Treatment system and method

Abstract

A system and method are directed to an implantable stimulation device having an anchor plate that is attachable to a portion of a subject, a first support rod that extends distally from the anchor plate, and a coil wrapped around at least a portion of the first support rod. The coil is configured to provide a field stimulation to tissue in the portion of the subject. The system also includes a signal generator electrically connected or connectable to the coil of the implantable stimulation device, the signal generator being configured to provide energizing signals to the coil to generate the field stimulation. The system further includes an internal power source that powers at least the signal generator.

Description

TREATMENT SYSTEM AND METHODCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to, and benefit of, U.S. Provisional Patent Application No. 63 / 777,981, filed on March 26, 2025, which is hereby incorporated by reference herein in its entirety.TECHNICAL FIELD

[0002] This disclosure relates generally to technologies associated with treating disease, and more particularly, to systems and methods for generating and / or providing tumor treating fields (TTFs).BACKGROUND

[0003] TTFs have been utilized in some cancer treatment protocols for certain brain cancers, such as glioblastoma multiforme (GBM), to slow tumor growth and extend patient survival. Conventional technologies that produce TTFs utilize patch devices worn on the scalp powered by an external battery. However, such patch devices require a patient to shave their head and carry a large battery pack for a long period of time (e.g., over 18 hours), which can be undesirable for a patient already facing difficult circumstances. Also, patch devices can cause skin irritation on the scalp, and may also be accidentally removed, risking interrupted treatment and improper repositioning.

[0004] Therefore, there is a need for improved technologies that can deliver therapeutic TTFs. The present disclosure provides a solution for these and other problems.SUMMARY

[0005] According to some implementations of the present disclosure, a treatment system is provided. In some aspects, the treatment system includes an implantable stimulation device with at least an anchor plate attachable to a portion of a subject, a first support rod that extends distally from the anchor plate, and a coil wrapped around at least a portion of the first support rod, the coil configured to provide a treatment field stimulation to tissue in the portion of the subject. The treatment system also includes a signal generator electrically connected or connectable to the coil of the implantable stimulation device, the signal generator configured to provide energizing signals to the coil to generate the treatment field stimulation. The 14917-6735-5280 1065472-001012WQPTtreatment system further includes an internal power source that powers at least the signal generator.

[0006] According to other implementations of the present disclosure, a method is provided. In some aspects, the method includes providing a treatment system comprising an implantable stimulation device with an anchor plate attachable to a portion of a subject, a support rod that extends distally from the anchor plate, and a coil wrapped around at least a portion of the support rod, the coil configured to provide a treatment field stimulation to tissue in the portion of the subject. The method also includes generating one or more energizing signals using a signal generator of the treatment system, wherein the signal generator receives power from an internal power source of the treatment system. The method further includes transmitting the one or more energizing signals generated using the signal generator to the coil of the implantable stimulation device via at least one electrical lead connected or connectable to the coil.

[0007] According to other implementations of the present disclosure, a method is directed to controlling cell growth in a tissue. The method includes providing an implantable stimulation device with a support rod that extends distally from an anchor plate, and a coil being wrapped around a portion of the support rod and communicatively coupled with a signal generator. The method further includes generating, via the signal generator, one or more energizing signals defined by a first frequency that is selected based at least in part on a type of tissue for which cell growth is being controlled. The method also includes transmitting the one or more energizing signals to the coil, thereby generating a field stimulation, and evaluating an effectiveness of the field stimulation based on acquired data in response to the field stimulation. The method further includes adjusting the first frequency to a second frequency based on the evaluating, wherein the adjusting is configured to affect cells of the tissue proximate to the implantable stimulation device.

[0008] The above summary is not intended to represent each embodiment or every aspect of the present disclosure. Rather, the foregoing summary merely provides an example of some of the novel aspects and features set forth herein. The above features and advantages, and other features and advantages of the present disclosure, will be readily apparent from the following detailed description of representative embodiments and modes for carrying out the present invention, when taken in connection with the accompanying drawings and the appended claims.24917-6735-5280 1065472-001012WOPTBRIEF DESCRIPTION OF THE DRAWINGS

[0009] The foregoing and other advantages of the present disclosure will become apparent upon reading the following detailed description and upon reference to the drawings.

[0010] FIG. l is a block diagram of a treatment system, according to aspects of the present disclosure.

[0011] FIG. 2A is an illustration of an implantable stimulation device, according to aspects of the present disclosure.

[0012] FIG. 2B is an illustration of another implantable stimulation device, according to aspects of the present disclosure.

[0013] FIG. 2C is another illustration of the implantable stimulation in FIG. 2C, according to aspects of the present disclosure.

[0014] FIG. 3 is an illustration of another implantable stimulation device, according to aspects of the present disclosure.

[0015] FIG. 4A is an illustration showing an example application for a treatment system, according to aspects of the present disclosure.

[0016] FIG. 4B is an illustration showing another example application for a treatment system, according to aspects of the present disclosure.

[0017] FIG. 4C is a graphical illustration showing an example treatment stimulation according to aspects of the present disclosure.

[0018] FIG. 5 is a flowchart setting forth steps of a process, according to aspects of the present disclosure.

[0019] FIG. 6 is a chart illustrating experimental data associated with a treatment system, according to aspects of the present disclosure.

[0020] FIG. 7A is a chart illustrating survival data for a first subset of the treatment groups evaluated in an in vivo experiment, according to aspects of the present disclosure.

[0021] FIG. 7B is a chart illustrating survival data for a second subset of the treatment groups evaluated in the in vivo experiment, according to aspects of the present disclosure.

[0022] FIG. 8A is a graphical illustration showing control and treatment groups evaluated in a second in vivo experiment, according to aspects of the present disclosure.

[0023] FIG. 8B is a chart illustrating survival data for the second in vivo experiment, according to aspects of the present disclosure.34917-6735-5280 1065472-001012WQPT

[0024] FIG. 9 shows photographs of post-treatment tumor sizes and data from the second in vivo experiment, according to aspects of the present disclosure.

[0025] FIG. 10A is a chart illustrating a tumor size overview, according to aspects of the present disclosure.

[0026] FIG. 10B is a table summarizing the overview of FIG. 10 and a mean sizing of tumor after treatment, according to aspects of the present disclosure.

[0027] FIG. 11 shows a graph with mean sizing of tumor after treatment for the second in vivo experiment, according to aspects of the present disclosure.

[0028] FIG. 12A is a plot illustrating natural killer T (“NKT”) cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.

[0029] FIG. 12B is a plot illustrating inducible nitric oxide synthase-positive (“iNOS+”) NKT cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.

[0030] FIG. 12C is a plot illustrating interferon-gamma-positive (“iFNy+”) NKT cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.

[0031] FIG. 12D is a plot illustrating a cluster of differentiation 4-positive (“CD4+”) cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.

[0032] FIG. 12E is a plot illustrating iNOS+CD4+cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.

[0033] FIG. 12F is a plot illustrating iFNy+CD4+cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.

[0034] FIG. 12G is a plot illustrating forkhead box P3-positive (“Foxp3+”) CD4+cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.

[0035] FIG. 13 A is a plot illustrating a cluster of differentiation 8-positive (“CD8+”) cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.

[0036] FIG. 13B is a plot illustrating iNOS+CD8+cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.

[0037] FIG. 13C is a plot illustrating iFNy+CD8+cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.

[0038] FIG. 13D is a plot illustrating natural killer (“NK”) and a cluster of differentiation 3-negative (“CD3 ”) cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.44917-6735-5280 1065472-001012WQPT

[0039] FIG. 13E is a plot illustrating iNOS+CD3' NK cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.

[0040] FIG. 13F is a plot illustrating iFNy+CD3' NK cells evaluated in the second in vivo experiment, according to aspects of the present disclosure.

[0041] While the present disclosure is susceptible to various modifications and alternative forms, specific implementations have been shown by way of example in the drawings and will be described in further detail herein. It should be understood, however, that the present disclosure is not intended to be limited to the particular forms disclosed. Rather, the present disclosure is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.DETAILED DESCRIPTION

[0042] Conventional technologies that provide tumor treatment fields (TTFs) for cancer treatment have a number of disadvantages. For instance, patch devices can be cumbersome to use, can cause skin irritation, and can be interrupt or affect treatment. Unlike such conventional technologies, the present disclosure provides an improved approach for providing TTFs.

[0043] As detailed further below, the present treatment system, in its various embodiments described, can provide a number of benefits and advantages over conventional approaches, such as an ability to deliver TTFs continuously, and in a more targeted manner. For instance, the present treatment system may be implanted in a resection cavity of a patient (e.g., an intracranial resection cavity) by a clinician, and utilized to locally control tumor cell cycle (e.g., abnormal cell division in glioblastoma multiforme (GBM)). Also, unlike conventional technologies, the present treatment system may be operated without a large external battery pack, and without need for a patient to shave their head. Further, unlike conventional technologies, the present treatment system need not generate signals that traverse a patient’s skull.

[0044] The present disclosure is described with reference to the attached figures, where like reference numerals are used throughout the figures to designate similar or equivalent elements. The figures are not drawn to scale, and are provided merely to illustrate the instant disclosure. Several aspects of the disclosure are described below with reference to example applications for illustration. It should be understood that numerous specific details, relationships, and methods are set forth to provide a full understanding of the disclosure. One having ordinary skill in the relevant art, however, will readily recognize that the disclosure can 54917-6735-5280 1065472-001012WQPTbe practiced without one or more of the specific details, or with other methods. In other instances, well-known structures or operations are not shown in detail to avoid obscuring the disclosure. The present disclosure is not limited by the illustrated ordering of acts or events, as some acts may occur in different orders and / or concurrently with other acts or events. Furthermore, not all illustrated acts or events are required to implement a methodology in accordance with the present disclosure.

[0045] Turning to FIG. 1, a schematic diagram of a treatment system 10, according to aspects of present disclosure, is shown. As illustrated, in some embodiments, the treatment system 10 may include an implantable stimulation device 100, connected or connectable via one or more conduits 110 (e.g., one or more electrical leads or cables) to a controller 120. As described in more detail herein, the implantable stimulation device 100 may be configured to provide a treatment field stimulation to or near (e.g., less than 5 centimeters (“cm”)) tissue in which the implantable stimulation device 100 may be implanted. In some applications, the implantable stimulation device 100 may be implanted in or near a resection cavity. For instance, the implantable stimulation device 100 may be implanted intracranially in or near a resection cavity produced by surgical removal of tumor tissue, such as GBM tissue.

[0046] The controller 120 may be configured to control a treatment field stimulation provided by the implantable stimulation device 100. To this end, the controller 120 may include various devices, components, and / or hardware configured to energize the implantable stimulation device 100 to provide the stimulation. In some embodiments, the controller 120 may include a signal generator 122 configured to generate and provide energizing signals to one or more coils of the implantable stimulation device 100 to generate the treatment field stimulation, as illustrated in FIG. 120. For instance, the signal generator 122 may include any number of devices, components, and / or hardware configured to produce and / or condition electrical signals (e.g., current signals, voltage signals, etc.). In some non-limiting examples, the signal generator 122 may include any converter, oscillator, modulator, amplifier, filter, attenuator, divider, resistor, capacitor, inductor, switch, transistor, diode, and so forth.

[0047] The electrical signals provided by the signal generator 122 may have various signal characteristics, including various amplitudes, frequencies, durations, phases, and so forth. In some applications, the signal generator 122 may be configured to provide electrical signals in a predetermined stimulation pattern, which may depend, for instance, on tissue being treated, on size of resection cavity, and so forth. For instance, in some applications, the predetermined stimulation pattern may include a series of electrical pulses with a predetermined pulse width,64917-6735-5280 1065472-001012WOPTa predetermined frequency, and a predetermined amplitude. In other applications, the predetermined stimulation pattern may include periodic, aperiodic, continuous stimulation with a predetermined duration, and a predetermined amplitude. By way of example, the electrical signals may be defined by one or more frequencies in a range approximately between 10 Hertz (“Hz”) and 300 kiloHertz (“kHz”), although other frequency values may be possible. In another non-limiting example, the electrical signals may be defined by one or more amplitudes in a range approximately between 0.1 Volts to 5 Volts, although other amplitude values may be possible. In some aspects, electrical signals provided by the signal generator 122 may be configured to produce continuous and / or static magnetic fields.

[0048] As illustrated in FIG. 1, in some embodiments, the controller 120 may include an internal power source 124, which may be configured to provide power to various components of the controller 120, such as the signal generator 122. For example, the internal power source 124 may include one or more batteries (e.g., one or more rechargeable batteries) that may provide up to 3.0 Volts, or more.

[0049] In some embodiments, the controller 120 may also include communication hardware 126. The communication hardware 126 may allow for various control of components in the controller 120. For instance, in some embodiments, the communication hardware 126 may be configured receive control signals or programming signals (e.g., via wiring and / or wirelessly), from an external system or external device, to select various characteristics of electrical signals to be generated by the signal generator 122, as described. In some embodiments, the communication hardware 126 may be configured to receive power signals, from an external charging system or an external charging device, to recharge the internal power source 124 (e.g., via wiring and / or wirelessly).

[0050] In some embodiments, the controller 120 may include a case configured to house various components therein, such as the signal generator 122, internal power source 124, and so forth. In some applications, the case may be configured, by way of shape and dimension, to be implantable in a subject. For example, the case may be implanted in a subject’s chest, skull, or any other portion of the subject.

[0051] Turning to FIGs. 2A and 2B, an implantable stimulation device 200, in accordance with aspects of the present disclosure, is illustrated. As shown, the implantable stimulation device 200 may include an anchor plate 202 and a support rod 204 extending distally from a surface of the anchor plate 202. In some embodiments, the anchor plate 202 may be configured to receive at least one fastener that may engage a subject’s skull, allowing the anchor plate 20274917-6735-5280 1065472-001012WOPTto attach to a subject’s skull. While FIGs. 2A and 2B illustrate the anchor plate 202 as a circular plate, a shape and dimension of the anchor plate 202 may vary.

[0052] The support rod 204 may be formed using various materials, and may include various features, textures, and so forth. For instance, the support rod 204 may include one or more material compatible with implantation in tissue. In some embodiments, the support rod 204 may include a metallic core or a magnetic core coated with a non-metallic material. In some embodiments, at least a portion of the support rod 204 may include a flexible material. A length of the support rod 204 may vary approximately between 2 cm and 10 cm, although other values may be possible. A diameter of the support rod 204 may vary approximately between 0.1 cm and 2 cm, although other values may be possible.

[0053] The implantable stimulation device 200 may also include a coil 206 (e.g., a solenoid) wrapped around at least a portion of the support rod 204, such as a distal portion 208 of the support rod 204. A number of turns of the coil 206 vary between 2 and 200, although other values may be possible. When energized, the coil 206 generates a treatment field stimulation (e.g., a magnetic field stimulation) to tissue in proximity (e.g., less than 5 cm) to the coil 206. Energizing signals may be provided via an electrical conduit 210, as illustrated in FIG. 2 A. While FIG. 2 A illustrates that that electrical conduit 210 may traverse the anchor plate 202 via an opening in the anchor plate 202, the electrical conduit 210 may traverse the anchor plate 202 in any manner, such as around the anchor plate 202, or via an opening, slot, or other feature in the anchor plate 202.

[0054] In some embodiments, the support rod 204 may include a hinge 212, which may be configured to allow a rotation of a portion of the support rod 204 about the hinge 212, as illustrated in FIGs. 2B and 2C. For instance, the distal portion 208 may pivot about the hinge 212 to change an orientation of the coil 206, and hence magnetic field generated by the coil 206. For example, an orientation of the magnetic field generated by the coil 206 may be changed from a longitudinal direction (along the y direction in FIG. 2B) to a transverse direction (along the x direction in FIG. 2C). In some embodiments, the hinge 212 may be configured to lock the distal portion 208 of the support rod 204 in one or more position. For example, the hinge 212 may be configured to lock the distal portion 208 in a first configuration shown in FIG. 2B, and in a second configuration shown in FIG. 2C, as well as various other configurations (i.e., at various rotation angles of the distal portion 208 about the hinge 212).

[0055] While FIGs. 2A-2C illustrate an embodiment of the implantable stimulation device 200 with one support rod 204, the implantable stimulation device 200 may include any number 84917-6735-5280 1065472-001012WOPTof support rods 204. For example, as illustrated in FIGs. 3, 4A, and 4B, an implantable stimulation device 300 may include a first support rod 304’, a second support rod 304”, and a third support rod 304’”, each having wrapped thereon a first coil 306’, second coil 306”, and third coil 306’”, respectively.

[0056] The implantable stimulation device 300 may be connected or connectable to a controller 320, via an electrical conduit 310 (e.g., a cable). In some embodiments, the implantable stimulation device 300 may include a first electrical lead 310’ connected or connectable to a first coil 306’, a second electrical lead 310” connected or connectable to a second coil 306”, and a third electrical lead 310’” connected or connectable to a third coil 306’” (FIG. 3). In some embodiments, the anchor plate 302 may be configured to allow for traversal of the first electrical lead 310’, the second electrical lead 310”, and / or the third electrical lead 310” ’ via one or more openings, slots, or other features configured in the anchor plate 302, as described. In some embodiments, windings of the first coil 306’, second coil 306”, and third coil 306’” may match. In other embodiments, windings of the first coil 306’, second coil 306”, and third coil 306’” may be different. Further, in some applications, the first coil 306’, second coil 306”, and third coil 306’” may be operated similarly (e.g., using substantially similar energizing signals) as well as differently (e.g., using different energizing signals). In this manner, a magnetic field profile about the implantable stimulation device 300, and more particularly about the distal portion 308 of the implantable stimulation device 300, may be controlled.

[0057] In some embodiments, one or more support rod 304 of the implantable stimulation device 300 may include a hinge 312 (FIG. 4B). As described, the hinge 312 may allow for a portion of the support rod 304 to pivot and rotate thereabout. For instance, in some embodiments, the first support rod 304’ may include a first hinge 312’, the second support rod 304” may include a second hinge 312”, the third support rod 304’” may include a third hinge’”, or a combination thereof.

[0058] The first hinge’, the second hinge”, and the third hinge’” need not rotate, or move in the same way, thereby allowing for selectively configuration of each support rod 304, and hence each coil 306, on the implantable stimulation device 300. Through such selective configuration, uniform as well as non-uniform magnetic field stimulation may be generated and provided to tissue in the subject’s skull (e.g., in or about a resection cavity). For instance, as shown in FIG. 4C, various magnetic field component, along various directions, may be94917-6735-5280 1065472-001012WOPTgenerated. In this manner, amplitude and orientation of magnetic field may be controlled in tissue being treated.

[0059] Turning to FIG. 5, a flowchart setting forth steps of a process 500, according to aspects of the present disclosure, is illustrated. Steps of the process 500 may be carried out using any combination of suitable devices, tools, hardware, systems, and so forth, such as the treatment system 10 described with reference to FIG. 1. In some embodiments, one or more steps of the process 500 may be implemented as instructions stored in non-transitory computer-readable media, as a program, firmware or software, and executed by various general-purpose, programmed or programmable computers, processors or other computing devices. In other embodiments, one or more steps of the process 500 may be hardwired in an application-specific computer, server, processor, dedicated system, or module. Although the process 500 is illustrated and described as a sequence of steps, it is contemplated that the steps may be performed in any order or combination, need not include all illustrated steps, and may include additional steps.

[0060] The process 500 may begin at process block 502 with providing a treatment system, in accordance with aspects of the present disclosure. In some implementations, the treatment system may include an implantable stimulation device with at least an anchor plate attachable to a subject’s skull, a first support rod that extends distally from the anchor, and a coil wrapped around at least a portion of the first support rod, the coil configured to provide a treatment field stimulation to tissue in the subject’s skull. The treatment system may also include a signal generator electrically connected or connectable to the coil of the implantable stimulation device, the signal generator configured to provide energizing signals to the coil to generate the treatment field stimulation. The treatment system may further include an internal power source that powers at least the signal generator.

[0061] As indicated by process block 504, various energizing signals may be generated. Energizing signals may be generated using various devices, components, and / or hardware of a signal generator configured to produce various electrical signals (e.g., current signals, voltage signals, etc.). As described, in some implementations, electrical signals generated by the signal generator may have various signal characteristics, including various amplitudes, frequencies, durations, phases, and so forth.

[0062] For instance, in some applications, the signal generator may generate electrical signals in a predetermined stimulation pattern, which may depend, for instance, on tissue being treated, on size of resection cavity, and so forth. For instance, in some applications, the 104917-6735-5280 1065472-001012WOPTpredetermined stimulation pattern may include a series of electrical pulses with a predetermined pulse width, a predetermined frequency, and a predetermined amplitude. In other applications, the predetermined stimulation pattern may include periodic, aperiodic, continuous stimulation with a predetermined duration, and a predetermined amplitude. By way of example, the electrical signals may be defined by one or more frequencies in a range approximately between 10 Hz and 300 kHz, although other frequency values may be possible. In another non-limiting example, the electrical signals may be defined by one or more amplitudes in a range approximately between 0.1 Volts to 5 Volts, although other amplitude values may be possible. In some applications, electoral signals generated at process block 504 may be configured to generate magnetic field values that are sufficient or effective to disrupt or affect tumor cell cycle (e.g., abnormal cell division in glioblastoma multiforme (GBM)), for instance, within a predetermined distance (e.g., less than 5 cm) from the implantable stimulation device.

[0063] Energizing signals generated may then be transmitted, as indicated by process block 506. As described, energizing signals may be directed to one or more coil on the implantable stimulation device using one or more electrical conduit (e.g., electrical lead or electrical cable). In this manner, a treatment field stimulation (i.e., a magnetic field stimulation) may be generated. In some implementations, generated energizing signals may be configured to produce continuous and / or static magnetic fields.

[0064] In some implementations, an effectiveness or impact of energizing signals generated and transmitted to the implantable device may be evaluated, as indicated by process block. For instance, certain data (e.g., ECoG (electrocorticography) data, EEG (electroencephalography) data, and so forth) may be acquired or accessed (e.g., from a data storage or database), and used to determine an effectiveness or impact of energizing signals generated using the implantable device. Such effectiveness or impact (e.g., as measured by one or more signal value or data point associated with acquired or accessed data exceeding or not exceeding one or more predetermined threshold) may then be utilized to adjust energizing signals generated at process block 504. In some implementations, a report may also be generated at process block indicative of the effectiveness or impact of energizing signals generated and transmitted to the implantable device. As shown in FIG. 5, process blocks 504 to 508 may be repeated a number of times, in a closed-loop manner.

[0065] Turning to FIG. 6, according to aspects of the present disclosure, experimental data associated with the treatment system 10 depicts preliminary results from in vitro and / or in vivo 114917-6735-5280 1065472-001012WOPTexperimentation conducted to evaluate the therapeutic effects of a treatment field stimulation generated by the implantable stimulation device 100 on tumor cell populations in a GBM model. More specifically, experimental studies were undertaken to assess the ability of a treatment field stimulation, such as a magnetic field stimulation generated by the coil 206 of the implantable stimulation device 200, to affect tumor cell viability, proliferation, and / or survival. In some embodiments, the experimental data represents foundational research demonstrating the potential therapeutic benefit of localized treatment field stimulation delivery using the implantable stimulation device 100, 200, 300, as described with reference to FIGs.1-5.

[0066] In other embodiments, the experimental data was generated using experimental protocols designed to evaluate the effects of various treatment parameters on tumor cell behavior, including, but not limited to, a frequency, an amplitude, a duration, and an orientation of the treatment field stimulation. For example, the experimental conditions include one or more treatment groups receiving the treatment field stimulation at varying frequencies and / or intensities, as well as one or more control groups receiving no treatment field stimulation or receiving standard-of-care treatment alone. By way of further example, the energizing signals provided by the signal generator 122 may be defined by one or more frequencies in a range approximately between 10 Hz and 300 kHz, and one or more amplitudes in a range approximately between 0.1 Volts to 5 Volts (as described with reference to FIG. 1 and although other values may be possible).

[0067] The one or more frequencies include a first frequency that is changed or adjusted to a second frequency after evaluating the effectiveness of the treatment field stimulation. The second frequency is intended to further disrupt, reduce, restore, or enhance cell growth. For example, improved abnormal cell reduction or disruption is achieved via the second frequency, after evaluating the effectiveness first attempted with the first frequency. Similarly, improved immune cell restoration or enhancement is achieved via the second frequency, after evaluating the effectiveness first attempted with the first frequency.

[0068] Moreover, the experimental data provides evidence supporting the development of the treatment system 10 as an improved approach for providing treatment field stimulation to tissue within a subject's skull. In particular, the experimental data supports the concept that the implantable stimulation device 100, 200, 300 may provide continuous treatment field stimulation to tissue in or proximate to a resection cavity following surgical removal of tumor tissue, such as GBM tissue, as described with reference to FIGs. 4 A and 4B.124917-6735-5280 1065472-001012WOPT

[0069] In yet other embodiments, the experimental data shows informed subsequent optimization of treatment parameters, including optimization of treatment field stimulation frequency and assessment of toxicity profiles, as further detailed in connection with subsequent figures herein. For example, experimental data illustrated in FIG. 6 contributes to identification of effective and ineffective stimulation frequencies and dosing parameters, which were subsequently optimized for further experimentation. Such optimization may include adjusting the predetermined stimulation pattern provided by the signal generator 122, as described with reference to FIG. 1.

[0070] According to some aspects of the present disclosure, the experimental data presented in FIG. 6 represents an initial phase of research that contributes to the development of optimized dosing protocols for the treatment system 10, including investigation of the effects of frequency, voltage, and magnetic field direction on treatment efficacy. The experimental results further illustrates advantages of the treatment system 10 over conventional patch devices, including an ability to deliver treatment field stimulation continuously without need for a large external battery pack or for a patient to shave their head, as described.

[0071] Turning to FIGs. 7A and 7B, survival curve data is illustrated based on an in vivo experiment associated with the treatment system 10, according to aspects of the present disclosure. More specifically, Kaplan-Meier survival curves are illustrated as generated from an in vivo study using GBM-bearing animal models (e.g., mice), in which multiple treatment groups were evaluated to assess the effects of stimulation alone and in combination with one or more chemotherapeutic agents on subject survival.

[0072] In FIG. 7A, survival data is illustrated for a first subset of the treatment groups evaluated in the in vivo experiment. In FIG. 7B, survival data is illustrated for a second subset of the treatment groups evaluated in the in vivo experiment. As described in more detail herein, the treatment groups evaluated in the in vivo experiment included, but were not limited to:(a) a treatment field stimulation group, in which subjects received transcranial magnetic field stimulation at a frequency of approximately 50 Hz and an amplitude of approximately 5 Volts, with a square waveform, a duty cycle of approximately 50%, and an offset of approximately 0.0%, administered for approximately 60 minutes per day over approximately 10 days;(b) a chemotherapeutic agent group, in which subjects received temozolomide (“TMZ”) administered intraperitoneally at a dosage of approximately 50 milligram (“mg”) / kilogram (“kg”) once daily for approximately 5 days;134917-6735-5280 1065472-001012WOPT(c) a combination treatment field stimulation and chemotherapeutic agent group, in which subjects received both the treatment field stimulation of group (a) and the TMZ of group (b) administered sequentially over approximately 10 days; (d) one or more additional chemotherapeutic agent groups, in which subjects received one or more additional therapeutic compounds administered intraperitoneally or intravenously at varying dosages and schedules; and (e) a control group, in which subjects received saline vehicle only.

[0073] In some embodiments, the treatment field stimulation administered in the in vivo experiment was delivered transcranially using a coil, such as the coil 206 of the implantable stimulation device 200, or comparable experimental apparatus configured to generate a magnetic field stimulation at the parameters described above. The energizing signals used were consistent with the signal characteristics described with reference to the signal generator 122 and FIG. 1.

[0074] As illustrated in FIGs. 7A and 7B, the survival curve data from the in vivo experiment revealed certain findings that informed subsequent experimental design and parameter optimization for the treatment system 10. In particular, the survival data indicated that certain stimulation frequencies were more effective than others for achieving a desired therapeutic effect on tumor cell populations in the GBM model. These findings contributed to the identification of respective parameters, which were subsequently optimized in further experimentation, as described herein.

[0075] Additionally, the survival data indicated that one or more of the additional chemotherapeutic agents administered in the in vivo experiment exhibited high toxicity in the animal model, which informed subsequent dosing optimization. Such optimization may include adjusting a dosage, a route of administration, a frequency of administration, or a combination thereof, for one or more therapeutic agents administered in conjunction with stimulation provided by the treatment system 10.

[0076] In some aspects of the present disclosure, the survival curves depicted in FIGs. 7A and 7B illustrate subject survival as a function of time (e.g., days after tumor cell inoculation) for each treatment group, thereby enabling comparison of therapeutic efficacy across groups via Kaplan-Meier analysis. In some embodiments, brains of all subjects in the in vivo experiment were collected for subsequent histological and / or molecular analysis, as further described herein.144917-6735-5280 1065472-001012WOPT

[0077] The experimental findings depicted in FIGs. 7A and 7B directly informed the design of subsequent experiments, in which the stimulation frequency was adjusted (e.g., to approximately 200 kHz) and chemotherapeutic dosing was optimized. Such adjustments to the predetermined stimulation pattern provided by the signal generator 122 are consistent with the closed-loop optimization process described with reference to FIG. 5.

[0078] Turning to FIGs. 8A and 8B, survival curve data is illustrated from a second in vivo experiment associated with the treatment system 10, according to aspects of the present disclosure. The second in vivo experiment provides data that shows Kaplan-Meier survival curves generated using GBM-bearing animal models (e.g., mice), in which treatment parameters were optimized based on the experimental findings of the previous (first) in vivo experiment described above and illustrated in FIGs. 7A and 7B.

[0079] FIG. 8A illustrates the control and treatment groups using mice, and FIG. 8B illustrates survival data evaluated in the second in vivo experiment. As described in more detail herein, the treatment groups evaluated in the second in vivo experiment included, but were not limited to:(a) a combination treatment field stimulation and chemotherapeutic agent group, in which subjects received treatment field stimulation at an optimized frequency of approximately 200 kHz and an amplitude of approximately 5 Volts for approximately 1 hour per session, in combination with TMZ administered intraperitoneally at a dosage of approximately 50 mg / kg for approximately 6 doses;(b) a chemotherapeutic agent group with sham stimulation, in which subjects received TMZ administered intraperitoneally at a dosage of approximately 50 mg / kg for approximately 6 doses, together with sham magnetic field exposure; (c) one or more additional treatment groups, in which subj ects received one or more additional therapeutic compounds, such as ETP or PGA-ETP conjugates, administered intraperitoneally or intravenously at varying dosages; and (d) a control group, in which the mice subjects received saline vehicle only.

[0080] In some embodiments, the treatment field stimulation administered in the second in vivo experiment was delivered transcranially using a coil, such as the coil 206 of the implantable stimulation device 200, or comparable experimental apparatus configured to generate a magnetic field stimulation at the optimized parameters described above. Notably, the stimulation frequency in the second in vivo experiment was increased to approximately 200154917-6735-5280 1065472-001012WQPTkHz from the approximately 50 Hz frequency used in the first in vivo experiment, as described with reference to FIGs. 7 A and 7B. The energizing signals used were consistent with the signal characteristics described with reference to the signal generator 122 and FIG. 1, and fell within the frequency range of approximately 10 Hz to 300 kHz and amplitude range of approximately 0.1 Volts to 5 Volts.

[0081] The survival analysis from the second in vivo experiment revealed that subjects receiving the combination of treatment field stimulation at the optimized frequency and TMZ exhibited a prolonged lifespan compared to control subjects. In particular, the survival data indicated that the combination of treatment field stimulation at approximately 200 kHz and TMZ was associated with improved survival outcomes relative to subjects receiving TMZ alone with sham stimulation, as well as relative to control subjects receiving saline vehicle only. These findings support the therapeutic efficacy of the treatment field stimulation provided by the treatment system 10 when administered at an optimized frequency and in combination with a chemotherapeutic agent.

[0082] Additionally, the survival data demonstrates that parameter optimization — including the adjustment of stimulation frequency from approximately 50 Hz to approximately 200 kHz, as well as adjustment of chemotherapeutic dosing — yielded measurably improved therapeutic outcomes compared to those observed in the first in vivo experiment, as depicted in FIGs. 7A and 7B. Such parameter optimization is consistent with the closed-loop process described with reference to FIG. 5, wherein the effectiveness of energizing signals may be evaluated and subsequently adjusted.

[0083] According to some aspects of the present disclosure, the survival curves of the second in vivo experiment illustrate subject survival as a function of time (e.g., days after tumor cell inoculation) for each treatment group, thereby enabling comparison of therapeutic efficacy across groups via Kaplan-Meier analysis. According to some embodiments, brains of all subjects in the second in vivo experiment were collected for subsequent histological and / or molecular analysis, including analysis of immune response markers, as further described herein.

[0084] The experimental findings of the second in vivo experiment provide further evidence that the treatment system 10, when operated at optimized stimulation parameters, may extend survival in GBM-bearing animal models. The data further supports the development of the treatment system 10 as an improved approach for delivering continuous treatment field164917-6735-5280 1065472-001012WOPTstimulation to tissue within a subject's skull, such as tissue in or proximate to a resection cavity following surgical removal of tumor tissue, as described with reference to FIGs. 4A and 4B.

[0085] Turning to FIG. 9, post-treatment tumor size data is illustrated from the second in vivo experiment associated with the treatment system 10, according to aspects of the present disclosure. More specifically, post-treatment tumor size measurements are shown (in millimeters (“mm”) for the following treatment groups:(a) a control group, in which subjects received saline vehicle only;(b) a chemotherapeutic agent group, in which subjects received TMZ administered intraperitoneally at a dosage of approximately 50 milligrams mg / kg;(c) a treatment field stimulation group, in which subjects received transcranial magnetic field stimulation at a frequency of approximately 200 kHz and an amplitude of approximately 5 Volts for approximately 1 hour per session, using an external coil modeling the coil 206 of the implantable stimulation device 200; and(d) a combination treatment field stimulation and chemotherapeutic agent group, in which subjects received both the treatment field stimulation of group (c) and the TMZ of group (b).

[0086] The gross pathological data of FIG. 9 reveals measurable differences in tumor size across the treatment groups evaluated in the second in vivo experiment. The control group exhibited the largest tumors, with an estimated mean tumor diameter of approximately 6.7 mm and individual tumors ranging from approximately 4 mm to approximately 10 mm. The TMZ group exhibited moderate tumor size reduction relative to the control group, with an estimated mean tumor diameter of approximately 4.4 mm. The treatment field stimulation group exhibited residual solid tumors with an estimated mean tumor diameter of approximately 2.75 mm. The combination treatment field stimulation and TMZ group exhibited the greatest overall tumor size reduction, with an estimated mean tumor diameter of approximately 2.9 mm, a majority of individual tumors measuring approximately 1 mm to 2 mm, and one residual tumor measuring approximately 4 mm.

[0087] FIG. 9 further includes representative photographs of subject brains from each treatment group, providing a visual comparison of gross tumor morphology and size following treatment. The photographs illustrate the relative reduction in tumor burden across the treatment groups, with the combination treatment field stimulation and TMZ group and the treatment field stimulation group exhibiting visibly smaller tumors compared to the control 174917-6735-5280 1065472-001012WQPTgroup and the TMZ group. In some subjects within the combination treatment field stimulation and TMZ group, no visible tumor tissue was observed upon gross examination, indicating potential complete macroscopic tumor regression in a subset of subjects.

[0088] Additionally, FIG. 9 includes a bar graph depicting individual and / or mean tumor size measurements for each treatment group, thereby enabling quantitative comparison of therapeutic efficacy across groups. The tumor size data depicted in FIG. 9 corroborates the survival data illustrated in FIGs. 8A and 8B, further demonstrating that the combination of treatment field stimulation at the optimized frequency of approximately 200 kHz and TMZ yielded improved therapeutic outcomes compared to either treatment alone or control. In particular, the tumor size reduction observed in the combination group supports the synergistic or additive therapeutic benefit of combining treatment field stimulation provided by the treatment system 10 with a chemotherapeutic agent.

[0089] The post-treatment tumor size data depicted in FIG. 9 provides further evidence supporting the development of the treatment system 10 as an improved approach for delivering continuous treatment field stimulation to tissue within a subject's skull, such as tissue in or proximate to a resection cavity following surgical removal of tumor tissue, as described with reference to FIGs. 4A and 4B. The data further demonstrates that treatment field stimulation, when delivered at optimized parameters using an external coil modeling the coil 206, may reduce tumor burden in GBM-bearing animal models, thereby validating the optimized stimulation parameters for subsequent implementation in the fully implantable stimulation device 100, 200, 300.

[0090] Turning to FIGs. 10A and 10B, immune response data is illustrated from the second in vivo experiment, according to aspects of the present disclosure. As described with reference to FIGs. 8 A, 8B, and 9, brains of all subjects in the second in vivo experiment were collected for subsequent histological and / or molecular analysis, including analysis of immune response markers. FIGs. 10A and 10B depict the results of such analysis, presenting flow cytometry data characterizing immune cell populations and their functional states within tumor-bearing brain tissue across the treatment groups evaluated in the second in vivo experiment.

[0091] Referring specifically to FIG. 10A, flow cytometry gating plots are illustrated for a set of immune cell populations, across each of the treatment groups evaluated in the second in vivo experiment:(a) a control group, in which subjects received saline vehicle only;184917-6735-5280 1065472-001012WOPT(b) a chemotherapeutic agent group, in which subjects received TMZ administered intraperitoneally at a dosage of approximately 50 mg / kg;(c) a treatment field stimulation group, in which subjects received transcranial magnetic field stimulation at a frequency of approximately 200 kHz and an amplitude of approximately 5 Volts for approximately 1 hour per session, using an external coil modeling the coil 206 of the implantable stimulation device 200; and(d) a combination treatment field stimulation and chemotherapeutic agent group, in which subjects received both the treatment field stimulation of group (c) and the TMZ of group (b).

[0092] FIG. 10B illustrates corresponding quantification for the set of immune cell populations represented in FIG. 10 A. The immune response data from the second in vivo experiment reveals that the treatment field stimulation, when delivered at the optimized frequency of approximately 200 kHz using the external coil modeling the coil 206, induced significant changes in immune cell functional states within tumor-bearing brain tissue, without substantially altering the abundance or frequency of the immune cell populations themselves. In particular, the data indicated that treatment field stimulation was sufficient to restore or enhance cytotoxic immune function across multiple immune cell populations, as described in more detail herein.

[0093] Taken together, the immune response data depicted in FIGs. 10A and 10B demonstrates that treatment field stimulation, when delivered at the optimized frequency of approximately 200 kHz using the external coil modeling the coil 206, induces functional reprogramming of cytotoxic immune cells across multiple immune populations. Notably, these effects were observed without altering immune cell frequencies, indicating that the observed immune activation is unlikely to result from immune cell proliferation, recruitment, or toxic effects. Rather, the data supports the conclusion that treatment field stimulation alone is sufficient to restore cytotoxic immune function without altering immune cell abundance, thereby validating the therapeutic mechanism of the treatment system 10.

[0094] The immune response data depicted in FIGs. 10A and 10B, together with the survival data depicted in FIGs. 8A and 8B and the tumor size data depicted in FIG. 9, provides comprehensive evidence supporting the development of the treatment system 10 as an improved approach for delivering continuous treatment field stimulation to tissue within a subject's skull, such as tissue in or proximate to a resection cavity following surgical removal 194917-6735-5280 1065472-001012WQPTof tumor tissue, as described with reference to FIGs. 4A and 4B. The data generated using the external coil modeling the coil 206 validates the optimized stimulation parameters for subsequent implementation in the fully implantable stimulation device 100, 200, 300.

[0095] Turning to FIG. 11, compiled bar graphs are shown illustrating quantified immune cell profiling data with statistical comparisons from the second in vivo experiment associated with the treatment system 10, according to certain aspects of the present disclosure. More specifically, a summary compilation of bar graph panels is presented depicting quantified immune cell frequencies and functional activation markers across the treatment groups evaluated in the second in vivo experiment, as described with reference to FIGs. 8A, 8B, 9, 10 A, and 10B.

[0096] According to some embodiments, FIG. 11 represents a further visualization of the immune response data generated from post-treatment tissue samples collected from GBM-bearing animal models (e.g., mice), providing a comprehensive, side-by-side quantitative comparison of immune cell populations and their functional states across different treatment groups. For example, the mean sizing at a low end experimental end is 2.75 mm for magnetic field (MF) treatment only (e.g., the treatment field stimulation via magnetic field exposure delivered transcranially at a frequency of approximately 200kHZ and an amplitude of approximately 5 Volts). The mean sizing at a high experimental end is 6.67 mm for untreated subjects. Between those two experimental ends, using the chemotherapeutic agent TMZ and the MF stimulation resulted in a 2.9 mm tumor size, while using just TMZ resulted in a 4.4 mm tumor size. Clearly, MF stimulation provides beneficial advantages, resulting in the smallest tumor size.

[0097] Referring generally to FIGs. 12A-12G, individual flow cytometry gating plots are depicted based on the results of the second in vivo experiment. The plots illustrate the gating strategy and representative data for each immune cell population evaluated across the treatment groups described with reference to FIGs. 8A, 8B, 9, 10A, 10B, and 11. Each of FIGs. 12A-12G presents flow cytometry dot plots for individual subjects within each treatment group, with axes corresponding to fluorochrome-conjugated antibody signals used to identify and quantify the respective immune cell population and its functional markers. Statistical gating boundaries and population percentages are annotated within each dot plot.

[0098] By way of example, the plots show that beneficial magnetic field exposure induces robust iFNy+production in NKT cells, which indicates rapid innate immune activation. In204917-6735-5280 1065472-001012WOPTanother beneficial example, CD4+cells are helper lymphocytes that coordinate adaptive immune responses by regulating cytotoxic and innate immune cells.

[0099] Referring specifically to FIG. 12A, the depicted plot shows NKT cells across all four treatment groups. For each individual group, FIG. 12A identifies the percentage of NKT cells, which is generally in the range of about 8% to about 17%.

[0100] Referring specifically to FIG. 12B, the depicted plot shows iNOS+NKT cells across all four treatment groups. For each individual group, FIG. 12B identifies the percentage of iNOS+NKT cells, which is generally in the range of about 2% to about 25%.

[0101] Referring specifically to FIG. 12C, the depicted plot shows iFNy+NKT cells across all four treatment groups. For each individual group, FIG. 12C identifies the percentage of iFNy+NKT cells, which is generally in the range of about 1% to about 60%.

[0102] Referring specifically to FIG. 12D, the depicted plot shows CD4+cells across all four treatment groups. For each individual group, FIG. 12D identifies the percentage of CD4+cells, which is generally in the range of about 35% to about 50%.

[0103] Referring specifically to FIG. 12E, the depicted plot shows iNOS+CD4+cells across all four treatment groups. For each individual group, FIG. 12E identifies the percentage of iNOS+CD4+cells, which is generally in the range of about 10% to about 35%.

[0104] Referring specifically to FIG. 12F, the depicted plot shows iFNy+CD4+cells across all four treatment groups. For each individual group, FIG. 12F identifies the percentage of iFNy+CD4+cells, which is generally in the range of about 1% to about 13%.

[0105] Referring specifically to FIG. 12G, the depicted plot shows Foxp3+CD4+cells across all four treatment groups. For each individual group, FIG. 12G identifies the percentage of Foxp3+CD4+cells, which is generally in the range of about 21% to about 43%.

[0106] Referring generally to FIGs. 13A-13F, individual flow cytometry gating plots are depicted for CD8+T cells and NK CD3 cells from the second in vivo experiment, continuing the individual immune cell subset analyses depicted in FIGs. 12A-12G. Each of FIGs. 13 A-13F presents flow cytometry dot plots for individual subjects within each of the four treatment groups described with reference to FIGs. 8A, 8B, 9, 10A, 10B, and 11. Statistical gating boundaries and population percentages are annotated within each dot plot.

[0107] By way of example, the plots show that beneficial magnetic field exposure significantly increases the fraction of iFNy' producing CD8+cells, which indicates restoration of cytotoxic function without altering CD8+cell abundance. As such, they are main effectors of tumor killing, directly killing tumor cells or virus-infected cells. The plots further show that 214917-6735-5280 1065472-001012WOPTinnate immune cells, primarily NK cells, and how many NK cells are functionally activated to produce iFNy.

[0108] Referring specifically to FIG. 13 A, the depicted plot shows CD8+cells across all four treatment groups. For each individual group, FIG. 13 A identifies the percentage of CD8+cells, which is generally in the range of about 22% to about 43%.

[0109] Referring specifically to FIG. 13B, the depicted plot shows iNOS+CD8+cells across all four treatment groups. For each individual group, FIG. 13B identifies the percentage of iNOS+CD8+cells, which is generally in the range of about 10% to about 45%.

[0110] Referring specifically to FIG. 13C, the depicted plot shows iFNy+CD8+cells across all four treatment groups. For each individual group, FIG. 13C identifies the percentage of iFNy+CD8+cells, which is generally in the range of about 1% to about 8%.

[0111] Referring specifically to FIG. 13D, the depicted plot shows NK CD3 cells across all four treatment groups. For each individual group, FIG. 13D identifies the percentage of NK CD3 cells, which is generally in the range of about 10% to about 25%.

[0112] Referring specifically to FIG. 13E, the depicted plot shows iNOS+CD3 NK cells across all four treatment groups. For each individual group, FIG. 13E identifies the percentage of iNOS+CD3 NK cells, which is generally in the range of about 15% to about 60%.

[0113] Referring specifically to FIG. 13F, the depicted plot shows iFNy+CD3 NK cells across all four treatment groups. For each individual group, FIG. 13F identifies the percentage of iFNy+CD3 NK cells, which is generally in the range of about 1% to about 35%.

[0114] One or more elements or aspects or steps, or any portion(s) thereof, from one or more of any of claims 1-16 below can be combined with one or more elements or aspects or steps, or any portion(s) thereof, from one or more of any of the other claims 1-16 or combinations thereof, to form one or more additional implementations and / or claims of the present disclosure.

[0115] While various examples of the present disclosure have been described above, it should be understood that they have been presented by way of example only, and not limitation. Numerous changes to the disclosed examples can be made in accordance with the disclosure herein without departing from the spirit or scope of the disclosure. Thus, the breadth and scope of the present disclosure should not be limited by any of the above described examples. Rather, the scope of the disclosure should be defined in accordance with the following claims and their equivalents. For example, it should be understood that the data illustrated in the drawings above is presented by way of example only, and not limitation. Various experimental 224917-6735-5280 1065472-001012WOPTconditions, treatment groups, stimulation frequencies, chemotherapeutic agents, dosing regimens, animal models, immune cell markers, flow cytometry panels, and outcome measures may be utilized in evaluating the efficacy and immunological effects of the treatment system 10, and the present disclosure is not limited to the specific data, conditions, immune cell populations, or groups illustrated by of example only in the above drawings.

[0116] Although the disclosure has been illustrated and described with respect to one or more implementations, equivalent alterations and modifications will occur to others skilled in the art upon the reading and understanding of this specification and the annexed drawings. In addition, while a particular feature of the disclosure may have been disclosed with respect to only one of several implementations, such feature may be combined with one or more other features of the other implementations as may be desired and advantageous for any given or particular application.

[0117] The terminology used herein is for the purpose of describing particular examples only and is not intended to be limiting of the disclosure. As used herein, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. Furthermore, to the extent that the terms “including,” “includes,” “having,” “has,” “with,” or variants thereof, are used in either the detailed description and / or the claims, such terms are intended to be inclusive in a manner similar to the term “comprising.”

[0118] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Furthermore, terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art, and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.4917-6735-5280 1065472-001012WOPT

Claims

CLAIMSWhat is claimed is:

1. A treatment system comprising:an implantable stimulation device comprising:an anchor plate attachable to a portion of a subject;a first support rod that extends distally from the anchor plate; and a coil wrapped around at least a portion of the first support rod, the coil configured to provide a treatment field stimulation to tissue in the portion of a subject;a signal generator electrically connected or connectable to the coil of the implantable stimulation device, the signal generator configured to provide energizing signals to the coil to generate the treatment field stimulation; andan internal power source that powers the signal generator.

2. The treatment system of claim 1, wherein the anchor plate is further configured to receive at least one fastener that engages the portion of a subject and attaches the anchor plate thereto.

3. The treatment system of claim 1, wherein the first support rod further comprises a metallic core coated with a non-metallic material.

4. The treatment system of claim 1, wherein the first support rod further comprises a flexible material.

5. The treatment system of claim 1, wherein the first support rod further comprises a first hinge that allows rotation of at least the portion of the first support rod.

6. The treatment system of claim 5, wherein the first hinge is further configured to lock the portion of the first support rod in at least one position.

7. The treatment system of claim 5, wherein the implantable stimulation device comprises a second support rod, a third support rod, or both.244917-6735-5280 1065472-001012WQPT8. The treatment system of claim 7, wherein the second support rod comprises a second hinge, the third support rod comprises a third hinge, or both.

9. The treatment system of claim 8, wherein a positioning of the first hinge, the second hinge, the third hinge, or a combination thereof, is configured to provide a uniform or a non-uniform magnetic field stimulation to the tissue in the portion of a subject.

10. The treatment system of claim 1, further comprising a case configured to house the signal generator and the internal power source.

11. The treatment system of claim 10, wherein the case is configured to be implantable in a subject.

12. The treatment system of claim 1, wherein the implantable stimulation device is further configured to be implanted in or near a resection cavity.

13. The treatment system of claim 1, wherein the signal generator is further configured to provide energizing signals in a predetermined stimulation pattern.

14. The treatment system of claim 1, wherein the signal generator is further configured to provide energizing signals in a frequency between 10 Hertz (Hz) and 300 kiloHertz (kHz).

15. The treatment system of claim 1, wherein the treatment system further comprises communication hardware configured to receive control signals, power signals, or both, from an external device.

16. The treatment system of claim 1, wherein the portion of the subject is a skull.

17. A method comprising:providing a treatment system that includes an implantable stimulation device with an anchor plate, the anchor plate being attachable to a portion of a subject, the treatment system further including a support rod that extends distally from the anchor plate and a coil wrapped254917-6735-5280 1065472-001012WQPTaround at least a portion of the support rod, the coil being configured to provide a treatment field stimulation to tissue in the portion of a subject;generating one or more energizing signals using a signal generator of the treatment system, the signal generator receiving power from an internal power source of the treatment system; andtransmitting the one or more energizing signals generated to the coil of the implantable stimulation device via at least one electrical lead connected or connectable to the coil.

18. The treatment system of claim 1, wherein the portion of the subject is a skull.

19. A method for controlling cell growth in a tissue, the method comprising:providing an implantable stimulation device with a support rod that extends distally from an anchor plate, a coil being wrapped around a portion of the support rod and communicatively coupled with a signal generator;generating, via the signal generator, one or more energizing signals defined by a first frequency that is selected based at least in part on a type of tissue for which cell growth is being controlled;transmitting the one or more energizing signals to the coil, thereby generating a field stimulation;evaluating an effectiveness of the field stimulation based on acquired data in response to the field stimulation; andadjusting the first frequency to a second frequency based on the evaluating, wherein the adjusting is configured to affect cells of the tissue proximate to the implantable stimulation device.

20. The method of claim 19, wherein at least the first frequency is in a range approximately between 10 Hertz (Hz) and 300 kiloHertz (kHz).

21. The method of claim 19, wherein the first frequency has a value configured to disrupt or reduce abnormal cells in the tissue proximate to the stimulation device.

22. The method of claim 19, wherein the new frequency has a value configured to restore or enhance immune cells in the tissue proximate to the stimulation device.264917-6735-5280 1065472-001012WQPT23. The method of claim 19, wherein the generating, the evaluating, and the adjusting are performed iteratively in a closed-loop manner.

24. The method of claim 19, wherein the acquired data includes electrocorticography data, electroencephalography data, or a combination thereof.

25. The method of claim 19, wherein the second frequency is associated with an improved therapeutic outcome relative to the first frequency.

26. The method of claim 25, wherein the first frequency is approximately 50 Hertz (Hz) and the second frequency is approximately 200 kiloHertz (kHz).

27. The method of claim 19, wherein the one or more energizing signals are further defined by a predetermined stimulation pattern that includes a series of electrical pulses with one or more of a predetermined pulse width, a predetermined frequency, and a predetermined amplitude, and wherein the predetermined stimulation pattern depends on the type of tissue being treated.

28. The method of claim 19, wherein the treatment field stimulation generates a magnetic field stimulation sufficient to affect a tumor cell cycle within a predetermined distance from the implantable stimulation device.

29. The method of claim 27, wherein the predetermined distance is less than 5 centimeters (cm).

30. The method of claim 19, wherein the treatment field stimulation restores cytotoxic immune function across one or more immune cell populations without substantially altering an abundance of the one or more immune cell populations.

31. The method of claim 19, further comprising generating a report indicative of the effectiveness of the field stimulation based on the evaluating.274917-6735-5280 1065472-001012WQPT

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