Sequential positioning of a set of electrode arrays at non-overlapping locations to improve skin stimulation during tumor treating field (TTFIELD) therapy

Abstract

An alternating current electric field can be applied to a subject's body by (a) applying an alternating current voltage between electrode elements positioned in four primary non-overlapping regions on the subject's body for a first time interval, and (b) applying an alternating current voltage between other electrode elements positioned in four secondary non-overlapping regions on the subject's body for a second time interval. None of the secondary regions overlap with any of the primary regions, and the first and second time intervals do not overlap. The non-overlapping nature, both in space and time, reduces the frequency of skin irritation. To the extent that skin irritation occurs during a given time interval, it may heal during a subsequent time interval.

Description

[Technical Field]

[0001] [CROSS-REFERENCE TO RELATED APPLICATIONS] 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 technology]

[0002] Tumor Treating Field (TTField) therapy is a proven approach to treating tumors using alternating current electric fields at frequencies between 50 kHz and 1 MHz (e.g., 150–250 kHz). In the prior art Optune® system, TTFields are delivered to the patient via four transducer arrays placed on the patient's skin near the tumor. The transducer arrays are arranged in two pairs, with one pair positioned on the left and right sides of the tumor and the other pair positioned in front and behind 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 to the anterior / posterior (A / P) pair of transducer arrays for 1 second to induce an electric field in the tumor in a first direction, and then (b) sends an AC current to the left / right (L / R) pair of arrays for 1 second to induce an electric field in the tumor in a second direction. Steps (a) and (b) are then repeated throughout the treatment. Each transducer array includes a plurality of (eg, 9 to 30) electrode elements.

[0003] Alternating current electric fields can also be used to treat conditions other than tumors. For example, as described in U.S. Patent No. 10,967,167 (incorporated herein by reference in its entirety), alternating current electric fields can be used to increase the permeability of the blood-brain barrier, allowing, for example, chemotherapy drugs to reach the brain.

[0004] When treating tumors with TTFields using the Optune® system, transducer arrays are affixed to the subject's skin in a location selected to deliver the strongest electric field within the tumor. The transducer arrays are attached to the subject's body using a self-adhesive backing and remain in the same location for an extended period of time (e.g., 3-4 days). After this extended period, the transducer arrays are removed, allowing the subject to shave and bathe. A new set of transducer arrays is then affixed to the subject's body in the same habitual location as before, offset by less than 1 inch from the previous position. (See the Optune Patient Information and Operation Manual, Document Number: QSD-QR-704. REV 05, January 2019.) Treatment with Optune® typically continues for months to years, with transducer arrays being replaced every 3-4 days.

[0005] Some patients experience skin irritation or itching beneath the transducer array. While these symptoms can usually be treated with steroid creams, a subset of these patients may find the irritation or itching very unpleasant. Summary of the Invention

[0006] Unlike prior art approaches in which consecutive sets of transducer arrays are all placed in the same regular locations on the subject's body (i.e., a set of four locations selected to deliver the strongest electric field within the tumor), the present application describes multiple alternative approaches for positioning consecutive sets of transducer arrays in different locations on the subject's body (e.g., every 3-4 days). More specifically, in some embodiments, consecutive sets of transducer arrays are placed on the subject's body in completely non-overlapping locations. In other embodiments, consecutive sets of transducer arrays are placed on the subject's body in locations that overlap by less than 20%. And, while no single location can deliver an absolutely strongest electric field to the tumor, each of these locations delivers an electric field of sufficient strength to effectively treat the tumor. And, notably, because consecutive sets of transducer arrays are placed in different locations on the subject's body (e.g., every 3-4 days), the subject experiences significantly less skin irritation. Furthermore, as long as a portion of the subject's skin is stimulated during a given 3-4 day interval, that area of ​​skin has the potential to heal during the next 3-4 day interval (during which the area is not covered by the transducer array).

[0007] One aspect of the present invention relates to a first method for applying an AC electric field to a target region within a subject's body, the body having a front, back, left, and right surface. The first method includes: (a) applying an AC voltage at a frequency between 50 kHz and 1 MHz between a first set of one or more electrode elements positioned in a first region on the front surface and a second set of one or more electrode elements positioned in a second region on the back surface during a plurality of first portions of a first time interval; and (b) applying an AC voltage at a frequency between 50 kHz and 1 MHz between a third set of one or more electrode elements positioned in a third region on the left surface and a fourth set of one or more electrode elements positioned in a fourth region on the right surface during a plurality of second portions of the first time interval. The first method also includes (b) applying, during a plurality of first portions of the second time intervals, an AC voltage at a frequency between 50 kHz and 1 MHz between a fifth set of one or more electrode elements positioned in a fifth region on the front surface and a sixth set of one or more electrode elements positioned in a sixth region on the rear surface, and applying, during a plurality of second portions of the second time intervals, an AC voltage at a frequency between 50 kHz and 1 MHz between a seventh set of one or more electrode elements positioned in a seventh region on the left surface and an eighth set of one or more electrode elements positioned in an eighth region on the right surface. The first time intervals and the second time intervals are non-overlapping. Less than 20% of the fifth region overlaps with the first region, less than 20% of the sixth region overlaps with the second region, less than 20% of the seventh region overlaps with the third region, and less than 20% of the eighth region overlaps with the fourth region.

[0008] In some examples 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 further, no portion of the eighth region overlaps with the fourth region.

[0009] Some examples of the first method further include alternatingly repeating steps (a) and (b) at least 10 times.

[0010] In some examples of the first method, the target region includes a tumor having a center of mass, and a line projected directly forward from the center of mass does not intersect with a first region, a line projected directly backward from the center of mass does not intersect with a second region, a line projected directly forward from the center of mass does not intersect with a fifth region, and a line projected directly backward from the center of mass does not intersect with a sixth region.

[0011] In some examples of the first method, the target region includes a tumor having a center of mass, and a line projected directly forward from the center of mass does not intersect with at least one of the first region and the fifth region, a line projected directly backward from the center of mass does not intersect with at least one of the second region and the sixth region, a line projected directly left from the center of mass does not intersect with at least one of the third region and the seventh region, and a line projected directly right from the center of mass does not intersect with at least one of the fourth region and the eighth region.

[0012] 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, the AC voltages each have a sinusoidal waveform. In some examples of the first method, the first, second, third, fourth, fifth, sixth, seventh, and eighth regions are each located on the abdomen of the subject.

[0013] Some examples of the first method further include: (c) positioning first, second, third, and fourth sets of one or more electrode elements on the first, second, third, and fourth regions, respectively, before the first time interval; (d) removing the first, second, third, and fourth sets of one or more electrode elements from the subject's body after the first time interval; (e) positioning fifth, sixth, seventh, and eighth sets of one or more electrode elements on the fifth, sixth, seventh, and eighth regions, respectively, before the second time interval; and (f) removing the fifth, sixth, seventh, and eighth sets of one or more electrode elements from the subject's body after the second time interval.

[0014] Optionally, the examples described in the previous paragraph may further include repeating steps (c), (a), (d), (e), (b), and (f), in that order, at least 10 times. Optionally, in these examples, the first, second, third, fourth, fifth, sixth, seventh, and eighth regions may each be located on the subject's abdomen.

[0015] Another aspect of the present invention relates to a second method for applying an alternating current electric field to a tumor in a subject's body. The second method includes (a) applying, during a first time interval, an alternating current voltage at a frequency between 50 kHz and 1 MHz between four primary sets of one or more electrode elements positioned in four primary non-overlapping regions on the subject's body. The second method also includes (b) applying, during a second time interval, an alternating current voltage at a frequency between 50 kHz and 1 MHz between four secondary sets of one or more electrode elements positioned in four secondary non-overlapping regions on the subject's body. The primary regions each have an area, and 0-20% of the area of ​​each primary region alone overlaps with all of the secondary regions combined. The first time interval and the second time interval are non-overlapping.

[0016] In some instances of the second method, no secondary region overlaps with any primary region.

[0017] Some examples of the second method further include alternatingly repeating steps (a) and (b) at least 10 times.

[0018] In some examples of the second method, the tumor has a center of mass, and a line projected directly forward from the center of mass misses all of the primary regions and all of the secondary regions, and a line projected directly backward from the center of mass misses all of the primary regions and all of the secondary regions.

[0019] In some examples of the second method, the second time interval is less than 48 hours apart from the first time interval. In some examples 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 examples of the second method, the AC voltages each have a sinusoidal waveform. In some examples of the second method, each primary region and each secondary region is located on the abdomen of the subject.

[0020] Some examples of the second method further include: (c) positioning a primary set of one or more electrode elements on the primary region 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 a secondary set of one or more electrode elements on the secondary region 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.

[0021] Optionally, the examples described in the previous paragraph may further include repeating steps (c), (a), (d), (e), (b), and (f), in that order, at least 10 times. Optionally, in these examples, each primary region and each secondary region is located on the subject's abdomen. [Brief explanation of the drawings]

[0022] [Figure 1] An example of four different views of a spherical target region T containing a tumor in the abdomen of a subject is shown. [Figure 2] FIG. 1 shows the area on a subject's body where a transducer array is conventionally positioned to treat a tumor in a target region T with TTFields. [Figure 3A] We demonstrate an alternative approach for positioning different sets of transducer arrays at various locations on a subject's body for various time intervals to treat a tumor in a target region T with TTFields. [Figure 3B]We demonstrate an alternative approach for positioning different sets of transducer arrays at various locations on a subject's body for various time intervals to treat a tumor in a target region T with TTFields.

[0023] Various embodiments are described in detail below with reference to the accompanying drawings, in which like reference numerals represent like elements, and in which: DETAILED DESCRIPTION OF THE INVENTION

[0024] FIG. 1 shows an example of four different views (ie, right, anterior, left, and posterior views) of a spherical target region T containing a tumor in the abdomen of a subject.

[0025] Figure 2 shows regions on the right, anterior, left, and posterior sides of a subject's body where transducer arrays are traditionally positioned to treat a tumor in a target region T with TTFields. As shown in Figure 2, one traditional approach to positioning the transducer array has been to position the transducer array's center of gravity directly to the right, anterior, left, and posterior of the center of gravity of the target region T. This approach is referred to herein as the dead reckoning approach. Another traditional approach has been to use specialized software (e.g., Novotal™ software) designed to suggest a set of transducer array positions that maximizes the electric field strength in the target region.

[0026] Notably, the proposals generated by such software deviate only a relatively small amount (e.g., less than 5 cm) from the dead reckoning positions shown in Figure 2. Given this relatively small deviation, using either of two conventional approaches, (1) a line projected directly forward from the center of mass of tumor T intersects the region where the front array is positioned, and (2) a line projected directly backward from the center of mass of tumor T intersects the region where the rear array is positioned.

[0027] Furthermore, as described above, each time a new set of transducer arrays was applied to the subject's body, the set of transducer arrays was applied in approximately the same location, less than 1 inch from the baseline position. Thus, each time a new set of transducer arrays was applied, they were still positioned such that (1) a line projected directly forward from the center of mass of tumor T intersected the area where the anterior arrays were positioned, and (2) a line projected directly backward from the center of mass of tumor T intersected the area where the posterior arrays were positioned.

[0028] 3A and 3B illustrate an alternative approach for positioning various sets of transducer arrays at various locations on a subject's body during various time intervals. In this approach, a first set of four transducer arrays S1-S4 was positioned over regions R1-R4 on the front, back, left, and right sides of the subject's body, respectively, during a first time interval (as shown in FIG. 3A). A second set of four transducer arrays S5-S8 was positioned over regions R5-R8 on the front, back, left, and right sides of the subject's body, respectively, during a second time interval (as shown in FIG. 3B). The first and second time intervals do not overlap. Each of the transducer arrays S1-S8 includes one or more electrode elements. Because the transducer arrays are positioned at various locations during various time intervals, skin irritation is dramatically reduced, and any given patch of skin has the potential to recover during alternating time intervals not covered by the transducer arrays.

[0029] The positioning of the transducer arrays can alternate between the positions shown in FIG. 3A and the positions shown in FIG. 3B, for example, every 3-4 days. For example, on days 1-3 of treatment, a first set of transducer arrays S1-S4 can be positioned over regions R1-R4, as shown in FIG. 3A. TTFields are applied to the subject's body using transducer arrays S1-S4 during this first time interval of 3 days, as described below. At the end of day 3, the first set of transducer arrays S1-S4 are removed and discarded. Then, on days 4-6 of treatment, a second set of transducer arrays S5-S8 is positioned over regions R5-R8, as shown in FIG. 3B. TTFields are applied to the subject's body using transducer arrays S5-S8 during this second time interval of 3 days, as described below. At the end of day 6, the second set of transducer arrays S5-S8 are removed and discarded.

[0030] Then, on days 7-9 of treatment, a new first set of transducer arrays S1-S4 is positioned over regions R1-R4. During this first time interval of three days, TTFields are applied to the subject's body using transducer arrays S1-S4. At the end of day 9, this set of transducer arrays S1-S4 is removed and discarded. Then, on days 10-12 of treatment, a new second set of transducer arrays S5-S8 is positioned over regions R5-R8. During this second time interval of three days, TTFields are applied to the subject's body using transducer arrays S5-S8. At the end of day 12, this set of transducer arrays S5-S8 is removed and discarded. This pattern of transducer array placement alternating every three days between regions R1-R4 during the first time interval and regions R5-R8 during the second time interval is repeated continuously for the duration of treatment. For example, if the duration of the treatment is 60 days, the steps of (a) positioning transducer arrays S1-S4 over regions R1-R4 for a first time interval, followed by (b) positioning transducer arrays S5-S8 over regions R5-R8 for a second time interval, are alternately repeated 10 times. If the duration of the treatment exceeds 60 days, these steps (a) and (b) are repeated more than 10 times.

[0031] In some embodiments, no portion of the fifth region R5 overlaps with the first region R1, no portion of the sixth region R6 overlaps with the second region R2, no portion of the seventh region R7 overlaps with the third region R3, and no portion of the eighth region R8 overlaps with the fourth region R4 (e.g., as shown in Figures 3A and 3B). In other embodiments (e.g., if a particular subject's anatomy does not support completely non-overlapping positioning), there may be only 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.

[0032] During each of the first time intervals, the direction of the electric field is alternating between the front / back direction and the left / right direction. This may be achieved by applying an AC voltage at a frequency between 50 kHz and 1 MHz (e.g., 100 kHz and 300 kHz) between a first transducer array S1 positioned over a first region R1 and a second transducer array S2 positioned over a second region R2 during a plurality of first portions of the first time interval, and applying an AC voltage at a similar frequency between a third transducer array S3 positioned over a third region R3 and a fourth transducer array S4 positioned over a fourth region R4 during a plurality of second portions of the first time interval. In some embodiments, (a) an AC voltage is applied between the first and second transducer arrays S1, S2, for example, for 1 second, and then (b) an AC voltage is applied between the third and fourth transducer arrays S3, S4, for example, for 1 second, and this two-step sequence (a) and (b) is repeated until the transducer arrays S1 to S4 are removed.

[0033] Similarly, during each second time interval, the direction of the electric field is alternating between the front / back direction and the left / right direction. This may be achieved by applying an AC voltage at a frequency between 50 kHz and 1 MHz (e.g., 100 kHz and 300 kHz) between a fifth transducer array S5 positioned on a fifth region R5 and a sixth transducer array S6 positioned on a sixth region R6 during a plurality of first portions of the second time interval, and applying an AC voltage at a similar frequency between a seventh transducer array S7 positioned on a seventh region R7 and an eighth transducer array S8 positioned on an eighth region R8 during a plurality of second portions of the second time interval. In some embodiments, (a) an AC voltage is applied between the fifth and sixth transducer arrays S5, S6, for example, 1 second, and then (b) an AC voltage is applied between the seventh and eighth transducer arrays S7, S8, for example, 1 second, and this two-step sequence (a) and (b) is repeated until the transducer arrays S5 to S8 are removed.

[0034] Unlike the prior art situation described above in connection with Figure 2, when transducer arrays S1-S4 are positioned in regions R1-R4 (as shown in Figure 3A), a line projected directly forward from the center of mass of tumor T does not intersect with the first region R1, and a line projected directly backward from the center of mass of tumor T does not intersect with the second region R2. Furthermore, when transducer arrays S5-S6 are positioned in regions R5-R6 (as shown in Figure 3B), a line projected directly forward from the center of mass of tumor T does not intersect with the fifth region R5, and a line projected directly backward from the center of mass of tumor T does not intersect with the sixth region R6.

[0035] The exact positioning parameters described in the previous paragraph are not required. Conversely, in some embodiments, some positioning is performed such that a ray projected directly forward or backward from the center of mass of tumor T intersects some, but not all, of the regions. For example, in some embodiments, a line projected directly forward from the center of mass of tumor T does not intersect with at least one of the first region R1 and the fifth region R5; a line projected directly backward from the center of mass of tumor T does not intersect with at least one of the second region R2 and the sixth region R6; a line projected directly to the left from the center of mass of tumor T does not intersect with at least one of the third region R3 and the seventh region R7; and a line projected directly to the right from the center of mass of tumor T does not intersect with at least one of the fourth region R4 and the eighth region R8.

[0036] Notably, even if not all of the transducer arrays are positioned directly anterior or posterior to the center of mass of the tumor T, simulations show that (a) the positioning shown in FIG. 3A can generate an electric field in the target region >1 V / cm strong enough to effectively treat the tumor, and (b) the positioning shown in FIG. 3B can also generate an electric field in the target region >1 V / cm strong enough to effectively treat the tumor. As the positioning of the transducer arrays changes between the positioning shown in FIG. 3A and the positioning shown in FIG. 3B, the subject is often exposed to an electric field strong enough to effectively treat the tumor. Furthermore, in some embodiments, because no area of ​​skin is covered for more than three days at a time, skin irritation is reduced, and to the extent skin irritation occurs, the skin is allowed to heal during the three-day interval of non-coverage. In other embodiments, because the area of ​​skin covered for more than three days at a time is dramatically reduced, this dramatically reduces the level of skin irritation relative to the prior art positioning shown in FIG. 2.

[0037] Because TTFields are more effective when the time between treatments is minimized, the time between the end of each first time interval and the start of the subsequent second time interval is preferably less than 96 hours, more preferably less than 48 hours, and even more preferably less than 24 hours.

[0038] In some preferred embodiments, the AC voltages described above each have a sinusoidal waveform, however, in other embodiments, alternative waveforms may be used, including but not limited to square waves, triangular waves, etc.

[0039] In some preferred embodiments, the first, second, third, fourth, fifth, sixth, seventh, and eighth regions R1-R8 are each located on the abdomen of the subject.

[0040] In the above example, the first time interval is 3 days and the second time interval is 3 days, but the duration of these intervals can vary, for example, each of these intervals can be at least 12 hours, at least 24 hours, or at least 48 hours.

[0041] In the above example, the first, second, third, and fourth regions are located on the anterior, posterior, left, and right sides of the subject's body, respectively, and the fifth, sixth, seventh, and eighth regions are located on the anterior, posterior, left, and right sides of the subject's body, respectively. However, the concepts described above are not limited to the specific orientations (i.e., anterior, posterior, left, and right) presented in the above example. For example, all of the sets of electrode elements shown in Figures 3A and 3B could be rotated 45° about the longitudinal axis of the subject's body, and the tumor T could still be treated with TTFields in a manner similar to the example described above in connection with Figures 3A and 3B.

[0042] 3A and 3B can be generalized to situations in which (a) during a first time interval, an AC voltage is applied at a frequency between 50 kHz and 1 MHz between four primary sets of one or more electrode elements (i.e., between transducer arrays S1 and S2 and between transducer arrays S3 and S4) positioned on four primary non-overlapping regions (i.e., regions R1-R4) on the subject's body, and (b) during a second time interval, an AC voltage is applied at a frequency between 50 kHz and 1 MHz between four secondary sets of one or more electrode elements (i.e., between transducer arrays S5 and S6 and between transducer arrays S7 and S8) positioned on four secondary non-overlapping regions (i.e., regions R5-R8) on the subject's body. Primary regions R1-R4 each have an area, and 0-20% of the area of ​​each primary region R1-R4 alone overlaps with all of the secondary regions R5-R6 combined. The first and second time intervals are non-overlapping. In some embodiments (including the examples shown in Figures 3A and 3B), no secondary region overlaps with any primary region.

[0043] Finally, it is important to note that the use of identifiers such as (a), (b), (c), and (d) in the following claims does not imply a particular temporal order of the corresponding steps. While step (a) may certainly precede step (b) in time, different ordering of these steps is also possible, unless a particular ordering is inconsistent with the internal language of the various steps or other language in the claims. For example, a step labeled (b) may precede in time the step labeled (a). It is also possible for two or more steps to occur simultaneously or to overlap to some extent, unless such simultaneousness or overlap is inconsistent with the internal language of the various steps or other language in the claims.

[0044] While the present invention has been disclosed with reference to several embodiments, many modifications, variations, and variations of the described embodiments are possible without departing from the field and scope of the invention, as defined in the appended claims. Accordingly, it is intended that the present invention not be limited to the described embodiments, but rather have the full scope defined by the language of the following claims and their equivalents.

Claims

1. 1. A method of applying an alternating electric field to a target region within a subject's body, comprising: The body has a front, a back, a left side, and a right side, and the method includes: (a) applying, during a plurality of first portions of a first time interval, an alternating current voltage at a frequency between 50 kHz and 1 MHz between a first set of one or more electrode elements positioned in a first region of the front surface and a second set of one or more electrode elements positioned in a second region of the rear surface, and applying, during a plurality of second portions of the first time interval, an alternating current voltage at a frequency between 50 kHz and 1 MHz between a third set of one or more electrode elements positioned in a third region of the left surface and a fourth set of one or more electrode elements positioned in a fourth region of the right surface; (b) applying, during a plurality of first portions of a second time interval, an alternating current voltage at a frequency between 50 kHz and 1 MHz between a fifth set of one or more electrode elements positioned in a fifth region of the front surface and a sixth set of one or more electrode elements positioned in a sixth region of the rear surface, and applying, during a plurality of second portions of the second time interval, an alternating current voltage at a frequency between 50 kHz and 1 MHz between a seventh set of one or more electrode elements positioned in a seventh region of the left surface and an eighth set of one or more electrode elements positioned in an eighth region of the right surface; the first time interval and the second time interval are non-overlapping; less than 20% of the fifth region overlaps with the first region; less than 20% of the sixth region overlaps with the second region; less than 20% of the seventh region overlaps with the third region; The method, wherein less than 20% of the eighth region overlaps with the fourth region.

2. 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; The method of claim 1 , wherein no portion of the eighth region overlaps with the fourth region.

3. 10. The method of claim 1, further comprising alternatingly repeating steps (a) and (b) at least 10 times.

4. the target region includes a tumor, the tumor having a centroid; a line projected directly forward from the center of gravity does not intersect with the first region; a line projected directly backward from the center of gravity does not intersect with the second region; a line projected directly forward from the center of gravity does not intersect with the fifth region; The method of claim 1 , wherein a line projected directly backward from the center of gravity does not intersect the sixth region.

5. the target region includes a tumor, the tumor having a centroid; a line projected directly forward from the center of gravity does not intersect with at least one of the first region and the fifth region; a line projected directly backward from the center of gravity does not intersect with at least one of the second region and the sixth region; a line projected directly to the left from the center of gravity does not intersect with at least one of the third region and the seventh region; The method of claim 1 , wherein a line projected directly to the right from the center of gravity does not intersect with at least one of the fourth region and the eighth region.

6. The method of claim 1 , wherein the second time interval is less than 48 hours apart from the first time interval.

7. 10. 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.

8. The method of claim 1 , wherein the AC voltages each have a sinusoidal waveform.

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

10. Furthermore, (c) positioning the first, second, third, and fourth sets of one or more electrode elements over the first, second, third, and fourth regions, respectively, prior to the first time interval; (d) removing the first, second, third, and fourth sets of one or more electrode elements from the subject's body after the first time interval; (e) positioning the fifth, sixth, seventh, and eighth sets of one or more electrode elements over the fifth, sixth, seventh, and eighth regions, respectively, prior to the second time interval; and (f) removing the fifth, sixth, seventh, and eighth sets of one or more electrode elements from the subject's body after the second time interval.

11. 11. The method of claim 10, further comprising repeating steps (c), (a), (d), (e), (b), and (f), in that order, at least 10 times.

12. 12. The method of claim 11, wherein the first, second, third, fourth, fifth, sixth, seventh, and eighth regions are each located in the abdomen of the subject.

13. 1. A method of applying an alternating electric field to a tumor within the body of a subject, comprising: The method comprises: (a) applying, during a first time interval, an alternating current voltage at a frequency between 50 kHz and 1 MHz between four primary sets of one or more electrode elements positioned at four primary non-overlapping regions on the subject's body; (b) applying, during a second time interval, an alternating current voltage at a frequency between 50 kHz and 1 MHz between four secondary sets of one or more electrode elements positioned at four secondary non-overlapping regions on the subject's body; each of the primary regions has an area, and 0-20% of the area of ​​each of the primary regions alone overlaps with all of the secondary regions combined; The method, wherein the first time interval and the second time interval do not overlap.

14. The method of claim 13 , wherein none of the secondary regions overlaps with any of the primary regions.

15. 14. The method of claim 13, further comprising alternatingly repeating steps (a) and (b) at least 10 times.

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

17. 14. 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. Furthermore, (c) positioning the primary set of one or more electrode elements over the primary region prior to 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; and (e) positioning the secondary set of one or more electrode elements over the secondary region prior to the second time interval; (f) removing the second set of one or more electrode elements from the subject's body after the second time interval.

19. 20. The method of claim 18, further comprising repeating steps (c), (a), (d), (e), (b), and (f), in that order, at least 10 times.

20. 20. The method of claim 19, wherein each of the primary regions and each of the secondary regions is located on the subject's abdomen.

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