Patent Description:
Alternating electric field (AEF) therapy, is a type of electromagnetic field therapy which uses low-intensity electrical fields to treat brain cancer tumors; glioblastoma in particular. Conventional cancer treatments include chemotherapy and radiation, which are associated with treatment-related toxicity and high rates of tumor recurrence. AEF uses an alternating electric field to disrupt cell division in cancer cells, thereby inhibiting cellular replication and initiating apoptosis (cell death). However, some topical AEF treatment methodologies are associated with skin irritation and rashes, as well as a requirement of the patient to maintain a shaved head and restrict physical activity.

It is with these observations in mind, among others, that various aspects of the present disclosure were conceived and developed.

<CIT> discloses an intratumoral modulation therapy (IMT) method for the treatment of nervous system and systemic tumor in a patient. <CIT> relates generally to the electrical treatment of malignant tumors and neoplasms by applying a voltage to affected tissue. <CIT> discloses a system and methods for determining placement of a transducer array relative to a subject's head, which may be used in treating cancer in the subject. <CIT> discloses TTField treatment with optimization of electrode positions on the head based on MRI-based conductivity measurements.

Corresponding reference characters indicate corresponding elements among the view of the drawings. The headings used in the figures do not limit the scope of the claims.

The present invention provides a system for the treatment of brain cancer as defined in appended claims <NUM> to <NUM>.

Alternating electric field application is a burgeoning cancer treatment type with the potential to reduce treatment related toxicity. In alternating electric field application, an alternating electric field is applied to a cancerous region of the brain, thereby disrupting cellular division for rapidly-dividing cancer cells. To administer alternating electric field treatment to a patient, a system for generating an alternating electric field of optimized strength at a desired location within a body to inhibit cellular division and/or initiate apoptosis of cancer cells at the targeted treatment location is disclosed herein.

The present system provides, among other aspects, a system of a subdural implant apparatus wherein, through the use of an array of subdural electrodes configured to be implanted subdurally and deep-stimulating electrodes configured to be implanted deep into the brain tissue, a targeted alternating electric field is generated for the treatment of rapidly dividing cancer cells. The array of stimulating electrodes is in operative communication with a controller module, wherein the controller module produces a waveform to create the alternating electric field and receives feedback from the array of stimulating electrodes. Referring to the drawings, embodiments of the present system are generally indicated as <NUM> in <FIG>.

Referring to <FIG> and <FIG>, in some embodiments of the present system <NUM>, a main array <NUM> including stimulating electrodes <NUM> and <NUM> is configured to be placed underneath the dura mater of a patient's brain. The main array <NUM> is in operative communication with a controller module <NUM> by way of a wire array <NUM>. The controller module <NUM> is operable to generate an alternating electric field, receive feedback from the main array <NUM>, and communicate with an external computer <NUM> for receiving operating parameters as well as exporting operating data related to the strength of the alternating electric field.

The main array <NUM> may include a plurality of subdural electrodes <NUM> as well as a plurality of deep-stimulating electrodes <NUM>, such that the subdural electrodes <NUM> and deep-stimulating electrodes <NUM> are operable to generate an alternating electric field that is applied to brain tissue. In one aspect, the alternating electric field is configured for appropriate strength and distribution such that cancerous cells in contact with the alternating electric field are prevented from dividing. In some embodiments, one or more wires <NUM>, each defining a respective distal end, extend from a respective subdural electrode <NUM> and terminates in a conductive contact. In one possible application, each of the plurality of subdural electrodes <NUM> are placed on the surface of the brain. In some embodiments, the subdural electrodes <NUM> may be thin enough to fit between the dura mater and the brain of the patient and may in some embodiments be surrounded by gel. Each subdural electrode <NUM> defines a proximal face <NUM> and a distal face (not shown), wherein the proximal face is in operative association with a distal end of each wire <NUM> and the distal face includes a transducing contact that is applied to the exterior of the brain. In some embodiments, the deep-stimulating electrodes <NUM> have elongated rod-shaped members comprising segmented strips of conductive material. The deep-stimulating electrodes <NUM> are implanted deep into the brain to facilitate penetration of the alternating electric field into the brain tissue. In some embodiments each of the deep-stimulating electrodes <NUM> defines a distal end and a proximal end, wherein the distal end of each of the deep-stimulating electrodes <NUM> is implanted into the brain tissue and the proximal end of each of the deep-stimulating electrodes <NUM> is in operative association with a respective wire <NUM>. In some embodiments, the deep-stimulating electrodes <NUM> are operable to measure aspects of the alternating electric field applied to various locations within the brain by the main array <NUM> and communicate measured aspects of the alternating electric field back to the controller module <NUM>. In one aspect, each subdural electrode <NUM> and deep-stimulating electrode <NUM> is operable to apply to tissue a current waveform through the wires <NUM>. An alternating electric field is generated by the application of the waveform to the brain from multiple sources.

One visual example of the placement of subdural electrodes <NUM> and deep-stimulating electrodes <NUM> relative to a cancerous region of the brain is shown in <FIG>. The optimal placement and number of subdural electrodes <NUM> and deep-stimulating electrodes <NUM> may vary between patients. Thus, a variety of imaging platforms may be used to scan the brain and determine optimal placement, types, and quantity of electrodes <NUM> and <NUM> to collectively create the array <NUM>.

Referring to <FIG>, in some embodiments the controller module <NUM> includes a waveform generator <NUM> and a processing unit <NUM>, wherein the waveform generator <NUM> is in operative communication with the array <NUM> by one or more wires <NUM>. The waveform generator <NUM> of the controller module <NUM> is operable to receive a set of operating parameters from the processing unit <NUM> and output a waveform such that when the waveform is distributed throughout the array <NUM>, an alternating electric field is applied to brain tissue. The processing unit <NUM> of the controller module <NUM>, such as a microprocessor or a microcontroller, is operable to output the set of operating parameters for the waveform generator <NUM>. The processing unit <NUM> is also operable to receive input from the array <NUM> pertaining to measured aspects of the alternating electric field and communicate the input to an external computer <NUM>, update the set of operating parameters, and communicate the updated set of operating parameters to the waveform generator <NUM>.

Empirical research for TTF therapy recommends a <NUM> standard waveform to be produced by the waveform generator <NUM> to generate the alternating electric field. Ideal waveform modulation and intensity parameters are determined by the external computer <NUM> and delivered to the waveform generator <NUM> through the processing unit <NUM>.

The controller module <NUM> may also include a wireless communication module <NUM> that allows communication between the processing unit <NUM> of the controller module <NUM> and external computer <NUM>. In this manner, the processing unit <NUM> of the controller module <NUM> is operable to wirelessly receive software updates and instructions from the external computer <NUM> as well as transmit the measured aspects of the alternating electric field to the external computer <NUM> for review and system optimization. The controller module <NUM> may also include an implantable battery (not shown) or other power supply.

A non-claimed method for the treatment of cancer using the system <NUM> is illustrated in <FIG>. At step <NUM> the disease is discovered and at step <NUM>, one or more cranial mapping techniques are employed to determine optimal placement and arrangement for the electrode array <NUM>. At step <NUM>, the electrode array <NUM>, wires <NUM>, and controller module <NUM> are surgically attached or implanted. Referring back to <FIG>, the electrode array <NUM> is implanted in the cranium of a patient, wherein the subdural electrodes <NUM> are placed subdurally on the surface of the brain and the deep-stimulating electrodes <NUM> are implanted deep into the brain. The controller module <NUM> may be surgically implanted or installed subclavically or in the abdomen. In other cases, the controller module <NUM> may be installed outside the body, depending on the anatomy of the patient.

Referring back to <FIG>, once the electrode array <NUM>, wires <NUM>, and control module <NUM> are attached or implanted, at step <NUM> the alternating electric field generated by the electrode array <NUM> is optimized using an initial set of parameters and the known location of each subdural electrode <NUM> and deep-stimulating electrode <NUM> on or within the patient's brain. The optimization process is performed using an external computer <NUM> that executes a simulation environment application to determine optimal waveform operating parameters for the controller module <NUM>. The simulation environment application may be embodied as a program or an application and may be installed and operated on the external computer <NUM>. When feedback information from the array <NUM> is available, the feedback is incorporated into the optimization step <NUM>. At step <NUM>, optimal waveform operating parameters are communicated to the controller module <NUM> and at step <NUM> the optimized alternating electric field is then applied to the brain of the patient by the array <NUM>. As the alternating electric field is delivered, one or more of the deep stimulating electrodes <NUM> measure aspects of the alternating electric field and communicate this data to the controller module <NUM>. The controller module <NUM> records and/or transmits the information to the external computer <NUM> at step <NUM>. In this manner, the optimization process can be iteratively repeated using feedback pertaining to measured aspects of the alternating electric field and the exact location of each subdural electrode <NUM> and deep-stimulating electrode <NUM> until the alternating electric field is at its most effective application strength.

In some embodiments of the system <NUM>, the simulation environment used in the optimization process using the external computer <NUM> is operable to obtain the exact positions of the subdural electrodes <NUM> and the deep-stimulating electrodes <NUM> as input as well as including information about the alternating electric field strength as measured by the deep-stimulating electrodes <NUM>. In addition, the simulation environment application is operable to allow the user to observe changes in the alternating electric field delivered to the brain by changes in the waveform delivered to any given electrode <NUM> or <NUM>. As changes in the delivered waveform are simulated, the simulation environment application is operable to optimize the alternating electric field generation by calculating and displaying a distribution of alternating electric field strength throughout the brain as a result of the changes in the delivered waveform, the exact positions of the electrodes <NUM> and <NUM>, and/or the unique anatomy of the patient's brain. This allows the user to determine the best configuration of electrode stimulation parameters for electrodes <NUM> and <NUM> to optimize the alternating electric field in the targeted region. A given parameter may then be initialized in the patient and altered while real-time data is acquired by one or more of the deep-stimulating electrodes <NUM> in the brain to ensure adequate alternating electric field strength is achieved.

Claim 1:
A system (<NUM>) for the treatment of brain cancer, comprising:
an alternating electric field generation apparatus, comprising: an electrode array (<NUM>), comprising:
a plurality of subdural electrodes (<NUM>), wherein each of the subdural electrodes (<NUM>) is configured to be implanted subdurally onto the brain of a patient;
a plurality of deep-stimulating electrodes (<NUM>), wherein each of the plurality of deep-stimulating electrodes (<NUM>) is configured to be implanted;
wherein the electrode array (<NUM>) delivers an alternating electric field to the tissue of the brain through the plurality of subdural electrodes (<NUM>) and the plurality of deep-stimulating electrodes (<NUM>); and
a controller module (<NUM>) in operative communication with the electrode array (<NUM>), wherein the controller module (<NUM>) is operable to generate a waveform representative of the alternating electric field, wherein the waveform is transmitted to the electrode array (<NUM>); and
an external computer (<NUM>), wherein the external computer (<NUM>) is operable to receive feedback from the controller module (<NUM>) and wherein the external computer (<NUM>) is operable to send commands to the controller module (<NUM>);
wherein the controller module (<NUM>) is operable to incorporate feedback from the electrode array (<NUM>) and communicate the feedback to the external computer (<NUM>).