectric layer disposed between the conductive element and the body. Other alternative configurations for implementing sensor arrays may also be used, so long as they are (a) capable of delivering TTFields to the individual's body and (b) positioned at the locations specified herein. Optionally, in any of the embodiments described herein, a layer of hydrogel may be disposed between the sensor array and the body of the individual.

For the layouts depicted above with respect to Figures 2-7, the mean intensity, median field intensity, and the percentage of ROIs with intensities above 1 V/cm were determined by the electrode elements within each sensor array as shown in Figure 2 Obtained by simulating the electric field when positioned as depicted in FIG. 7 . It should be noted, however, that the positions of the sensor arrays (and/or the elements within each of those arrays) may differ from the exact positions depicted in their figures, as long as the movement is small enough to make the difference above The anatomical description remains the same. For example, the electrode elements positioned on the head in Figure 3B can be moved up, down, or to either side as long as they remain positioned on the upper back of the individual's head. Similarly, the electrode element positioned on the chest in Figure 3A can be moved up, down, or to either side as long as it remains on the upper chest.

Within this limited range of motion, simulations (eg, finite element simulations) for each individual individual can be used to calculate the resulting electric fields for each combination of positions of the sensor array and selected to provide the best results (eg, with intensities above 1 V/cm) the highest percentage of ROIs) to determine the best location for each of the sensor arrays. An indication of the selected combination is then output to the care provider using, for example, a suitable display or printout. The care provider would then apply the sensor array to the individual's location indicated by the output, connect the set of electrode elements to the AC signal generator 50, and begin TTFields therapy.

Figure 9 depicts one example of using simulation to determine the best location for each of the sensor arrays. First, in step S20, a 3D model of the AC conductivity (at the frequency to be used for TTFields treatment) of the relevant anatomical volume is obtained using any of a variety of methods that will be apparent to those skilled in the relevant art. This model specifies the conductivity of each voxel.

Optimizing the array layout means finding an array layout that optimizes the electric field within the ROI. This optimization can be carried out by performing the following four steps: (S21) identifying the volume within the model targeted by the treatment (target volume); (S22) automatically placing a sensor array on the model and setting boundary conditions; (S23) After the array has been placed on the model and boundary conditions are applied, calculate the electric field generated within the model; and (S24) run an optimization algorithm to find a layout that produces the best electric field distribution within the target volume . A detailed example for implementing one of these four steps is provided below, but alternative methods that will be apparent to those skilled in the relevant art may replace the steps described below.

Step S21 involves locating the target volume within the model (ie, defining the region of interest). The first step in finding a layout that produces the best electric field distribution in the patient is to correctly identify the location and target volume where the electric field will be optimized.

In some embodiments, the target volume will be a Gross Tumor Volume (GTV) or a Clinical Target Volume (CTV). GTV is the approximate extent and location of tumor presentation, while CTV includes tumor presentation (if present) and any other tissue with a presumed tumor. In many cases, the CTV is found by defining the volume containing the GTV and adding a tolerance to the predefined width around the GTV.

To identify GTV or CTV, it may be necessary to identify the volume of the tumor within the MRI image. This can be performed manually by the user, automatically or using semi-automatic methods using user-assisted algorithms. When this task is performed manually, the MRI data can be presented to the user and the user can be asked to delineate the volume of the CTV based on the data. The user may be asked to outline the CTV on the 3D volumetric representation of the MRI, or the user may be given the option to view individual 2D tiles of the data and mark the CTV boundaries on each tile. Once the boundaries have been marked on each tile, the CTV within the anatomical volume (and thus the model) can be found. In this case, the volume marked by the user will correspond to the GTV. In some embodiments, the CTV can then be found by adding a margin of predefined width to the GTV. Similarly, in other embodiments, the user may be required to label the CTV using a similar procedure.

An alternative to the manual method is to use an automatic segmentation algorithm to find the CTV. These algorithms perform automatic segmentation algorithms to identify CTVs using structural MRI data.

Optionally, semi-automatic segmentation of MRI data can be performed. In one example of these methods, the user iteratively provides input to the algorithm (eg, the location of the tumor on the image, roughly marking the boundaries of the tumor, demarcating the boundaries of the region of interest where the tumor is located), the input for the analysis The segment algorithm is then used. The user can then be given the option to refine the segmentation to obtain a better estimate of CTV location and volume in vivo.

Whether automated or semi-automated methods are used, the identified tumor volume will correspond to the GTV, and can then be determined by expanding the GTV volume by a predefined amount (eg, defining the CTV as the volume that includes a 20 mm wide margin around the tumor) Automatically find CTV.

It should be noted that in some cases it may be sufficient for the user to define the region of interest for which he wants to optimize the electric field. This region of interest can be, for example, a square volume, a spherical volume, or a volume of any shape in the anatomical volume containing the tumor. When this method is used, complex algorithms for accurately identifying tumors may not be required.

Step S22 involves automatically calculating the position and orientation of the array on the model for a given iteration. Each sensor array used to deliver TTFields included a collection of ceramic disk electrodes coupled to the patient's body through a layer of medical gel. When the array is placed on a real patient, as the medical gel deforms to match the contours of the human body, the disks are naturally aligned parallel to the skin and make good electrical contact between the array and the skin. However, virtual models are made of rigidly defined geometric structures. Therefore, placing the array on the model requires an accurate method of finding the orientation and profile of the model surface at the location where the array is to be placed and the thickness/geometry of the gel needed to ensure good contact between the model array and the patient model . In order to be able to perform a fully automatic optimization of the field distribution, these calculations must be performed automatically.

Various algorithms can be used to perform this task, and one such algorithm is described in US Pat. No. 10,188,851, which is incorporated herein by reference in its entirety.

Step S23 involves calculating the electric field distribution within the model for a given iteration. Once the model is constructed and the sensor array (ie the electrode array) used to apply the field has been placed on the model, a volume mesh suitable for finite element (FE) method analysis can be generated. Next, boundary conditions can be applied to the model. Examples of boundary conditions that can be used include a Dirichlet boundary condition (constant voltage) for sensor arrays, a Neumann boundary condition (constant current) for sensor arrays, or setting the potential at that boundary A floating potential boundary condition such that the integral of the normal component of the current density equals the specified magnitude. The model can then be solved using a suitable finite element solver (eg, a low frequency quasi-static electromagnetic solver) or alternatively a finite difference (FD) algorithm. Meshing, imposition of boundary conditions and solution of the model can be performed using existing software packages such as Sim4Life, Comsol Multiphysics, Ansys or Matlab. Alternatively, custom computer code that implements the FE (or FD) algorithm can be written. The code can utilize existing open source software resources such as C-Gal (for mesh generation) or FREEFEM++ (software written in C++ for rapid testing and finite element simulation). The final solution of the model will be a data set describing the electric field distribution or related quantity (such as electric potential) within the computational model (phantom) for a given iteration.

Step S24 is an optimization step. An optimization algorithm is used to find an array layout that optimizes electric field delivery to a diseased region of the patient's body, such as a tumor. The optimization algorithm will utilize methods for automatic array placement and methods for solving the electric fields within the model in a well-defined order to find the best array layout. The optimal placement will be one that maximizes or minimizes a certain objective function of the electric field in the affected area of the body. This objective function can be, for example, the maximum intensity within the diseased region or the average intensity within the diseased region. Choose the best layout for later use.

There are a variety of methods that can be used to find the optimal array layout for a patient, two of which are described below. One optimization method is exhaustive search. In this approach, the optimizer will include a library with a limited number of array layouts to be tested. The optimizer performs a simulation of all array layouts in the library (eg, by repeating steps S22 and S23 for each layout), and picks the array layout that produces the best field strength in the tumor (the best layout is the one that produces the best field strength in the library). Optimizing the placement of the highest (or lowest) value of the objective function (eg electric field strength delivered to the tumor).

Another optimization method is iterative search. This method covers the use of algorithms such as minimum descent optimization methods and simplex search optimization. Using this method, the algorithm iteratively tests different array layouts on the body and calculates an objective function of the electric field in the tumor for each layout. Therefore, this method also involves repeating steps S22 and S23 for each layout. At each iteration, the algorithm automatically selects a configuration to test based on the results of the previous iterations. The algorithm is designed to converge such that it maximizes (or minimizes) the defined objective function of the tumor midfield.

It should be noted that alternative optimization schemes can be used to find array layouts that optimize the electric field to the diseased region of the body. For example, the algorithm combines the various methods mentioned above.

Once a layout is determined to optimize the electric field within the diseased region of the patient's body (eg, using any of the methods described herein), electrodes can be attached to the determined locations.

After attaching the sensor arrays as described above, proceed to step S25 in which an AC voltage is applied between the sensor arrays (eg, as described in US Pat. No. 7,565,205, which is incorporated herein by reference) to treat disease. In some embodiments, the frequency of the AC voltage is between 100 kHz and 300 kHz. In some embodiments, the frequency of the AC voltage is 150 kHz.

Advantageously, the arrangements described herein can be used to deliver TTFields to the neck at therapeutically effective levels (ie, greater than 1 V/cm).

It should be noted that although the embodiments described herein depict sensor arrays positioned on the surface of an individual's skin, sensor arrays or subsets thereof may also be implanted under the surface of an individual's skin.

While the present invention has been disclosed with reference to certain embodiments, numerous modifications, changes, and changes to the described embodiments are possible without departing from the sphere and scope of the invention as defined in the appended claims . Therefore, it is intended that the present invention not be limited to the described embodiments, but have the full scope defined by the language of the following claims and their equivalents.

S20: Steps S21: Steps S22: Step S23: Step S24: Step S25: Steps

[Figs. 1A and IB] depict regions of interest where TTFields can be used to treat cancer using the sensor array layout described herein.

[Figs. 2A and 2B] depict one example of a sensor array layout that provides a sufficiently high field strength in the region of interest.

[FIG. 2C and FIG. 2D] Grayscale graphs depicting the field strength of the FIG. 2A/FIG. 2B layout.

[Figs. 3A and 3B] depict another example of a sensor array layout that provides a sufficiently high field strength in the region of interest.

[FIG. 3C and FIG. 3D] Grayscale graphs depicting the field strength of the FIG. 3A/FIG. 3B layout.

[Figs. 4A and 4B] depict another example of a sensor array layout that provides a sufficiently high field strength in the region of interest.

[Figs. 4C and 4D] Grayscale graphs depicting the field strength of the Fig. 4A/Fig. 4B layout.

[FIG. 5A] depicts another example of a sensor array layout that provides a sufficiently high field strength in the region of interest.

[Figs. 5B and 5C] Grayscale graphs depicting the field strength of the layout of Fig. 5A.

[FIG. 6A] An example of a poor sensor array layout is depicted.

[Figs. 6B and 6C] Grayscale graphs depicting the field strength of the layout of Fig. 6A.

[FIG. 7A] Another example of a poor sensor array layout is depicted.

[Figs. 7B and 7C] Grayscale graphs depicting the field strength of the layout of Fig. 7A.

[FIG. 8] Scale depicting all grayscale images in this application.

[FIG. 9] depicts one example of how to use simulation to determine the best location for each of the sensor arrays.

Various embodiments are described in detail below with reference to the accompanying drawings, in which like reference numerals refer to like elements.

S20: Steps

S21: Steps

S22: Step

S23: Step

S24: Step

S25: Steps

Claims (19)

A method of treating a tumor in or near the neck of an individual or preventing metastases, the method comprising: attaching a first set of electrode elements having a first center of mass to the head of the individual, wherein the first center of mass is positioned on the head of the individual; attaching a second set of electrode elements to the individual's chest; and applying an alternating voltage between the first set of electrode elements and the second set of electrode elements, wherein the applying is performed after attaching the first set of electrode elements and the second set of electrode elements. The method of claim 1, wherein the electrode elements in the first electrode element set and the second electrode element set are capacitively coupled. The method of claim 1, wherein the alternating voltage applied between the first set of electrode elements and the second set of electrode elements has a frequency between 100 kHz and 300 kHz. The method of claim 1, wherein the first set of electrode elements includes a plurality of electrode elements wired in parallel, and wherein the second set of electrode elements includes a plurality of electrode elements wired in parallel. The method of claim 1, wherein the first centroid is positioned overhead. The method of claim 1, wherein the first centroid is positioned on the upper surface of the individual's head. The method of claim 1, wherein the second set of electrode elements is positioned immediately below the root of the neck. A method of planning the positioning of a first set of electrode elements and a second set of electrode elements on the body of an individual, the method comprising the steps of: obtaining a 3D model of the electrical conductivity or resistivity of an anatomical volume within the individual's body at a given frequency, wherein the anatomical volume is located in or near the neck of the individual; identify the location of the target tissue within the anatomical volume; Based on respective ones of the plurality of layouts of the first set of electrode elements and the second set of electrode elements, the 3D model of the electrical conductivity or the resistivity, and the identified location of the target tissue, analyzing and analyzing the plurality of layouts the associated electric field; and One of the plurality of layouts is selected based on the results of the analysis, wherein the first set of electrode elements has a first centroid, and wherein in each of the plurality of layouts, (a) the first set of electrode elements is positioned on the head of the individual, wherein the first centroid is positioned on the head of the individual, and (b) The second set of electrode elements is positioned on the individual's chest. The method of claim 8, wherein the first centroid is positioned overhead. The method of claim 8, wherein the first centroid is positioned on the upper surface of the individual's head. The method of claim 8, wherein the second set of electrode elements is positioned immediately below the root of the neck. The method of claim 8, wherein the given frequency is between 100 and 300 kHz. The method of claim 8, further comprising the following steps: attaching the first set of electrode elements and the second set of electrode elements to the individual's body at locations corresponding to the selected layout; and An electrical signal is applied between the first set of electrode elements and the second set of electrode elements after the attaching step to impose an electric field in the target tissue. The method of claim 8, wherein the 3D model of the electrical conductivity or the resistivity is a 3D model of electrical conductivity. A method of treating a tumor in or near the neck of an individual or preventing metastases, the method comprising: attaching the first set of electrode elements to the back of the neck of the individual; attaching a second set of electrode elements to the individual's chest; and applying an alternating voltage between the first set of electrode elements and the second set of electrode elements, wherein the applying is performed after attaching the first set of electrode elements and the second set of electrode elements. The method of claim 15, wherein the electrode elements in the first electrode element set and the second electrode element set are capacitively coupled. The method of claim 15, wherein the alternating voltage applied between the first set of electrode elements and the second set of electrode elements has a frequency between 100 kHz and 300 kHz. The method of claim 15, wherein the first set of electrode elements includes a plurality of electrode elements wired in parallel, and wherein the second set of electrode elements includes a plurality of electrode elements wired in parallel. The method of claim 15, wherein the second set of electrode elements is positioned immediately below the root of the neck.

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