Apparatus and methods for electric field optimization and adaptation for treatment of multiple tumors in metastatic disease patients

Abstract

The invention relates to a method of delivering a tumor treatment electric field to a patient's body. The method comprises scanning the patient's body to identify at least two tumor fill regions. The method further comprises determining a spatial relationship between the at least two tumor fill regions. The method further comprises arranging an array of insulated electrode elements on the patient's body. The method further comprises implementing at least two sub-array emission configurations of the array of insulated electrode elements at least partly in accordance with the spatial relationship between the at least two tumor fill regions to treat the at least two tumor fill regions such that each sub-array emission configuration treats a respective tumor fill region. The invention further relates to a method of configuring a tumor treatment field device and a tumor treatment field device comprising an array of insulated electrode elements coupled to a control device.

Description

[0001] Cross Reference to Related Applications

[0002] This application is based on U.S. Provisional Patent Application No. 62 / 948,600, filed December 16, 2019, entitled “APPARATUS AND METHOD FOR OPTIMIZING AND ADAPTING TREATMENT OF MULTIPLE TUMORS IN PATIENTS WITH METASTATIC DISEASE BY ELECTRIC FIELD,” which is incorporated herein by reference. TECHNICAL FIELD

[0003] The present invention relates to the selective destruction of multiple solid tumors in large areas of the entire torso of a patient containing metastatic cancer. More specifically, the present invention relates to apparatus and methods for optimizing the destruction of multiple tumors without damaging normal cells, and further adapting the optimization of the destruction of multiple tumors over time as the size, number, and location of multiple tumors occurring within a metastatic patient change. BACKGROUND

[0004] Alternating electric fields, also known as Tumor Treating Fields (TTFs), can be used as a cancer treatment therapy by using low-intensity electromagnetic fields. These low-intensity fields rapidly change direction thousands of times per second. Since TTFs are electric fields, they do not cause muscle twitching or serious adverse side effects to other electrically active tissues. The growth rate of metastatic disease is typically higher than that of normal healthy cells. The alternating electric field therapy takes advantage of this high growth rate characteristic. TTFs are used to disrupt the mitotic process and cytokinesis of cancer cells by manipulating their polarizable intracellular components, i.e., tubulin, which forms the mitotic spindle that pulls the genetic material in the nucleus into two daughter cells. TTFs interrupt mitotic spindle microtubule assembly, preventing cell division. Metastatic disease cells treated with TTFs will typically enter programmed cell death within 4 to 5 hours. The result is a significant reduction in tumor size and the potential for complete elimination of solid tumors. TTFs are tuned to treat specific cancer cells, leaving normal cells unharmed. TTF therapy can be used as a standalone treatment method, or can be combined with traditional dosing mechanisms.

[0005] The following is an explanation of how the electric field selectively kills cancer cells. The basic physics behind using an electric field to trigger an immunogenic response to selectively kill cancer cells involves the known properties of charged particles. That is, like charges repel and opposite charges attract. One or more key proteins essential for mitosis have a high dipole moment. That is, they are negative on one side and positive on the other.

[0006] In a constant field, charged particles will migrate toward the opposite charge. Upon exposure to an alternating electric field, the dipole proteins essential for mitosis spin back and forth with the alternating charge of the field.

[0007] The electric field that causes cancer cell death is an electric field that is generated across a solid tumor at a frequency between 100 and 300 hKz depending on the size of the cancer cell. The first question to answer is what does the electric field interact with inside the cancer cell to perturb tumor growth.

[0008] The key protein complex involved in mitosis is the Septin, which has a very high dipole moment. Septins have many functions and are involved in cellular structural support. In the presence of an alternating electric field, at the optimal frequency, the positioning required for the Septin to perform its function is reduced. The result of electric field exposure during mitosis does not prevent tumor daughter cell formation, but causes them to be malformed. The exogenous nature of the daughter cells that develop under the optimal electric field is such that an immune response is triggered. Immunogenic cell death occurs, resulting in tumor reduction.

[0009] The above mechanism of action using Septins can be further verified by the fact that patients receiving electric field therapy for malignant glioma who have an impaired immune system (CD8 cell count < 144 cells / mm 2 , CD4 / CD8 ratio < 1.09) do not respond to electric field therapy as compared to people with a healthy immune system. Such patients with an impaired immune status can not benefit from receiving treatment.

[0010] Of course, the outcome of the treatment can depend on a properly adjusted electric field that can penetrate the cell wall. Whether the electric field can penetrate the cancer cell wall depends on the relationship between the field frequency and the cell size.

[0011] The effective electric field frequency is inversely related to the size of the cancer cell. The larger the cancer cell, the lower the frequency needed to penetrate its cell wall. The smaller the cancer cell, the higher the frequency needed to break through the cell wall. In fact, the efficacy of the electric field in reducing solid tumors is related to the frequency, and each cancer cell type can have a specific frequency at which the inhibitory effect is greatest. Thus, the selection of which metastatic cancers to treat with adaptive electric field therapy can be determined in part by the range of cell sizes. No other attribute indicates that an electric field should be used for one cancer versus another, as its mechanism of action is based on disrupting the most universal process of all cancer cells, mitosis. As long as the cancer selected for treatment can be effectively treated in the frequency range of 100 kHz - 300 kHz without harming normal cells, it can be treated.

[0012] The secondary mechanism of action of sending a selective electric field through a solid tumor is called dielectrophoresis. In the late stages of mitosis, the electric field can push polarizable macromolecules and / or organelles toward the mitotic furrow. This often results in the furrow bursting, causing cell destruction. This secondary killing action is implemented when the electric field lines are parallel to the furrow lines. No dielectrophoresis occurs when the electric field is perpendicular to the furrow lines. Because the axis of division (furrow lines) can be random in a cancer tumor, only a small fraction of cells can be exposed to the potential for dielectrophoresis when only one angle is delivered. It can not be possible to achieve enough angles to produce this phenomenon at the level needed to eliminate the tumor. Nonetheless, the reduction of the tumor can be facilitated by adding additional angles to the treatment.

[0013] In addition to the frequency and the number of angles delivered (dielectrophoresis), there are other variables that can affect the success of electric field therapy in reducing tumors. These include the field strength, the speed at which one angle is switched to the next, and the patient’s compliance.

[0014] Known devices and methods for treating tumors focus on local tumors. Thus, the prior art treatment with dedicated array elements can not be versatile enough to adequately address multiple disease locations.

[0015] There is a need in the art for devices and methods that treat advanced, widely disseminated cancers in a more holistic and adaptive manner over time. SUMMARY

[0016] The present invention relates to devices and methods for optimizing the destruction of multiple solid tumors and / or diffuse tumors throughout the human torso by maximizing the benefits of the immunogenic response caused by a specifically tailored electric field.

[0017] The present invention provides solutions to optimize the immunogenic response to reduce multiple / disseminated solid tumors. Thus, the present invention focuses on disseminated disease or multi-locational disease in patients with advanced cancer. The present invention device accomplishes this by:

[0018] 1. Treatment of multiple TTFs (simultaneous and / or alternating treatment of two or more strategic areas).

[0019] 2. Adaptation of the delivery of multiple or simultaneous electric fields by the spatial relationship of the multiple tumors to each other and to vital organs.

[0020] 3. Tracking and changing the electric field strength as it changes in response to changes in other variables (angle, frequency, interaction with other fields, etc.). In order to optimize the effectiveness of the electric field strength.

[0021] 4. Maximizing the number of angles of delivery (to reduce the duty cycle of the array elements).

[0022] 5. Frequency of the tumor treatment field and adaptation of all other variables when the frequency changes.

[0023] 6. Adaptation of the treatment to patient compliance.

[0024] 7. Use of predictive data (such as predictive blood tests and / or predictive modeling) to design a prophylactic treatment regimen in order to minimize the likelihood of recurrence once remission is achieved.

[0025] The devices and methods of the present invention allow for more effective application of each of these variables, thereby making electric field therapy for treatment of solid tumors available to metastatic cancer patients with disseminated disease or two or multi-locational disease.

[0026] Another form of the present invention relates to a method of delivering a tumor treatment electric field to a patient's body. The method includes scanning the patient's body to identify at least two tumor-filled regions. The method also includes determining a spatial relationship between the at least two tumor-filled regions. The method also includes arranging an array of insulated electrode elements on the patient's body. The array of insulated electrode elements is coupled to a control device. The method also includes implementing at least two sub-array firing configurations of the array of insulated electrode elements to treat the at least two tumor-filled regions based at least in part on the spatial relationship between the at least two tumor-filled regions, such that each sub-array firing configuration treats a corresponding tumor-filled region.

[0027] The present invention also provides a method of configuring a tumor treatment field device for delivering a tumor treatment electric field to a patient, wherein the device includes an array of insulated electrode elements coupled to a control device, the method comprising the steps of:

[0028] a) receiving a scan of the patient's body;

[0029] b) identifying at least two tumor-filled regions on the scan, each tumor-filled region having at least one tumor;

[0030] c) determining a spatial relationship between the at least two tumor-filled regions; and

[0031] d) determining at least two subarray firing configurations of the array of insulated electrode elements for targeting the at least two tumor-filled regions, the at least two subarray firing configurations depending at least in part on the spatial relationship between the at least two tumor-filled regions.

[0032] Another form of the present disclosure relates to a method of delivering tumor treatment electric fields to a patient's body. The method includes scanning the patient's body to identify at least two tumor-filled regions. Each tumor-filled region has at least one tumor. The method also includes determining a spatial relationship between the at least two tumor-filled regions. The method also includes disposing an array of insulated electrode elements on the patient's body. The array of insulated electrode elements is coupled to a control device. The method also includes classifying tumors in the at least two tumor-filled regions to obtain a classification strategy. The method also includes implementing at least two subarray firing configurations of the array of insulated electrode elements to treat the at least two tumor-filled regions such that each subarray firing configuration treats a corresponding tumor-filled region, at least in part according to the spatial relationship between the at least two tumor-filled regions and the classification strategy.

[0033] Yet another form of the present disclosure relates to a method of delivering tumor treatment electric fields to a patient's body. The method includes scanning the patient's body to identify at least two tumor-filled regions. Each tumor-filled region has at least one tumor. The method also includes determining a spatial relationship between the at least two tumor-filled regions. The method also includes disposing an array of insulated electrode elements on the patient's body. The array of insulated electrode elements is coupled to a control device. The method also includes determining at least two subarray firing configurations of the array of insulated electrode elements at least in part according to the spatial relationship between the at least two tumor-filled regions. Each subarray firing configuration is configured for treating a corresponding tumor-filled region. The method also includes determining whether the at least two subarray firing configurations are implementable simultaneously or sequentially. The method also includes implementing the at least two subarray firing configurations for treating the at least two tumor-filled regions simultaneously or sequentially.

[0034] Yet another form of the present application relates to a method of delivering a tumor treating electric field to a patient's body. The method comprises scanning the patient's body to identify at least one tumor filled region. Each tumor filled region has at least one tumor therein. The method further comprises arranging an array of insulated electrode elements on the patient's body. The array of insulated electrode elements is coupled to a control device. The method further comprises implementing at least one initial subarray firing configuration of the array of insulated electrode elements to treat the at least one tumor filled region. The method further comprises sensing a temperature of an insulated electrode element of the array of insulated electrode elements. The method further comprises implementing at least one alternative subarray firing configuration of the array of insulated electrode elements to treat the at least one tumor filled region, in dependence on the sensed temperature.

[0035] The present application also provides a tumor treating field device comprising an array of insulated electrode elements coupled to a control device; wherein the device is configured to:

[0036] i) determine a spatial relationship between at least two tumor filled regions on a patient scan;

[0037] ii) determine and / or implement at least two subarray firing configurations of the array of insulated electrode elements for targeting the at least two tumor filled regions, the at least two subarray firing configurations being at least partially dependent on the spatial relationship between the at least two tumor filled regions. The device can be configured for performing the method of the present application.

[0038] An advantage of the present application is that the insulated electrode system and method thereof can treat multiple spatially distant tumors or clusters thereof simultaneously, wherein two or more firing configurations use different electrode elements. BRIEF DESCRIPTION OF DRAWINGS

[0039] The above-mentioned and other features and advantages of this application, and the manner of attaining them, will become more apparent and the application itself will be better understood by reference to the following description of embodiments of the application taken together with the accompanying drawings, wherein:

[0040] Figures 1A-1B A flowchart of a method for applying an adaptive tumor treating field is illustrated;

[0041] Figure 2 A flowchart of a method for increasing patient compliance is illustrated;

[0042] Figures 3A-3C A flowchart of a method for optimizing electric field therapy when all tumors are of equal threat is illustrated;

[0043] Figures 4A-4C A flowchart of a method for optimizing electric field therapy when all tumors are not of equal threat is illustrated;

[0044] Figure 5 a flowchart illustrating a method for a system configuration process is shown;

[0045] Figure 6 a flowchart illustrating a method for a system operation process is shown;

[0046] Figure 7 a flowchart illustrating a method for a system adaptive tumor therapy field process is shown;

[0047] Figure 8 a flowchart illustrating a method for a system green zone temperature measurement process is shown;

[0048] Figure 9 a flowchart illustrating a method for a system red zone temperature measurement process is shown;

[0049] Figure 10 a flowchart illustrating a method for a system blue zone temperature measurement process is shown; and

[0050] Figure 11 a flowchart illustrating a method for a system yellow zone temperature measurement process is shown.

[0051] Corresponding reference numerals indicate corresponding parts throughout the several views. The examples set forth herein illustrate embodiments of the application and should not be construed as limiting the scope of the application in any manner. DETAILED DESCRIPTION

[0052] Referring now to Figures 1A-1B a flowchart of a process summary of applying an adaptive tumor therapy field (ATTF) is shown. An insulated electrode system (or tumor therapy field device) can include a control device, an array of insulated electrode elements, a field generator, and one or more sensors for sensing real-time temperature of the insulated electrode elements. The insulated electrode system can also include a scanner (e.g., a 3D scanner). A multilayer flexible circuit can couple the insulated electrode elements, the control device, and the field generator to one another. The control device can be programmed to send signals to the field generator, including a range of frequencies to be sent to the array electrode elements and what array electrode elements to use in what emission configuration and sequence.

[0053] The control device can or can not perform certain steps of the method described herein. For example, the control device can calculate or determine at least two sub-array emission configurations of the array of insulated electrode elements. Alternatively, the control device can receive at least two sub-array emission configurations from a 3D simulator. Therein, the control device can evaluate the real-time system conditions and determine which pre-loaded emission configuration(s) can be implemented. This calculation can depend on the spatial relationship between two or more tumor filled areas, the classification strategy, the duty cycle of individual insulated electrode elements, the sensed temperature of individual insulated electrode elements, the peak power consumption of the array of insulated electrode elements, the total power consumption of the array of insulated electrode elements, the power availability of the field generator of the insulated electrode system, and / or time constraints (e.g. 1 to 3 seconds between emission fields) to maintain an optimal treatment effect. The control device can determine the peak and / or total power consumption. For example, when more electrode elements are activated at the same time, more power will be drawn from the field generator and this power rating or total power limit of the field generator cannot be exceeded in any particular emission configuration. If the insulated electrode system is operated by a battery power source, the power limit can also be determined by the available battery life. The control device can track the time spent on the battery power source in order to change the emission configuration.

[0054] As used herein, a tumor filled area is an area of the patient's body where one or more tumors are located. The tumor filled areas can be spaced apart from each other by a certain distance such that a single electric field from a given emission configuration cannot be used to treat both tumor filled areas. Thereby, the spatial relationship between tumors or clusters thereof requires the use of two or more electrode elements to deliver an optimized treatment field to individual tumors or clusters thereof.

[0055] The control device can implement the emission configurations simultaneously and / or sequentially throughout the treatment period. The control device can optimize the treatment process by treating as many tumor filled areas as possible at the same time. The control device can also assign respective groups of insulated electrode elements to individual sub-array emission configurations. The groups can consist of different electrode elements such that the groups do not share exactly the same electrode elements. For example, the groups can share some common electrode elements among them or the groups can consist of completely different electrode elements.

[0056] The process of treating diffuse tumors can include scanning the patient's body. The scanner can or can not be a component of the insulated electrode system. Thus, the control device can identify the tumors and their spatial relationship to each other. The control device can integrate the tumor scans into a phantom to map the locations. The control device can run a transmission simulation and / or mathematical algorithm to determine how many individual transmission configurations are needed to produce a treatment field that optimally treats the tumor-filled area. The control device can then sort the tumors or clusters thereof. The control device can also determine which tumors or clusters thereof can be treated together with a single disc transmission configuration, treated with a simultaneous application of individual transmission configurations, and / or treated with a sequential application of individual transmission configurations. The control device can incorporate any desired limiting characteristics in determining the transmission configurations. For example, the control device can incorporate target array element duty cycles and / or limitations on power available from the field generator. Alternatively, the control device can receive information about the tumors, such as spatial relationships and their sorting strategy. For example, the control device can receive and store one or more locations of one or more tumors, transmission configurations, sorting strategies, etc., which can be predetermined by a simulator and / or medical professional.

[0057] The control device can also optimize the overall treatment plan. For example, the control device can determine which transmission configurations should be included in individual treatment sessions (i.e., which tumors will be treated each day) and which tumors will be treated on a less frequent schedule to optimize the overall TTF therapy. It can not be possible or necessary to treat every tumor or cluster thereof in every transmission sequence due to one or more of tumor location, heating, power consumption, sorting strategy, etc. The control device can optimize the overall treatment of the patient for the patient's entire situation, thereby adapting or changing the treatment plan as the situation changes. Advantageously, one or more arrays of insulated electrode elements can be placed on the patient's body each time, but the software of the control device changes the treatment, such as reconfiguring one or more transmission configurations of the individually programmable electrode elements, in order to optimize one or more treatment sessions. For example, the transmission configurations and sequences can be different over the course of a day, or from one day to the next, as some tumors can be treated each time while some tumors can be treated less frequently on certain days of the week or month, depending on the factors listed herein, results seen in body scans, blood tests, etc. An overall plan can be formed based on all of the previously mentioned parameters, which varies according to the hour, day, time of day (sleep vs. wake time), week, month. Another way to optimize the overall treatment plan can include treating lower priority tumors between periods when the temperature of the electrode elements used to treat higher priority tumors needs to cool. In other words, downtime of overheated array elements in a first (e.g., higher priority) group can allow other array elements in a second (e.g., lower priority) group to be used for treatment of lower priority tumors that allow the high priority discs to cool in temperature.

[0058] 3D Simulation : Load scans (CT scans, MRIs, etc.) showing the patient's disease location into a 3D simulation program that uses finite element methods or other physics solvers to determine the characteristics of the electric field passing through the human body (at block 102). Such a program uses mathematical algorithms, phantoms, or avatars to simulate the patient. A phantom that closely matches the patient is selected and can then be image warped to further match the size of the patient. By using one or more 2D or 3D scans (CT scans, MRIs, etc.) of the patient, the tumor locations can be accurately determined, and their spatial distances relative to each other determined by importing the locations into the simulator. It should be understood that the control device can or can not include the simulation program.

[0059] Establishing frequency : Biopsies of one or more of the patient's tumors are used to determine the absolute average cell size of the cancer. In cases where biopsies are not available, a database knowledge of cell sizes by cancer type is used to reference the cell size of the cancer type. Based on the cell size, the frequency that is most effective for the patient's cancer is selected. If the initial treatment is not successful, this step can be repeated (at block 104).

[0060] Spatial relationship of tumor : Using the 3D simulation, establish the spatial relationship of the multiple tumors to each other with respect to the variables of the tumor treatment field. For example, a late stage patient can have 14 different tumors. By running the simulation, the following types of questions are posed and answered (at block 106). If the initial treatment is not successful, this step can be repeated. It should be understood that the spatial relationship of the multiple tumors can or can not be determined by the control device. For example, the control device can receive a predetermined spatial relationship calculated by the 3D simulation.

[0061] • Are any of the 14 tumors clustered together to the extent that they can be treated by one shot configuration (a shot configuration is a sequence of tumor treatment fields delivered at different frequencies and timings from different angles on a given region)? Or do the tumors require 14 separate and distinct shot sequences?

[0062] • Are there any tumors or clusters of tumors on the body that are far apart (indicating that two electric fields can be used simultaneously with minimal interaction between the two electric fields)?

[0063] • Are the placement of the tumors such that the duty cycle of the array electrode elements is not burdened by overheating such that all of the tumors can be treated from the start? Or must the tumors be categorized and treated in a priority order. As the tumors of the early treatment are eliminated or brought under control, some are categorized and treated now, and some are categorized and treated later.

[0064] • Does the placement of the tumors require special emission configurations (e.g. coplanar field or non-uniform array pair)?

[0065] • Additional similar questions will be answered.

[0066] Classification strategy In the above example, once the spatial relationship between the tumors is understood, the tumors can be classified in order to obtain a classification strategy. The classification strategy outlines which tumor(s) should be treated more than others. Individual tumors or clusters of tumors must be ranked or assigned a priority value according to their degree of threat to the patient's life. If certain tumors are particularly life threatening, these tumors will be given priority. Since the addition of extra emission sequences from different angles within the same region has been shown to accelerate tumor reduction, high priority tumors will receive more delivery angles. This can mean that lower ranked tumors that are less of a threat to life can have to wait to receive treatment until the more threatening tumors are addressed. If the initial treatment is not successful, the step can be repeated (block 108). It should be appreciated that the control device can or can not determine the classification strategy. For example, the control device can receive a classification strategy determined by a medical professional. Additionally, for example, the control device can determine the classification strategy alone or in cooperation with a medical professional by ranking the tumors according to one or more characteristics. After one or more rounds of treatment, the control device and / or the medical professional can reclassify the tumors to obtain an updated classification strategy. Thus, the classification ranking of the tumors can change over time as new information is obtained (e.g. relative growth, growth vs. expectation, new tumors, success rate, patient compliance, etc.). The control device and / or the medical professional can re-determine the priority of treatment via array emission configuration over several treatment sessions or within a treatment session.

[0067] Interactive optimization process Based on the spatial relationship between the tumors and the classification rank of individual tumors, an initial emission sequence is designed. The initial emission sequence is then optimized using 3D simulation. The optimization takes into account all variables that contribute to the effectiveness of the treatment and the interactions between them. The optimization occurs for each emission angle as the emission sequence occurs and takes into account the duty cycle of the array electrode elements as a whole (at block 110).

[0068] For example, the dominant frequency for a cancer type can have been determined to be 150 kHz, with the optimal intensity through the target tumor being 2.5 V / cm. This combination of frequency and intensity can prove to be implementable for a first delivery angle. However, a second delivery angle can show a drop in intensity to 1.5 V / cm, which is less than ideal. This is because the travel path for the second angle can have a different distance, and can pass through different organs. The optimization process then begins testing variations in frequency and power output to see if the second angle can implement the optimal intensity. For example, the frequency can be varied to 140 kHz or 160 kHz. These relatively modest frequency adjustments can increase the intensity back to the desired 2.5 V / cm, as the frequency produces intensity differences when passing through organs with different dielectric constants. This would represent an optimization, as it is believed that maintaining intensity is more important than modest fluctuations in frequency.

[0069] In a similar manner, the optimization process will test whether the power output at the second emission can be increased without raising the array electrode element temperature above safe levels. Assume that increasing the power level successfully maintains the intensity at 2.5 V / cm, but does raise the temperature of the array electrode elements above the desired level. The optimization process will then begin testing decreasing the duty cycle of the array electrode elements in order to maintain the new power level without raising the temperature. The final optimization must require that all target tumors be exposed to the electric field at the optimized frequency and intensity every 1 to 3 seconds.

[0070] The above are just some examples of how the optimization process considers how all of the variables of the electric field therapy interact with each other to produce an optimal emission sequence. This results in the most effective therapy for treating multiple tumors. It should be understood that not all variables are listed here, but are all included in the interactive optimization process.

[0071] Once the electric field therapy begins, the adaptive process requires periodic blood draws to look for tumor markers and periodic scans to see if changes have occurred that require adaptation 112.

[0072] This close monitoring determines whether the therapy should continue without any changes, or whether adaptation is required. Adaptation can be made for both positive and negative results. If a negative result is obtained, a new biopsy can be required to see if the frequency should be changed. Or, if a new cancer has erupted, a re-optimization can be required. If a successful result is observed, then low-priority untreated tumors can now be treated 114.

[0073] Predictive tool to guide preventive treatment: Once remission or significant improvement is observed, a predictive tool is used to form a prophylactic treatment plan. The predictive tool determines the most likely area of next recurrence, e.g., lung, liver, peritoneal cavity, etc. The predictive tool works in a number of ways. Some predictive tools use genetic markers collected through blood tests or biopsies. Some predictive tools use a pooled database from a large number of cancer patients with different types of disease. Statistical probabilities and algorithms are used to predict the most likely area of recurrence. Other predictive tools not mentioned can also be used (at block 116).

[0074] Once the area of likely recurrence is determined, an initial prophylactic emission sequence is formed. The initial emission sequence is then subjected to the optimization process described above. This process determines the optimal emission sequence for prophylactic treatment. The prophylactic treatment is scheduled, which can vary depending on the patient and the severity of their disease. The prophylaxis can range from alternating periods (e.g., on for a month, off for two months) or a prescription of every year, every two years, or every quarter. Regular blood tests and scans to track tumor markers are performed to monitor the prophylactic treatment. If needed, adjustments or the entire optimization process is repeated. The maintenance treatment can also include sweeping the body in areas not previously infected to remove undetectable tumors (at block 118).

[0075] Patient compliance : It is known that the success of electric field therapy depends greatly on patient compliance. Electric field therapy is an on-off therapy. That is, when it is on, it works, and when it is off, its efficacy stops. Patient compliance has been documented as high, but needs improvement. The process 200 can be run continuously to improve patient compliance Figure 2 ). The control device (e.g., wave generator) can record daily variables (at block 202). The control device can also establish an activity report (at block 204). Thereafter, a master report can be generated (at block 206). Surveys can then be conducted and patients can be interviewed regarding their treatment experience accordingly (at block 208). If there are issues, the process 200 can include addressing the issues to improve the patient’s treatment experience (at block 210).

[0076] In yet another invention, when all tumors or tumor groups (T groups) are equally threatening, the optimization of electric field therapy is prioritized. In this case, it can not be possible to include and optimize all T groups using a 50% array element duty cycle and treat each T group within 1 to 3 seconds. In this case, the selection of which T group to exclude from treatment is based on how the absence of that T group would enhance the optimization of the other T groups that would remain in treatment Figures 3A-3C ).

[0077] Method 300 can include loading scans into a simulator (at block 302). The scans can be calibrated to a phantom (at block 304). The tumors can be classified (at block 306). The tumors can then be grouped by distance and classification strategy (at block 308). The tumor groups can then be classified (at block 310). Thereafter, the tumor groups can be queried as to whether they are equally threatening (at block 312). If so, the firing sequence can be designed accordingly (at block 314). If not, an alternative process, such as method 400, can be initiated (at block 316). Method 300 can then include eliminating firing angles that produce less than 2.35 V / cm (at block 318). If modest frequency adjustments can add back the angles at 2.35 V / cm, then those angles will be added back (at block 320). The above steps 318, 320 can then be repeated for all tumor groups (at block 322). The test can then be run at the optimal switching speed (at block 324). The groups can then be queried as to whether they are treated within 1 to 3 seconds (at block 326). If not, certain firing sequences can be removed (at block 328). If so, a query can be made as to whether all remaining T groups have three or more treatment angles (at block 330). If so, method 300 can continue by determining the duty cycle characteristics (at block 338). If not, a query can be made as to whether two T groups are sufficiently separated to fire simultaneous fields (at block 332). If not, method 300 can allow the lowest threat group two angles (at block 334). If so, the firing sequence can be redesigned to use simultaneous groups (at block 336). If individual array elements have 50% or less duty cycle, the firing configuration can be prepared (at block 348). If individual array elements do not have 50% or less duty cycle, the method can determine whether changing the firing sequence will reduce the duty cycle (at block 340). If so, the firing configuration can be prepared (at block 348). If not, the group that will allow the remaining groups to have the most delivery angles but still below 50% can be culled (at block 342). Method 300 can then query as to whether the duty cycle goal was implemented with at least two angles per group (at block 344). If so, the firing configuration can be prepared (at block 348). If not, certain firing sequences can be removed (at block 346). Thereafter, the firing configuration can be prepared (at block 348).

[0078] In yet another invention, when all tumors are not equally threatening, the optimization of the electric field therapy is prioritized. In this case, it can not be possible to include and optimize all T groups using a 50% array element duty cycle and treat each T group within 1 to 3 seconds. In this case, based on the degree of threat to life of one T group compared to the other T groups, that T group is selected to be culled from treatment Figures 4A-4C ).

[0079] The method 400 can include loading the scan into a simulator (at block 402). The scan can be calibrated to a phantom (at block 404). The tumors can be classified (at block 406). The tumors can then be grouped by distance and classification strategy (at block 408). The tumor groups can then be classified (at block 410). Thereafter, the method 400 can inquire whether the tumor groups are of equal threat (at block 412). If not, the firing sequence can be designed accordingly (at block 414). If so, an alternative process, such as the method 300, can be initiated (at block 416). The method 400 can then include eliminating firing angles that produce less than 2.35 V / cm (at block 418). If modest frequency adjustments can add back the angles at 2.35 V / cm, then those angles will be added back (at block 420). The steps 418, 420 can then be repeated for all tumor groups (at block 422). The method 400 can then run a firing test at the optimal switching speed (at block 424). It can then be inquired whether the individual groups are treated within 1 to 3 seconds (at block 426). If so, the method 400 can continue by determining the duty cycle characteristics, where the method 400 determines whether individual array elements have a duty cycle of 50% or less (at block 442). If not, certain firing sequences can be removed (at block 428). The method 400 can then inquire whether all remaining T groups have three or more treatment angles (at block 430). If so, the method 400 can continue with step 442. If not, it can be inquired whether two T groups are sufficiently separated to fire simultaneous fields (at block 432). If not, the method 400 can remove the firing sequence of angles from three to two until the entire firing sequence can be completed within 1 to 3 seconds for a given tumor group (at block 434). If so, the method 400 can redesign the firing sequence using the simultaneous groups with the largest angles at the optimal frequency (at block 436). After the method 400 removes certain firing sequences in step 434, the method 400 can inquire whether the timing goal of 1 to 3 seconds can be implemented with at least two angles per tumor group (at block 438). If so, the method 400 can continue to step 442. If not, the method 400 can eliminate groups that are the least life threatening until the timing goal is implemented (at block 440). To determine which groups should be eliminated, the method 400 can incorporate the classification strategy of the current tumor and / or a predictive threat analysis. The method 400 can then continue to step 442 to determine whether individual array elements have a duty cycle of 50% or less. If individual array elements have a duty cycle of 50% or less, the firing configuration can be prepared (at block 450). If individual array elements do not have a duty cycle of 50% or less, the method 400 can determine whether changing the firing sequence will decrease the duty cycle (at block 444).If yes, the sequence can be changed (at block 446). Thereafter, the transmission configuration can be prepared (at block 450). If no, then the method 400 can begin removing the transmission sequence of angles from three to two until the entire sequence can be completed in 1 to 3 seconds with a 50% duty cycle (at block 448). Thereafter, the method 400 can continue to step 450 to prepare the transmission configuration.

[0080] In yet another invention, the daily treatment of the electric field starts at a low power and slowly ramps up, giving the patient time to adjust.

[0081] In yet another invention, the wave generator contains wireless and / or remote monitoring / reporting, reprogramming or updating of the system via a wireless modem. This can include cellular, Wi-Fi, Bluetooth or other wireless technology.

[0082] In yet another invention, the array elements are assembled or changed to have different characteristics to improve efficiency based on the frequency used.

[0083] In yet another invention, a process for minimizing peripheral nerve stimulation (PNS) is used. A test array is placed on the patient. The power level is slowly adjusted upward to determine where the patient is susceptible to PNS. Those areas susceptible to PNS are loaded into a 3D simulator. Areas sensitive to PNS are avoided when designing the transmission configuration. A compensating transmission configuration is designed.

[0084] The invention consists of a master array of insulated array elements placed on the patient's body. The master array consists of individual insulated array elements. Each array element is computerized. Each array element has its own unique address. The master array is divided into pairs of sub-arrays, which consist of 2 or more array elements that are energized together to deliver low frequency electric fields through the body. These fields have been shown to reduce cancer tumors. The sub-array elements are software configured to be energized in a favorable order based on a treatment simulation performed on each patient. However, the initial sub-array configuration can be overridden by introducing alternative configurations that are activated based on variables affecting the sub-array elements (temperature, adhesion, voltage, failure, etc.) and as a result of real-time monitoring of the patient's condition and actions taken by the patient or caregiver during treatment that affect the beneficial sub-array configuration. For example, the control device can select an initial transmission configuration and subsequently reselect an alternative transmission configuration based on real-time conditions. This is done to optimize the beneficial treatment to the patient. Additionally, the control device can select alternative transmission configurations that are optimized to treat potential tumor areas based on a preventative treatment regimen.

[0085] Definitions:

[0086] 1. Subarray configuration: The Lifebridge system utilizes output from an external numerical calculation model that uses various physical and electrical (size, tissue type, organ placement, heat, electricity) characteristics to simulate the human body. These characteristics enable the Lifebridge 10000 to simulate the effects of many array element subarray configurations. These simulations inform the distribution of subarray configuration variables:

[0087] a. Address of array elements that are excited together

[0088] b. Phase assigned to individual array element addresses or groups of addresses

[0089] c. Voltage applied to individual array elements or groups of addresses

[0090] d. Order in which individual arrays or groups of array elements are excited

[0091] e. Duration of time individual arrays or groups of array elements are excited

[0092] f. Frequency at which individual arrays or groups of array elements are operated. Note that there can be periods of time where no array elements are excited.

[0093] 2. Adaptive tumor treatment field: Arrays in a subarray are excited together so that they form the desired treatment field on the target area. Array elements can be dynamically (adaptively) reassigned to new subarray configurations determined by the Lifebridge 10000 system algorithms.

[0094] 3. Adaptive optimization: Better subarray configurations, subarray sequences, subarray durations are produced that are determined by a combination of weighted values for treatment field delivery and duty cycle of array elements for given states (current temperature, expected voltage vs. measured voltage, communication status, etc.) of the array elements. The control device can determine whether individual electrode elements are in one of the following zones, after which a corresponding temperature process is performed to optimize the insulated electrode system.

[0095] 4. Blue zone: Temperature measurement that is significantly lower than the temperature measurement of adjacent array elements.

[0096] 5. Green zone: Temperature measurement of array elements that is within an acceptable range that does not require a change to the initial subarray configuration values

[0097] 6. Yellow zone: Temperature measurement that is higher than the green zone value but lower than the red zone value. The yellow zone will have 2 to 25 increments. These increments will be used to differentiate between the absolute change in array element temperature and the direction of change (increase or decrease).

[0098] 7. Red Zone: Temperature measurements equal to or above a temperature at which the element will turn off and cannot be re-energized until the measured temperature is within the values assigned to the Yellow or Green Zone by the Lifebridge 10000 system.

[0099] 8. System Controller or Control Device: The control system that implements the tumor treatment electromagnetic field by independent and / or individual control of the electrode elements. The control system can be composed of computing and storage elements contained in the Lifebridge 10000 system. These elements can be located in the electrical system physically integrated into the wave generator, and / or connected to the wave generator via an external communication port and / or computer or mobile device, and can be located entirely or partially in a server or cloud service. Some or all system control functions will be performed in a distributed computing environment. The control system or device can include the wave generator, the simulator, and / or a controller with memory.

[0100] According to one aspect of the application, the controller, or more specifically the software within the memory of the controller, can or can not perform the following processes:

[0101] Determination of sub-array configuration process overview: 1) Data and images found, for example, in MRI, X-ray, or other medical imaging are entered into a medical numerical computing model that creates a “phantom” torso in which a cancer tumor is located in a similar location as in the patient. 2) Various simulations are run to determine the optimal array element energization procedure. This procedure determines which array elements, in what order, at what voltage, and for how long are energized for each step in the system treatment procedure. This creates a list of sub-array configurations. The array that is energized for a given time period (typically 0.5 to 3 seconds) is assigned to the same sub-array for that time period in the procedure. 3) The sub-array configuration procedure is then loaded into the system controller (i.e., the wave generator).

[0102] Method 500 describes the Lifebridge 10000 system configuration process Figure 5). Initially, the system controller (SC) is activated with the power switch and the SC runs self diagnostics and hardware checks. This includes temperature, current, voltage, communication ports, valid program load, system ID operation authorization, etc. (at block 502). If the SC passes the diagnostic checks (at block 504), then continue to the next step. If a fault is found, the system will stop its startup sequence, store the diagnostic values in memory for immediate and / or delayed reporting to a local and / or remote computer or mobile database / display. The software will trigger the local alarm indicator and / or voice or tone (at block 518). Once the diagnostics are checked and all values are within acceptable ranges, the SC assigns a unique software address to each master array element physically present in the system and / or slave array elements logically present in the system (at block 506). The SC then runs a diagnostic sequence on each array element (at block 508). This diagnostic checks program load, voltage, temperature sensor status, relay machine status (open or closed), etc. If the element passes the diagnostic checks, then continue to the next step (at block 510). If a serious fault is found, the system will stop its startup sequence, store the diagnostic values in memory for immediate and / or delayed reporting to a local and / or remote computer or mobile database / display. The software will trigger the local alarm indicator and / or voice or tone (at block 518). If no serious fault is found, if the master / slave arrangement is appropriate for the given physical and / or logical array element array, the SC loads the array energizing program (subarray configuration) into the memory of each array or master array(s) (at block 512). The program stored in the array elements is then verified against the master copy of the program via checksum, hash, or other bit-perfect verification method (at block 514). If a fault is found, the system will stop its startup sequence, store the diagnostic values in memory for immediate and / or delayed reporting to a local and / or remote computer or mobile database / display. The software will trigger the local alarm indicator and / or voice or tone (at block 518). If the array program load is verified by the SC, the SC places the Lifebridge 10000 system in a system ready state (at block 516). At any time during this sequence, the stop button is activated (at block 520). The system will stop its startup sequence, store the event in memory for immediate and / or delayed reporting to a local and / or remote computer or mobile database / display. The software will trigger the local alarm indicator and / or voice or tone (at block 518).

[0103] The method 600 describes the Lifebridge 10000 system operational process (FIG. 600). The system is in a ready state (at block 602). A start button or switch 606 is physically engaged on the SC to start the execution of the subarray configuration sequence (at block 604). The SC communicates the start of the subarray sequence to all arrays (at block 622) and wave generators (at block 608), which set the appropriate wave generator parameters and element phases controlled by the element switches. Wave generator diagnostics are performed by the SC while the system subarray program is running (at blocks 610-624). If an undercurrent condition is found in the wave generator (i.e., below the expected current value), the SC will trigger an alarm and alert the patient and caregiver that the array elements can not be fully adhered to the patient (at blocks 618-620). If a serious fault is found in the wave generator (over temperature, over current, over voltage, etc.), the system will stop, store the diagnostic values in memory for immediate and / or delayed reporting to a local and / or remote computer or mobile database / display. The software will trigger the local alarm indicators and / or voice or tone (at block 644). At the same time, array element diagnostics are performed by the array elements and / or the SC while the system subarray program is running (at blocks 632-638). If a fault is found in the array element or array element group by the diagnostics, the program will stop the element, store the diagnostic values in memory for immediate and / or delayed reporting to a local and / or remote computer or mobile database / display (at block 640). Depending on the severity and type of array element fault, the SC can trigger additional alarms and notifications, and perform a system stop and activate the appropriate alarms (at block 644). The system response is commensurate with the severity of the fault, and the system determines the fault handling process based on a set of algorithms. If no faults are detected during the execution of the subarray configuration, the system program will issue a "step subarray" at a time increment determined by the system program (at block 642). This will continue until one of the following occurs: the stop button / switch is engaged (at block 646), a SC wave generator diagnostic fault is detected (under / over voltage, under / over temperature, under / over current, array communication fault) (at blocks 612-628), or an array fault is detected (under / over voltage, under / over temperature) (at blocks 632-638).

[0104] In addition to the method 600 as described above, the Lifebridge 10000 system can have an enhanced process for handling temperature measurements to optimize treatment delivery. The generation of the tumor treatment field, due to the generation of the alternating electric field through the patient, results in some heating of the array elements. The circuitry on the array as well as the resistance in the wires and other resistive elements also generates some heat. While some degree of heating is expected, heating that results in element and patient skin temperatures in excess of 105 F is unacceptable.

[0105] Further, the temperature of the elements is monitored so that appropriate mitigation steps are taken to minimize, stabilize or reduce the heat generated in the elements so as to slow down or stop their temperature rise before the elements and the patient's skin reach unacceptable temperatures. Among other things, the control device can monitor the temperature of the electrode elements through temperature sensors associated with each electrode element and, depending on the sensed temperature, the control device can reselect and implement another alternative firing configuration that uses one or more different electrode elements to cool down one or more overheated electrode elements.

[0106] The present application includes adaptive tumor treatment capabilities that include various proactive steps that are taken to modify the treatment program (subarray configuration) while allowing the disc temperature to stabilize or decrease before reaching unacceptable levels. This can be implemented by implementing alternative subarray configurations that change one or more of the following parameters in the configuration:

[0107] 1. Duty cycle: duration and timing of the heat generating, energized elements, time / duration of the elements not energized, number of times the elements are energized in a program sequence, voltage applied, field strength generated in the body when one addressable array element is activated, etc.

[0108] 2. Voltage assigned to the subarray configuration of groups of addressable array elements

[0109] 3. Control of external devices that can assist in element cooling or temperature stabilization (fans, cooling pads, etc.).

[0110] 4. Actions suggested for the patient and / or caregiver to take, such as changing body position in the chair or bed, loosening clothing or garments, increasing air conditioning of the surrounding environment, adjusting or turning on fans, etc. See next application below.

[0111] In addition to the method 600 as described above, the LifeBridge 10000 system can also have enhanced patient and / or caregiver suggested actions and proactive progress notifications for the LifeBridge 10000 ATTF system. For out-of-tolerance conditions (e.g., over-temperature, under-temperature, voltage or communication of array elements out of tolerance, etc.) that can be improved or resolved through actions that can be taken by the patient and / or caregiver, enhanced notifications are presented with suggested actions and progress toward improving or resolving the out-of-tolerance condition. These actions can include changing position in the chair or bed, loosening or removing clothing, resetting loose connections, turning on fans or other cooling devices, moving array elements that are out of tolerance closer to the cooling devices, checking that the insulating array is properly adhered to the skin, etc.

[0112] The system will notify the patient and / or caregiver of the suggested action via a display, tone, voice command directly from the system and / or via a computer or mobile device notification via text, voice, email or computer or mobile app selected by the patient and / or caregiver.

[0113] The system will monitor the out of tolerance condition and provide feedback periodically (0.5 to 10 minute intervals depending on the severity of the out of tolerance condition, the type of out of tolerance condition, the suggested action, etc.) indicating that the action taken is improving or has resolved the out of tolerance condition until the condition is resolved or a preset limit of notifications is reached.

[0114] The system will notify the patient and / or caregiver of the effect (improvement, no change or worsening of the out of tolerance condition) via a similar display, tone, voice command directly from the system and / or via a computer or mobile device notification via text, voice, email or computer or mobile app selected by the patient and / or caregiver. These notification settings can be changed, muted or stopped based on the time of day (i.e. mute or do not disturb settings). The patient and / or caregiver can stop these notifications via a button or switch on the system or via a command on the website, text or computer or mobile app.

[0115] According to another aspect of the application, the system (e.g. Lifebridge 10000 system) can also perform the following process:

[0116] 1. Are there suggested actions that the patient and / or caregiver can take to help alleviate and / or correct the out of tolerance condition?

[0117] 2. Yes

[0118] a. Incentive indicator / display, prompt tone or voice prompt and / or send a notification to a computer or mobile device stored in the system memory via electronic means

[0119] b. Monitor the out of tolerance condition as above and report improvement, no change or worsening of the condition

[0120] c. Repeat the appropriate notifications until a set number, duration of notification time limit, do not disturb period begins, or a stop command is received from the caregiver or patient through the system or computer or mobile communication

[0121] d. Record the time and time of the notifications sent and any interactions initiated by the patient and / or caregiver

[0122] 3. No:

[0123] a. Follow the notification process for the out of tolerance condition.

[0124] According to another aspect of the application, a system such as the Lifebridge 10000 system can also perform the following method 700 Figure 7 ). The method 700 can be considered an adaptive tumor treatment field process controlled by array element temperature measurements. The method 700 can include measuring array element temperature and reporting the value to the system controller (at block 702). Thereafter, the method 700 can determine whether the temperature is in the green zone, yellow zone, red zone, blue zone, or non-zone (at block 704). If the temperature value is in the green zone (at block 706), then the green zone system temperature process will be followed (at block 708). If the temperature value is in the yellow zone (at block 710), then the subsequent yellow zone system temperature process will be followed (at block 712). If the temperature value is in the red zone (at block 714), then the red zone system temperature process will be followed (at block 716). If the temperature value is in the blue zone (at block 718), then the subsequent blue zone system temperature process will be followed (at block 720). If the measured temperature value is in the non-zone (at block 722), then the method 700 can disconnect the array element (at block 724). The method 700 can then store the element address with the temperature sensor fault for reporting to the local or computer or mobile device (at block 726). The method will then determine if an alternative acceptable subarray configuration is available (at block 728). If yes, then the method 700 can load the new subarray configuration for the affected array element (at block 732). The appropriate alarm indicator, tone, or both will then be activated (at block 734). If no, then the method 700 can disconnect all array elements (at block 730). Thereafter, the alarm indicator, tone, or both can be activated to reflect the appropriate alarm, with the alarm being appropriately issued by text, voice, email, computer or mobile app, or other electronic device (at block 734). The method 700 can then enter the next system process (at block 736).

[0125] The method 800 describes the green zone temperature measurement process Figure 8). Method 800 can have the SC check the array element address in memory to determine if the address is stored in memory with a green, yellow, red, or blue temperature flag (at block 802). Green zone flag: if yes, then continue with the existing subarray configuration (at block 804); or if no, then remove the array element yellow zone, red zone, or blue zone flag and record the element address with a green zone flag along with a time stamp (at block 806). Thereafter, method 800 can determine if there is an alternative acceptable subarray configuration available (at block 808). If yes, then the new subarray configuration for the affected array element can be loaded (at block 810). If the device (e.g., fan, cooling pad, cooling vest, or other similar device) is wired or wirelessly connected so as to be able to be triggered / controlled by the Lifebridge 10000 system to change state, then the system will switch one or more devices or communicate with one or more devices to take appropriate action (at block 812). The patient and / or caregiver can be instructed by an alarm indicator by text, email, computer or mobile app, or other electronic means of action they can take to reduce the temperature of the affected array element as instructed in training (at block 814). Method 800 can record the instructions, alarms, and state changes in memory for reporting (at block 816). If no, then method 800 can disconnect all array elements, record the time stamp and action (at block 820). Method 800 can then energize an alarm indicator, tone, or both to reflect the appropriate alarm, sound the alarm appropriately by text, email, computer or mobile app, or other electronic means (at block 822). If the device (e.g., fan, cooling pad, cooling vest, or other similar device) is wired or wirelessly connected so as to be able to be triggered / controlled by the Lifebridge 10000 SC to change state, then the SC communicates with one or more devices to take appropriate action (at block 824). The method can record the instructions, alarms, and state changes in memory for reporting (at block 826). Method 800 can then proceed to the next system process (at block 736).

[0126] Method 1100 describes the yellow zone temperature measurement process Figure 11). Method 1100 can have the SC check the array element address in memory to determine if the address is stored in memory with a yellow temperature flag (at block 1102). If so, is the temperature in the same yellow zone increment as the previous measurement (at block 1104)? If so, method 1100 will continue the current subarray configuration (at block 1106). If not, is the temperature measurement in a higher increment or a lower increment (at block 1108)? If higher, is an alternative acceptable subarray configuration available (at block 1110)? If so, method 1100 will load a new subarray configuration for the array element (at block 1112). If devices (e.g., fans, cooling pads, cooling garments, or other similar devices) are wired or wirelessly connected so as to be able to be triggered / controlled by the Lifebridge 10000 system to change state, the system will switch one or more devices or communicate with one or more devices to take appropriate action (at block 1114). Method 1100 can then determine if the system will activate an alarm indicator, tone, and / or voice (at block 1116). The patient and / or caregiver can be instructed by the alarm indicator by way of text, email, computer or mobile app, or other electronic means of actions they can take to lower the temperature of the affected array element as instructed in training (at block 1118). The instructions sent to the connected devices and the state changes can be recorded in memory for reporting (at block 1120). Method 1100 can then enter the next system process (at block 736). If not, method 1100 can disconnect all array elements (at block 1122). Method 1100 can then activate an alarm indicator, tone, or both to reflect the appropriate alarm (at block 1124). If devices (e.g., fans, cooling pads, cooling garments, or other similar devices) are wired or wirelessly connected so as to be able to be triggered / controlled by the Lifebridge 10000 SC to change state, the SC communicates with one or more devices to take appropriate action (at block 1126). The patient and / or caregiver can be instructed by the alarm indicator by way of text, email, computer or mobile app, or other electronic means of actions they can take to lower the temperature of the affected array element as instructed in training (at block 1128). The instructions sent to the connected devices and the state changes can be recorded in memory for reporting (at block 1130). Method 1100 can then enter the next system process (at block 736). If the temperature increment is lower, is an alternative acceptable subarray configuration available (at block 1132)? If so, load a new subarray configuration for the affected array element (at block 1134).If devices (e.g., fans, cooling pads, cooling garments, or other similar devices) are wired or wirelessly connected so as to be able to be triggered / controlled by the Lifebridge 10000 system to change state, the system will toggle one or more devices or communicate with one or more devices to take appropriate action (at block 1136). The method 1100 can then determine whether the system will disengage the alarm indicator, tone, and / or voice notification (at block 1138). The patient and / or caregiver can be instructed by the alarm indicator via text, email, computer or mobile app, or other electronic means to take action to reduce the temperature of the affected array elements as instructed in the training (at block 1140). The instructions and state changes can be recorded in memory for reporting (at block 1142). The method 1100 can then enter the next system process (at block 736). If no acceptable alternative subarray configuration is available, the method 1100 can disengage all array elements (at block 1122). The alarm indicator, tone, or both can then be activated to reflect the appropriate alarm (at block 1124). If devices (e.g., fans, cooling pads, cooling garments, or other similar devices) are wired or wirelessly connected so as to be able to be triggered / controlled by the Lifebridge 10000 SC to change state, the SC communicates with one or more devices to take appropriate action (at block 1126). The patient and / or caregiver can be instructed by the alarm indicator via text, email, computer or mobile app, or other electronic means to take action to reduce the temperature of the affected array elements as instructed in the training (at block 1128). The instructions sent to the connected devices and state changes can be recorded in memory for reporting (at block 1130). The method 1100 can then enter the next system process (at block 736). If the address has not been flagged as a yellow zone, the method 1100 can store the green zone, red zone, or blue zone flag from the array element and record the element address with the new yellow zone flag in the correct increment (at block 1144). Is an alternative acceptable subarray configuration available (at block 1146)? If so, the new subarray configuration of array element addresses can be loaded (at block 1148). If devices (e.g., fans, cooling pads, cooling garments, or other similar devices) are wired or wirelessly connected so as to be able to be triggered / controlled by the Lifebridge 10000 system to change state, the system will toggle one or more devices or communicate with one or more devices to take appropriate action (at block 1150). If the previous flag was green, the patient and / or caregiver can be instructed by the alarm indicator via text, email, computer or mobile app, or other electronic means to take action to reduce the temperature of the affected array elements as instructed in the training (at block 1152).Or, if the previous flag was red or blue, the patient and / or caregiver can be instructed by the alarm indicator via text, email, computer or mobile app or other electronic device to take action to reduce the temperature of the affected array element (at block 1152). The method 1100 can then energize the alarm indicator, tone, or both to reflect the appropriate alarm, appropriately sounding the alarm via text, email, computer or mobile app or other electronic device (at block 1154). The instructions and status changes can be recorded in memory for reporting (at block 1156). The method 1100 can then proceed to the next system process (at block 736). If no, the method 1100 can disconnect all array elements (at block 1158). The method 1100 can then energize the alarm indicator, tone, or both to reflect the appropriate alarm (at block 1160). If the device (e.g., fan, cooling pad, cooling vest, or other similar device) is wired or wirelessly connected so as to be able to be triggered / controlled by the Lifebridge 10000 SC to change state, the SC communicates with the device(s) to take appropriate action (at block 1162). If the previous flag was green, the patient and / or caregiver can be instructed by the alarm indicator via text, email, computer or mobile app or other electronic device to take action to reduce the temperature of the affected array element as instructed in training (at block 1164). The instructions and status changes can then be recorded in memory for reporting (at block 1166). The method 1100 can continue to monitor the temperature measurements of all array elements. The method 1100 can then proceed to the next system process (at block 736).

[0127] The method 900 describes a red zone temperature measurement process Figure 9). The method 900 can have the SC check the array element address in memory to determine if the address is stored in memory with a yellow, red, or blue temperature flag (at block 902). Red zone flag: if yes, continue with existing subarray configuration (at block 904); if no, turn off array element (at block 906). The method 900 can remove the green, yellow, or blue zone flag from the array element address and record the element address with a red zone flag (at block 908). The method 900 can then determine if an alternate acceptable subarray configuration is available (at block 910). If yes, the method 900 can load the new subarray configuration for the affected array element (at block 912). If devices (e.g., fans, cooling pads, cooling garments, or other similar devices) are wired or wirelessly connected so as to be able to be triggered / controlled by the Lifebridge 10000 system to change state, the system will switch one or more devices or communicate with one or more devices to take appropriate action (at block 914). The method 900 can energize the alarm indicator, tone, or both to reflect the appropriate alarm, issue the alarm appropriately by text, email, computer or mobile app, or other electronic means (at block 916). The patient and / or caregiver can be instructed by the alarm indicator by text, email, computer or mobile app, or other electronic means of actions they can take to reduce the temperature of the affected array element as instructed in training (at block 918). The instructions, alarm, and state change can be recorded in memory for reporting (at block 920). If no, the method 900 can turn off all array elements (at block 922). The method 900 can energize the alarm indicator, tone, or both to reflect the appropriate alarm (at block 924). If devices (e.g., fans, cooling pads, cooling garments, or other similar devices) are wired or wirelessly connected so as to be able to be triggered / controlled by the Lifebridge 10000 SC to change state, the SC communicates with one or more devices to take appropriate action (at block 926). If the previous flag was green or yellow, the patient and / or caregiver can be instructed by the alarm indicator by text, email, computer or mobile app, or other electronic means of actions they can take to reduce the temperature of the affected array element as instructed in training (at block 928). The instructions, alarm, and state change can be recorded in memory for reporting (at block 930). The method 900 can then proceed to the next system process (at block 736).

[0128] According to another aspect of the application, the system can operate under blue zone as follows. Array elements that are failing to efficiently or completely couple the generated electric field will typically operate at a lower temperature than array elements that are efficiently coupled to the electric field (operating in the blue temperature zone), provided that these array elements are part of the same subarray emission. Conditions that can affect array element coupling include: poor adhesion to the skin surface or electrical breakdown in the insulation of array elements or wiring that results in current flow to the skin and other similar fault conditions in the array elements.

[0129] By comparing the temperature of an array element to its surrounding array elements (including in the same subarray emission), low temperature conditions can be detected and appropriate action taken.

[0130] The system will store a database containing the address of each insulated array element on the patient and a list of adjacent subarray elements. The temperature of each individual array element will be compared to other array elements in the same subarray. The appropriate neighbor element comparison list can contain from 1 to the entire element subarray with the same voltage polarity. The number and location of appropriate neighbors for comparison will vary based on location, current temperature state, and active or inactive state assignments within the active subarray. This process can be used to track and compare other variables such as voltage, element switch state, etc.

[0131] The system will compare the subarray element to the average temperature and median temperature computed for the group of neighbor subarray elements identified in the neighbor database.

[0132] If the temperature of the array element is 0.5 to 10 degrees lower than the neighbor list computation (the value will depend on the location of the primary array element, system subarray configuration factors (duty cycle, operating voltage, number of active auxiliary array elements, etc.), then the array element will be removed from all active subarray configurations, flagged in the system memory using a blue zone temperature indicator, and the SC will determine if a replacement subarray configuration is acceptable or if the system will enter a safe mode.

[0133] Method 1000 describes the blue zone temperature test and process Figure 10). Method 1000 can create a blue zone read array element temperature. Method 1000 can measure array element temperature and report it to the SC and calculate and store average and median neighbor list array element temperature (at block 1002). Method 1000 can include scaling factors in the comparison algorithm as appropriate (adaptive optimization). Scaling factors are derived from duty cycle, subarray configuration parameters, element location within the physical array, location of the main array on the body, etc. Method 1000 can include a step of determining if the array element is in the blue zone (at block 1004)? If no, then method 1000 can continue the current subarray configuration (at block 1008). If yes, then does the address have a blue zone flag (at block 1006)? If yes, then method 1000 can continue the existing subarray configuration (at block 1008). Method 1000 can then proceed to the next system process (at block 736). If no, then method 1000 can disconnect the array element (at block 1010). Method 1000 can then remove the green, yellow, or red zone flag from the array element address and record the element address with a blue zone flag (at block 1012). Is an alternative acceptable subarray configuration available (at block 1014)? If yes, then a new configuration for the affected array element can be loaded (at block 1016). If devices (such as fans, cooling pads, cooling garments, or other similar devices) are wired or wirelessly connected so as to be able to be triggered / controlled by the Lifebridge 10000 system to change state, then the system will toggle one or more devices or communicate with one or more devices to take appropriate action. Method 1000 can record the instructions sent to the connected devices and the state change (at block 1018). Method 1000 can energize an alarm indicator, tone, and / or voice to reflect the appropriate alarm (at block 1020). The patient and / or caregiver can be instructed by the alarm indicator by text, email, computer or mobile app, or other electronic means of actions they can take to reattach or isolate the affected array element as instructed in the training (at block 1022). Method 1000 can record the instructions, alarms, and state changes in memory for reporting (at block 1024). Method 1000 can then proceed to the next system process (at block 736). If an alternative acceptable subarray is not available, then method 1000 can disconnect all array elements and record the action in memory (at block 1026). Method 1000 can energize an alarm indicator, tone, or both to reflect the appropriate alarm (at block 1028). If devices (such as fans, cooling pads, cooling garments, or other similar devices) are wired or wirelessly connected so as to be able to be triggered / controlled by the Lifebridge 10000 system to change state, then the system will toggle one or more devices or communicate with one or more devices to take appropriate action (at block 1030).The patient and / or caregiver can be instructed by the alarm indicator via text, voice, email, computer or mobile application or other electronic means of actions they can take to reattach or isolate the affected array element as instructed in training (at block 1032). The instructions, alarms, and status changes can be recorded in memory for reporting (at block 1034). The method 1000 can then proceed to the next system process (at block 736).

[0134] While the application has been described with respect to at least one embodiment, the application can be further modified within the spirit and scope of the disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the application using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which the application pertains and fall within the limits of the appended claims.

Claims

1. A method of configuring a tumor treating field device for delivering a tumor treating electric field to a patient, wherein, The apparatus comprises an array of insulated electrode elements coupled to a control device, the method comprising the steps of: a) receiving a scan of the patient's body; b) identifying at least two tumor-filled regions on the scan, each tumor-filled region having at least one tumor; c) determining a spatial relationship between the at least two tumor-filled regions; and d) determining at least two subarray firing configurations of the array of insulated electrode elements for targeting the at least two tumor-filled regions, the at least two subarray firing configurations depending at least in part on the spatial relationship between the at least two tumor-filled regions. Further comprising:

2. The method of claim 1, wherein, allocating respective groups of insulated electrode elements of the array of insulated electrode elements to each subarray firing configuration. The respective groups of insulated electrode elements share some common insulated electrode elements of the array of insulated electrode elements.

3. The method of claim 2, wherein, The respective groups of insulated electrode elements do not share any common insulated electrode elements of the array of insulated electrode elements.

4. The method of claim 2, wherein, Further comprising:

5. The method of claim 1, wherein, determining the at least two subarray firing configurations according to one or more of a classification strategy, a duty cycle of each insulated electrode element, a peak power consumption of the array of insulated electrode elements, and a total power consumption of the array of insulated electrode elements. Further comprising:

6. The method of claim 1, wherein, classifying the tumors in the at least two tumor-filled regions to obtain a classification strategy; and wherein determining the at least two subarray firing configurations depends at least in part on the spatial relationship between the at least two tumor-filled regions and the classification strategy. The classification comprises assigning a priority value to the at least one tumor in each tumor-filled region.

7. The method of claim 6, wherein, Further comprising:

8. The method of claim 7, wherein, optimizing one or more of a total amount of treatment time, a duration of field strength, and a number of angles of electric field delivery dedicated to the at least one tumor in each tumor-filled region according to the assigned priority values of the tumors in the at least two tumor-filled regions. Further comprising:

9. The method of claim 6, wherein, determining the at least two subarray firing configurations according to one or more of a duty cycle of each insulated electrode element, a peak power consumption of the array of insulated electrode elements, and a total power consumption of the array of insulated electrode elements. After determining the at least two subarray firing configurations, the method further comprises determining at least two alternative subarray firing configurations according to a preventive treatment regimen.

10. The method of claim 6, wherein, Further comprising: determining whether the at least two subarray firing configurations are implementable simultaneously or sequentially.

11. The method of claim 1, wherein, Determining whether the at least two subarray firing configurations are implementable simultaneously or sequentially depends on one or more of an interaction of electric fields of the at least two subarray firing configurations, a power availability of an insulated electrode system, a duty cycle of each insulated electrode element, a classification strategy, a peak power consumption of the array of insulated electrode elements, a total power consumption of the array of insulated electrode elements, and a time constraint to maintain an optimal treatment effect.

12. The method of claim 11, wherein, ​

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