Combination tumor therapy electric field and radiation therapy plan

Abstract

A computer-implemented method includes: obtaining a three-dimensional model of a subject; identifying radiation therapy regions in the model to deliver radiation therapy to a tumor of the subject, the radiation therapy regions including first and second radiation therapy regions for receiving first and second doses, respectively, of radiation therapy; identifying a tumor therapy electric field therapy region in the model to deliver tumor therapy electric field therapy to the tumor, the tumor therapy electric field therapy region including the first radiation therapy region; identifying a first dose of the tumor therapy electric field therapy for the first radiation therapy region to compensate for the first dose of radiation therapy being less than the second dose of radiation therapy; and selecting one or more transducer layouts to deliver a tumor therapy electric field to the subject based on the first dose of the tumor therapy electric field therapy for the first radiation therapy region.

Description

[0001] Cross-references to related applications

[0002] This application claims the benefit and priority of U.S. Provisional Application No. 63 / 456,298, filed March 31, 2023, and U.S. Patent Application No. 18 / 613,280, filed March 22, 2024, the contents of each of which are incorporated herein by reference in their entirety. Background Technology

[0003] Tumor therapeutic electric fields (TTFields) are low-intensity alternating electric fields in the mid-frequency range (e.g., 50 kHz to 1 MHz) that can be used to treat tumors, as described in U.S. Patent No. 7,565,205. TTFields are non-invasively induced into a region of interest by placing transducers on the patient's body and applying an alternating current (AC) voltage between the transducers. Typically, transducers used to generate TTFields include multiple electrode elements comprising ceramic discs. One side of each ceramic disc is positioned against the patient's skin, and the other side of each disc has a conductive backing. Electrical signals are applied to the conductive backing, and these signals are capacitively coupled into the patient's body through the ceramic discs. Conventional transducer designs involve an array of ceramic discs attached to the subject's body via a conductive skin contact layer, such as a hydrogel. An AC voltage is applied between a pair of transducers at time intervals to generate an electric field having field lines extending generally in a front-back direction. Then, an AC voltage is applied between at least another pair of transducers at the same frequency at another time interval to generate an electric field having field lines extending generally in a left-right direction. The system then repeats these two steps throughout the treatment process. Attached Figure Description

[0004] Figure 1 An example method for selecting one or more transducer layouts to deliver TTFields to a subject is described.

[0005] Figures 2A to 2D Examples of various therapeutic areas are depicted.

[0006] Figure 3 An example device for applying an alternating electric field to a subject's body is depicted.

[0007] Figure 4 An example system for attaching a transducer to a subject's head to deliver TTFields is depicted.

[0008] Figure 5A and Figure 5B An example structure of a transducer array is depicted.

[0009] Figure 6An example of a device for determining the location of a transducer to which TTFields are applied to a subject's head is depicted. Detailed Implementation

[0010] This application describes exemplary techniques for computationally selecting and determining at least one transducer array layout to deliver TTFields to a subject.

[0011] Traditionally, in cancer treatment, radiation is applied to treat the location where the tumor has been identified and located. Radiation therapy often causes serious side effects and can be difficult to administer. For example, the inherent toxicity of radiation therapy can cause side effects that may outweigh the benefits of treating the tumor. Furthermore, the body may have a lifetime maximum tolerance to radiation therapy. Additionally, it may not be desirable to apply radiation therapy to certain areas of a subject's body.

[0012] As an alternative or complementary treatment, TTFields can be delivered to subjects, where they may have fewer side effects and offer greater flexibility in tailoring tumor treatment plans. Typically, to apply TTFields to a subject's body, one or more pairs of transducers are positioned on the subject's body. Usually, at least two pairs of transducers are used. The transducers used to apply TTFields to a subject's body typically include multiple electrode elements coupled together on a substrate.

[0013] The inventors have discovered a computational technique for determining and selecting one or more transducer layouts to deliver TTFields to subjects in addition to existing radiotherapy. Specifically, this technique is integrated into practical applications. For example, in some embodiments, treatment at more sites on a subject may have fewer side effects compared to radiation alone. For example, in some embodiments, flexible deployment and combinations of tumor treatment methods and dosages can be employed to provide beneficial treatment for the subject's tumor. In some embodiments, treatment gaps may occur because the body may have a lifetime maximum limit to the effectiveness of radiation therapy, or these gaps can be prevented by using TTFields. Therefore, TTFields can be used to fill radiation therapy coverage gaps by treating areas of the subject that cannot receive radiation due to radiation-induced side effects and / or the lifetime maximum limit of radiation. In some embodiments, the use of TTFields can also simplify and / or accelerate radiation therapy planning, as healthcare professionals can use a more streamlined radiation plan / procedure and supplement with TTFields as needed.

[0014] Figure 1An example computer-implemented method 100 for selecting one or more transducer layouts to deliver TTFields to a subject is described. Method 100 can be implemented by a computer including one or more processors and a memory accessible by the one or more processors, the memory storing instructions that, when executed by the one or more processors, cause the computer to perform the steps of method 100. Method 100 can be modified, added to, or omitted.

[0015] At step 102, method 100 includes obtaining a three-dimensional (3D) model of the subject. The model includes voxels. Each voxel of the model may be assigned a tissue type (e.g., bone, organ, body fluid, skin, or tumor) and / or an electrical conductivity associated with that tissue type. As an example, the model of the subject may represent the subject's head. As another example, the model of the subject may represent the subject's torso. In other embodiments, other body parts of the subject may be represented in the model of the subject.

[0016] In some implementations, the model can be obtained using image data (e.g., identifying different tissue types from the image data via a computer). This image data may include one or more medical images (e.g., X-ray images, magnetic resonance imaging (MRI) images, computed tomography (CT) images, ultrasound images, or any image providing an internal view of the subject's body) of a part of the subject's body. Each medical image may include the external shape of a part of the subject and a region corresponding to a region of interest (e.g., a tumor) within the subject's body. The 3D model can be obtained, for example, locally or via a network from computer memory.

[0017] At step 104, method 100 may include identifying a radiotherapy region in a 3D model of the subject to deliver radiotherapy to the subject's tumor. In some embodiments, the radiotherapy region may have a first radiotherapy region for receiving a first dose of radiotherapy and a second radiotherapy region for receiving a second dose of radiotherapy. In particular, the first radiotherapy region (e.g., spinal cord region, optic chiasm, optic tract, pituitary gland, brainstem, hypothalamus, parotid gland, intestine, or skin) may not safely tolerate the second dose of radiotherapy. In some embodiments, the first dose of radiotherapy may be based on user input. In particular, the first and second doses of radiotherapy may be in units of energy / mass.

[0018] In some implementations, the first radiation therapy region may correspond to a region in the subject that is more sensitive to radiation therapy than a region in the subject corresponding to the second radiation therapy region. In some implementations, the first radiation therapy region may correspond to a region in the subject's spinal cord. In some implementations, the first radiation therapy region may correspond to a region in the subject that is more difficult to treat with radiation therapy than a region in the subject corresponding to the second radiation therapy region.

[0019] In some embodiments, the first dose of radiotherapy may be below a first threshold for the first radiotherapy region, wherein the first threshold is based on minimizing radiotherapy side effects in the subject and / or on a limit to the amount of radiotherapy that can be applied to the first therapy region. In some embodiments, the first dose of radiotherapy may be based on a region in the subject corresponding to the first radiotherapy region.

[0020] In some embodiments, the first dose of radiation therapy may be up to 50% smaller or up to 50% larger than the second dose of radiation therapy, or may be any amount in between. In some embodiments, the first dose of radiation therapy is less than or equal to 50% of the second dose of radiation therapy and greater than 0% of the second dose of radiation therapy. In some embodiments, the first dose of radiation therapy is less than or equal to 20% of the second dose of radiation therapy and greater than 0% of the second dose of radiation therapy. For example, the first dose of radiation therapy may be 45 Gy and the second dose of radiation therapy may be 75 Gy. The first dose of radiation therapy may be 35 Gy, 40 Gy, 45 Gy, 50 Gy, 55 Gy, 60 Gy, 65 Gy, 70 Gy, or 75 Gy, or any value in between. The area receiving the first dose of radiation therapy may overlap, partially overlap, or not overlap with the area receiving the second dose of radiation therapy.

[0021] In some implementations, the first and second doses of radiotherapy may depend on the location of the tumor in the subject relative to the subject's other tissues and / or organs. The dose of radiotherapy may be limited by a predetermined radiation tolerance level in the subject's tissues and / or organs.

[0022] Examples of predetermined radiation tolerance values ​​for subjects' tissues and / or organs are discussed in the following, for example: Emami B., “Tolerance of normal tissues to therapeutic radiation,” *Reports of Radiotherapy and Oncology*, Spring 2013, Vol. 1, No. 1, pp. 35–48 (hereinafter “Emami 2013”); Bisello S. et al., “Dose-volume constraint (CORSAIR) of organs at risk in radiotherapy: a practical, one-stop, multicenter, multidisciplinary review,” *Contemporary Oncology*, 2022, Vol. 29, pp. 7021–7050 (hereinafter “Bisello 2022”); Emami B. et al., “Tolerance of normal tissues to therapeutic irradiation,” *International Journal of Radiation Oncology, Biology and Physics*, 1991, Vol. 21: 109–122 (hereinafter “Emami 1991”); and Marks LB et al., “Application of Probability Model of Complications in Normal Tissues in Clinical Practice”, International Journal of Radiation Oncology, Biology and Physics, Vol. 76, No. 3, Supplement, S10-S19, 2010 (hereinafter referred to as “Marks 2010”), the full text of each of these references is incorporated herein by reference.

[0023] For example, predetermined radiation tolerance values ​​for the subject's tissues and / or organs are discussed in, for example, Table 2 of Emami 2013, which is reproduced below as Table 1; Table 1 of Bisello 2022; Table 1 of Emami 1991; and Table 1 of Marks 2010.

[0024] Table 1: Reproduced as Table 2 in Emami 2013.

[0025]

[0026]

[0027]

[0028] Parotid gland 1, protects unilateral parotid gland; Parotid gland 2, integrates bilateral parotid glands; Kidney 1, bilateral partial kidney RT; Kidney 2, bilateral whole kidney; Vx, organ volume receiving ≥x Gy; Dx, minimum dose received by x% of the organ; D max Maximum radiation dose; D mean Average radiation dose.

[0029] As discussed herein with respect to dosage, the terms "first" and "second" are used to specify individual doses and do not necessarily indicate the order of dose administration. In some embodiments, the first dose of radiotherapy may be administered at separate times in one, two, or more portions to obtain the first dose of radiotherapy. In some embodiments, the second dose of radiotherapy may be administered at separate times in one, two, or more portions to obtain the second dose of radiotherapy. In some embodiments, a portion of the first dose of radiotherapy and a portion of the second dose of radiotherapy may be administered to the subject at the same time or at different times.

[0030] In some implementations, more than two radiation therapy zones may be required. The number of radiation therapy zones can depend on the location of the tumor and / or their location relative to the subject's tissues and / or organs.

[0031] At step 106, method 100 may include identifying a TTFields therapy region in a 3D model of the subject to deliver TTFields therapy to the subject's tumor. In some embodiments, the TTFields therapy region may at least partially include a first radiotherapy region. In some embodiments, the TTFields therapy region may at least partially include a second radiotherapy region.

[0032] At step 108, method 100 may include identifying a first dose of TTFields therapy targeting a first radiotherapy region to supplement the first dose of radiotherapy, thereby achieving a cumulative dose. This cumulative dose may be a predetermined therapeutic dose sufficient to treat or remove a tumor or cancerous tissue. In some embodiments, the cumulative dose may be substantially equal to or greater than a second radiation dose. In some embodiments, the first dose of tumor-treating electric field therapy targeting the first radiotherapy region may be based on the first dose of radiotherapy targeting the first radiotherapy region. In particular, the first dose of TTFields therapy may be in units of energy / volume.

[0033] More specifically, identifying a first dose of tumor therapeutic electric field therapy targeting a first radiotherapy region may include determining an approximate equivalent first dose of radiotherapy targeting the first radiotherapy region, in energy / volume units, and determining a first dose of tumor therapeutic electric field therapy targeting the first radiotherapy region based on the approximate equivalent first dose of radiotherapy targeting the first radiotherapy region.

[0034] In some embodiments, the combination of a first dose of TTFields therapy to the first radiotherapy region and a first dose of radiotherapy to the first radiotherapy region (cumulative dose) may meet or exceed a treatment dose threshold for treating the tumor in the first radiotherapy region with radiotherapy alone. In some embodiments, the first dose of radiotherapy to the first radiotherapy region may be less than a treatment dose threshold for treating the tumor in the first radiotherapy region with radiotherapy alone. In some embodiments, the combination of a first dose of TTFields therapy to the first radiotherapy region and a first dose of radiotherapy to the first radiotherapy region (cumulative dose) may be less than a treatment dose threshold for treating the tumor in the first radiotherapy region with radiotherapy alone. In some embodiments, the combination of a first dose of TTFields therapy to the first radiotherapy region and a first dose of radiotherapy to the first radiotherapy region (cumulative dose) may be approximately equivalent to a second dose of radiotherapy.

[0035] Different organs or regions of a subject have various treatment dose thresholds for treating tumors using radiotherapy alone. For example, the intestinal region of a subject may have a treatment dose threshold between 45 Gy and 50 Gy, and the spinal cord region of a subject may have a treatment dose threshold between 45 Gy and 54 Gy. As an example, when radiotherapy is applied to the pancreatic region, the treatment dose threshold for treating tumors in the radiotherapy region may be 45 Gy, because higher doses may cause perforation of the intestine located adjacent to the pancreas in the subject. In such examples, when treating tumors in the pancreatic region, in addition to the 45 Gy dose of radiotherapy targeting the first radiotherapy region, a dose of TTFields therapy targeting the first radiotherapy region may be applied, resulting in a combination of doses exceeding the treatment dose thresholds for radiotherapy alone.

[0036] At optional step 110, method 100 may include identifying a second dose of TTFields therapy for the second radiotherapy region based on a second dose of radiotherapy for the second radiotherapy region. However, in some embodiments, the method may include identifying a second dose of tumor-treating electric field therapy for the second radiotherapy region without considering a second dose of radiotherapy for the second radiotherapy region.

[0037] In some implementations, more than two tumor treatment doses may be required. The number of tumor treatment doses can depend on the number of tumor sites, the radiation dose, the radiation therapy area, and / or the location of the radiation therapy area relative to the subject's tissues and / or organs.

[0038] At step 112, method 100 may include determining a plurality of transducer layouts to deliver TTFields to a subject. In some embodiments, the transducer layouts of the plurality of transducer layouts may differ in at least one of the following: location on the subject, size of the transducer, shape of the transducer, number of electrodes of the transducer, size of the electrodes of the transducer, shape of the electrodes of the transducer, or the applied material and / or structure of the transducer.

[0039] At step 114, method 100 may include selecting one or more transducer layouts from the plurality of transducer layouts to deliver TTFields to the subject. In some embodiments, the selection may be based on a first dose of TTFields therapy targeting a first radiotherapy region. In some embodiments, the selection may be further based on a second dose of tumor therapeutic electric field therapy targeting a second radiotherapy region.

[0040] In some embodiments, at least one of the selected transducer arrangements may be capable of providing a first dose of tumor therapeutic electric field therapy to a first radiotherapy region and a second dose of tumor therapeutic electric field therapy to a second radiotherapy region. In some embodiments, at least one of the selected transducer arrangements may be capable of providing a first dose of tumor therapeutic electric field therapy to a first radiotherapy region and of providing different doses of tumor therapeutic electric field therapy to at least one other region of the subject. Specifically, the first dose and the second dose of tumor therapeutic electric field therapy may be different.

[0041] At step 116, method 100 may include applying a transducer to the subject using the selected transducer layout.

[0042] At step 118, method 100 may include delivering TTFields to the subject.

[0043] Figures 2A to 2D Examples of various therapeutic areas are depicted. For example, Figure 2AA radiotherapy region 202 with therapy regions 204 and 206 and a TTFields therapy region 208 with therapy regions 206 and 210 are shown. Therapy regions 204 and 206 can receive different radiotherapy treatments, and therapy regions 206 and 210 can receive different TTFields treatments. Therapy region 204 can receive only radiotherapy and can correspond to a segment of the tumor that is far from a sensitive or inaccessible region. Therapy region 206 can receive both radiotherapy and TTFields treatment and can correspond to a segment of the tumor that is located within or adjacent to a sensitive or inaccessible region. Therapy region 210 can receive only TTFields treatment.

[0044] Figure 2B A radiotherapy region 212 that completely overlaps with the TTFields therapy region 214 is shown. Such regions may correspond to tumors that are located entirely within or adjacent to sensitive or difficult-to-reach tissues.

[0045] Figure 2C A radiotherapy region 216 is shown, which has a therapy region 218 that receives only radiation and can correspond to a segment of the tumor that is far from a sensitive or inaccessible region. A region 220 receiving both radiotherapy and TTField therapy is located within the radiotherapy region 216. Region 220 can correspond to a segment of the tumor located within a sensitive or inaccessible region, or adjacent to a sensitive or inaccessible region.

[0046] Figure 2D A TTFields therapy region 222 is shown, which has a therapy region 224 that receives only TTFields therapy and corresponds to a segment of the tumor located in a sensitive or inaccessible region, or adjacent to a sensitive or inaccessible region, and / or includes a segment of the potential location of the tumor. Three radiotherapy regions 226, 228, and 230, receiving both radiotherapy and TTFields therapy, are located within the TTFields therapy region 222. Regions 226, 228, and 230 may correspond to segments of the tumor that are far from sensitive or inaccessible regions. In some embodiments, the number of radiotherapy regions may not be limited to three and may be one, two, four, five, or more.

[0047] Anatomically, the tumor may be adjacent to normal tissue and / or adjacent to one or more organs of the subject. The interaction between TTFields therapy and radiotherapy can effectively reduce the radiation dose when the treatment is administered to the subject. In some implementations, Figure 2AThis can refer to applying treatment to a tumor adjacent to an organ, such as a tumor adjacent to the subject's intestine. For example, TTFields therapy in region 208 can increase or compensate for the treatment dose applied only to therapy region 206, such that the radiation dose applied to therapy region 206 can be reduced and / or not exceed the corresponding treatment dose threshold for radiation therapy alone.

[0048] In some implementation schemes, Figure 2B This can refer to the application of treatment to a tumor in the middle of an organ or region, such as a tumor in the spinal cord region of a subject. For example, TTFields therapy in region 214 can increase or compensate for the treatment dose applied to the entire therapy region 212, such that the radiation dose applied to therapy region 212 can be reduced and / or can not exceed the corresponding treatment dose threshold for radiation therapy alone.

[0049] In some implementation schemes, Figure 2B This can also refer to applying treatment to a tumor in an organ with a limited radiation dose. For example, one (or both) lungs of a subject may have a limit on the radiation dose they can receive based on lung size. When applying radiation therapy to the lungs, the radiation dose may need to be applied at a minimum level across the entire lung region, while the tumor region requires a higher dose. This could result in the total radiation dose applied to the lungs exceeding the radiation dose limit. In such an example, TTFields therapy could be applied to the entire therapy area 212 to compensate for the radiation dose applied to the entire lung region, ensuring that the overall radiation dose does not exceed the radiation limit.

[0050] In some implementation schemes, Figure 2C This could represent another example of applying treatment to a tumor in an organ where radiation dose is limited. For example, in addition to radiation therapy region 218, which applies radiation therapy to a region such as the lungs of a subject, TTFields therapy could also be applied to TTFields therapy region 220 to compensate for the treatment dose applied to the tumor, such that the overall radiation dose does not exceed the radiation limit.

[0051] In some implementation schemes, Figure 2C It can also refer to applying treatment to a tumor surrounding an organ of the subject. For example, when applying radiotherapy to a radiotherapy region 218 (such as adjacent to and / or located within the subject's intestines), TTFields therapy can be applied to a TTFields therapy region 220 located only within the intestinal region, such that region 220 can receive an additional treatment dose.

[0052] In some implementation schemes, Figure 2DThis can be interpreted as treatment being administered when not all tumor locations (e.g., a long, thin tumor in the subject's brain) are detectable. For example, the subject's whole brain may include more than one tumor location, and there may be concerns that not all tumor locations are detectable on medical images. In such cases, the whole brain may need to receive radiation therapy; however, the overall necessary dose of radiation therapy could lead to neurotoxicity. For example, the tolerable radiation dose for the whole brain might be 60 Gy, but a minimum dose of 60 Gy might be required to treat each individual tumor location. In such examples, radiation therapy could be applied at a lower dose to local areas 226, 228, and 230 identified as tumor locations, such as 10 Gy per local area 226, 228, and 230. Furthermore, TTFields therapy could be applied to TTFields therapy areas 224 of the whole brain (including local areas 226, 228, and 230 identified as having tumors and areas in the brain where tumors have not yet been detected) to compensate for the treatment dose applied to the whole brain.

[0053] Exemplary device

[0054] Figure 3 An example apparatus for applying alternating electric fields (e.g., TTFields) to a subject's body is depicted. A first transducer array 301 includes 13 electrode elements 303 positioned on a substrate 304, and the electrode elements 303 are electrically and mechanically connected to each other via conductive lines 309. A second transducer array 302 includes 13 electrode elements 305 positioned on a substrate 306, and the electrode elements 305 are electrically and mechanically connected to each other via conductive lines 310. The first transducer array 301 and the second transducer array 302 are connected to an AC voltage generator 307 and a controller 308. The controller 308 may include one or more processors and a memory accessible by the one or more processors. The memory may store instructions that, when executed by the one or more processors, control the AC voltage generator 307 to implement one or more embodiments of the invention. In some embodiments, the AC voltage generator 307 and the controller 308 may be integrated into the first transducer array 301 and the second transducer array 302, forming a first electric field generator and a second electric field generator.

[0055] The transducer can take various forms. The transducer can be fixed to the subject's body or attached to or integrated into clothing covering the subject's body. The transducer may include suitable materials for attaching the transducer to the subject's body. For example, such suitable materials may include fabric, foam, flexible plastic, and / or conductive medical gel. The transducer may be conductive or non-conductive. In some embodiments, the target region may be in the subject's brain, and TTFields may be located via two pairs of transducer arrays positioned on the subject's head (e.g., such as...). Figure 4 As shown, it has four transducer arrays 400) that are delivered to the subject's head. As another example, the target area can be in the subject's lungs, and TTFields can be delivered to the subject's body via two pairs of transducer arrays positioned around the chest and back of the subject's body.

[0056] The transducer may include any desired number of electrode elements. These electrode elements may use a variety of shapes, sizes, and materials. Any structure, as long as it is capable of: (a) delivering TTFields to the subject's body and (b) being positioned at the location specified herein, can be used to implement the transducer (or electric field generating device) used with embodiments of the invention. In some embodiments, at least one electrode element of the first, second, third, or fourth transducer may include at least one ceramic disk adapted to generate an alternating electric field. In a non-limiting embodiment, at least one electrode element of the first, second, third, or fourth transducer includes a polymer film adapted to generate an alternating electric field.

[0057] Figure 5A An example of an alternative design for the transducer array is depicted. The transducer array 501 includes 20 electrode elements 502 positioned on a substrate 503, and the electrode elements 502 are electrically and mechanically connected to each other via conductive lines 504. In some embodiments, the electrode elements 502 may comprise ceramic discs.

[0058] Figure 5BAn example of an alternative design for the transducer array is depicted. Transducer 505 may include substantially flat electrode elements 506. In some embodiments, electrode element 506 is a non-ceramic dielectric material positioned on a plurality of flat conductors. Examples of non-ceramic dielectric materials positioned on flat conductors may include polymer films disposed on pads on a printed circuit board or on a flat piece of metal. In other embodiments, electrode element 506 is a ceramic element. In non-limiting embodiments, electrode elements 502 and 506 may have various shapes. For example, these electrode elements may be triangular, rectangular, circular, elliptical, quasi-elliptical, oval, or standard elliptical in shape, or substantially triangular, substantially rectangular, substantially circular, substantially elliptical, substantially quasi-elliptical, substantially oval, or substantially standard elliptical in shape.

[0059] Figure 6 Example computer apparatuses for use with the embodiments described herein are depicted. For example, apparatus 600 may be a computer for implementing certain inventive techniques disclosed herein, such as... Figure 1 The selection of at least one transducer layout is used to deliver TTFields to the subject. For example, Figure 1 Steps 102 to 114 can be performed by a computer (such as computer device 600). For example, device 600 can be used as... Figure 3 The controller 308, or used as a separate computer device remote from the controller 308. For example, Figure 1 Step 118 can be performed by a controller (such as controller 308). Device 600 may include one or more processors 602, memory 604, and one or more output devices 606.

[0060] In one example, based on input 608, the one or more processors 602 generate control signals for the control voltage generator. As an example, input 608 is user input from one or more input devices (not shown). As another example, input 608 may come from another computer communicating with the controller device 600. Memory 604 can be accessed by the one or more processors 602 (e.g., via link 603) such that the one or more processors 602 can read information from memory 604 and write information to memory. Memory 604 may store instructions that, when executed by the one or more processors 602, implement one or more methods of this disclosure. The one or more output devices 606 can provide the operating status of the invention, such as transducer layout selection, the voltage being generated, and other operating information. According to certain embodiments of the invention, output device 606 can provide visualized data.

[0061] Exemplary implementation plan

[0062] The present invention includes other exemplary embodiments (“Simplifications”) as follows.

[0063] Implementation Scheme 1: A computer-implemented method for selecting at least one transducer layout to deliver a tumor therapeutic electric field to a subject, the method comprising: obtaining a three-dimensional model of the subject, the model including voxels; identifying a radiotherapy region in the three-dimensional model of the subject to deliver radiotherapy to the subject's tumor, the radiotherapy region including a first radiotherapy region for receiving a first dose of radiotherapy and a second radiotherapy region for receiving a second dose of radiotherapy, the first dose of radiotherapy being less than the second dose of radiotherapy; identifying a tumor therapeutic electric field therapy region in the three-dimensional model of the subject to deliver tumor therapeutic electric field therapy to the subject's tumor, the tumor therapeutic electric field therapy region including the first radiotherapy region; identifying a first dose of the tumor therapeutic electric field therapy for the first radiotherapy region to compensate for the first dose of radiotherapy being less than the second dose of radiotherapy; and selecting one or more transducer layouts to deliver a tumor therapeutic electric field to the subject based on the first dose of the tumor therapeutic electric field therapy for the first radiotherapy region.

[0064] Implementation Scheme 2: The computer-implemented method according to claim 1, wherein the first radiotherapy region corresponds to a region in the subject, the region being more sensitive to radiotherapy than a region in the subject corresponding to the second radiotherapy region.

[0065] Implementation Scheme 3: The computer-implemented method according to claim 2, wherein the first radiotherapy region corresponds to the spinal cord region of the subject.

[0066] Implementation Scheme 4: The computer-implemented method of claim 1, wherein the first dose of radiotherapy is below a first threshold for the first radiotherapy region, wherein the first threshold is based on minimizing radiotherapy side effects on the subject.

[0067] Implementation Scheme 5: The computer-implemented method of claim 1, wherein the first radiotherapy region corresponds to a region in the subject, the region being more difficult to treat with radiotherapy than a region in the subject corresponding to the second radiotherapy region.

[0068] Implementation Scheme 6: The computer-implemented method according to claim 4, wherein the first radiotherapy region corresponds to a brain or lung region of the subject.

[0069] Implementation Scheme 7: The computer-implemented method according to claim 1, wherein the first radiotherapy region cannot safely tolerate the second dose of radiotherapy.

[0070] Implementation Scheme 8: The computer-implemented method of claim 1, wherein the first dose of radiotherapy is based on a region in the subject corresponding to the first radiotherapy region.

[0071] Implementation Scheme 9: The computer-implemented method according to claim 1, wherein the first dose of radiotherapy is less than or equal to 50% and greater than 0% of the second dose of radiotherapy.

[0072] Implementation Scheme 10: The computer-implemented method according to claim 1, wherein the first dose of radiotherapy is less than or equal to 20% and greater than 0% of the second dose of radiotherapy.

[0073] Implementation Scheme 11: The computer-implemented method of claim 1, wherein the first dose of radiotherapy is based on user input.

[0074] Implementation Scheme 12: The computer-implemented method of claim 1, wherein the first dose of the tumor therapeutic electric field therapy for the first radiotherapy region is based on the first dose of radiotherapy for the first radiotherapy region.

[0075] Implementation Scheme 13: The computer-implemented method of claim 1, wherein the tumor therapeutic electric field therapy region in the three-dimensional model of the subject includes a portion or all of the second radiotherapy region, wherein the method further includes identifying a second dose of the tumor therapeutic electric field therapy for the second radiotherapy region based on a second dose of radiotherapy for the second radiotherapy region, and wherein one or more transducer arrangements are selected to deliver the tumor therapeutic electric field to the subject further based on the second dose of the tumor therapeutic electric field therapy for the second radiotherapy region.

[0076] Implementation Scheme 14: The computer-implemented method of claim 1, wherein the tumor therapeutic electric field therapy region in the three-dimensional model of the subject includes a portion or all of the second radiotherapy region, wherein the method further includes identifying a second dose of the tumor therapeutic electric field therapy targeting the second radiotherapy region without regard to a second dose of radiotherapy targeting the second radiotherapy region, and wherein one or more transducer arrangements are selected to deliver the tumor therapeutic electric field to the subject further based on the second dose of the tumor therapeutic electric field therapy targeting the second radiotherapy region.

[0077] Implementation Scheme 15: The computer-implemented method of claim 1, wherein the combination of the first dose of the tumor therapeutic electric field therapy for the first radiotherapy region and the first dose of the radiotherapy for the first radiotherapy region satisfies or exceeds a treatment dose threshold for treating the tumor in the first radiotherapy region with radiotherapy alone, wherein the first dose of the radiotherapy for the first radiotherapy region is less than the treatment dose threshold for treating the tumor in the first radiotherapy region with radiotherapy alone.

[0078] Implementation Scheme 16: The computer-implemented method of claim 1, wherein the combination of the first dose of the tumor therapeutic electric field therapy for the first radiotherapy region and the first dose of the radiotherapy for the first radiotherapy region is less than a treatment dose threshold for treating the tumor in the first radiotherapy region using only the radiotherapy.

[0079] Implementation Scheme 17: The computer-implemented method of claim 1, wherein the first dose of radiotherapy is in units of energy / mass, wherein the first dose of tumor therapeutic electric field therapy is in units of energy / volume, wherein identifying the first dose of the tumor therapeutic electric field therapy for the first radiotherapy region comprises: determining an approximately equivalent first dose of radiotherapy for the first radiotherapy region, in units of energy / volume; and determining the first dose of the tumor therapeutic electric field therapy for the first radiotherapy region based on the approximately equivalent first dose of radiotherapy for the first radiotherapy region.

[0080] Implementation Scheme 18: The computer-implemented method according to claim 1, wherein the first dose and the second dose of the radiotherapy are in units of energy / mass, wherein the cumulative dose of the first dose of the tumor therapeutic electric field therapy for the first radiotherapy region and the first dose of the radiotherapy for the first radiotherapy region is approximately equivalent to or greater than the second dose of the radiotherapy.

[0081] Implementation Scheme 19: The computer-implemented method of claim 1, wherein at least one of the selected transducer layouts is capable of providing a first dose of the tumor therapeutic electric field therapy for the first radiotherapy region and a second dose of the tumor therapeutic electric field therapy for the second radiotherapy region, wherein the first dose of the tumor therapeutic electric field therapy and the second dose of the tumor therapeutic electric field therapy are different.

[0082] Implementation Scheme 20: The computer-implemented method of claim 1, wherein at least one of the selected transducer layouts is capable of providing the first dose of the tumor therapeutic electric field therapy to the first radiotherapy region and of providing different doses of the tumor therapeutic electric field therapy to at least one other region of the subject.

[0083] Implementation Scheme 21: The computer-implemented method of claim 1, further comprising determining a plurality of transducer layouts to deliver a tumor therapeutic electric field to the subject, wherein the at least one transducer layout is selected from the plurality of transducer layouts, wherein the transducer layouts of the plurality of transducer layouts differ in at least one of the following: location on the subject, size of the transducer, shape of the transducer, number of electrodes of the transducer, size of the electrodes of the transducer, and shape of the electrodes of the transducer.

[0084] Implementation Scheme 22: An apparatus for selecting at least one transducer layout to deliver a tumor therapeutic electric field to a subject, the apparatus comprising: one or more processors; and a memory accessible by the one or more processors, the memory storing instructions that, when executed by the one or more processors, cause the apparatus to: obtain a three-dimensional model of the subject, the model including voxels; identify a radiotherapy region in the three-dimensional model of the subject to deliver radiotherapy to a tumor of the subject, the radiotherapy region including a first radiotherapy region for receiving a first dose of radiotherapy, the first dose of radiotherapy being less than a therapeutic dose for treating the tumor in the first radiotherapy region. Threshold; identifying a tumor therapeutic electric field therapy region in the three-dimensional model of the subject to deliver tumor therapeutic electric field therapy to the tumor of the subject, the tumor therapeutic electric field therapy region including the first radiotherapy region; identifying a first dose of the tumor therapeutic electric field therapy for the first radiotherapy region, wherein the combination of the first dose of radiotherapy in the first radiotherapy region and the first dose of the tumor therapeutic electric field therapy satisfies or exceeds a treatment threshold for treating the tumor in the first radiotherapy region; and selecting one or more transducer arrangements based on the first dose of the tumor therapeutic electric field therapy for the first radiotherapy region to deliver the tumor therapeutic electric field to the subject.

[0085] Implementation Scheme 23: A non-transitory processor-readable medium having thereon a set of instructions, which, when executed by a processor, cause the processor to: obtain a three-dimensional model of the subject, the model including voxels; identify a radiotherapy region in the three-dimensional model of the subject to deliver radiotherapy to the subject's tumor, the radiotherapy region including a first radiotherapy region for receiving a first dose of radiotherapy and a second radiotherapy region for receiving a second dose of radiotherapy, the first dose of radiotherapy being less than the second dose of radiotherapy; identify a tumor therapeutic electric field therapy region in the three-dimensional model of the subject to deliver tumor therapeutic electric field therapy to the subject's tumor, the tumor therapeutic electric field therapy region including the first radiotherapy region; identify a first dose of tumor therapeutic electric field therapy for the first radiotherapy region based on the first dose of radiotherapy for the first radiotherapy region; and select one or more transducer arrangements to deliver a tumor therapeutic electric field to the subject based on the first dose of tumor therapeutic electric field therapy for the second radiotherapy region.

[0086] Unless otherwise indicated herein or clearly contradicted by the context, embodiments illustrated under any heading or in any part of this disclosure may be combined with embodiments illustrated under the same or any other heading or in any other part of this disclosure. For example, but not limited to, embodiments described in the form of dependent claims for a given embodiment (e.g., a given embodiment described in the form of independent claims) may be combined with other embodiments (described in the form of independent claims or dependent claims).

[0087] Various modifications, alterations, and changes can be made to the described embodiments without departing from the scope of the invention as defined by the claims. It is intended that the invention is not limited to the described embodiments, but has the full scope defined by the language of the following claims and their equivalents.

Claims

1. A computer-implemented method for selecting at least one transducer layout to deliver a tumor therapeutic electric field to a subject, the method comprising: A three-dimensional model of the subject is obtained, the model comprising voxels; Identify a radiotherapy region in the three-dimensional model of the subject to deliver radiotherapy to the subject's tumor, the radiotherapy region including a first radiotherapy region for receiving a first dose of radiotherapy and a second radiotherapy region for receiving a second dose of radiotherapy, the first dose of radiotherapy being less than the second dose of radiotherapy; Identify a tumor therapeutic electric field therapy region in the three-dimensional model of the subject to deliver tumor therapeutic electric field therapy to the tumor of the subject, the tumor therapeutic electric field therapy region including the first radiotherapy region; Identify a first dose of the tumor-treating electric field therapy targeting the first radiotherapy region to compensate for the first dose of radiotherapy being less than the second dose of radiotherapy; as well as One or more transducer configurations are selected based on the first dose of the tumor therapeutic electric field therapy targeting the first radiotherapy region to deliver the tumor therapeutic electric field to the subject.

2. The computer-implemented method of claim 1, wherein the first radiotherapy region corresponds to a region in the subject, the region being more sensitive to radiotherapy than a region in the subject corresponding to the second radiotherapy region.

3. The computer-implemented method of claim 1, wherein the first dose of radiotherapy is below a first threshold for the first radiotherapy region, wherein the first threshold is based on minimizing radiotherapy side effects on the subject.

4. The computer-implemented method of claim 1, wherein the first radiotherapy region corresponds to a region in the subject, the region being more difficult to treat with radiotherapy than a region in the subject corresponding to the second radiotherapy region.

5. The computer-implemented method of claim 1, wherein the first dose of radiotherapy is less than or equal to 50% and greater than 0% of the second dose of radiotherapy.

6. The computer-implemented method of claim 1, wherein the first dose of the tumor therapeutic electric field therapy for the first radiotherapy region is based on the first dose of radiotherapy for the first radiotherapy region.

7. The computer-implemented method of claim 1, wherein the tumor therapeutic electric field therapy region in the three-dimensional model of the subject includes a portion or all of the second radiotherapy region. The method further includes identifying a second dose of the tumor-treating electric field therapy for the second radiotherapy region based on the second dose of radiotherapy for the second radiotherapy region, and One or more transducer configurations are selected to deliver a tumor therapeutic electric field to the subject, further based on a second dose of the tumor therapeutic electric field therapy targeting the second radiotherapy region.

8. The computer-implemented method of claim 1, wherein the tumor therapeutic electric field therapy region in the three-dimensional model of the subject includes a portion or all of the second radiotherapy region. The method further includes identifying a second dose of the tumor-treating electric field therapy targeting the second radiotherapy region, regardless of the second dose of radiotherapy targeting the second radiotherapy region, and One or more transducer configurations are selected to deliver a tumor therapeutic electric field to the subject, further based on a second dose of the tumor therapeutic electric field therapy targeting the second radiotherapy region.

9. The computer-implemented method of claim 1, wherein the combination of the first dose of the tumor therapeutic electric field therapy targeting the first radiotherapy region and the first dose of radiotherapy targeting the first radiotherapy region satisfies or exceeds a treatment dose threshold for treating the tumor in the first radiotherapy region using radiotherapy alone. The first dose of radiotherapy to the first radiotherapy region is less than the treatment dose threshold for treating the tumor in the first radiotherapy region using radiotherapy alone.

10. The computer-implemented method of claim 1, wherein the first dose of radiotherapy is in units of energy / mass. The first dose of the tumor therapeutic electric field therapy is expressed in units of energy per volume, and The first dose of the tumor-treating electric field therapy targeting the first radiotherapy region includes: Determine the approximate equivalent first dose of radiotherapy for the first radiotherapy region, in energy / volume units; as well as The first dose of the tumor therapeutic electric field therapy for the first radiotherapy region is determined based on the approximately equivalent first dose of the radiotherapy for the first radiotherapy region.

11. The computer-implemented method of claim 1, wherein the first dose and the second dose of radiotherapy are in units of energy / mass. The cumulative dose of the first dose of the tumor treatment electric field therapy targeting the first radiotherapy region and the first dose of the radiotherapy targeting the first radiotherapy region is approximately equivalent to or greater than the second dose of the radiotherapy.

12. The computer-implemented method of claim 1, wherein at least one of the selected transducer arrangements is capable of providing a first dose of the tumor therapeutic electric field therapy for the first radiotherapy region and a second dose of the tumor therapeutic electric field therapy for the second radiotherapy region. The first dose and the second dose of the tumor therapeutic electric field therapy are different.

13. The computer-implemented method of claim 1, wherein at least one of the selected transducer layouts is capable of providing the first dose of the tumor therapeutic electric field therapy to the first radiotherapy region and of providing different doses of the tumor therapeutic electric field therapy to at least one other region of the subject.

14. An apparatus for selecting at least one transducer configuration to deliver a tumor therapeutic electric field to a subject, the apparatus comprising: One or more processors; and a memory accessible by the one or more processors, the memory storing instructions that, when executed by the one or more processors, cause the device to: A three-dimensional model of the subject is obtained, the model comprising voxels; Identify a radiotherapy region in the three-dimensional model of the subject to deliver radiotherapy to the subject's tumor, the radiotherapy region including a first radiotherapy region for receiving a first dose of radiotherapy, the first dose of radiotherapy being less than a treatment threshold for treating the tumor in the first radiotherapy region; Identify a tumor therapeutic electric field therapy region in the three-dimensional model of the subject to deliver tumor therapeutic electric field therapy to the tumor of the subject, the tumor therapeutic electric field therapy region including the first radiotherapy region; Identify a first dose of the tumor therapeutic electric field therapy for the first radiotherapy region, wherein the first dose of the combined radiotherapy in the first radiotherapy region and the first dose of the tumor therapeutic electric field therapy meet or exceed a treatment threshold for treating the tumor in the first radiotherapy region. and One or more transducer configurations are selected based on the first dose of the tumor therapeutic electric field therapy targeting the first radiotherapy region to deliver the tumor therapeutic electric field to the subject.

15. A non-transitory processor-readable medium having thereon a set of instructions, said set of instructions causing the processor, when executed by a processor, to: A three-dimensional model of the subject is obtained, the model comprising voxels; Identify a radiotherapy region in the three-dimensional model of the subject to deliver radiotherapy to the subject's tumor, the radiotherapy region including a first radiotherapy region for receiving a first dose of radiotherapy and a second radiotherapy region for receiving a second dose of radiotherapy, the first dose of radiotherapy being less than the second dose of radiotherapy; Identify a tumor therapeutic electric field therapy region in the three-dimensional model of the subject to deliver tumor therapeutic electric field therapy to the tumor of the subject, the tumor therapeutic electric field therapy region including the first radiotherapy region; The first dose of the tumor treatment electric field therapy for the first radiotherapy region is identified based on the first dose of the radiotherapy for the first radiotherapy region. One or more transducer configurations are selected based on the first dose of the tumor therapeutic electric field therapy targeting the second radiotherapy region to deliver the tumor therapeutic electric field to the subject.

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