Application of a tumor treatment field (TT field) to body parts in at least three different directions using an array of five electrode elements.

Abstract

Due to the directional nature of the tumor treatment field (TT field), increasing the number of directions to which the TT field is applied can increase the effectiveness and volume of TT field therapy. The approach described herein relies on five sets of electrode elements placed on the subject's body to guide the TT field in three or more directions. The first, second, third, and fourth sets are placed on the anterior, posterior, right, and left sides of the subject's body, respectively. The fifth set is placed in a different posterior position. The therapy is performed by applying alternating voltages between (a) the anterior and posterior sets, (b) the left and right sets, and (c) the fifth set between at least one of the anterior, left, and right sets, during consecutive time slots. This approach can increase the volume covered by the TT field and also provide thermal management advantages.

Description

Technical Field

[0001] [Cross - Reference to Related Applications] This application claims the benefit of U.S. Provisional Application No. 63 / 456,041, filed Mar. 31, 2023, which is hereby incorporated by reference in its entirety.

Background Art

[0002] Tumor treating electric field (TT - field) therapy is a proven approach for treating tumors using alternating electric fields at frequencies between 50 kHz and 1 MHz (e.g., 50 kHz - 1 MHz, 50 - 500 kHz, 75 - 300 kHz, or 150 - 250 kHz). FIG. 1 shows a prior - art Optune® system that delivers a 200 kHz TT - field to a patient via four transducer arrays placed on the patient's skin near the tumor. The transducer arrays are arranged in two pairs. One pair of transducer arrays 10L, 10R is placed on the left and right of the tumor, and the other pair of transducer arrays 10A, 10P is placed in front of and behind the tumor. Each transducer array is connected to an AC signal generator 15 via a multi - wire cable. The AC signal generator (a) sends an alternating current to the anterior / posterior (A / P) pair of transducer arrays for 1 second, inducing an electric field in the first direction in the tumor, then (b) sends an alternating current to the left / right (L / R) pair of arrays for 1 second, inducing an electric field in the second direction in the tumor, and then repeats steps (a) and (b) during treatment. In the version of Optune® used to treat glioblastoma, each transducer array includes nine electrode elements.

Summary of the Invention

[0003] One aspect of the present invention relates to a first method for treating a tumor in the head of a subject or preventing its metastasis using an alternating electric field. The first method includes the steps of: placing a first set of one or more first electrode elements on a first front surface of the subject's head; placing a second set of one or more second electrode elements on a first rear surface of the subject's head; placing a third set of one or more third electrode elements on the left side of the subject's head; placing a fourth set of one or more fourth electrode elements on the right side of the subject's head; and placing a fifth set of one or more fifth electrode elements on at least one of the subject's neck and the subject's torso. The first method also includes the steps of applying an alternating voltage between the first set and the second set for a plurality of first times within a series of treatments; applying an alternating voltage between the third set and the fourth set for a plurality of second times within a series of treatments; and applying an alternating voltage between the fifth set and at least one of the first set, the second set, the third set, and the fourth set for a plurality of third times within a series of treatments.

[0004] In some examples of the first method, the first time, the second time, and the third time are mutually exclusive, and the first time, the second time, and the third time are interleaved with each other.

[0005] In some examples of the first method, the first time, the second time, and the third time are mutually exclusive and are interleaved with each other in a repeating pattern that is repeated at least 100 times.

[0006] In some examples of the first method, the fifth set is positioned at the back of the subject's neck, and the step of applying the AC voltage between the fifth set and at least one of the first set, the second set, the third set, and the fourth set for a plurality of third periods of time includes applying the AC voltage between the fifth set and the first set.

[0007] In some examples of the first method, the step of applying an alternating voltage between the fifth set and at least one of the first, second, third, and fourth sets for a plurality of third periods includes (a) applying the alternating voltage between the fifth set and the first set for a portion of the third period, (b) applying the alternating voltage between the fifth set and the third set for a portion of the third period, and (c) applying the alternating voltage between the fifth set and the fourth set for a portion of the third period. Optionally, in these examples, the fifth set may be positioned on the back of the subject's neck.

[0008] Another aspect of the present invention relates to a second method for treating a tumor in the head of a subject or preventing its metastasis using an alternating electric field. The second method includes applying an alternating voltage between a first set of one or more first electrode elements positioned on the anterior surface of the subject's head and a second set of one or more second electrode elements positioned on the posterior surface of the subject's head for a plurality of first times in a series of treatments. The second method also includes applying an alternating voltage between a third set of one or more third electrode elements positioned on the left surface of the subject's head and a fourth set of one or more fourth electrode elements positioned on the right surface of the subject's head for a plurality of second times in a series of treatments. The second method also includes applying an alternating voltage between a fifth set of one or more fifth electrode elements positioned on at least one of the first set, the second set, the third set, and the fourth set for a plurality of third times in a series of treatments.

[0009] Some examples of the second method further include the steps of: placing the first set on the front surface; placing the second set on the rear surface; placing the third set on the left surface; placing the fourth set on the right surface; and placing the fifth set on at least one of the subject's neck and the subject's torso.

[0010] In some examples of the first method, the first time, the second time, and the third time are mutually exclusive, and the first time, the second time, and the third time are interleaved with each other.

[0011] In some examples of the first method, the first time, the second time, and the third time are mutually exclusive and are interleaved with each other in a repeating pattern that is repeated at least 100 times.

[0012] In some examples of the first method, the fifth set is positioned at the back of the subject's neck, and the step of applying the alternating voltage between the fifth set and at least one of the first, second, third, and fourth sets for a plurality of third periods of time includes applying the alternating voltage between the fifth set and the first set.

[0013] In some examples of the first method, the step of applying an alternating voltage between the fifth set and at least one of the first, second, third, and fourth sets for a plurality of third periods includes (a) applying the alternating voltage between the fifth set and the first set for a portion of the third period, (b) applying the alternating voltage between the fifth set and the third set for a portion of the third period, and (c) applying the alternating voltage between the fifth set and the fourth set for a portion of the third period. In these examples, the fifth set may optionally be positioned at the back of the subject's neck, at the front of the subject's torso, or both at the back of the subject's neck and at the front of the subject's torso.

[0014] Another aspect of the present invention relates to a first apparatus comprising a signal generator, a plurality of switches, and a controller. The signal generator is configured to produce an AC output voltage. The plurality of switches are configured to operate in a first state, depending on the state of at least one control input, such that (a) the AC output voltage is routed to appear across a first and second output; (b) the AC output voltage is routed to appear across a third and fourth output; or (c) the AC output voltage is routed to appear across a fifth output and at least one of the first, second, third, and fourth outputs. The controller is configured to transmit a control signal to the at least one control input, the control signal instructing the plurality of switches to operate in the first state for a plurality of first times in a series of treatments, in the second state for a plurality of second times in a series of treatments, and in the third state for a plurality of third times in a series of treatments.

[0015] In some embodiments of the first apparatus, the controller is configured such that the first time, the second time, and the third time are mutually exclusive and interleaved with each other.

[0016] In some embodiments of the first apparatus, the controller is configured such that the first time, the second time, and the third time are mutually exclusive and interleaved with each other in a repeating pattern that repeats at least 100 times.

[0017] In some embodiments of the first device, the plurality of switches are configured to route the AC output voltage so that it appears across the fifth output and the first output when operating in the third state.

[0018] In some embodiments of the first apparatus, the controller and the plurality of switches are configured to route the AC output voltage so that the plurality of switches appear across the fifth output and the first output for a portion of the third time, to route the AC output voltage so that the plurality of switches appear across the fifth output and the third output for a portion of the third time, and to route the AC output voltage so that the plurality of switches appear across the fifth output and the fourth output for a portion of the third time.

[0019] Some embodiments of the first apparatus further include: a first set of one or more first electrode elements positioned on the front surface of the subject's head and wired to the first output; a second set of one or more second electrode elements positioned on the rear surface of the subject's head and wired to the second output; a third set of one or more third electrode elements positioned on the left surface of the subject's head and wired to the third output; a fourth set of one or more fourth electrode elements positioned on the right surface of the subject's head and wired to the fourth output; and a fifth set of one or more fifth electrode elements positioned on at least one of the subject's neck and the subject's torso and wired to the fifth output.

[0020] Another aspect of the present invention relates to a third method for treating a tumor in a subject's body or preventing its metastasis using an alternating electric field. The third method includes the steps of: placing a first set of one or more first electrode elements on a first front surface of the subject's body; placing a second set of one or more second electrode elements on a first rear surface of the subject's body; placing a third set of one or more third electrode elements on the left surface of the subject's body; placing a fourth set of one or more fourth electrode elements on the right surface of the subject's body; and placing a fifth set of one or more fifth electrode elements on at least one of the second front surface and the second rear surface of the subject's body. The third method also includes the steps of applying an alternating voltage between the first set and the second set for a plurality of first times within a series of treatments; applying an alternating voltage between the third set and the fourth set for a plurality of second times within a series of treatments; and applying an alternating voltage between the fifth set and at least one of the first, second, third, and fourth sets for a plurality of third times within a series of treatments.

[0021] In some examples of the first method, the first time, the second time, and the third time are mutually exclusive, and the first time, the second time, and the third time are interleaved with each other.

[0022] In some examples of the third method, the fifth set is placed on the second rear surface of the subject's body. In these examples, the step of applying the alternating voltage between the fifth set and at least one of the first, second, third, and fourth sets for a plurality of third periods of time includes applying the alternating voltage between the fifth set and the first set.

[0023] In some examples of the third method, the step of applying an alternating voltage between the fifth set and at least one of the first, second, third, and fourth sets for a plurality of third periods includes (a) applying the alternating voltage between the fifth set and the first set for a portion of the third period, (b) applying the alternating voltage between the fifth set and the third set for a portion of the third period, and (c) applying the alternating voltage between the fifth set and the fourth set for a portion of the third period. Optionally, in these examples, the fifth set is positioned on the second rear surface of the subject's body.

[0024] Another aspect of the present invention relates to a fourth method for treating a tumor in a subject's body or preventing its metastasis using an alternating electric field. The fourth method includes applying an alternating voltage between a first set of one or more first electrode elements positioned on a first front surface of the subject's body and a second set of one or more second electrode elements positioned on a first rear surface of the subject's body for a plurality of first times in a series of treatments. The fourth method also includes applying an alternating voltage between a third set of one or more third electrode elements positioned on the left surface of the subject's body and a fourth set of one or more fourth electrode elements positioned on the right surface of the subject's body for a plurality of second times in a series of treatments. The fourth method also includes applying an alternating voltage between a fifth set of one or more fifth electrode elements positioned on at least one of the first, second, third, and fourth sets for a plurality of third times in a series of treatments.

[0025] Some examples of the fourth method further include the steps of: placing the first set on the first front surface; placing the second set on the first rear surface; placing the third set on the left surface; placing the fourth set on the right surface; and placing the fifth set on at least one of the second front surface and the second rear surface of the subject's body.

[0026] In some examples of the fourth method, the first time, the second time, and the third time are mutually exclusive, and the first time, the second time, and the third time are interleaved with each other.

[0027] In some examples of the fourth method, the fifth set is disposed on the second posterior surface of the subject's body, and during the plurality of third times, the step of applying the alternating voltage between the fifth set and at least one of the first, second, third, and fourth sets includes applying the alternating voltage between the fifth set and the first set.

[0028] In some examples of the fourth method, during the plurality of third times, the step of applying an alternating voltage between a fifth set and at least one of the first, second, third, and fourth sets includes: (a) applying the alternating voltage between the fifth set and the first set during a portion of the third time; (b) applying the alternating voltage between the fifth set and the third set during a portion of the third time; and (c) applying the alternating voltage between the fifth set and the fourth set during a portion of the third time. In these examples, the fifth set may optionally be disposed on the second posterior surface of the subject's body or on both the posterior portion of the subject's neck and the anterior portion of the subject's torso.

[0029] Another aspect of the present invention relates to a second device. The second device includes a signal generator, a plurality of switches, and a controller. The signal generator is configured to generate an alternating current output voltage. The plurality of switches are configured to operate in a first state in which (a) the alternating current output voltage is routed to appear across a first output and a second output, (b) a second state in which the alternating current output voltage is routed to appear across a third output and a fourth output, or (c) a third state in which the alternating current output voltage is routed to appear across a fifth output and at least one of the first, second, third, and fourth outputs, depending on the state of at least one control input. Further, the controller is configured to transmit a control signal to the at least one control input, and the control signal causes the plurality of switches to operate in the first state during a plurality of first times within a series of treatments, operate in the second state during a plurality of second times within the series of treatments, and operate in the third state during a plurality of third times within the series of treatments.

[0030] In some embodiments of the second device, the controller is configured such that the first time, the second time, and the third time are mutually exclusive and are interleaved with each other. In some embodiments of the second device, the controller is configured such that the first time, the second time, and the third time are mutually exclusive and are interleaved with each other in a repeating pattern that repeats at least 100 times. In some embodiments of the second device, the plurality of switches are configured to route the alternating current output voltage to appear across the fifth output and the first output when operating in the third state.

[0031] In some embodiments of the second apparatus, the controller and the plurality of switches are configured to route the AC output voltage so that the plurality of switches appear across the fifth output and the first output for a portion of the third time, to route the AC output voltage so that the plurality of switches appear across the fifth output and the third output for a portion of the third time, and to route the AC output voltage so that the plurality of switches appear across the fifth output and the fourth output for a portion of the third time.

[0032] Some embodiments of the second apparatus further include: a first set of one or more first electrode elements positioned on a first front surface of the subject's body and wired to the first output; a second set of one or more second electrode elements positioned on a first rear surface of the subject's body and wired to the second output; a third set of one or more third electrode elements positioned on the left surface of the subject's body and wired to the third output; a fourth set of one or more fourth electrode elements positioned on the right surface of the subject's body and wired to the fourth output; and a fifth set of one or more fifth electrode elements positioned on at least one of the second front surface and the second rear surface of the subject's body and wired to the fifth output. [Brief explanation of the drawing]

[0033] [Figure 1] This shows the conventional Optune® system, which uses four transducer arrays to deliver a 200 kHz TT field to a patient. [Figure 2] Another embodiment is shown in which four sets of electrode elements are placed on the subject's head and a fifth set of electrode elements are placed on the subject's neck. [Figure 3A] Figure 2 shows an example of a timing diagram for applying current to the electrode element set shown in Figure 2, which applies a TT field to the subject's brain in an additional direction. [Figure 3B]Another example of a timing diagram for energizing the set of electrode elements shown in Figure 2, which applies a TT field to the subject's brain in an additional direction. [Figure 4] Figure 2 shows an example of a hardware block diagram that can be used to apply voltage to the set of electrode elements shown. [Figure 5] Another example of a timing diagram for energizing the set of electrode elements shown in Figure 2, which applies a TT field to the subject's brain in an additional direction. [Figure 6] Another embodiment is shown in which four sets of electrode elements are placed on the subject's head and a fifth set of electrode elements are placed on the subject's torso. [Figure 7] Another embodiment is shown in which five sets of electrode elements are arranged around a body part. [Figure 8] Another embodiment is shown in which five sets of electrode elements are arranged around a body part. Various embodiments are described in detail below with reference to the accompanying drawings. Here, the same reference numerals represent the same elements. [Modes for carrying out the invention]

[0034] The TT field is most effective when the lines of force of the electric field are oriented nearly parallel to the long axis of the hourglass-shaped cell during mitosis. Furthermore, applying the TT field at different times and in different directions increases the overall efficacy of the treatment because the most effective field orientation is applied to a larger population of tumor cells as the tumor cells divide. In the conventional Optune® system, the direction of the TT field alternates between two different directions, each of which depends on a pair of transducer arrays (the two members of any given pair are positioned on either side of the subject's head).

[0035] This application describes various approaches to increase the effectiveness of a TT field by increasing the number of directions in which the TT field is applied. The approaches described herein can also be used to increase the effectiveness of a TT field by increasing the overall volume covered by the TT field (which may be advantageous when the body part being treated includes multiple regions of interest or a single region of interest occupying a large volume within the subject's body), and / or to provide thermal management benefits (for example, by reducing the duty cycle of a transducer array that may approach a temperature limit, the amount of time the TT field can be applied can be increased).

[0036] A first approach to increasing the effectiveness of the TT field relies on additional pairs of transducer arrays (i.e., in addition to the forward / backward and left / right transducer arrays described above in relation to Optune® and shown in Figure 1). Each of these transducer arrays contains a set of one or more electrode elements (e.g., 1 to 30 electrode elements). The additional pairs of transducer arrays are used to induce an electric field nearly perpendicular to the subject's head. More specifically, one member of the additional pair is positioned at the crown of the subject's head, and the other member of the additional pair is positioned at the subject's neck or upper torso. To use this approach, the system (a) energizes an anterior / posterior pair for a period (e.g., 1 s) to guide the electric field through the tumor in a first direction; then (b) energizes a left / right pair for a period to guide the electric field through the tumor in a second direction; then (c) energizes an upper / lower pair for a period to guide the electric field through the tumor in a third direction; and then repeats this three-step sequence for the duration of treatment. In particular, by adding an upper / lower pair of transducer arrays, a third substantially vertical direction is added to the original two substantially horizontal directions.

[0037] However, implementing this first approach can be difficult because, as seen in Figure 1, the anterior, posterior, left, and right transducer arrays 10A / P / L / R occupy so much space that there is little room to place additional transducer arrays on the top of the subject's head. This difficulty can be addressed by reducing the size of the transducer arrays 10A / P / L / R to create space for additional transducer arrays, but reducing the size of the transducer arrays presents two problems. First, it reduces the volume in the subject's brain covered by the nearly horizontal TT field created using the original transducer arrays 10A / P / L / R. Second, due to thermal considerations, smaller transducer arrays typically have to operate at lower currents to prevent overheating. Also, operating at lower currents is undesirable because lower currents reduce the strength of the electric field (and thus reduce the effectiveness of the treatment).

[0038] Figures 2-5 illustrate a second approach to increasing the effectiveness of the TT field by increasing the number of directions to which the TT field is applied. In this approach, as best seen in Figure 2, a first set 20A of one or more first electrode elements is placed on the front surface of the subject's head, a second set 20P of one or more second electrode elements is placed on the rear surface of the subject's head, a third set 20L of one or more third electrode elements is placed on the left surface of the subject's head, and a fourth set 20R of one or more fourth electrode elements is placed on the right surface of the subject's head. In addition, a fifth set 20F of one or more fifth electrode elements is placed on the subject's neck (for example, on the back of the subject's neck as shown in Figure 2).

[0039] Figure 3A shows an example timing diagram for energizing one or more sets of electrode elements 20A, 20P, 20L, 20R, and 20F that apply a TT field to the subject's brain in three or more directions. During the first second of operation (i.e., between t=0 and t=1), an AC voltage is applied between the front set 20A and the rear set 20P, which induces an electric field in the subject's brain in the general direction running from front to back. During the second second of operation (i.e., between t=1 and t=2), an AC voltage is applied between the left set 20L and the right set 20R, which induces an electric field in the subject's brain in the general direction running from left to right. Then, during the third second of operation (i.e., between t=2 and t=3), an AC voltage is applied between the fifth set of electrode elements 20F and the front set of electrode elements 20A, which induces an electric field in the subject's brain in a direction having a vertical component. Next, this three-part pattern is repeated over the duration of the treatment (i.e., from t=3 onwards) (e.g., at least 100 times). Note that in the example above, each time interval is 1 second long, but shorter or longer durations (e.g., 0.1s to 100s) can also be used. Note also that in the example above, the anterior / posterior, left / right, and fifth / anterior time slots are interleaved with each other and mutually exclusive.

[0040] In particular, this approach applies the TT field to the subject's brain in three directions without reducing the size of the transducer arrays positioned on the anterior, posterior, left, and right surfaces of the subject's head. Furthermore, the directionality of the TT field, by adding a new direction with a vertical component to the two original nearly horizontal directions, can favorably increase the overall efficacy of the treatment. This approach also increases the overall volume covered by the TT field (which can be advantageous when the body part being treated contains multiple regions of interest or a single region of interest occupying a large volume within the subject's body).

[0041] Figure 4 shows an example of a hardware block diagram that can be used to apply voltage to various sets of one or more electrode elements 20A, 20P, 20L, 20R, and 20F, as described above in relation to Figure 3A. In this example, the AC signal generator 30 generates AC output voltages with frequencies of 50kHz to 1MHz (e.g., 50kHz to 1MHz, 50 to 500kHz, 75 to 300kHz, or 150 to 250kHz). A bank of electronic switches 40 (which may be implemented using, for example, a set of FETs) is configured to route the output of the AC signal generator to one of the following, depending on the state of the control signals arriving from the controller 50: (1) appearing across terminals A and P, (2) appearing across terminals L and R, or (3) appearing across terminals F and A. The controller 50 is programmed to generate the A / P, L / R, and F / A control signals shown in Figure 3A, in the order indicated. These control signals instruct the switch 40 to operate in a first state (i.e., A / P state) for several first times within a series of treatments, in a second state (i.e., L / R state) for several second times within a series of treatments, and in a third state (i.e., F / A state) for several third times within a series of treatments.

[0042] Figure 3B shows another example of a timing diagram for energizing one or more sets of electrode elements 20A, 20P, 20L, 20R, and 20F that apply a TT field to the subject's brain in three or more directions. During the first second of operation (i.e., between t=0 and t=1), an AC voltage is applied between the front set 20A and the rear set 20P, which induces an electric field in the subject's brain in a general direction running from front to back. During the second second of operation (i.e., between t=1 and t=2), an AC voltage is applied between the left set 20L and the right set 20R, which induces an electric field in the subject's brain in a general direction running from left to right. Then, during the third second of the operation (i.e., between t=2 and t=3), an alternating voltage is applied between (i) the fifth set 20F of electrode elements and (ii) the anterior set 20A, left set 20L, and right set 20R of electrode elements, which induces an electric field in the subject's brain in a direction having a vertical component. This three-part pattern is then repeated over the duration of the series of treatments (i.e., from t=3 onwards) (e.g., at least 100 times). Note that in the above example, each time interval is 1 second long, but shorter or longer durations (e.g., 0.1s to 100s) can also be used. Note that in the above example, the anterior / posterior, left / right, and fifth / (anterior+left+right) time slots are interleaved with each other and mutually exclusive.

[0043] In particular, this approach applies the TT field to the subject's brain in three directions without reducing the size of the transducer arrays positioned on the anterior, posterior, left, and right surfaces of the subject's head. Furthermore, the directionality of the TT field, by adding a new direction with a vertical component to the two original nearly horizontal directions, can favorably increase the overall efficacy of the treatment. This approach can also increase the overall volume covered by the TT field (which can be advantageous when the body part being treated includes multiple regions of interest or a single region of interest occupying a large volume within the subject's body), and / or (for example, by reducing the duty cycle of the transducer arrays, which may approach the temperature limit, the amount of time the TT field can be applied can be increased).

[0044] The same hardware described above in relation to Figure 4 can be used to implement the sequence shown in Figure 3B. In this example, the AC signal generator 30 generates an AC output voltage with a frequency of 50 kHz to 1 MHz (e.g., 50 kHz to 1 MHz, 50 to 500 kHz, 75 to 300 kHz, or 150 to 250 kHz). A bank of electronic switches 40 (which may be implemented using, for example, a set of FETs) is configured to route the output of the AC signal generator to one of the following, depending on the state of the control signals arriving from the controller 50: (1) appearing across terminals A and P, (2) appearing across terminals L and R, or (3) appearing across terminal F and (A, L and R). The controller 50 is programmed to generate the A / P, L / R, and F / (A+L+R) control signals shown in Figure 3B in the order indicated. These control signals instruct the switch 40 to operate in a first state (i.e., A / P state) for several first times within a series of treatments, in a second state (i.e., L / R state) for several second times within a series of treatments, and in a third state (i.e., F / (A+L+R state)) for several third times within a series of treatments.

[0045] Figure 5 shows another example of a timing diagram for energizing various sets of one or more electrode elements 20A, 20P, 20L, 20R, and 20F to apply a TT field to the subject's brain in additional directions. During the first second of operation (i.e., between t=0 and t=1), an AC voltage is applied between the front set 20A and the rear set 20P, which induces an electric field in the subject's brain in the general direction running from front to back. During the second second of operation (i.e., between t=1 and t=2), an AC voltage is applied between the left set 20L and the right set 20R, which induces an electric field in the subject's brain in the general direction running from left to right. Then, during the third second of operation (i.e., between t=2 and t=3), an AC voltage is applied between the fifth set of electrode elements 20F and the front set of electrode elements 20A, which induces an electric field in the subject's brain in a nearly perpendicular direction. The operation between t=3 and t=5 is identical to the operation between t=0 and t=2. During the second following the operation (i.e., between t=5 and t=6), an AC voltage is applied between the fifth set of electrode elements 20F and the left set of electrode elements 20L, which induces an electric field in the subject's brain in a direction that is approximately vertical but tilted upward to the left. The operation between t=6 and t=8 is identical to the operation between t=0 and t=2. During the second following the operation (i.e., between t=8 and t=9), an AC voltage is applied between the fifth set of electrode elements 20F and the right set of electrode elements 20R, which induces an electric field in the subject's brain in a direction that is approximately vertical but tilted upward to the right. This nine-part pattern is then repeated over the duration of the treatment (i.e., from t=9 onward) (e.g., at least 100 times). Note that in the example above, each time interval is 1 second long, but shorter or longer durations (e.g., 0.1s to 100s) can also be used. Also note that in the example above, the different time slots are interleaved with each other and mutually exclusive.

[0046] In this case as well, this approach applies the TT field to the subject's brain in additional directions without reducing the size of the transducer arrays positioned on the anterior, posterior, left, and right surfaces of the subject's head. Furthermore, the directionality of the TT field, by adding three new directions with vertical components to the two original substantially horizontal directions, can favorably increase the overall efficacy of the treatment. This approach can also increase the overall volume covered by the TT field (which can be advantageous when the body part being treated includes multiple regions of interest or a single region of interest occupying a large volume within the subject's body), and / or (for example, by reducing the duty cycle of the transducer arrays which may approach the temperature limit, the amount of time the TT field can be applied can be increased).

[0047] Hardware for implementing the timing in Figure 5 can be the same as the hardware described above in relation to Figure 4, except that a bank of electronic switches is configured to route the output of the AC signal generator for any of the following, depending on the state of the control signals arriving from the controller 50: (1) appearing across terminals A and P, (2) appearing across terminals L and R, (3) appearing across terminals F and A, (4) appearing across terminals F and L, or (5) appearing across terminals F and R. In this embodiment, the controller 50 is programmed to generate the A / P, L / R, F / A, F / L, and F / R control signals shown in Figure 5 in the order shown. These control signals instruct the switch 40 to operate in a first state (i.e., the A / P state) for a plurality of first times in a series of treatments, in a second state (i.e., the L / R state) for a plurality of second times in a series of treatments, or in one of three possible third states (i.e., the F / A state, the F / L state, or the F / R state) for a plurality of third times in a series of treatments.

[0048] In particular, in addition to the advantages provided by imposing the TT field in more directions, implementing the timing shown in Figure 5 offers another advantage with respect to the timing shown in Figure 3A. This is because, in the approach in Figure 3A, the forward set 20A is activated at 66% of the time. This can cause the forward set to heat up, which may require a reduction in current to prevent that set from overheating. In contrast, when the approach in Figure 5 is used, the forward set 20A, the left set 20L, and the right set 20R are each activated at only 44% of the time, which distributes the heating more evenly among those sets, in which case overheating would be less of a concern.

[0049] It should be noted that a fifth set of one or more electrode elements does not need to be placed on the subject's neck, as shown in Figure 2. Conversely, the fifth set can be placed on the subject's torso (for example, on the upper front of the subject's torso, as shown in Figure 6) instead of the arrangement shown in Figure 2. When the fifth set is placed on the subject's torso, both the timing and hardware are the same as in the situations described above in relation to Figures 2-5. As yet another alternative, the fifth set can be distributed between the two positions, with some of the electrode elements in the fifth set placed on the subject's neck and the rest of the electrode elements in the fifth set placed on the subject's torso. In this case, both the timing and hardware are the same as in the situations described above in relation to Figures 2-5.

[0050] The approaches and embodiments described above in relation to Figures 2-6 are explained in the context of four sets of electrode elements placed on the subject's head and a fifth set of electrode elements placed on the subject's neck or chest. These approaches and embodiments can be extended to various other body parts, including but not limited to the torso, abdomen, legs, and head, as described below in relation to Figures 7 and 8.

[0051] More specifically, Figure 7 illustrates another approach to increasing the effectiveness of the TT field by increasing the number of directions in which the TT field is applied. In this approach, a first set 20A of one or more first electrode elements is placed on the front surface of the subject's body, a second set 20P of one or more second electrode elements is placed on the first rear surface of the subject's body, a third set 20L of one or more third electrode elements is placed on the left side of the subject's body, and a fourth set 20R of one or more fourth electrode elements is placed on the right side of the subject's body. In addition, a fifth set 20F of one or more fifth electrode elements is placed on the second rear surface of the subject's body (in the example shown in Figure 7, this is above the first rear surface, but may also be below the first rear surface).

[0052] One timing sequence for energizing various sets of one or more electrode elements 20A, 20P, 20L, 20R, and 20F in Figure 7 is a repeating pattern of the three parts described above in relation to Figure 3A (using similar durations). The same hardware block diagram shown in Figure 4 can be used to apply voltage to various sets of one or more electrode elements 20A, 20P, 20L, 20R, and 20F when this timing sequence is used. When this approach is used, the TT field is applied to the body part in three directions instead of only two. In addition, this approach also increases the overall volume covered by the TT field (this can be advantageous when the body part being treated contains multiple regions of interest or a single region of interest occupying a large volume within the subject's body).

[0053] Another timing sequence for energizing various sets of one or more electrode elements 20A, 20P, 20L, 20R, and 20F in Figure 7 is a repeating pattern of the three parts described above in relation to Figure 3B (using similar durations). The same hardware block diagram shown in Figure 4 can be used to apply voltage to various sets of one or more electrode elements 20A, 20P, 20L, 20R, and 20F when this timing sequence is used. When this approach is used, the TT field is applied to the body part in three directions instead of only two. This approach also increases the overall volume covered by the TT field (this can be advantageous when the body part being treated contains multiple regions of interest or a single region of interest occupying a large volume within the subject's body). Furthermore, this approach can offer thermal management advantages (for example, by reducing the duty cycle of the transducer array which may approach the temperature limit, the amount of time the TT field can be applied can be increased).

[0054] A further different timing sequence for energizing various sets of one or more electrode elements 20A, 20P, 20L, 20R, and 20F in Figure 7 is a repeating pattern of the nine parts described above in relation to Figure 5 (using similar durations). When this timing sequence is used, the same hardware block diagram shown in Figure 4 (with the modifications described above in relation to Figure 5) is used to apply voltage to various sets of one or more electrode elements 20A, 20P, 20L, 20R, and 20F. As a result, the TT field is applied to the body part in many different directions, rather than just two. This approach also increases the overall volume covered by the TT field (which can be advantageous when the body part being treated contains multiple regions of interest or a single region of interest occupying a large volume within the subject's body). Furthermore, this approach can provide the thermal management advantages described above in relation to Figure 5.

[0055] Finally, the fifth set 20F of one or more electrode elements does not need to be positioned behind the subject's body, as shown in Figure 7. Conversely, the fifth set can be positioned in front of the subject's body, as shown in Figure 8. When the fifth set 20F of one or more electrode elements is positioned in front of the subject's body, both the timing and hardware are mirror images of the situation described above in relation to Figure 7. As yet another alternative, the fifth set can be distributed between the two positions, with some of the electrode elements in the fifth set positioned behind the subject's body and the rest of the electrode elements in the fifth set positioned in front of the subject's body. In this case, both the timing and hardware are mirror images of the situation described above in relation to Figures 2-5.

[0056] While the present invention is disclosed with reference to specific embodiments, numerous modifications, changes, and variations are possible with respect to the embodiments described, without departing from the scope and scope of the invention, as defined in the appended claims. Therefore, the present invention is not limited to the embodiments described, but is intended to encompass the entire scope defined by the following claims and their equivalents. [Explanation of Symbols]

[0057] 10A transducer array 10L transducer array 10P transducer array 10R transducer array 15 AC signal generator 20A First set (front set) 20F Set 5 20L, third set 20L Left Set 20P Second set (rear set) 20R, 4th set (right set) 30 AC signal generators 40 electronic switches 40 switches 50 Controllers A terminal F terminal L terminal P terminal R terminal

Claims

1. A method for treating tumors in a subject's body or preventing metastasis using an alternating electric field, The steps include: placing a first set of one or more first electrode elements on a first front surface of the subject's body; The steps include placing a second set of one or more second electrode elements on the first posterior surface of the subject's body, The steps include placing a third set of one or more third electrode elements on the left side of the subject's body, The steps include placing a fourth set of one or more fourth electrode elements on the right side of the subject's body, The steps include placing a fifth set of one or more fifth electrode elements on at least one of the second front surface and the second rear surface of the subject's body, The steps include applying an alternating voltage between the first set and the second set for a plurality of first time intervals within a series of treatments, The steps include applying an alternating voltage between the third set and the fourth set for a plurality of second time periods within the series of treatments, A method comprising the step of applying an alternating voltage between the fifth set and at least one of the first set, the second set, the third set, and the fourth set for a plurality of third times within the series of treatments.

2. The first time, the second time, and the third time are mutually exclusive. The method according to claim 1, wherein the first time, the second time, and the third time are interleaved with each other.

3. The first time, the second time, and the third time are mutually exclusive. The method according to claim 1, wherein the first time, the second time, and the third time are interleaved with each other in a repeating pattern that is repeated at least 100 times.

4. The fifth set is placed on the second rear surface of the subject's body, The method according to claim 1, wherein the step of applying the AC voltage between the fifth set and at least one of the first set, the second set, the third set, and the fourth set for a plurality of third periods of time includes applying the AC voltage between the fifth set and the first set.

5. The method according to claim 1, wherein the step of applying an alternating voltage between the fifth set and at least one of the first, second, third, and fourth sets for a plurality of third periods comprises (a) applying the alternating voltage between the fifth set and the first set for a portion of the third period; (b) applying the alternating voltage between the fifth set and the third set for a portion of the third period; and (c) applying the alternating voltage between the fifth set and the fourth set for a portion of the third period.

6. The method according to claim 5, wherein the fifth set is placed on the second posterior surface of the subject's body.

7. A method for treating tumors in a subject's body or preventing metastasis using an alternating electric field, The steps include applying an alternating voltage between a first set of one or more first electrode elements positioned on a first anterior surface of the subject's body and a second set of one or more second electrode elements positioned on a first posterior surface of the subject's body for a plurality of first time intervals within a series of treatments, The steps include applying an alternating voltage between a third set of one or more third electrode elements positioned on the left side of the subject's body and a fourth set of one or more fourth electrode elements positioned on the right side of the subject's body for a plurality of second periods within the series of treatments, A method comprising the steps of applying an alternating voltage between a fifth set of one or more fifth electrode elements positioned on at least one of the first set, the second set, the third set, and the fourth set for a plurality of third times within the series of treatments.

8. The steps of placing the first set on the first front surface, The steps of placing the second set on the first rear surface, The steps include placing the third set on the left surface, The steps include placing the fourth set on the right surface, The method according to claim 7, further comprising the step of placing the fifth set on at least one of the second front surface and the second rear surface of the subject's body.

9. The first time, the second time, and the third time are mutually exclusive. The method according to claim 1, wherein the first time, the second time, and the third time are interleaved with each other.

10. The first time, the second time, and the third time are mutually exclusive. The method according to claim 1, wherein the first time, the second time, and the third time are interleaved with each other in a repeating pattern that is repeated at least 100 times.

11. The fifth set is placed on the second rear surface of the subject's body, The method according to claim 1, wherein the step of applying the AC voltage between the fifth set and at least one of the first set, the second set, the third set, and the fourth set for a plurality of third periods of time includes applying the AC voltage between the fifth set and the first set.

12. The method according to claim 1, wherein the step of applying an AC voltage between the fifth set and at least one of the first set, the second set, the third set, and the fourth set for a plurality of third periods comprises (a) applying the AC voltage between the fifth set and the first set for a portion of the third period; (b) applying the AC voltage between the fifth set and the third set for a portion of the third period; and (c) applying the AC voltage between the fifth set and the fourth set for a portion of the third period.

13. The method according to claim 5, wherein the fifth set is placed on the second posterior surface of the subject's body.

14. The method according to claim 12, wherein the fifth set is positioned on both the rear of the subject's neck and the front of the subject's torso.

15. A signal generator configured to produce an AC output voltage, A plurality of switches configured to operate in the following ways, depending on the state of at least one control input: (a) in a first state in which the AC output voltage is routed to appear across a first output and a second output; (b) in a second state in which the AC output voltage is routed to appear across a third output and a fourth output; or (c) in a third state in which the AC output voltage is routed to appear across a fifth output and at least one of the first output, the second output, the third output, and the fourth output; A device comprising: a controller configured to transmit a control signal to at least one control input, wherein the control signal instructs the plurality of switches to operate in a first state for a plurality of first time periods in a series of treatments, to operate in a second state for a plurality of second time periods in a series of treatments, and to operate in a third state for a plurality of third time periods in a series of treatments.

16. The apparatus according to claim 15, wherein the controller is configured such that the first time, the second time, and the third time are mutually exclusive and the first time, the second time, and the third time are interleaved with each other.

17. The apparatus according to claim 15, wherein the controller is configured such that the first time, the second time, and the third time are mutually exclusive, and the first time, the second time, and the third time are interleaved with each other in a repeating pattern that is repeated at least 100 times.

18. The apparatus according to claim 15, wherein the plurality of switches are configured to route the AC output voltage so that it appears across the fifth output and the first output when operating in the third state.

19. The controller and the plurality of switches are, During a portion of the third time, the plurality of switches route the AC output voltage so that it appears across the fifth output and the first output. During a portion of the third time, the plurality of switches route the AC output voltage so that it appears across the fifth output and the third output, and The apparatus according to claim 15, wherein for a portion of the third time, the plurality of switches are configured to route the AC output voltage so that it appears across the fifth output and the fourth output.

20. A first set of one or more first electrode elements, positioned on a first frontal surface of the subject's body and wired to the first output, A second set of one or more second electrode elements, positioned on the first posterior surface of the subject's body and wired to the second output, A third set of one or more third electrode elements is positioned on the left side of the subject's body and wired to the third output, A fourth set of one or more fourth electrode elements, positioned on the right side of the subject's body and wired to the fourth output, The apparatus according to claim 15, further comprising a fifth set of one or more fifth electrode elements positioned on at least one of the second front surface and the second rear surface of the subject's body and wired to the fifth output.

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