Adaptation of array configuration considering tumor progression

Abstract

The computer implementation method includes obtaining a three-dimensional model of a subject, the model comprising voxels; identifying a macroscopic tumor volume relative to the three-dimensional model, the macroscopic tumor volume representing the current location of the tumor within the subject; identifying a primary clinical target volume relative to the three-dimensional model, the primary clinical target volume having a larger volume than the macroscopic tumor volume and representing an approximation of the current location of the tumor within the subject; identifying a predicted clinical target volume relative to the three-dimensional model, the predicted clinical target volume having a larger volume than the primary clinical target volume and representing the predicted future location of the tumor within the subject; and selecting at least one transducer layout for delivering a tumor treatment field to the subject based on the primary clinical target volume and the predicted clinical target volume.

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims priority to U.S. Patent Application No. 18 / 675,714, filed on May 28, 2024, and U.S. Provisional Application No. 63 / 523,853, filed on June 28, 2023, the contents of which are hereby incorporated by reference in their entirety.

Background Art

[0002] [[ID=thirteen]] Tumor treating fields (TT fields) are low - intensity alternating electric fields within an intermediate frequency range (e.g., 50 kHz to 1 MHz) and may be used for the treatment of tumors as described in U.S. Patent No. 7,565,205. TT fields are non - invasively induced in the region of interest by applying an alternating voltage between transducers placed on a patient's body. Conventionally, transducers used to generate TT fields include a plurality of electrode elements including ceramic disks. One side of each ceramic disk is placed in contact with the patient's skin, and a conductive backing is attached to the other side of each disk. Electrical signals are applied to this conductive backing, and these signals are capacitively coupled into the patient's body through the ceramic disks. Conventional transducer designs include an array of ceramic disks attached to a subject's body through a conductive skin - contact layer such as a hydrogel. At time intervals, an AC voltage is applied between a pair of transducers, generating an electric field with electric field lines running generally in the anterior - posterior direction. Next, an AC voltage is applied at another time interval at the same frequency between at least another pair of transducers, generating an electric field with electric field lines running generally in the left - right direction. The system repeats this two - step sequence over the course of treatment.

Summary of the Invention

Means for Solving the Problems

[0003] This application describes exemplary techniques for computationally selecting and determining at least one transducer array layout for delivering TT fields over a subject. [Brief explanation of the drawing]

[0004] [Figure 1] This document presents an example of a method for determining the position of a transducer to deliver a TT field to a subject. [Figure 2A] An example of a target volume is shown. [Figure 2B] An example of a target volume is shown. [Figure 2C] An example of a target volume is shown. [Figure 2D] An example of a target volume is shown. [Figure 2E] An example of a target volume is shown. [Figure 3] An example of a device that applies an alternating electric field to a subject's body is shown. [Figure 4A] A schematic diagram of an example transducer design for applying an alternating current electric field is shown. [Figure 4B] A schematic diagram of an example transducer design for applying an alternating current electric field is shown. [Figure 5] An example of transducer placement on the subject's head is shown. [Figure 6] An example of a computer device is shown. Forms for giving form to an invention

[0005] This application describes exemplary techniques for computationally selecting and determining at least one transducer array layout to deliver a TT field onto a subject.

[0006] Traditionally, in tumor treatment, radiation is applied to the area where the tumor has been identified and its location confirmed. Applying radiation to a wider area based on predicted diffusion can lead to serious side effects. For example, the inherent toxicity of radiation therapy may cause side effects that outweigh the benefits of treating the tumor. Furthermore, the human body may also have a maximum lifespan limit to the effectiveness of radiation therapy. In addition, applying radiation to predicted areas where the tumor may metastasize may reduce the effectiveness of subsequent radiation therapy.

[0007] As an alternative or supplemental treatment, TT fields can be introduced and delivered to a subject's body, which may have very few side effects and offer greater flexibility in tailoring tumor treatment plans. Generally, one or more pairs of transducers are placed on the subject's body to apply the TT field. Generally, at least two pairs of transducers are desirable. Transducers used to apply the TT field to a subject's body often contain multiple electrode elements coupled to each other on a substrate. Determining the predicted extent of tumor and the corresponding locations for transducer placement on the subject involves using very large datasets and computationally solving complex algorithms that can be time-consuming.

[0008] The inventors have discovered a computational technique for determining one or more predicted clinical target volumes of a tumor, where the predicted clinical target volume represents the predicted future location of the tumor in the subject. Treatment of the predicted future location of the tumor in the subject can reduce the likelihood of tumor expansion and / or the formation of another tumor in the subject. The technique of the present invention is particularly integrated into practical applications. The ingenious technique allows for tumor treatment of a wider area in the subject with fewer side effects compared to the use of radiation alone. The technique of the present invention allows for the determination of the location of more transducers much more quickly than the prior art. Furthermore, the technique of the present invention enables flexible development and combination of tumor treatment methods and dosages.

[0009] Figure 1 shows an exemplary computer implementation method 100 for selecting at least one transducer array layout for delivering a TT field to a subject. Method 100 may be implemented by a computer, which includes one or more processors and memory accessible by one or more processors, the memory storing instructions that, when executed by one or more processors, cause the computer to perform the steps of Method 100. Modifications, additions, or omissions may be made to Method 100.

[0010] Method 100 includes obtaining a three-dimensional (3D) model of the subject in step S102. This model includes voxels. Each voxel in the model may be assigned a tissue type (e.g., bone, organ, fluid, skin, or tumor) and / or a conductivity associated with the tissue type. In one example, the model of the subject may represent the subject's head. In another example, the model of the subject may represent the subject's torso. Other body parts of the subject may be represented in the model of the subject in other embodiments.

[0011] The model may be acquired using image data, for example, via a computer that identifies different types of tissue from the image data. The image data may include one or more medical images of parts of the subject's body (e.g., X-ray images, magnetic resonance imaging (MRI), computed tomography (CT) images, ultrasound images, or any images that provide an internal view of the subject's body). Each medical image may include the outline of a part of the subject and a region corresponding to the subject's area of ​​interest (e.g., a tumor). The 3D model may be acquired, for example, from computer memory locally or via a network.

[0012] In step S104, method 100 may include identifying gross tumor volume (GTV) relative to a three-dimensional model. Gross tumor volume may be the extent and location of a malignant tumor that is palpable or visible / identifiable to the naked eye. Gross tumor volume may include all lesions observed on physical examination by endoscopy and imaging. Gross tumor volume may represent one or more current locations of at least one tumor within the subject. For example, gross tumor volume may be based on user input.

[0013] To aid in explaining Method 100, Figures 2A-2E are also described. Figures 2A-2E show examples of various target volumes in a two-dimensional display, such as target volumes in slices passing through a medical image. For convenience, the entire slice is not shown; instead, only the target volume is displayed. For example, in Figure 2A, the gross tumor volume (GTV) 202 may represent the current location of the tumor within the subject.

[0014] In step 106, method 100 may include identifying a primary clinical target volume (CTV) for a three-dimensional model. The primary clinical target region may include the macroscopic tumor volume and the proximal margin beyond the identified macroscopic tumor volume. The primary clinical target volume may represent an approximation of the current location of at least one tumor within the subject. In one example, the primary clinical target volume may represent the location within the subject being treated, for example, by radiation and / or a TT field. In one example, the approximation of the current location of at least one tumor within the subject, represented by the primary clinical target volume, shall account for at least one of the errors in identifying the macroscopic tumor volume or the portion of the tumor not detected within the macroscopic tumor volume. In one example, the primary clinical target volume may be greater than the macroscopic tumor volume. In one example, the macroscopic tumor volume may be based on user input.

[0015] In Figure 2B, the primary clinical target volume (CTV) 204 may represent an approximation of the current location of the tumor within the subject. In some cases, the CTV 204 may have approximately the same shape as the macroscopic tumor volume 202 (shown by the dashed line in Figure 2B), but may be larger in volume than the macroscopic tumor volume 202. In some cases, the distance 206 between the surface of the CTV 204 and the surface of the macroscopic tumor volume 202 may be between approximately 1 mm and 5 mm, or between approximately 1 mm and 10 mm. In some cases, the CTV 204 may be approximately 1% to 5%, or 2% to 3%, larger than the macroscopic tumor volume 202. In one case, the volume between the CTV 204 and the macroscopic tumor volume 202 may be the tumor periphery.

[0016] In step 108, method 100 may include identifying at least one predicted clinical target volume for a three-dimensional model. In one example, step 108 may include identifying one predicted clinical target volume and / or identifying multiple predicted clinical target volumes, including one predicted clinical target volume. In one example, at least one predicted clinical target volume may include multiple discontinuous volumes. At least one predicted clinical target volume may represent at least one predicted future location and potential spread of at least one tumor in the subject. In one example, the predicted clinical target volume may be set based on the temporal progression of the tumor in the subject, which could be, for example, one to six months.

[0017] In one example, a predictive model may be used to determine the predicted clinical target volume, which is used to predict the occurrence and location of tumors similar to the subject's tumor. For example, the predictive model may determine the future location of the tumor in the subject based on at least one of the following: the current location of the tumor, the type / signs of the tumor, the initial growth rate of the tumor, the initial location of the tumor, and the subject's biometric data. For example, the predictive model may determine the future location of the tumor in the subject based on the current location of the tumor, as well as at least one of the following: the subject's medical background, the signs or type of the tumor, the subtype or classification of the tumor, and the past progression of the tumor. In one example, the predictive model may be a machine learning model trained on multiple tumors similar to the subject's tumor. In one example, the predictive model may be trained to predict the future location of the tumor in the subject, and / or also trained to predict the future location of tumors similar to the subject's tumor.

[0018] In FIG. 2C, the predicted clinical target volumes 208A, 208B, and 208C (collectively referred to as 208) may represent the predicted future positions of tumors in a subject. In one example, the predicted clinical target volume 208 is larger in volume and / or different in shape than the primary clinical target volume 204 (shown by the dashed line in FIG. 2C). The predicted clinical target volume may include a plurality of non - contiguous volumes. In particular, the predicted clinical target volume may include a plurality of non - contiguous volumes such as, for example, 208A, 208B, and 208C.

[0019] In step 110, method 100 may include identifying a differential clinical target volume as the difference between the primary clinical target volume and the predicted clinical target volume. In one example, the differential clinical target volume may include a plurality of non - contiguous volumes.

[0020] In FIG. 2D, the differential clinical target volumes 210A, 210B, and 210C (collectively referred to as 210) may represent the difference between the primary clinical target volume 204 and the predicted clinical target volume 208. In FIG. 2D, the differential clinical target volume 210 is shown as the shaded portion. The differential clinical target volume may include a plurality of non - contiguous volumes such as, for example, 210A, 210B, and 210C.

[0021] In FIG. 2E, the various target volumes in FIGS. 2A, 2B, 2C, and 2D are shown together.

[0022] In step 112, method 100 may include determining a plurality of transducer array layouts for delivering a TT field to a subject. In one example, the transducer array layout in the plurality of transducer array layouts is different in at least one of the position on the subject, the size of the transducer, the shape of the transducer, the number of electrodes of the transducer, the electrode size of the transducer, or the electrode shape of the transducer. In one example, step 112 includes determining four transducer array layouts.

[0023] In step 114, method 100 may include calculating a first TT field dose relative to a primary clinical target volume. Step 114 may also include calculating a first TT field dose for each determined transducer array layout. In one example, the first TT field dose relative to a primary clinical target volume may be a predetermined minimum dose for tumors similar to the subject's tumor. In one example, the first TT field dose relative to a primary clinical target volume may be determined based on local mean linear intensity and / or local power density within the target range. In one example, the first TT field dose relative to a primary clinical target volume may be determined based on local field intensity and / or local power density within the primary clinical target volume.

[0024] In step 116, method 100 may include calculating a second TT field dose relative to the differential clinical target volume. In some cases, the second TT field dose relative to the differential clinical target volume may be less than a predetermined minimum dose. In some cases, the second TT field dose relative to the differential clinical target volume may be calculated as a percentage of the first TT field dose relative to the primary clinical target volume. In some cases, the second TT field dose relative to the differential clinical target volume and the first TT field dose relative to the primary clinical target volume are not identical. For example, the second TT field dose relative to the differential clinical target volume may be less than or more than the first TT field dose relative to the primary clinical target volume. In some cases, the second TT field dose relative to the differential clinical target volume may be a predetermined minimum dose for a tumor similar to the subject's tumor. For example, the second TT field dose relative to the differential clinical target volume may be determined based on local mean field intensity and / or local power density within the target range. For example, the second TT field dose relative to the differential clinical target volume may be determined based on the local field intensity and / or local power density within the predicted clinical target volume.

[0025] For example, the calculation of the dosage for TT field therapy is described in more detail in U.S. Patent Application Publication No. 2020 / 0023179, titled "USING POWER LOSS DENSITY AND RELATED MEASURES TO QUANTIFY THE DOSE OF TUMOR TREATING FIELDS (TTFIELDS)," and U.S. Patent Application Publication No. 2021 / 0196943, titled "METHODS, SYSTEMS, AND APPARATUSES FOR FAST APPROXIMATION OF ELECTRIC FIELD DISTRIBUTION," both of which are incorporated herein by reference as a whole. It should be noted that these calculations in steps 114 and 116 involve solving complex algorithms using large datasets related to subjects, and therefore require the use of computer equipment as human intelligence cannot perform the necessary calculations.

[0026] Furthermore, the first and second TT field doses may be calculated individually. For example, the first TT field dose may be calculated assuming that the second TT field dose is not applied simultaneously with the first dose. In another example, the second TT field dose may be calculated assuming that the first TT field dose is not applied simultaneously with the second TT field dose.

[0027] In some cases, the differential clinical target volume may include multiple discontinuous volumes. Therefore, the TT field dose may be determined for each of the discontinuous regions of the clinical target volume. In some cases, at least two of the discontinuous volumes of the differential clinical target volume have different TT field doses. In other cases, a non-zero TT field dose may be determined for each of the discontinuous regions of the clinical target volume.

[0028] In some cases, two or more predicted clinical target volumes may be determined. Each predicted clinical target volume may be assigned a weight, each weight representing the likelihood of the predicted future location of the tumor within the subject for the individual predicted clinical target volume. For example, as shown in Figure 2C, the first weight of the first predicted clinical target volume 208A may be greater than the second weight of the second predicted clinical target volume 208B, in which case the first predicted clinical target volume 208A may be assigned a larger TT field dose than the second predicted clinical target volume 208B. The second weight of the second predicted clinical target volume 208B may be the same as the third weight of the third predicted clinical target volume 208C, in which case the second predicted clinical target volume 208B may be assigned the same TT field dose as the third predicted clinical target volume 208C.

[0029] In step 118, method 100 may include selecting at least one transducer array layout for delivering the TT field to a subject, the at least one transducer array layout may be selected from a plurality of transducer array layouts determined in step 112. In one example, the selection may be based on the primary clinical target volume and the predicted clinical target volume. In one example, the selection may be based on the primary clinical target volume, a plurality of predicted clinical target volumes, and weights for the plurality of predicted clinical target volumes. In one example, the selection may be based on the calculated first and / or second TT field dose. In one example, the selection may be based on one or more desired intensities of primary CTV or differential CTV. Using the selected at least one transducer array layout, the physician may select a transducer array layout that achieves the minimum dose to treat the subject's tumor.

[0030] In step 120, method 100 may include applying the transducer to the subject using the selected transducer layout. Step 120 will be described in more detail with reference to Figures 4A, 4B, and 5.

[0031] In step 122, method 100 may include delivering the TT field to the subject based on the selected transducer array layout. In particular, when delivering the TT field, the subject may be temporarily detached from one or more treatment areas (e.g., primary clinical target volume), and the selected array layout may be moved to shift focus to another treatment area (e.g., predicted clinical target volume), while the skin of the previous treatment area recovers. Exemplary device

[0032] Figure 3 shows an exemplary apparatus 300 for applying an alternating current electric field (e.g., a TT field) to a subject's body. This system can be used to treat a target area of ​​a subject's body with the alternating current electric field. In one example, the target area may be within the subject's brain, and the alternating current electric field may be delivered to the subject's body via two pairs of transducer arrays (e.g., four transducers 500 in Figure 5) positioned above the subject's head. In another example, the target area may be within the subject's torso, and the alternating current electric field is delivered to the subject's body via two pairs of transducer arrays positioned on at least one of the subject's chest, abdomen, or one or both thighs. Other transducer array layouts on the subject's body are also possible.

[0033] Exemplary apparatus 300 illustrates an exemplary system having four transducers (or “transducer arrays”) 300A–D. Each transducer 300A–D may include substantially flat electrode elements 302A–D that are arranged on substrates 304A–D and electrically and physically connected (e.g., via conductive wiring 306A–D). For each substrate 304A–D, the individual electrode elements 302A–D on the substrate may be electrically connected to each other and physically connected to their individual substrates 304A–D. In one example, the electrode elements 302A–D are controlled as a group, so that the electrode elements 302A–D can receive and execute the same command signal. In another example, the electrode elements 302A–D are controlled individually, so that each electrode element can receive and execute different commands than those received and executed by another electrode element.

[0034] The substrates 304A-D may include, for example, cloth, foam, flexible plastic, and / or conductive medical gel. Two transducers (e.g., 300A and 300D) may be a first pair of transducers configured to apply an alternating electric field to a target area of ​​the subject's body. Two other transducers (e.g., 300B and 300C) may be a second pair of transducers similarly configured to apply an alternating electric field to a target area.

[0035] Transducers 300A-D may be coupled to an AC voltage generator 320, and the system may further include a controller 310 communicatively coupled to the AC voltage generator 320. The controller 310 may include a computer including one or more processors 324 and a memory 326 accessible by one or more processors. The memory 326 may store instructions, when executed by one or more processors, for controlling the AC voltage generator 320 to induce an alternating electric field between transducer pairs 300A-D according to one or more voltage waveforms, and / or causing the computer to perform one or more methods disclosed herein. The controller 310 may monitor operations performed by the AC voltage generator 320 (e.g., via processor(s) 324). One or more sensors 328 may be coupled to the controller 310 to provide the controller 310 with measurements or other information.

[0036] Electrode elements 302A to D may be capacitively coupled. In one example, electrode elements 302A to D are ceramic electrode elements coupled to each other via conductive wiring 306A to D. The ceramic electrode elements may be circular or non-circular when viewed from a direction perpendicular to their surface. In other embodiments, the array of electrode elements is not capacitively coupled, and there is no dielectric material (such as a ceramic or high-dielectric polymer layer) associated with the electrode elements.

[0037] The structure of transducers 300A-D can take various forms. The transducer may be fixed to the subject's body, or attached to or incorporated into clothing covering the subject's body. The transducer may include suitable materials for attaching it to the subject's body. For example, suitable materials may include cloth, foam, flexible plastic, and / or conductive medical gel. The transducer may be conductive or non-conductive.

[0038] A transducer may include any desired number of electrode elements. Electrode elements may be of various shapes, sizes, and materials. Any structure for implementing a transducer (or electric field generator) used in conjunction with embodiments of the present invention may be used, insofar as they enable (a) delivery of an TT field to the body of a subject and (b) placement in the locations specified herein. In certain embodiments, at least one electrode element of a first, second, third, or fourth transducer may include at least one ceramic disc adapted to generate an alternating electric field. In non-limiting embodiments, at least one electrode element of a first, second, third, or fourth transducer may include a polymer film adapted to generate an alternating electric field.

[0039] Figure 4A shows a schematic diagram illustrating an exemplary design of a transducer for applying an alternating electric field. The transducer 401 includes 20 electrode elements 402 arranged on a substrate 403, which are electrically and physically connected to one another by conductive wiring 404. In some embodiments, the electrode elements 402 may include ceramic disks.

[0040] Figure 4B shows a schematic diagram illustrating an exemplary design of a transducer for applying an alternating electric field. The transducer 405 may include one or more substantially flat electrode elements 406. In some embodiments, the electrode elements 406 are non-ceramic dielectric materials arranged across a plurality of flat conductors. Examples of non-ceramic dielectric materials arranged on flat conductors may include polymer films arranged on pads on a printed circuit board or on substantially flat metal pieces. In some embodiments, such polymer films have a high dielectric constant, such as a dielectric constant greater than 10. In some embodiments, the electrode elements 406 may have a variety of shapes. For example, the electrode elements may be triangular, rectangular, circular, oval, ovaloid, ovoid, or elliptical in shape, or substantially triangular, substantially rectangular, substantially circular, substantially oval, substantially ovaloid, substantially ovoid, or substantially elliptical in shape. In some embodiments, each of the electrode elements 406 may have the same shape, a similar shape, and / or a different shape.

[0041] Figure 6 shows an example of a computer device for use in embodiments of the present invention. In one example, the device 600 may be a computer for implementing certain inventive techniques disclosed herein, such as selecting a transducer layout for delivering a TT field to a subject, as shown in Figure 1. For example, steps 102-118 in Figure 1 may be performed by a computer, such as the computer device 600. In one example, the device 600 may be used as the controller 310 in Figure 3, or as a separate computer device located remotely from the controller 310. For example, step 122 in Figure 1 may be performed by a controller, such as the controller 310. The device 600 may include one or more processors 602, memory 603, one or more input devices, and one or more output devices 605.

[0042] In one example, based on input 601, one or more processors 602 generate control signals for controlling a voltage generator. In one example, input 601 may be a user input. In another example, input 601 may be from another computer communicating with the controller device 600. Input 601 may be received in conjunction with one or more input devices (not shown) of the device 600.

[0043] Memory 703 is accessible by one or more processors 602 (for example, via link 604), which may read information from and write information to memory 603. Memory 603 may store instructions that, when executed by one or more processors 602, implement one or more methods of the present disclosure. Memory 603 may also be a non-temporary computer-readable medium (or non-temporary processor-readable medium) containing a set of instructions for selecting at least one transducer layout for delivering a tumor treatment site to a subject, and the instructions, when executed by a processor (such as one or more processors 602), cause the processor to perform one or more methods described herein.

[0044] One or more output devices 605 may provide information about the operation of the present invention, such as the selection of the transducer layout, the voltage generated, and other operational information. One or more output devices 605 may provide visualization data according to certain embodiments described herein.

[0045] The apparatus 600 may be an apparatus for selecting at least one transducer layout for delivering a tumor treatment site to a subject, the apparatus including one or more processors (such as one or more processors 602), and a memory accessible by one or more processors (such as memory 603) that, when executed by one or more processors, stores instructions causing the apparatus to perform one or more of the methods described herein. Exemplary Embodiments

[0046] The present invention includes other exemplary embodiments ("Embodiments") as follows:

[0047] Embodiment 1: A computer implementation method for selecting at least one transducer layout for delivering a tumor treatment site to a subject, the method comprising: acquiring a three-dimensional model of the subject, the model comprising voxels; identifying a macroscopic tumor volume relative to the three-dimensional model, the macroscopic tumor volume representing the current location of the tumor within the subject; identifying a primary clinical target volume relative to the three-dimensional model, the primary clinical target volume having a larger volume than the macroscopic tumor volume, the primary clinical target volume representing an approximation of the current location of the tumor within the subject; identifying a predicted clinical target volume relative to the three-dimensional model, the predicted clinical target volume having a larger volume than the primary clinical target volume, representing the predicted future location of the tumor within the subject; and selecting at least one transducer layout for delivering a tumor treatment site to the subject based on the primary clinical target volume and the predicted clinical target volume.

[0048] Embodiment 2: The computer implementation method according to Embodiment 1, wherein the main clinical target volume and the macroscopic tumor volume have substantially the same shape.

[0049] Embodiment 3: The computer implementation method according to Embodiment 1, wherein the surface of the main clinical target volume is located about 1 mm to about 5 mm outside the surface of the macroscopic tumor volume.

[0050] Embodiment 4: The computer implementation method according to Embodiment 1, wherein the volume between the primary clinical target volume and the macroscopic tumor volume is the tumor peripheral boundary region.

[0051] Embodiment 5: The computer implementation method according to Embodiment 1, wherein the primary clinical target volume represents the current location within the subject where the tumor is to be treated with radiation.

[0052] Embodiment 6: The computer implementation method according to Embodiment 1, wherein the approximation of the current location of the tumor in the subject, represented by the primary clinical target volume, accounts for at least one of the errors in determining the macroscopic tumor volume or the portion of the tumor that was not detected by the macroscopic tumor volume.

[0053] Embodiment 7: The computer implementation method according to Embodiment 1, wherein at least one of the primary clinical target volume and the macroscopic tumor volume is based on user input.

[0054] Embodiment 8: The computer implementation method according to Embodiment 1, wherein the predicted clinical target volume and the primary clinical target volume have different shapes.

[0055] Embodiment 9: The computer implementation method according to Embodiment 1, wherein the predicted clinical target volume includes a plurality of discontinuous volumes.

[0056] Embodiment 10: The computer implementation method according to Embodiment 1, wherein the predicted clinical target volume is based on the temporal progression of the tumor in the subject.

[0057] Embodiment 11: The computer implementation method according to Embodiment 10, wherein the elapsed time is 1 to 6 months.

[0058] Embodiment 12: The computer implementation method according to Embodiment 1, wherein the predicted clinical target volume is determined using a predictive model for tumors similar to the tumor in the subject.

[0059] Embodiment 13: The computer implementation method according to Embodiment 12, wherein the predictive model determines the future location of the tumor in the subject based on the current location of the tumor, as well as at least one of the subject's medical background, the signs or type of the tumor, the subtype or classification of the tumor, and the past progression of the tumor.

[0060] Embodiment 14: The computer implementation method according to Embodiment 1, wherein the predicted clinical target volume is determined using a trained machine learning model, and the trained machine learning model is trained to predict the future location of tumors similar to the tumor within the subject.

[0061] Embodiment 15: A computer implementation method according to Embodiment 1, comprising: identifying a plurality of predicted clinical target volumes for the three-dimensional model, wherein the plurality of predicted clinical target volumes include the predicted clinical target volume; and assigning a weight to each of the predicted clinical target volumes, wherein each weight represents the likelihood of the predicted future location of the tumor within the subject for the individual predicted clinical target volume, and the selection of at least one transducer layout for delivering the tumor treatment field to the subject is made based on the primary clinical target volume, the plurality of predicted clinical target volumes, and the weights for the plurality of predicted clinical target volumes.

[0062] Embodiment 16: The computer implementation method according to Embodiment 15, wherein the first weight of the first predicted clinical target volume is greater than the second weight of the second predicted clinical target volume, and the first predicted clinical target volume is assigned a tumor treatment dose greater than that of the second predicted clinical target volume.

[0063] Embodiment 17: The computer implementation method according to Embodiment 1, further comprising: identifying a differential clinical target volume as the difference between the primary clinical target volume and the predicted clinical target volume; calculating a first tumor treatment dose for the primary clinical target volume; and calculating a second tumor treatment dose for the differential clinical target volume, wherein the second tumor treatment dose for the differential clinical target volume and the first tumor treatment dose for the primary clinical target volume are not the same.

[0064] Embodiment 18: The computer implementation method according to Embodiment 15, wherein the second tumor treatment dose relative to the differential clinical target volume is smaller than the first tumor treatment dose relative to the primary clinical target volume.

[0065] Embodiment 19: The computer implementation method according to Embodiment 15, wherein the second tumor treatment dose relative to the differential clinical target volume is smaller than the first tumor treatment dose relative to the primary clinical target volume.

[0066] Embodiment 20: The computer implementation method according to Embodiment 15, wherein the first tumor treatment dose for the primary clinical target volume is a predetermined maximum dose for a tumor similar to the tumor of the subject, and the second tumor treatment dose for the differential clinical target volume is smaller than the predetermined maximum dose.

[0067] Embodiment 21: The computer implementation method according to Embodiment 15, wherein the second tumor treatment dose relative to the differential clinical target volume is calculated as a percentage of the first tumor treatment dose relative to the primary clinical target volume.

[0068] Embodiment 22: The computer implementation method according to Embodiment 15, wherein the differential clinical target volume includes a plurality of discontinuous volumes, a tumor treatment dose is determined for each of the discontinuous volumes of the differential clinical target volume, and at least two of the discontinuous volumes of the differential clinical target volume have different tumor treatment doses.

[0069] Embodiment 23: The computer implementation method according to Embodiment 13, wherein the differential clinical target volume includes a plurality of discontinuous volumes, and a non-zero tumor treatment dose is determined for each of the discontinuous volumes of the differential clinical target volume.

[0070] Embodiment 24: The computer implementation method according to Embodiment 13, wherein the first tumor treatment dose is calculated assuming that the second tumor treatment dose is not delivered at the same time as the first tumor treatment dose, and the second tumor treatment dose is calculated assuming that the first tumor treatment dose is not delivered at the same time as the second tumor treatment dose.

[0071] Embodiment 25: The computer implementation method according to Embodiment 1, further comprising determining a plurality of transducer layouts for delivering a tumor treatment site to the subject, wherein at least one transducer layout is selected from the plurality of transducer layouts, and the transducer layout among the plurality of transducer layouts differs in at least one aspect of 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, or shape of the electrodes of the transducer.

[0072] Embodiment 26: Apparatus for selecting at least one transducer layout for delivering a tumor treatment field to a subject, wherein the apparatus comprises one or more processors and a memory accessible by the one or more processors, wherein the memory, when executed by the one or more processors, allows the apparatus to acquire a three-dimensional model of the subject, the model comprising voxels; identify a macroscopic tumor volume relative to the three-dimensional model, the macroscopic tumor volume representing the current location of the tumor within the subject; and identify a primary clinical target volume relative to the three-dimensional model. A device that stores instructions to: identify a primary clinical target volume, wherein the primary clinical target volume has a larger volume than the macroscopic tumor volume, and the primary clinical target volume represents an approximation of the current location of the tumor in the subject; identify a predicted clinical target volume for the three-dimensional model, wherein the predicted clinical target volume has a larger volume than the primary clinical target volume, and is based on the temporal progression of the tumor in the subject; and select at least one transducer layout for delivering a tumor treatment site to the subject based on the primary clinical target volume and the predicted clinical target volume.

[0073] Embodiment 27: A non-transient processor-readable medium for selecting at least one transducer layout for delivering a tumor treatment site to a subject, wherein the non-transient processor-readable medium is a set of instructions, which, when executed by a processor, cause the processor to acquire a three-dimensional model of the subject, the model comprising voxels; to identify a macroscopic tumor volume relative to the three-dimensional model, the macroscopic tumor volume representing the current location of the tumor within the subject; and to identify a primary clinical target volume relative to the three-dimensional model, the primary clinical target volume representing the macroscopic tumor A non-transient processor-readable medium comprising a set of instructions to cause the following to be performed: identify a primary clinical target volume having a volume greater than the tumor volume, wherein the primary clinical target volume represents an approximation of the current location of the tumor within the subject; identify a predicted clinical target volume for the three-dimensional model, wherein the predicted clinical target volume has a volume greater than the primary clinical target volume, and represents the predicted future location of the tumor within the subject; and select at least one transducer layout for delivering a tumor treatment site to the subject based on tumor treatment site doses for the primary clinical target volume and the predicted clinical target volume.

[0074] Embodiments shown in any heading or portion of this disclosure may be combined with embodiments shown in the same or other headings or portions of this disclosure, unless otherwise stated herein or unless the context expressly contradicts the description. For example, but not limited to, an embodiment described in dependent claim form with respect to a given embodiment (e.g., a given embodiment described in independent claim form) may be combined with other embodiments (described in independent or dependent claim form).

[0075] Numerous modifications, alterations, and changes are possible to the embodiments described without departing from the scope of the invention as defined in the claims. The invention is not limited to the embodiments described and is intended to have the entire scope as defined by the following claims and their equivalents. [Explanation of Symbols]

[0076] 202 Gross Tumor Volume (GTV) 204 Major Clinical Target Volume (CTV) 206 distance 208 Predicted clinical target volume 208A First predicted clinical target volume, predicted clinical target volume 208B Second predicted clinical target volume, predicted clinical target volume 208C Third Predicted Clinical Target Volume 210 Differential Clinical Target Volume 210A Differential Clinical Target Volume 210B Differential Clinical Target Volume 300 equipment 300A transducers, transducer arrays, transducer pairs 300B transducers, transducer arrays, transducer pairs 300C transducers, transducer arrays, transducer pairs 300D transducers, transducer arrays, transducer pairs 302A Electrode Element 302B Electrode Element 302C electrode element 302D Electrode Element 304A circuit board 304B circuit board 304C board 304D PCB 306A conductive wiring 306B Conductive wiring 306C conductive wiring 306D Conductive Wiring 310 Controller 320 AC Voltage Generator 324 processors (multiple processors are possible) 326 memory 328 sensors (multiple sensors possible) 401 Transducer 402 Electrode elements 403 circuit board 404 Conductive wiring 405 Transducer 406 Electrode elements 500 transducers 600 devices, computer devices, controller devices 601 Input 602 Processors 603 memory 604 Link 605 Output device 605 Output Device 703 memory

Claims

1. A computer implementation method for selecting at least one transducer layout for delivering a tumor treatment site to a subject, wherein the method is: Obtaining a three-dimensional model of the subject, wherein the model includes voxels. Identifying the macroscopic tumor volume relative to the three-dimensional model, wherein the macroscopic tumor volume represents the current location of the tumor within the subject, Identifying a primary clinical target volume for the three-dimensional model, wherein the primary clinical target volume is larger than the macroscopic tumor volume, and the primary clinical target volume represents an approximation of the current location of the tumor within the subject. To identify a predicted clinical target volume for the three-dimensional model, wherein the predicted clinical target volume has a larger volume than the primary clinical target volume and represents the predicted future location of the tumor within the subject. A computer implementation method comprising selecting at least one transducer layout for delivering a tumor treatment site to the subject based on the primary clinical target volume and the predicted clinical target volume.

2. The computer implementation method according to claim 1, wherein the main clinical target volume and the macroscopic tumor volume have substantially the same shape.

3. The computer mounting method according to claim 1, wherein the surface of the main clinical target volume is located about 1 mm to about 5 mm outside the surface of the macroscopic tumor volume.

4. The computer implementation method according to claim 1, wherein the approximation of the current location of the tumor in the subject, represented by the primary clinical target volume, accounts for at least one of the errors in determining the macroscopic tumor volume or the portion of the tumor that was not detected by the macroscopic tumor volume.

5. The computer implementation method according to claim 1, wherein the predicted clinical target volume and the primary clinical target volume have different shapes.

6. The computer implementation method according to claim 1, wherein the predicted clinical target volume includes a plurality of discontinuous volumes.

7. The computer implementation method according to claim 1, wherein the predicted clinical target volume is based on the temporal progression of the tumor within the subject.

8. The computer implementation method according to claim 1, wherein the predicted clinical target volume is determined using a predictive model for tumors similar to the tumor in the subject, the predictive model determines the future location of the tumor in the subject based on the current location of the tumor, as well as at least one of the subject's medical background, the signs or type of the tumor, the subtype or classification of the tumor, and the past progression of the tumor.

9. The computer implementation method according to claim 1, wherein the predicted clinical target volume is determined using a trained machine learning model, and the trained machine learning model is trained to predict the future location of tumors similar to the tumor within the subject.

10. The process involves identifying a plurality of predicted clinical target volumes for the three-dimensional model, wherein the plurality of predicted clinical target volumes include a plurality of predicted clinical target volumes, and the process involves identifying a plurality of predicted clinical target volumes that include the aforementioned predicted clinical target volume. The method further includes assigning a weight to each of the predicted clinical target volumes, where each weight represents the likelihood of the predicted future location of the tumor within the subject for each individual predicted clinical target volume. The computer implementation method according to claim 1, wherein the selection of at least one transducer layout for delivering the tumor treatment area to the subject is made based on the primary clinical target volume, the plurality of predicted clinical target volumes, and the weights for the plurality of predicted clinical target volumes.

11. The differential clinical target volume is identified as the difference between the primary clinical target volume and the predicted clinical target volume. To calculate the first tumor treatment dose relative to the aforementioned primary clinical target volume, The computer implementation method according to claim 1, further comprising calculating a second tumor treatment dose for the differential clinical target volume, wherein the second tumor treatment dose for the differential clinical target volume and the first tumor treatment dose for the primary clinical target volume are not the same.

12. The computer implementation method according to claim 11, wherein the second tumor treatment dose relative to the differential clinical target volume is smaller than the first tumor treatment dose relative to the primary clinical target volume.

13. The first tumor treatment dose is calculated on the premise that the second tumor treatment dose is not applied simultaneously with the first tumor treatment dose, and The computer implementation method according to claim 11, wherein the second tumor treatment dose is calculated on the premise that the first tumor treatment dose is not applied simultaneously with the second tumor treatment dose.

14. An apparatus for selecting at least one transducer layout for delivering a tumor treatment site to a subject, wherein the apparatus is One or more processors, A memory accessible by the one or more processors, wherein when the one or more processors execute, the device Obtaining a three-dimensional model of the subject, wherein the model includes voxels. Identifying the macroscopic tumor volume relative to the three-dimensional model, wherein the macroscopic tumor volume represents the current location of the tumor within the subject, Identifying a primary clinical target volume for the three-dimensional model, wherein the primary clinical target volume is larger than the macroscopic tumor volume, and the primary clinical target volume represents an approximation of the current location of the tumor within the subject. The method involves identifying a predicted clinical target volume for the three-dimensional model, wherein the predicted clinical target volume is larger than the primary clinical target volume, and the predicted clinical target volume is determined based on the temporal progression of the tumor within the subject. A device that stores instructions to select at least one transducer layout for delivering a tumor treatment site to a subject based on the primary clinical target volume and the predicted clinical target volume.

15. A non-transient processor-readable medium for selecting at least one transducer layout for delivering a tumor treatment site to a subject, wherein the non-transient processor-readable medium is a series of instructions, which, when executed by a processor, the processor Obtaining a three-dimensional model of the subject, wherein the model includes voxels, Identifying the macroscopic tumor volume relative to the three-dimensional model, wherein the macroscopic tumor volume represents the current location of the tumor within the subject, Identifying a primary clinical target volume for the three-dimensional model, wherein the primary clinical target volume is larger than the macroscopic tumor volume, and the primary clinical target volume represents an approximation of the current location of the tumor within the subject. To identify a predicted clinical target volume for the three-dimensional model, wherein the predicted clinical target volume has a larger volume than the primary clinical target volume and represents the predicted future location of the tumor within the subject. A non-transient processor-readable medium comprising a set of instructions to select at least one transducer layout for delivering a tumor therapeutic site to a subject based on the primary clinical target volume and the predicted clinical target volume.

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