Sequential positioning of sets of electrode arrays at non-overlapping locations to mitigate skin stimulation during tumor therapy electric field (TTFields) therapy

Abstract

An alternating electric field may be applied to a subject's body by: (a) applying an alternating voltage between electrode elements positioned on four predominantly non-overlapping regions on the subject's body during a first time interval; and (b) applying an alternating voltage between other electrode elements positioned on four secondary non-overlapping regions on the subject's body during a second time interval. All of the secondary regions do not overlap with any of the primary regions, and the first time interval does not overlap with the second time interval. Due to the non-overlapping properties in space and time, the incidence of skin irritation will be reduced. And, if skin irritation does occur during a given time interval, the skin will have an opportunity to heal during a subsequent time interval.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 444,725, filed February 10, 2023, which is incorporated herein by reference in its entirety. Background Art

[0003] Tumor Treating Fields (TTFields) therapy is an effective method for treating tumors using alternating electric fields with a frequency between 50kHz and 1MHz (e.g., 150kHz to 250kHz). In the system, TTFields are delivered to the patient via four transducer arrays placed on the patient's skin near the tumor. These transducer arrays are arranged in two pairs, with one pair of transducer arrays positioned on the left and right sides of the tumor and the other pair of transducer arrays positioned on the front and back sides of the tumor. Each transducer array is connected to an AC signal generator via a multi-wire cable. The AC signal generator (a) sends an AC current through the pair of anterior / posterior (A / P) transducer arrays for 1 second, which induces an electric field with a first direction through the tumor; then (b) sends an AC current through the pair of left / right (L / R) arrays for 1 second, which induces an electric field with a second direction through the tumor; and then repeats steps (a) and (b) for the duration of the treatment. Each transducer array includes a plurality (e.g., 9 to 30) electrode elements.

[0004] Alternating electric fields can also be used to treat medical conditions other than tumors. For example, as described in U.S. Pat. No. 10,967,167 (incorporated herein by reference in its entirety), alternating electric fields can be used to increase the permeability of the blood-brain barrier, allowing, for example, chemotherapy drugs to reach the brain.

[0005] when When the system is used to treat a tumor using TTFields, the transducer arrays are attached to the subject's skin at locations selected to provide the strongest electric fields within the tumor. The transducer arrays are attached to the subject's body using a self-adhesive backing and remain attached at the same locations for an extended period of time (e.g., 3 to 4 days). After the extended period of time, the transducer arrays are removed so that the subject's skin can be shaved and cleaned. A new set of transducer arrays is then attached to the subject's body at the same approximate locations as before, offset by less than one inch from the previous locations. (See Optune Patient Information and Operation Manual, Document No. QSD-QR-704.REV 05, January 2019.) Use Treatment is typically continued for several months or even years, with the transducer array replaced every 3 to 4 days.

[0006] Some patients experience skin irritation or itching beneath the transducer array, and while these conditions can often be treated with steroid creams, some of these patients may find the irritation or itching very bothersome. Summary of the Invention

[0007] In prior art methods, successive groups of transducer arrays are placed at the same general location on the subject's body (i.e., a group of four locations is selected to provide the strongest electric field within the tumor). Unlike prior art methods, the present application describes various alternative methods in which successive groups of transducer arrays are positioned at different locations on the subject's body (e.g., once every 3 to 4 days). More specifically, in some embodiments, successive groups of transducer arrays are placed at completely non-overlapping locations on the subject's body. In other embodiments, successive groups of transducer arrays are placed at locations on the subject's body that overlap by no more than 20%. Moreover, while all of these locations may not deliver the absolute strongest electric field to the tumor, each of these locations will provide a sufficiently strong electric field to effectively treat the tumor. Furthermore, notably, because successive groups of transducer arrays are placed at different locations on the subject's body (e.g., once every 3 to 4 days), the subject will experience much less skin irritation. Furthermore, if a portion of a subject's skin is indeed irritated during a given 3 to 4 day interval, that portion of skin will have an opportunity to heal during the following 3 to 4 day interval (during which time that portion of skin will not be covered by the transducer array).

[0008] One aspect of the present invention relates to a first method for applying an alternating electric field to a target area in a body of a subject. The body has an anterior surface, a posterior surface, a left surface, and a right surface. The first method comprises: (a) applying an alternating voltage having a frequency between 50 kHz and 1 MHz between a first set of one or more electrode elements positioned on a first area of ​​the anterior surface and a second set of one or more electrode elements positioned on a second area of ​​the posterior surface during first portions of a first time interval, and (b) applying an alternating voltage having a frequency between 50 kHz and 1 MHz between a third set of one or more electrode elements positioned on a third area of ​​the left surface and a fourth set of one or more electrode elements positioned on a fourth area of ​​the right surface during second portions of the first time interval. The first method further includes: (b) applying an alternating voltage having a frequency between 50 kHz and 1 MHz between a fifth set of one or more electrode elements located on a fifth region of the front surface and a sixth set of one or more electrode elements located on a sixth region of the rear surface during first portions of a second time interval, and applying an alternating voltage having a frequency between 50 kHz and 1 MHz between a seventh set of one or more electrode elements located on a seventh region of the left surface and an eighth set of one or more electrode elements located on an eighth region of the right surface during second portions of the second time interval. The first time interval does not overlap with the second time interval. The fifth region has less than 20% overlap with the first region, the sixth region has less than 20% overlap with the second region, the seventh region has less than 20% overlap with the third region, and the eighth region has less than 20% overlap with the fourth region.

[0009] In some instances of the first method, no portion of the fifth region overlaps with the first region, no portion of the sixth region overlaps with the second region, no portion of the seventh region overlaps with the third region, and no portion of the eighth region overlaps with the fourth region.

[0010] Some examples of the first method further include repeating steps (a) and (b) in alternating order at least ten times.

[0011] In some examples of the first method, the target region includes a tumor having a centroid, and a ray projected directly forward from the centroid does not intersect the first region, a ray projected directly backward from the centroid does not intersect the second region, a ray projected directly forward from the centroid does not intersect the fifth region, and a ray projected directly backward from the centroid does not intersect the sixth region.

[0012] In some examples of the first method, the target region includes a tumor having a centroid, and a ray projected directly forward from the centroid does not intersect at least one of the first region and the fifth region, a ray projected directly backward from the centroid does not intersect at least one of the second region and the sixth region, a ray projected directly leftward from the centroid does not intersect at least one of the third region and the seventh region, and a ray projected directly rightward from the centroid does not intersect at least one of the fourth region and the eighth region.

[0013] In some examples of the first method, the second time interval is less than 48 hours apart from the first time interval. In some examples of the first method, the first time interval is at least 12 hours, and the second time interval is at least 12 hours. In some examples of the first method, each of the alternating voltages has a sinusoidal waveform. In some examples of the first method, each of the first, second, third, fourth, fifth, sixth, seventh, and eighth regions is located on the abdomen of the subject.

[0014] Some examples of the first method further include: (c) before the first time interval, positioning the first, second, third and fourth groups of one or more electrode elements on the first area, second area, third area and fourth area, respectively; (d) after the first time interval, removing the first, second, third and fourth groups of one or more electrode elements from the subject's body; (e) before the second time interval, positioning the fifth, sixth, seventh and eighth groups of one or more electrode elements on the fifth area, sixth area, seventh area and eighth area, respectively; and (f) after the second time interval, removing the fifth, sixth, seventh and eighth groups of one or more electrode elements from the subject's body.

[0015] Optionally, the examples described in the previous paragraphs can further include: repeating step (c), step (a), step (d), step (e), step (b), and step (f) in this order at least ten times. Optionally, in these examples, each of the first region, second region, third region, fourth region, fifth region, sixth region, seventh region, and eighth region can be located in the abdomen of the subject.

[0016] Another aspect of the present invention relates to a second method for applying an alternating electric field to a tumor in a subject's body. The second method comprises: (a) applying an alternating voltage having a frequency between 50 kHz and 1 MHz between four primary sets of one or more electrode elements positioned at four primary non-overlapping areas on the subject's body during a first time interval. Furthermore, the second method further comprises: (b) applying an alternating voltage having a frequency between 50 kHz and 1 MHz between four secondary sets of one or more electrode elements positioned at four secondary non-overlapping areas on the subject's body during a second time interval. Each of the primary areas has an area, and all of the secondary areas in the secondary areas collectively overlap with 0% to 20% of the area of ​​each individual primary area in the primary area. The first time interval does not overlap with the second time interval.

[0017] In some examples of the second method, none of the secondary regions of the secondary region overlap with any primary region of the primary region.

[0018] Some examples of the second method further comprise: repeating step (a) and step (b) in an alternating order at least ten times.

[0019] In some examples of the second method, the tumor has a centroid, rays projected directly forward from the centroid leave all primary regions in the primary region and all secondary regions in the secondary region untouched, and rays projected directly backward from the centroid leave all primary regions in the primary region and all secondary regions in the secondary region untouched.

[0020] In some instances of the second method, the second time interval is less than 48 hours from the first time interval. In some instances of the second method, the first time interval is at least 12 hours, and the second time interval is at least 12 hours. In some instances of the second method, each of the alternating voltages has a sinusoidal waveform. In some instances of the second method, each of the primary regions and each of the secondary regions is located in the abdomen of the subject.

[0021] Some examples of the second method further include: (c) positioning the primary set of one or more electrode elements on the primary area before the first time interval; (d) removing the primary set of one or more electrode elements from the subject's body after the first time interval; (e) positioning the secondary set of one or more electrode elements on the secondary area before the second time interval; and (f) removing the secondary set of one or more electrode elements from the subject's body after the second time interval.

[0022] Optionally, the examples described in the previous paragraphs can further include: repeating step (c), step (a), step (d), step (e), step (b), and step (f) in this order at least ten times. Optionally, in these examples, each of the primary regions and each of the secondary regions is located on the abdomen of the subject. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 Depicted are examples of four different views of a spherical target area T including a tumor in the abdomen of a subject.

[0024] Figure 2 Depicted are the general locations on a subject's body for a transducer array to treat a tumor at a target region T using TTFields.

[0025] Figure 3A and Figure 3B An alternative method is depicted for positioning different sets of transducer arrays at different locations on a subject's body during different time intervals to treat a tumor at a target region T using TTFields.

[0026] Various embodiments are described in detail below with reference to the drawings, wherein like reference numerals represent like elements. DETAILED DESCRIPTION

[0027] Figure 1 One example of four different views (ie, right view, front view, left view, and back view) of a spherical target area T including a tumor in the abdomen of a subject is depicted.

[0028] Figure 2 The conventional locations of the transducer array on the right, front, left, and back sides of the subject's body are depicted for treating a tumor at a target region T using TTFields. One conventional method for positioning the transducer array is to position the centroid of the transducer array directly to the right, front, left, and back of the centroid of the target region T, as shown in FIG. Figure 2 This method is referred to herein as the dead reckoning method. Another conventional method is to use specialized software (e.g., Novotal TM software) that is designed to recommend a set of locations for the sensor array that will maximize the electric field strength in the target area.

[0029] It is worth noting that the recommendations generated by such software are Figure 2The depicted dead reckoning positions deviate only by a relatively small amount (e.g., less than 5 cm). Given this relatively small positional offset, when using either of the two conventional methods, the positioning is such that: (1) a ray cast directly forward from the center of mass of the tumor T intersects the region where the anterior array is located; and (2) a ray cast directly backward from the center of mass of the tumor T intersects the region where the posterior array is located.

[0030] Furthermore, as explained above, each time a new set of transducer arrays is attached to the subject's body, the set of transducer arrays is attached at the same approximate location, with a deviation of less than one inch from the baseline position. Thus, each time a new set of transducer arrays is attached, the positioning is still such that: (1) a ray projected directly forward from the centroid of the tumor T intersects the region where the anterior array is located; and (2) a ray projected directly backward from the centroid of the tumor T intersects the region where the posterior array is located.

[0031] Figure 3A and Figure 3B An alternative method is described for positioning different sets of transducer arrays at different locations on a subject's body during different time intervals. In this method, during a first time interval, a first set of four transducer arrays S1 to S4 are positioned on respective regions R1 to R4 of the front, back, left, and right surfaces of the subject's body (e.g., Figure 3A Also, during a second time interval, a second set of four transducer arrays S5 to S8 are positioned on respective regions R5 to R8 of the front, back, left, and right surfaces of the subject's body (as depicted). Figure 3B (depicted). The first time interval does not overlap with the second time interval. Each of transducer arrays S1 to S8 includes one or more electrode elements. Because the transducer arrays are positioned at different locations during different time intervals, skin irritation is significantly reduced, and any given patch of skin has an opportunity to recover during alternating time intervals when it is not covered by the transducer arrays.

[0032] The positioning of the transducer array can be Figure 3A The depicted location and Figure 3B The positions depicted may be alternated, for example, every 3 to 4 days. For example, on days 1 to 3 of treatment, the first set of transducer arrays may be positioned on regions R1 to R4, as shown. Figure 3A During the first three-day interval, transducer arrays S1 to S4 were used to apply TTFields to the subject's body, as described below. At the end of Day 3, the first set of transducer arrays S1 to S4 were removed and discarded. Then, on Days 4 to 6 of treatment, a second set of transducer arrays S5 to S8 were positioned over regions R5 to R8, as described below. Figure 3BDuring the second time interval of three days, transducer arrays S5 to S8 were used to apply TTFields to the subject's body, as described below. At the end of day 6, the second set of transducer arrays S5 to S8 were removed and discarded.

[0033] Then, on days 7 to 9 of treatment, a new first set of transducer arrays S1 to S4 is positioned over regions R1 to R4. During this three-day first time interval, transducer arrays S1 to S4 are used to apply TTFields to the subject's body. At the end of day 9, this set of transducer arrays S1 to S4 is removed and discarded. Then, on days 10 to 12 of treatment, a new second set of transducer arrays S5 to S8 is positioned over regions R5 to R8. During this three-day second time interval, transducer arrays S5 to S8 are used to apply TTFields to the subject's body. At the end of day 12, this set of transducer arrays S5 to S8 is removed and discarded. The transducer arrays alternate every three days between placement over regions R1 to R4 during the first time interval and over regions R5 to R8 during the second time interval, and this pattern is repeated continuously for the duration of treatment. For example, if the treatment duration is 60 days, the following steps will be repeated 10 times in an alternating order: (a) during a first time interval, transducer arrays S1 to S4 are positioned over regions R1 to R4, and then (b) during a second time interval, transducer arrays S5 to S8 are positioned over regions R5 to R8. If the treatment duration exceeds 60 days, these steps (a) and (b) will be repeated more than 10 times.

[0034] In some embodiments, any portion of the fifth region R5 does not overlap with the first region R1, any portion of the sixth region R6 does not overlap with the second region R2, any portion of the seventh region R7 does not overlap with the third region R3, and any portion of the eighth region R8 does not overlap with the fourth region R4 (e.g., as shown in FIG. Figure 3A and Figure 3B ). In other embodiments (e.g., when the anatomy of a particular subject does not support completely non-overlapping positioning), there may be a small amount of overlap. In these embodiments, less than 20% of the fifth region R5 overlaps with the first region R1, less than 20% of the sixth region R6 overlaps with the second region R2, less than 20% of the seventh region R7 overlaps with the third region R3, and less than 20% of the eighth region R8 overlaps with the fourth region R4.

[0035] During each first time interval in the first time interval, the direction of the electric field alternates between a front / back direction and a left / right direction. This can be achieved by applying an alternating voltage having a frequency between 50 kHz and 1 MHz (e.g., 100 kHz to 300 kHz) between the first transducer array S1 positioned on the first region R1 and the second transducer array S2 positioned on the second region R2 during the first portions of the first time interval, and applying an alternating voltage having a similar frequency between the third transducer array S3 positioned on the third region R3 and the fourth transducer array S4 positioned on the fourth region R4 during the second portions of the first time interval. In some embodiments, (a) the alternating voltage is applied between the first transducer array S1 and the second transducer array S2 for, for example, one second, and then (b) the alternating voltage is applied between the third transducer array S3 and the fourth transducer array S4 for, for example, one second; and this two-step sequence (a) and (b) is repeated until the transducer arrays S1 to S4 are removed.

[0036] Similarly, during each second time interval in the second time interval, the direction of the electric field alternates between the front / back direction and the left / right direction. This can be achieved by applying an alternating voltage having a frequency between 50 kHz and 1 MHz (e.g., 100 kHz to 300 kHz) between the fifth transducer array S5 positioned on the fifth region R5 and the sixth transducer array S6 positioned on the sixth region R6 during the first portions of the second time interval, and applying an alternating voltage having a similar frequency between the seventh transducer array S7 positioned on the seventh region R7 and the eighth transducer array S8 positioned on the eighth region R8 during the second portions of the second time interval. In some embodiments, (a) the alternating voltage is applied between the fifth transducer array S5 and the sixth transducer array S6 for, for example, one second, and then (b) the alternating voltage is applied between the seventh transducer array S7 and the eighth transducer array S8 for, for example, one second; and this two-step sequence (a) and (b) is repeated until the transducer arrays S5 to S8 are removed.

[0037] Combined with the above Figure 2 Different from the prior art, when the transducer arrays S1 to S4 are positioned at the regions R1 to R4 (e.g. Figure 3A ), a ray projected directly forward from the center of mass of the tumor T does not intersect the first region R1, and a ray projected directly backward from the center of mass of the tumor T does not intersect the second region R2. In addition, when the transducer arrays S5 to S6 are positioned at the regions R5 to R6 (as shown in FIG. Figure 3B ), a ray projected directly forward from the center of mass of the tumor T does not intersect the fifth region R5, and a ray projected directly backward from the center of mass of the tumor T does not intersect the sixth region R6.

[0038] The strict positioning parameters described in the previous paragraph are not mandatory. Instead, in some embodiments, some of these positioning parameters are such that a ray projected directly forward or backward from the center of mass of the tumor T will intersect some, but not all, of these regions. For example, in some embodiments, a ray projected directly forward from the center of mass of the tumor T does not intersect at least one of the first region R1 and the fifth region R5; a ray projected directly backward from the center of mass of the tumor T does not intersect at least one of the second region R2 and the sixth region R6; a ray projected directly to the left from the center of mass of the tumor T does not intersect at least one of the third region R3 and the seventh region R7; and a ray projected directly to the right from the center of mass of the tumor T does not intersect at least one of the fourth region R4 and the eighth region R8.

[0039] It is worth noting that although not all transducers in the transducer array are positioned directly in front of or behind the centroid of the tumor T, the simulation shows that: (a) Figure 3A The depicted positioning can generate a sufficiently strong electric field >1 V / cm in the target area to effectively treat the tumor; and (b) Figure 3B The depicted positioning can also generate a sufficiently strong electric field >1 V / cm in the target area to effectively treat tumors. Figure 3A The positioning depicted Figure 3B The subject will alternate between the depicted positionings so that they always receive a sufficiently strong electric field to effectively treat the tumor. In addition, in some embodiments, because no portion of the skin is ever covered for more than three days at a time, skin irritation will be reduced, and if it does occur, the skin will have a chance to heal during the three-day interval in which it remains uncovered. In other embodiments, the portion of the skin that is covered for more than three days at a time will be significantly reduced, as shown in FIG. Figure 2 The depicted positioning significantly reduces skin irritation compared to the prior art.

[0040] Because TTFields are more effective when treatment gaps are minimized, the gap between the end of each first time interval and the beginning of the subsequent second time interval is preferably less than 96 hours, more preferably less than 48 hours, and still more preferably less than 24 hours.

[0041] In some preferred embodiments, each of the alternating voltages described above has a sinusoidal waveform. However, in other embodiments, alternative waveforms including but not limited to square waves, triangle waves, etc. may be used.

[0042] In some preferred embodiments, each of the first, second, third, fourth, fifth, sixth, seventh, and eighth regions R1 to R8 is located on the abdomen of the subject.

[0043] Although in the example provided above, the first time interval is 3 days and the second time interval is 3 days, the duration of these intervals may be different. For example, each of these intervals may be at least 12 hours, at least 24 hours, or at least 48 hours.

[0044] In the examples described above, the first area, the second area, the third area, and the fourth area are located on the front surface, the back surface, the left surface, and the right surface of the subject's body, respectively; and the fifth area, the sixth area, the seventh area, and the eighth area are located on the front surface, the back surface, the left surface, and the right surface of the subject's body, respectively. However, the concepts described above are not limited to the specific directions (i.e., the front, back, left, and right) that appear in the examples described above. For example, Figure 3A and Figure 3B All of the depicted sets of electrode elements can be rotated 45° about the longitudinal axis of the subject's body and the tumor T can still be imaged using TTFields similar to the above combined Figure 3A and Figure 3B The treatment is performed in the manner described as an example.

[0045] Therefore, the above combined Figure 3A and Figure 3B The example described can be summarized as follows: (a) during a first time interval, an alternating voltage having a frequency between 50 kHz and 1 MHz is applied between four primary sets of one or more electrode elements located on four primary non-overlapping regions (i.e., regions R1 to R4) on a subject's body (i.e., between transducer array S1 and transducer array S2, and between transducer array S3 and transducer array S4); and (b) during a second time interval, an alternating voltage having a frequency between 50 kHz and 1 MHz is applied between four secondary sets of one or more electrode elements located on four secondary non-overlapping regions (i.e., regions R5 to R8) on the subject's body (i.e., between transducer array S5 and transducer array S6, and between transducer array S7 and transducer array S8). Each of the primary regions R1 to R4 has a certain area, and all of the secondary regions R5 to R6 together overlap with 0% to 20% of the area of ​​each individual primary region of the primary regions R1 to R4. The first time interval does not overlap with the second time interval. In some embodiments (including Figure 3A and Figure 3BIn the example depicted), none of the secondary areas overlap with any primary area in the primary area.

[0046] Finally, it is important to note that the use of the designators (a), (b), (c), (d), etc., in the claims below does not imply a specific temporal ordering of the corresponding steps. While it is certainly possible for step (a) to precede step (b) in time, a different ordering of the steps is also possible, unless a specific ordering is inconsistent with the internal language of the individual steps or other language in the claims. For example, the step labeled (b) may precede the step labeled (a) in time. It is also possible for two or more steps to occur simultaneously or overlap to some extent, unless the concurrence or overlap is inconsistent with the internal language of the individual steps or other language in the claims.

[0047] Although the present invention has been disclosed with reference to certain embodiments, numerous modifications, variations, and changes may be made to the described embodiments without departing from the field and scope of the invention as defined in the appended claims. It is therefore intended that the present invention not be limited to the described embodiments, but rather have the full scope defined by the language of the appended claims and their equivalents.

Claims

1. A method of applying an alternating electric field to a target area in a body of a subject, the body having a front surface, a back surface, a left surface, and a right surface, the method comprising: (a) applying an alternating voltage having a frequency between 50 kHz and 1 MHz between a first set of one or more electrode elements positioned on a first area of ​​the front surface and a second set of one or more electrode elements positioned on a second area of ​​the rear surface during first portions of a first time interval, and applying an alternating voltage having a frequency between 50 kHz and 1 MHz between a third set of one or more electrode elements positioned on a third area of ​​the left surface and a fourth set of one or more electrode elements positioned on a fourth area of ​​the right surface during second portions of the first time interval; as well as (b) applying an alternating voltage having a frequency between 50 kHz and 1 MHz between a fifth set of one or more electrode elements positioned on a fifth area of ​​the front surface and a sixth set of one or more electrode elements positioned on a sixth area of ​​the rear surface during a plurality of first portions of the second time interval, and applying an alternating voltage having a frequency between 50 kHz and 1 MHz between a seventh set of one or more electrode elements positioned on a seventh area of ​​the left surface and an eighth set of one or more electrode elements positioned on an eighth area of ​​the right surface during a plurality of second portions of the second time interval, wherein the first time interval and the second time interval do not overlap, wherein less than 20% of the fifth region overlaps with the first region, wherein less than 20% of the sixth region overlaps with the second region, wherein less than 20% of the seventh region overlaps with the third region, and The eighth region overlaps with the fourth region by less than 20%.

2. The method according to claim 1, wherein any portion of the fifth region does not overlap with the first region, wherein any portion of the sixth region does not overlap with the second region, wherein any portion of the seventh region does not overlap with the third region, Wherein any part of the eighth region does not overlap with the fourth region.

3. The method according to claim 1, further comprising: Step (a) and step (b) are repeated at least ten times in alternating order.

4. The method of claim 1 , wherein the target region comprises a tumor, the tumor having a centroid, wherein a ray cast directly forward from the centroid does not intersect the first region, wherein a ray cast directly backward from the centroid does not intersect the second region, wherein a ray cast directly forward from the centroid does not intersect the fifth region, and A ray directly cast backward from the center of mass does not intersect the sixth region.

5. The method of claim 1 , wherein the target region comprises a tumor, the tumor having a centroid, wherein a ray cast directly forward from the centroid does not intersect at least one of the first region and the fifth region, wherein a ray cast directly back from the centroid does not intersect at least one of the second region and the sixth region, wherein a ray cast directly to the left from the centroid does not intersect at least one of the third region and the seventh region, and A ray projected directly to the right from the centroid does not intersect at least one of the fourth region and the eighth region. The method of claim 1 , wherein the second time interval is less than 48 hours apart from the first time interval.

7. The method of claim 1, wherein the first time interval is at least 12 hours and the second time interval is at least 12 hours. The method according to claim 1 , wherein each of the alternating voltages has a sinusoidal waveform.

9. The method of claim 1, wherein each of the first region, the second region, the third region, the fourth region, the fifth region, the sixth region, the seventh region, and the eighth region is located in the abdomen of the subject.

10. The method according to claim 1, further comprising: (c) prior to the first time interval, positioning the first, second, third, and fourth groups of one or more electrode elements on the first region, second region, third region, and fourth region, respectively; (d) removing the first, second, third, and fourth groups of one or more electrode elements from the subject after the first time interval; (e) prior to the second time interval, positioning the fifth, sixth, seventh, and eighth groups of one or more electrode elements on the fifth, sixth, seventh, and eighth regions, respectively; and (f) after the second time interval, removing the fifth, sixth, seventh, and eighth groups of one or more electrode elements from the subject's body.

11. The method according to claim 10, further comprising: Step (c), step (a), step (d), step (e), step (b), and step (f) are repeated in the stated order at least ten times. 12 . The method of claim 11 , wherein each of the first region, the second region, the third region, the fourth region, the fifth region, the sixth region, the seventh region, and the eighth region is located in the abdomen of the subject.

13. A method of applying an alternating electric field to a tumor in a subject's body, the method comprising: (a) applying, during a first time interval, an alternating voltage having a frequency between 50 kHz and 1 MHz between primarily four groups of one or more electrode elements positioned on four primarily non-overlapping areas on the subject's body; as well as (b) applying an alternating voltage having a frequency between 50 kHz and 1 MHz between secondary four groups of one or more electrode elements positioned at four secondary non-overlapping areas on the subject's body during a second time interval, wherein each of the primary regions has an area, and wherein all of the secondary regions collectively overlap with 0% to 20% of the area of ​​each individual primary region in the primary region, and The first time interval and the second time interval do not overlap. The method of claim 13 , wherein none of the secondary areas overlaps with any of the primary areas.

15. The method according to claim 13, further comprising: Step (a) and step (b) are repeated at least ten times in alternating order.

16. The method of claim 13, wherein the second time interval is less than 48 hours apart from the first time interval.

17. The method of claim 13, wherein the first time interval is at least 12 hours and the second time interval is at least 12 hours.

18. The method according to claim 13, further comprising: (c) prior to said first time interval, positioning said primary set of one or more electrode elements over said primary area; (d) removing the primary set of one or more electrode elements from the subject's body after the first time interval; (e) prior to said second time interval, positioning said secondary set of one or more electrode elements over said secondary area; as well as (f) after the second time interval, removing the secondary set of one or more electrode elements from the subject's body.

19. The method according to claim 18, further comprising: Step (c), step (a), step (d), step (e), step (b), and step (f) are repeated in the stated order at least ten times.

20. The method of claim 19, wherein each of the primary regions and each of the secondary regions are located in the abdomen of the subject.

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