Patent Publication Number: US-2023149713-A1

Title: Systems and methods for treatment of cancer using alternating electric field generation

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This is a continuation application that claims benefit from U.S. 371 National patent application Ser. No. 17/260,019 filed Jan. 13, 2021, which claims the benefit of International Application No. PCT/US2019/042197, filed Jul. 17, 2019, which claims benefit from U.S. provisional application Ser. No. 62/699,146 filed on Jul. 17, 2018, which is incorporated by reference in its entirety. 
    
    
     FIELD 
     The present disclosure generally relates to the treatment of cancer, and in particular to treatment of brain cancer via electric field generation. 
     BACKGROUND 
     Alternating electric field 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. TTF uses an alternating electric field to disrupt cell division in cancer cells, thereby inhibiting cellular replication and initiating apoptosis (cell death). However, some topical TTF 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. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1    is a diagram showing an electrode array and controller module of the present system with the electrode array implanted into a brain and the controller module with wires operatively connected to the electrode array; 
         FIG.  2    is an illustration of the system of  FIG.  1    relative to the body of a patient; 
         FIG.  3    is an illustration showing how the arrangement of the electrode array of the system of  FIG.  1    may surround a cancerous region of the brain; 
         FIG.  4    is a simplified block diagram showing how the hardware of the controller module, the external computer, and the electrode array of the system of  FIG.  1    interact; and 
         FIG.  5    is a flowchart showing the process of treatment and optimization for a patient using the system of  FIG.  1   ; 
     
    
    
     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. 
     DETAILED DESCRIPTION 
     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 and method for an alternating electric field generation apparatus, herein referred to as “the present 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 and method of a subdural implant apparatus wherein, through the use of a array of subdural electrodes implanted subdurally and deep-stimulating electrodes implanted deep into the brain tissue, a targeted alternating electric field is generated for the treatment of rapidly dividing cancer cells. In one aspect, 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  100  in  FIGS.  1 - 5   . 
     Referring to  FIGS.  1  and  2   , in some embodiments of the present system  100 , a main array  101  including stimulating electrodes  103  and  104  is configured to be placed underneath the dura mater of a patient&#39;s brain. The main array  101  is in operative communication with a controller module  120  by way of a wire array  110 . The controller module  120  is operable to generate an alternating electric field, receive feedback from the main array  101 , and communicate with an external computer  200  for receiving operating parameters as well as exporting operating data related to the strength of the alternating electric field. 
     The main array  101  may include a plurality of subdural electrodes  103  as well as a plurality of deep-stimulating electrodes  104 , such that the subdural electrodes  103  and deep-stimulating electrodes  104  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  102 , each defining a respective distal end, extend from a respective subdural electrode  103  and terminates in a conductive contact. In one possible application, each of the plurality of subdural electrodes  103  are placed on the surface of the brain. In some embodiments, the subdural electrodes  103  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  103  defines a proximal face  105  and a distal face (not shown), wherein the proximal face is in operative association with a distal end of each wire  102  and the distal face includes a transducing contact that is applied to the exterior of the brain. In some embodiments, the deep-stimulating electrodes  104  have elongated rod-shaped members comprising segmented strips of conductive material. The deep-stimulating electrodes  104  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  104  defines a distal end and a proximal end, wherein the distal end of each of the deep-stimulating electrodes  104  is implanted into the brain tissue and the proximal end of each of the deep-stimulating electrodes  104  is in operative association with a respective wire  102 . In some embodiments, the deep-stimulating electrodes  104  are operable to measure aspects of the alternating electric field applied to various locations within the brain by the main array  101  and communicate measured aspects of the alternating electric field back to the controller module  120 . In one aspect, each subdural electrode  103  and deep-stimulating electrode  104  is operable to apply to tissue a current waveform through the wires  102 . 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  103  and deep-stimulating electrodes  104  relative to a cancerous region of the brain is shown in  FIG.  3   . The optimal placement and number of subdural electrodes  103  and deep-stimulating electrodes  104  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  103  and  104  to collectively create the array  101 . 
     Referring to  FIG.  4   , in some embodiments the controller module  120  includes a waveform generator  124  and a processing unit  122 , wherein the waveform generator  124  is in operative communication with the array  101  by one or more wires  110 . The waveform generator  124  of the controller module  120  is operable to receive a set of operating parameters from the processing unit  122  and output a waveform such that when the waveform is distributed throughout the array  101 , an alternating electric field is applied to brain tissue. The processing unit  122  of the controller module  120 , such as a microprocessor or a microcontroller, is operable to output the set of operating parameters for the waveform generator  124 . The processing unit  122  is also operable to receive input from the array  101  pertaining to measured aspects of the alternating electric field and communicate the input to an external computer  200 , update the set of operating parameters, and communicate the updated set of operating parameters to the waveform generator  124 . 
     Empirical research for TTF therapy recommends a 200 kHz standard waveform to be produced by the waveform generator  124  to generate the alternating electric field. Ideal waveform modulation and intensity parameters are determined by the external computer  200  and delivered to the waveform generator  124  through the processing unit  122 . 
     The controller module  120  may also include a wireless communication module  126  that allows communication between the processing unit  122  of the controller module  120  and external computer  200 . In this manner, the processing unit  122  of the controller module  120  is operable to wirelessly receive software updates and instructions from the external computer  200  as well as transmit the measured aspects of the alternating electric field to the external computer  200  for review and system optimization. The controller module  120  may also include an implantable battery (not shown) or other power supply. 
     A method for the treatment of cancer using the system  100  is illustrated in  FIG.  5   . At step  300  the disease is discovered and at step  302 , one or more cranial mapping techniques are employed to determine optimal placement and arrangement for the electrode array  101 . At step  304 , the electrode array  101 , wires  110 , and controller module  120  are surgically attached or implanted. Referring back to  FIG.  2   , the electrode array  101  is implanted in the cranium of a patient, wherein the subdural electrodes  103  are placed subdurally on the surface of the brain and the deep-stimulating electrodes  104  are implanted deep into the brain. The controller module  120  may be surgically implanted or installed subclavically or in the abdomen. In other cases, the controller module  120  may be installed outside the body, depending on the anatomy of the patient. 
     Referring back to  FIG.  5   , once the electrode array  101 , wires  102 , and control module  120  are attached or implanted, at step  306  the alternating electric field generated by the electrode array  101  is optimized using an initial set of parameters and the known location of each subdural electrode  103  and deep-stimulating electrode  104  on or within the patient&#39;s brain. The optimization process is performed using an external computer  200  that executes a simulation environment application to determine optimal waveform operating parameters for the controller module  120 . The simulation environment application may be embodied as a program or an application and may be installed and operated on the external computer  200 . When feedback information from the array  101  is available, the feedback is incorporated into the optimization step  306 . At step  308 , optimal waveform operating parameters are communicated to the controller module  120  and at step  310  the optimized alternating electric field is then applied to the brain of the patient by the array  101 . As the alternating electric field is delivered, one or more of the deep stimulating electrodes  104  measure aspects of the alternating electric field and communicate this data to the controller module  120 . The controller module  120  records and/or transmits the information to the external computer  200  at step  312 . 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  103  and deep-stimulating electrode  104  until the alternating electric field is at its most effective application strength. 
     In some embodiments of the system  100 , the simulation environment used in the optimization process using the external computer  200  is operable to obtain the exact positions of the subdural electrodes  103  and the deep-stimulating electrodes  104  as input as well as including information about the alternating electric field strength as measured by the deep-stimulating electrodes  104 . 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  103  or  104 . 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  103  and  104 , and/or the unique anatomy of the patient&#39;s brain. This allows the user to determine the best configuration of electrode stimulation parameters for electrodes  103  and  104  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  104  in the brain to ensure adequate alternating electric field strength is achieved. 
     It should be understood from the foregoing that, while particular embodiments have been illustrated and described, various modifications can be made thereto without departing from the spirit and scope of the invention as will be apparent to those skilled in the art. Such changes and modifications are within the scope and teachings of this invention as defined in the claims appended hereto.