Apparatus and method for treating multiple tumors in patients with metastatic disease by electric field optimization and adaptation

Abstract

The present invention relates to a method for delivering a tumor treating 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 positioning an array of insulated electrode elements on the patient's body. The method also includes implementing at least two sub-array transmit configurations of the insulated electrode element array 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 transmit configuration treats a corresponding tumor-filled region. The present invention also relates to a method for configuring a tumor treating field device and a tumor treating field device including an array of insulated electrode elements coupled to a control device.

Description

[0001] This application is a divisional application of application number 202080096801.6, application date December 14, 2020, and invention name “Device and method for optimizing and adapting the treatment of multiple tumors in patients with metastatic disease by electric fields”.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application is based on U.S. Provisional Patent Application No. 62 / 948,600, filed on December 16, 2019, entitled “APPARATUS AND METHOD FOR OPTIMIZING AND ADAPTTINGTREATMENT OF MULTIPLE TUMORS IN PATIENTS WITH METASTATIC DISEASE BY ELECTRICFIELD,” which is incorporated herein by reference. Technical Field

[0004] The present invention relates to selectively destroying multiple solid tumors across a large region encompassing the entire torso of a patient with metastatic cancer. More particularly, the present invention relates to devices 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 changes in the size, number, and location of the multiple tumors occur within a metastatic patient. Background Art

[0005] Alternating electric fields, also known as tumor treating fields (TTF), can be used as a cancer treatment therapy by using low-intensity electromagnetic fields. These low-intensity fields change direction rapidly thousands of times per second. Because TTFs are electric fields, they do not cause muscle twitching or serious adverse side effects to other electrically activated tissues. The growth rate of metastatic diseases is generally higher than that of normal healthy cells. Alternating electric field therapy takes advantage of this high growth rate characteristic. TTF is used to disrupt the mitotic process and cytokinesis of cancer cells by manipulating the polarizable intracellular components of the cell (i.e., microtubules that form the mitotic spindle that pulls the genetic material in the cell nucleus into two sister cells). TTF interrupts the assembly of mitotic spindle microtubules, thereby preventing cell division. Metastatic disease cells treated with TTF will typically enter programmed cell death within 4 to 5 hours. The result is a significant reduction in tumor size and the potential to completely eliminate solid tumors. TTF is adjusted to treat specific cancer cells, thereby not damaging normal cells. TTF therapy can be used as a separate treatment method or can be combined with traditional drug delivery mechanisms.

[0006] The following is an explanation of how electric fields selectively kill cancer cells. The fundamental physics behind using electric fields to trigger an immunogenic response to selectively kill cancer cells involves the known properties of charged particles: that like charges repel and opposite charges attract. One or more key proteins necessary for mitosis possess a high dipole moment; that is, they are negative on one side and positive on the other.

[0007] In a constant electric field, charged particles will migrate toward charges of opposite polarity. Under exposure to an alternating electric field, the dipolar proteins necessary for mitosis rotate back and forth with the alternating charge of the field.

[0008] The electric field that causes cancer cell death is generated by passing through solid tumors at a frequency between 100 hKz and 300 hKz, depending on the size of the cancer cells. The first question to be answered is how the electric field interacts with the cancer cells to disrupt tumor growth.

[0009] A key protein complex involved in mitosis is septin, which has a very high dipole moment. Septin has numerous functions and is involved in supporting cellular structure. In the presence of an alternating electric field, at an optimal frequency, the localization required for septin to perform its functions is reduced. Exposure to electric fields during mitosis does not prevent the formation of tumor daughter cells, but rather causes them to become deformed. The foreign nature of the daughter cells developing under the optimal electric field triggers an immune response. Immunogenic cell death occurs, leading to tumor reduction.

[0010] The above mechanism of action of membrane proteins can be further verified by the fact that people with impaired immune system (CD8 cell count <144 cells / mm) 2 Patients with malignant gliomas who received TTF with a CD4 / CD8 ratio <1.09 (<1.09) did not respond to TTF. Patients with this compromised immune status may not benefit from treatment.

[0011] Of course, the outcome of treatment may depend on a properly tuned 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 size of the cell.

[0012] The effective electric field frequency is inversely proportional to the size of the cancer cell. The larger the cancer cell, the lower the frequency required to penetrate its cell wall. The smaller the cancer cell, the higher the frequency required to break through the cell wall. In fact, the efficacy of the electric field in reducing solid tumors is frequency-dependent, and each cancer cell type may have a specific frequency that has the greatest inhibitory effect. Therefore, the selection of which metastatic cancers to treat with adaptive electric field therapy can be determined in part by the cell size range. There is no other attribute that indicates that the electric field should be used for one cancer type rather than another, because its mechanism of action is based on disrupting the most common process in all cancer cells, namely mitosis. As long as the cancer selected for treatment can be effectively treated within the frequency range of 100kHz-300kHz, which has been shown to not harm normal cells, it is sufficient.

[0013] The auxiliary mechanism of action of sending a selective electric field through a solid tumor is called dielectrophoresis. In the late stage of mitosis, the electric field can push polarizable macromolecules and / or organelles toward the mitotic furrow. This usually causes the cleavage furrow to burst, resulting in cell destruction. This auxiliary killing effect is implemented when the electric field lines are parallel to the cleavage furrow lines. When the electric field is perpendicular to the cleavage furrow lines, dielectrophoresis does not occur. Because the division axis (cleavage furrow lines) may be random in cancer tumors, when only one angular field is delivered, only a small part of the cells may be exposed to possible dielectrophoresis. It may not reach enough angles to produce this phenomenon at the level required to eliminate the tumor. Nevertheless, tumor reduction can be promoted by adding additional angles to the treatment.

[0014] Besides frequency and the number of delivery angles (dielectrophoresis), other variables may influence the success of electric field therapy in reducing tumors. These include field strength, the speed of switching from one angle to the next, and patient compliance.

[0015] Known devices and methods for treating tumors focus on localized tumors. Therefore, prior art treatments utilizing specialized array elements may not be versatile enough to adequately address multiple disease locations.

[0016] There is a need in the art for devices and methods that employ a more comprehensive and adaptive approach to treating advanced, widespread cancers over time. Summary of the Invention

[0017] The present invention relates to devices and methods for optimizing the destruction of multiple solid and / or disseminated tumors throughout the human torso by maximizing the benefit of the immunogenic response induced by specifically tailored electric fields.

[0018] The present invention provides a solution for optimizing the immunogenic response to reduce multiple / diffuse solid tumors. Thus, the present invention focuses on disseminated disease or multi-site disease in patients with advanced cancer. The present invention device achieves this by:

[0019] 1. Treat multiple TTFs (treat two or more strategic areas simultaneously and / or in rotation).

[0020] 2. Adapt the delivery of multiple or simultaneous electric fields by the spatial relationship of multiple tumors to each other and vital organs.

[0021] 3. Track and vary 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.

[0022] 4. Maximize the number of delivery angles (to reduce the duty cycle of the array elements).

[0023] 5. The frequency of the tumor treating field and adapting all other variables as the frequency changes.

[0024] 6. Adapt treatment to patient compliance.

[0025] 7. Use predictive data (e.g., predictive blood tests and / or predictive modeling) to design preventive treatment regimens to minimize the likelihood of relapse once remission is achieved.

[0026] The devices and methods of the present invention allow for more effective application of each of these variables, thereby enabling the use of therapeutic electric fields for treating solid tumors in patients with metastatic cancer who have disseminated disease or disease in two or more locations.

[0027] The present invention, in another form, relates to a method for delivering a tumor-treating electric field to a patient's body. The method includes scanning the patient's body to identify at least two tumor-filling regions. The method also includes determining a spatial relationship between the at least two tumor-filling regions. The method also includes positioning 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 transmit configurations of the array of insulated electrode elements to treat the at least two tumor-filling regions based at least in part on the spatial relationship between the at least two tumor-filling regions, such that each sub-array transmit configuration treats a corresponding tumor-filling region.

[0028] The present invention also provides a method of configuring a tumor treating field device for delivering a tumor treating electric field to a patient, wherein the device comprises an array of insulated electrode elements coupled to a control device, the method comprising the steps of:

[0029] a) receiving a scan of a patient's body;

[0030] b) identifying at least two tumor-filled regions on the scan, each having at least one tumor in the respective tumor-filled regions;

[0031] c) determining a spatial relationship between at least two tumor-filled regions; and

[0032] d) determining at least two sub-array transmit configurations of the array of insulated electrode elements for targeting the at least two tumor-filled regions, the at least two sub-array transmit configurations being dependent at least in part on a spatial relationship between the at least two tumor-filled regions.

[0033] The present invention in another form is directed to a method for delivering a tumor treating electric field 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 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 classifying the tumors in the at least two tumor-filled regions to obtain a classification strategy. The method also includes implementing at least two sub-array transmit 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 and the classification strategy, such that each sub-array transmit configuration treats a corresponding tumor-filled region.

[0034] Yet another form of the present invention relates to a method for delivering a tumor treating electric field 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 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 determining at least two sub-array transmit configurations of the array of insulated electrode elements based at least in part on the spatial relationship between the at least two tumor-filled regions. Each sub-array transmit configuration is configured to treat a corresponding tumor-filled region. The method also includes determining whether the at least two sub-array transmit configurations are implementable simultaneously or sequentially. The method also includes implementing simultaneously or sequentially the at least two sub-array transmit configurations for treating the at least two tumor-filled regions.

[0035] Yet another form of the present invention relates to a method for delivering a tumor treating electric field to a patient's body. The method includes scanning the patient's body to identify at least one tumor-filled region. Each tumor-filled region has at least one tumor. 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 implementing at least one initial sub-array transmit configuration of the array of insulated electrode elements to treat the at least one tumor-filled region. The method also includes sensing a temperature of the insulated electrode elements of the array of insulated electrode elements. The method also includes implementing at least one alternate sub-array transmit configuration of the array of insulated electrode elements based on the sensed temperature to treat the at least one tumor-filled region.

[0036] The present invention 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:

[0037] i) determining a spatial relationship between at least two tumor-filled regions on a patient scan;

[0038] ii) determining and / or implementing at least two sub-array transmit configurations of an array of insulated electrode elements for targeting at least two tumor-filled regions, the at least two sub-array transmit configurations being at least partially dependent on a spatial relationship between the at least two tumor-filled regions. The apparatus may be configured to perform the method of the present invention.

[0039] One advantage of the present invention is that the insulated electrode system and method thereof can simultaneously treat multiple spatially distant tumors or clusters thereof, wherein two or more transmission configurations use different electrode elements. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] The above and other features and advantages of the present invention and their implementation will become more apparent, and the present invention will be better understood by referring to the following description of the embodiments of the present invention in conjunction with the accompanying drawings, in which:

[0041] Figure 1A to Figure 1B A flow chart illustrating a method for applying an adaptive tumor treating field;

[0042] Figure 2 A flow chart illustrating a method for increasing patient compliance;

[0043] Figures 3A to 3C A flow chart illustrating a method for optimizing electric field therapy when all tumors are equally threatening;

[0044] Figures 4A to 4C A flow chart illustrating a method for optimizing electric field therapy when all tumors are not equally threatening;

[0045] Figure 5 A flow chart illustrating a method for a system configuration process;

[0046] Figure 6 A flow chart illustrating a method for a system operation process;

[0047] Figure 7 A flow chart illustrating a method for a system's adaptive tumor treating fields process;

[0048] Figure 8 A flow chart illustrating a method for a green zone temperature measurement process for a system;

[0049] Figure 9 A flow chart illustrating a method for a red zone temperature measurement process for a system;

[0050] Figure 10 A flow chart illustrating a method for a blue zone temperature measurement process for a system; and

[0051] Figure 11 A flow chart illustrating a method for a yellow zone temperature measurement process for a system.

[0052] Corresponding reference characters indicate corresponding parts throughout the several views.The exemplifications set out herein illustrate embodiments of the invention and are not to be construed as limiting the scope of the invention in any way. DETAILED DESCRIPTION

[0053] Now refer to Figure 1A to Figure 1B , a flow chart showing an overview of the process of applying an adaptive tumor treating field (ATTF). The insulated electrode system (or tumor treating field apparatus) may include a control device, an array of insulated electrode elements, a field generator, and one or more sensors for sensing the real-time temperature of the insulated electrode elements. The insulated electrode system may also include a scanner (e.g., a 3D scanner). A multi-layer flexible circuit may couple the insulated electrode elements, the control device, and the field generator to each other. The control device may be programmed to send signals to the field generator including the frequency range to be sent to the array electrode elements and what array electrode elements to use in what transmission configuration and sequence.

[0054] The control device may or may not perform certain steps of the methods described herein. For example, the control device may calculate or determine at least two sub-array transmit configurations for the insulated electrode element array. Alternatively, the control device may receive at least two sub-array transmit configurations from a 3D simulator. The control device may assess real-time system conditions and determine which preloaded transmit configuration(s) to implement. This calculation may depend on the spatial relationship between two or more tumor-filled regions, the classification strategy, the duty cycle of each insulated electrode element, the sensed temperature of each insulated electrode element, the peak power consumption of the insulated electrode element array, the total power consumption of the insulated electrode element array, the power availability of the field generator of the insulated electrode system, and / or time constraints (e.g., 1 to 3 seconds between field transmissions) to maintain optimal therapeutic effect. The control device may determine the peak and / or total power consumption. For example, as more electrode elements are activated simultaneously, more power will be drawn from the field generator, and the field generator's rated power or total power limit cannot be exceeded in any particular transmit configuration. If the insulated electrode system is operated on battery power, the power limit may also be determined by the available battery life. The control device may track the time spent on battery power in order to change the transmit configuration.

[0055] As used herein, a tumor-filled region is a region of a patient's body where one or more tumors are located. Tumor-filled regions may be separated from one another by a distance such that a single electric field from a given transmit configuration cannot be used to treat both tumor-filled regions. Thus, the spatial relationship between tumors or clusters thereof requires the use of two or more electrode elements to deliver an optimized treatment field to each tumor or cluster thereof.

[0056] The control device can implement the transmit configurations simultaneously and / or sequentially throughout the treatment session. The control device can optimize the treatment process by simultaneously treating as many tumor-filled areas as possible. The control device can also assign corresponding insulated electrode element groups to each subarray transmit configuration. Groups can be composed of different electrode elements, such that groups do not share identical electrode elements. For example, groups can share some common electrode elements, or groups can be composed of completely different electrode elements.

[0057] The process of treating diffuse tumors may include scanning the patient's body. The scanner may or may not be part of the insulated electrode system. Thus, the control device can identify the tumors and their spatial relationships relative to one another. The control device can integrate the tumor scan into the phantom to map their locations. The control device can run a transmission simulation and / or a 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 classify the tumors or their clusters. The control device can also determine which tumors or their clusters can be treated together with a single dish transmission configuration, with separate transmission configurations applied simultaneously, and / or with separate transmission configurations applied sequentially. The control device can incorporate any desired limiting characteristics when determining the transmission configurations. For example, the control device can incorporate a target array element duty cycle and / or a limit on the power available from the field generator. Alternatively, the control device can receive information about the tumors, such as their spatial relationships and their classification strategy. For example, the control device can receive and store one or more locations, transmission configurations, classification strategies, etc. for one or more tumors, which information can be predetermined by the simulator and / or medical professionals.

[0058] The control device can also optimize the overall treatment plan. For example, the control device can determine which emission configurations should be included in each treatment session (i.e., which tumors will be treated each day) and which tumors will be treated less frequently in order to optimize the overall TTF therapy. Due to one or more tumor locations, heat generation, power consumption, classification strategies, etc., it may not be possible or necessary to treat every tumor or cluster in every emission sequence. The control device can optimize the overall treatment for the patient's overall condition, thereby adapting or changing the treatment plan accordingly as the condition changes. Advantageously, one or more arrays of insulated electrode elements can be placed on the patient's body at all times, but the control device software changes the treatment, such as reconfiguring one or more emission configurations of the independently programmable electrode elements, to optimize one or more treatment sessions. For example, the emission configurations and sequences can vary throughout the day, or from one day to the next, as some tumors may be treated every time, while others may be treated less frequently on certain days of the week or month, depending on the factors listed herein, findings from body scans, blood tests, etc. An overall plan can be formed based on all of the previously mentioned parameters, and this plan can vary by hour, day, time of day (sleep vs. wake time), week, or month. Another way to optimize the overall treatment plan can include treating lower priority tumors during periods when the temperature of electrode elements used to treat higher priority tumors needs to cool. In other words, downtime of overheating 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 to treat lower priority tumors while allowing the high priority disk to cool in temperature.

[0059] 3D simulation : A scan (CT scan, MRI, etc.) showing the location of the patient's disease is loaded 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 box 102). Such a program uses mathematical algorithms, phantoms, or avatars to simulate the patient. A phantom that closely matches the patient is selected and the image can then be deformed to further match the size of the patient. By using one or more 2D or 3D scans (CT scan, MRI, etc.) of the patient, the tumor location can be accurately determined, and their spatial distance relative to each other can be determined by importing the locations into the simulator. It should be understood that the control device may or may not include the simulation program.

[0060] Establish frequency Biopsies of one or more patient tumors are used to determine the absolute average cell size of the cancer. If a biopsy is not available, a database of cell sizes by cancer type is used to reference the cell size of the cancer type. Based on the cell size, the frequency most effective for the patient's cancer is selected. If the initial treatment is unsuccessful, this step can be repeated (at block 104).

[0061] Spatial relationship of tumors : Using the 3D simulation, establish the spatial relationships of the multiple tumors relative to each other and the variables of the tumor treatment field. For example, a terminally ill patient may have 14 different tumors. The following types of questions are asked and answered by running the simulation (at block 106). If the initial treatment is unsuccessful, this step can be repeated. It should be understood that the spatial relationships of the multiple tumors may or may not be determined by the control device. For example, the control device may receive a predetermined spatial relationship calculated by the 3D simulation.

[0062] Are any of the 14 tumors clustered together to the extent that the cluster can be treated with one transmit configuration (a transmit configuration is a sequence of tumor treatment fields delivered from different angles, with different frequencies, and timings over a given area)? Or do the tumors require 14 separate and distinct transmit sequences?

[0063] 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 fields)?

[0064] Are tumors positioned so that the duty cycle of the array electrode elements is not burdened by overheating, allowing all tumors to be treated from the outset? Or do tumors have to be prioritized and treated, with some being prioritized and treated now and some later, as tumors treated earlier are eliminated or controlled?

[0065] Does tumor placement require a special transmit configuration (e.g., coplanar field or inhomogeneous array pairs)?

[0066] ● Additional similar questions will be answered.

[0067] Classification strategy : In the example above, once the spatial relationships between tumors are understood, the tumors can be classified to obtain a classification strategy. The classification strategy outlines which tumor(s) should receive more treatment than other tumors. Individual tumors or tumor clusters must be graded or assigned a priority value based on how life-threatening they are to the patient. If certain tumors are particularly life-threatening, these tumors will be given priority. Since adding additional transmission sequences from different angles within the same region has been shown to accelerate tumor reduction, high-priority tumors will receive more delivery angles. This may mean that lower-grade tumors that are less life-threatening may have to wait to receive treatment until more threatening tumors are resolved. If the initial treatment is unsuccessful, this step (box 108) can be repeated. It should be understood that the control device may or may not determine the classification strategy. For example, the control device may receive a classification strategy determined by a medical professional. In addition, the control device may determine the classification strategy alone or in collaboration with a medical professional, for example, by ranking tumors according to one or more characteristics. After one or more rounds of treatment, the control device and / or the medical professional may reclassify the tumors to obtain an updated classification strategy. Thus, the classification ranking of tumors may change over time as new information becomes available (e.g., relative growth, growth versus expectation, new tumors, success rates, patient compliance, etc.) Control equipment and / or medical professionals may reprioritize treatment via array transmission configurations over or within a few treatment sessions.

[0068] Interactive optimization process Based on the spatial relationships between tumors and the classification grade of each tumor, an initial transmit sequence is designed. 3D simulation is then used to optimize the initial transmit sequence. Optimization considers all variables that contribute to treatment effectiveness and their interactions. As the transmit sequence occurs, optimization occurs for each transmit angle and considers the duty cycle of the array electrode elements as a whole (at block 110).

[0069] For example, the dominant frequency for one cancer type may have been determined to be 150 kHz, with an optimal intensity of 2.5 V / cm across the target tumor. This frequency and intensity combination may prove feasible for a first delivery angle. However, a second delivery angle may show an intensity drop to 1.5 V / cm, which is less than ideal. This is because the travel path for the second angle may have a different distance and may pass through different organs. The optimization process then begins testing variations in frequency and power output to see if the second angle can achieve the optimal intensity. For example, the frequency may be changed to 140 kHz or 160 kHz. These relatively modest frequency adjustments can increase the intensity back to the desired 2.5 V / cm because the frequency creates intensity differences when passing through organs with different dielectric constants. This would represent an optimization, as maintaining intensity is considered more important than moderate fluctuations in frequency.

[0070] In a similar manner, the optimization process will test whether the power output of the second shot can be increased without raising the temperature of the array electrode elements above a safe level. Suppose it is determined that increasing the power level successfully maintains the intensity at 2.5 V / cm, but does increase the temperature of the array electrode elements above the desired level. The optimization process will then begin testing reducing the duty cycle of the array electrode elements to maintain the new power level without increasing the temperature. The final optimization must require that all target tumors be exposed to the electric field every 1 to 3 seconds at the optimized frequency and intensity.

[0071] The above are just some examples of how the optimization process considers how all variables of electric field therapy interact to produce the optimal transmission 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 included in the interactive optimization process.

[0072] Once electric field therapy begins, the adaptation process requires regular blood draws to look for tumor markers and regular scans to see if any changes have occurred that require adaptation.112

[0073] This close monitoring determines whether treatment should continue without change or whether adjustments are needed. Adjustments can be made for both positive and negative results. If a negative result is obtained, a new biopsy may be ordered to see if the frequency should be changed. Alternatively, if a new cancer flares up, reoptimization may be necessary. If a successful outcome is observed, the low-priority, untreated tumor can now be treated. 114

[0074] Predictive tools to guide preventive treatmentOnce remission or significant improvement is observed, a predictive tool is used to form a preventive treatment plan. The predictive tool determines the most likely area for the next relapse, such as the lungs, liver, peritoneal cavity, etc. Predictive tools work in a variety of ways. Some predictive tools use genetic markers collected through blood tests or biopsies. Some predictive tools use aggregated databases from a large number of cancer patients with different types of the disease. Statistical probabilities and algorithms are used to predict the areas most likely to relapse. Other predictive tools not mentioned can also be used (at box 116).

[0075] Once the areas of potential recurrence are identified, an initial preventive shot sequence is formed. The initial shot sequence is then subjected to the optimization process described above. This process determines the optimal shot sequence for preventive treatment. Preventive treatment is scheduled, which can vary depending on the patient and the severity of their disease. Prevention can be on an alternating schedule (e.g., one month on, two months off) or prescribed annually, biennially, or quarterly. Regular blood tests and scans that track tumor markers are performed to monitor preventive treatment. If necessary, adjustments are made or the entire optimization process is repeated. Maintenance therapy can also include sweeping the body in previously unaffected areas to remove undetectable tumors (at box 118).

[0076] Patient compliance : It is known that the success of electric field therapy depends largely 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 recorded as high, but needs to be improved. Process 200 can be run continuously to improve patient compliance ( Figure 2 ). A control device (e.g., a wave generator) may record daily variables (at block 202). The control device may also create an activity report (at block 204). Thereafter, a master report may be generated (at block 206). A survey may then be conducted and the patient may be interviewed regarding their treatment experience accordingly (at block 208). If a problem exists, process 200 may include resolving the problem to improve the patient's treatment experience (at block 210).

[0077] In yet another invention, when all tumors or groups of tumors (T groups) are equally threatening, optimization of electric field therapy is prioritized. In this case, it may 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, a T group is selected for exclusion from treatment based on how its absence would enhance the optimization of other T groups that would be retained in treatment. Figures 3A to 3C ).

[0078] Method 300 may include loading a scan into a simulator (at block 302). The scan may be calibrated against a phantom (at block 304). Tumors may be classified (at block 306). Tumors may then be grouped by distance and classification strategy (at block 308). Tumor groups may then be classified (at block 310). Thereafter, a query may be made as to whether the tumor groups are of equal threat (at block 312). If so, a transmit sequence may be designed accordingly (at block 314). If not, an alternative process, such as method 400, may be initiated (at block 316). Method 300 may then include eliminating transmit angles that produce less than 2.35 V / cm (at block 318). If a moderate frequency adjustment can add back angles below 2.35 V / cm, these angles are added back (at block 320). Steps 318 and 320 are then repeated for all tumor groups (at block 322). The test may then be run at the optimal switching speed (at block 324). The method 300 may then inquire whether each group is treated within 1 to 3 seconds (at block 326). If not, certain transmit sequences may be removed (at block 328). If so, it may be inquired whether all remaining T groups have three or more treatment angles (at block 330). If so, the method 300 may continue by determining the duty cycle characteristics (at block 338). If not, it may be inquired whether the two T groups are sufficiently spaced to transmit simultaneous fields (at block 332). If not, the method 300 may allow the lowest threat group two angles (at block 334). If so, the transmit sequence may be redesigned to use simultaneous groups (at block 336). If each array element has a duty cycle of 50% or less, the transmit configuration may be prepared (at block 348). If each array element does not have a duty cycle of 50% or less, the method may determine whether changing the transmit sequence will reduce the duty cycle (at block 340). If so, the transmit configuration may be prepared (at block 348). If not, then the group that would allow the remaining groups to have the most delivered angles but still be below 50% can be eliminated (at block 342). Method 300 can then inquire whether the duty cycle target is being achieved with at least two angles per group (at block 344). If so, a transmit configuration can be prepared (at block 348). If not, then certain transmit sequences can be removed (at block 346). Thereafter, a transmit configuration can be subsequently prepared (at block 348).

[0079] In yet another invention, when all tumors are not equally threatening, optimization of the electric field therapy is prioritized. In this case, it may 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, a T group is selected for exclusion from treatment based on how life-threatening it is compared to other T groups ( Figures 4A to 4C ).

[0080] Method 400 may include loading a scan into a simulator (at block 402). The scan may be calibrated against a phantom (at block 404). Tumors may be classified (at block 406). Tumors may then be grouped by distance and classification strategy (at block 408). Tumor groups may then be classified (at block 410). Thereafter, method 400 may inquire whether the tumor groups are of equal threat (at block 412). If not, the transmit sequence may be designed accordingly (at block 414). If so, an alternative process, such as method 300, may be initiated (at block 416). Method 400 may then include eliminating transmit angles that produce less than 2.35 V / cm (at block 418). If appropriate frequency adjustments can add back angles below 2.35 V / cm, then these angles will be added back (at block 420). Steps 418 and 420 are then repeated for all tumor groups (at block 422). The method 400 may then run a transmit test at the optimal switching speed (at block 424). It may then be asked whether each group is being treated within 1 to 3 seconds (at block 426). If so, the method 400 may continue by determining the duty cycle characteristics, wherein the method 400 determines whether each array element has a duty cycle of 50% or less (at block 442). If not, certain transmit sequences may be removed (at block 428). The method 400 may then ask whether all remaining T groups have three or more treatment angles (at block 430). If so, the method 400 may continue with step 442. If not, it may be asked whether two T groups are sufficiently spaced to transmit simultaneous fields (at block 432). If not, the method 400 may reduce the transmit sequence of angles from three to two until the entire transmit sequence can be completed within 1 to 3 seconds for a given tumor group (at block 434). If so, method 400 may redesign the transmit sequence using the simultaneous group with the largest angle at the optimal frequency (at block 436). After method 400 removes certain transmit sequences in step 434, method 400 may inquire whether a timing target of 1 to 3 seconds can be achieved with at least two angles per tumor group (at block 438). If so, method 400 may continue to step 442. If not, method 400 may eliminate the least life-threatening groups until the timing target is achieved (at block 440). To determine which groups should be eliminated, method 400 may incorporate current tumor classification strategies and / or predictive threat analysis. Method 400 may then continue to step 442 to determine whether each array element has a duty cycle of 50% or less. If each array element has a duty cycle of 50% or less, the transmit configuration may be prepared (at block 450). If the individual array elements do not have a duty cycle of 50% or less, the method 400 may determine whether changing the transmit sequence will reduce the duty cycle (at block 444).If yes, the sequence can be changed (at block 446). Thereafter, the transmit configuration can be prepared (at block 450). If no, the method 400 can begin reducing the transmit sequence from three to two angles until the entire sequence can be completed in 1 to 3 seconds at a 50% duty cycle (at block 448). Thereafter, the method 400 can continue to step 450 to prepare the transmit configuration.

[0081] In yet another invention, daily treatments with electric fields begin at low power and ramp up slowly, giving the patient time to adjust.

[0082] In yet another invention, the wave generator incorporates 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 technologies.

[0083] In yet another invention, array elements are assembled or modified to have different characteristics to improve efficiency based on the frequency used.

[0084] In another invention, a process for minimizing peripheral nerve stimulation (PNS) is used. A test array is placed on a patient. The power level is slowly adjusted upward to determine locations on the patient susceptible to PNS. Those areas susceptible to PNS are loaded into a 3D simulator. The transmit configuration is designed to avoid areas susceptible to PNS. A compensating transmit configuration is designed.

[0085] The present invention consists of a main array of insulating array elements placed on the patient's body. The main array is composed of individual insulating array elements. Each array element is computerized and has its own unique address. The main array is divided into sub-array pairs, each consisting of two or more array elements that are activated 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 activated in a favorable sequence based on treatment simulations performed on individual patients. However, the initial sub-array configuration can be overridden by introducing alternative configurations. These alternative configurations are activated based on variables affecting the sub-array elements (temperature, adhesion, voltage, faults, etc.) and as a result of real-time monitoring of the patient's condition and actions taken by the patient or caregiver that affect a beneficial sub-array configuration during treatment. For example, a 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 for the patient. Alternatively, the control device can select alternative transmission configurations optimized to treat potential tumor areas based on a preventative treatment plan.

[0086] definition:

[0087] 1. Subarray Configuration: The Lifebridge system utilizes output from an external numerical computational model that simulates the human body using various physical and electrical (size, tissue type, organ placement, thermal, electrical) properties. These properties enable the Lifebridge 10000 to simulate the effects of many array element subarray configurations. These simulations inform the assignment of subarray configuration variables:

[0088] a. The addresses of array elements that are excited together

[0089] b. The phase assigned to each array element address or address group

[0090] c. Voltage applied to each array element or address group

[0091] d. The order in which each array or array element group is excited

[0092] e. Duration of excitation of each array or array element group

[0093] f. The frequency at which each array or group of array elements operates. Note that there may be periods of time when no array elements are excited.

[0094] 2. Adaptive Tumor Treatment Field: The arrays in the subarray are energized together so that they form the desired treatment field on the target area. Array elements can be dynamically (adaptively) reallocated to new subarray configurations determined by the Lifebridge 10000 system algorithm.

[0095] 3. Adaptive Optimization: Generates a more optimal subarray configuration, subarray sequence, and subarray duration, determined by a combination of the weighted values of therapeutic field delivery and the duty cycle of the array elements for a given state of the subarray elements (current temperature, expected and measured voltage, communication status, etc.). The control device can determine whether each electrode element is in one of the following regions and then perform a corresponding temperature process to optimize the insulated electrode system.

[0096] 4. Blue Zone: Temperature measurements that are significantly lower than those of adjacent array elements.

[0097] 5. Green Zone: Temperature measurements of array elements within acceptable ranges that do not require changes to initial subarray configuration values

[0098] 6. Yellow Zone: Temperature measurements above the Green Zone value but below the Red Zone value. The Yellow Zone will have 2 to 25 increments. These increments will be used to distinguish the absolute change in array element temperature and the direction of change (increase or decrease).

[0099] 7. Red Zone: A temperature measurement at or above a certain temperature at which the element will disconnect and cannot be re-energized until the measured temperature is within the value assigned to the Yellow or Green Zone by the Lifebridge 10000 system.

[0100] 8. System Controller or Control Device: A control system that implements the tumor-treating electromagnetic field by independently and / or individually controlling the electrode elements. The control system may consist of the computing and storage components included in the Lifebridge 10000 system. These components may be physically integrated into the electrical system of the wave generator and / or connected to the wave generator via external communication ports and / or a computer or mobile device, and may be located entirely or partially on a server or cloud service. Some or all system control functions will be performed in a distributed computing environment. The control system or device may include the wave generator, simulator, and / or controller with memory.

[0101] According to one aspect of the present invention, the controller, or more specifically the software within the memory of the controller, may or may not perform the following processes:

[0102] Overview of the process for determining subarray configurations: 1) Data and images, such as those found in MRI, X-ray, or other medical imaging, are entered into a medical numerical computational model, which creates a "phantom" torso with cancerous tumors located in a similar position to those in a patient. 2) Various simulations are run to determine the optimal array element excitation program. This program determines which array elements are excited, in what order, at what voltage, and for how long, for each step in the system's treatment program. This creates a list of subarray configurations. Arrays excited within a given time period (typically 0.5 to 3 seconds) are assigned to the same subarray within that time period in the program. 3) The subarray configuration program is then loaded into the system controller (i.e., the wave generator).

[0103] Method 500 describes the Lifebridge 10000 system configuration process ( Figure 5). Initially, the system controller (SC) is activated using 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 box 502). If the SC passes the diagnostic check (at box 504), then proceed to the next step. If a fault is found, the system will stop its startup sequence and store the diagnostic values in memory for immediate and / or delayed reporting to local and / or remote computers or mobile databases / displays. The software will trigger a local alarm indicator and / or voice or tone (at box 518). Once the diagnostics have been 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 a slave array element logically present in the system (at box 506). The SC then runs a diagnostic sequence on each array element (at box 508). The diagnostic checks program load, voltage, temperature sensor status, relay machine status (open or closed), etc. If the element passes the diagnostic check, then proceed to the next step (at box 510). If a critical fault is detected, the system will halt its startup sequence and store 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 a local alarm indicator and / or voice or tone (at block 518). If no critical fault is detected, and if the master / slave arrangement is appropriate for the given array of physical and / or logical array elements, the SC will load the array activation program (subarray configuration) into the memory of each array or one or more master arrays (at block 512). The program stored in the array elements is then verified against the master copy of the program via a checksum, hash, or other bit-perfect verification method (at block 514). If a fault is detected, the system will halt its startup sequence and store 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 a 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 the 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 and store the event in memory for immediate and / or delayed reporting to local and / or remote computers or mobile databases / displays. The software will trigger a local alarm indicator and / or voice or tone (at block 518).

[0104] Method 600 describes the Lifebridge 10000 system operation process ( Figure 6The system is in a ready state (at block 602). A start button or switch 606 is physically engaged on the SC to begin executing the subarray configuration sequence steps (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 as controlled by the element switches. Wave generator diagnostics are performed by the SC while the system subarray program is running (at blocks 610 to 624). If an undercurrent condition (i.e., lower than expected current value) is detected in the wave generator, the SC will activate an alarm and warn the patient and caregiver that the array elements may not be adequately adhered to the patient (at blocks 618 to 620). If the diagnostics detect a serious fault in the wave generator (overtemperature, overcurrent, overvoltage, etc.), the system will stop and the diagnostic values will be stored in memory for immediate and / or delayed reporting to a local and / or remote computer or mobile database / display. The software will trigger a local alarm indicator and / or voice or tone (at block 644). Simultaneously, array element diagnostics are performed by the array element and / or the SC while the system subarray program is running (at blocks 632 through 638). If the diagnostics discover a fault in an array element or group of array elements, the program will shut down the element and store the diagnostic values in memory for immediate and / or delayed reporting to local and / or remote computers or mobile databases / displays (at block 640). Depending on the severity and type of array element fault, the SC may trigger additional alarms and notifications, initiate a system shutdown, and activate appropriate alarms (at block 644). The system's 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 fault is detected during the execution of the subarray configuration, the system program will issue "Step Subarray" at time increments determined by the system program (at block 642). This will continue until the following occurs: the stop button / switch is engaged (at block 646), an SC wave generator diagnostic fault is detected (under / over voltage, under / over temperature, under / over current, array communication fault) (at blocks 612 to 628), or an array fault is detected (under / over voltage, under / over temperature) (at blocks 632 to 638).

[0105] In addition to method 600 as described above, the Lifebridge 10000 system can also include enhanced processes for processing temperature measurements to optimize therapy delivery. The generation of a tumor treatment field results in some heating of the array elements due to the generation of an alternating electric field across the patient. The resistance in the circuitry on the array, as well as the wires and other resistive elements, also generates some heat. While some heating is expected, heating that causes element and patient skin temperatures exceeding 105°F is unacceptable.

[0106] Furthermore, the temperature of the elements is monitored so that appropriate mitigation steps can be taken to minimize, stabilize, or reduce the heat generated in the elements, thereby slowing or stopping the temperature rise of the elements and the patient's skin before it reaches an unacceptable temperature. The control device can monitor the temperature of the electrode elements via temperature sensors associated with the respective electrode elements, and based on the sensed temperature, the control device can reselect and implement another alternative transmission configuration that uses one or more different electrode elements to cool one or more overheated electrode elements.

[0107] The present invention includes adaptive tumor treatment capabilities that include various proactive steps taken to modify the treatment program (subarray configuration) while allowing the disk temperature to stabilize or decrease before reaching unacceptable levels. This can be achieved by implementing alternative subarray configurations that change one or more of the following parameters in the configuration:

[0108] 1. Duty cycle: real-time or predicted heating, duration and timing of element activation, time / duration of element inactivity, number of times an element is activated in a programmed sequence, applied voltage, field strength generated in the body when an addressable array element is activated, etc.

[0109] 2. Voltages assigned to sub-array configurations of addressable array element groups

[0110] 3. Control of external equipment (fans, cooling pads, etc.) that can assist in component cooling or temperature stabilization.

[0111] 4. Suggesting actions for the patient and / or caregiver to take, such as changing body position in a chair or bed, loosening clothing or outer clothing, increasing air conditioning of the surrounding environment, adjusting or turning on a fan, etc. See next invention below.

[0112] Furthermore, in addition to the method 600 described above, the LifeBridge 10000 system may also include 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, array element voltage or communication out of tolerance, etc.) that may be improved or resolved through actions that the patient and / or caregiver can take, enhanced notifications with suggested actions and progress toward improving or resolving the out-of-tolerance condition are provided. These actions may include changing position in a chair or bed, loosening or removing clothing, resetting a loose connection, turning on a fan or other cooling device, moving the out-of-tolerance array element closer to the cooling device, checking that the insulation array is properly adhered to the skin, etc.

[0113] The system will notify the patient and / or caregiver of the suggested action via a display directly from the system, tone, voice command, and / or via a computer or mobile device notification via text, voice, email, or computer or mobile application of the patient's and / or caregiver's choice.

[0114] The system will monitor the out-of-tolerance situation and provide feedback periodically (0.5 to 10 minute intervals, depending on the severity of the out-of-tolerance situation, the type of out-of-tolerance situation, the recommended action, etc.) indicating that the actions taken are improving or have resolved the out-of-tolerance situation until the situation is resolved or a preset limit on the number of notifications is reached.

[0115] The system will notify the patient and / or caregiver of the effect (improvement, no change, or worsening of the condition beyond tolerance) 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 application of the patient's and / or caregiver's choice. These notification settings can be changed, muted, or stopped based on the time of day (i.e., silent 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 website, text, or command on a computer or mobile application.

[0116] According to another aspect of the present invention, a system (such as the Lifebridge 10000 system) may also perform the following process:

[0117] 1. Are there recommended actions the patient and / or caregiver can take to help alleviate and / or correct the out-of-tolerance condition?

[0118] 2. Yes

[0119] a. Actuate an indicator / display, sound or voice prompt and / or send a notification via electronic means to a computer or mobile device stored in system memory

[0120] b. Monitor out-of-tolerance conditions as above and report improvement, no change, or deterioration

[0121] c. Repeat appropriate notifications until a set number, the duration of the notification time limit, the start of the Do Not Disturb period, or a stop command is received from the caregiver or patient via the system or computer or mobile communication

[0122] d. Record the time and date of notifications sent and any interactions initiated by the patient and / or caregiver

[0123] 3. No:

[0124] a. Follow the out-of-tolerance notification process.

[0125] According to another aspect of the present invention, a system (eg, Lifebridge 10000 system) may also perform the following method 700 ( Figure 7 ). Method 700 can be considered an adaptive tumor treatment field process controlled by array element temperature measurement. Method 700 may include: measuring the array element temperature and reporting the value to the system controller (at box 702). Thereafter, method 700 may determine whether the temperature is in the green zone, yellow zone, red zone, blue zone, or non-zone (at box 704). If the temperature value is in the green zone (at box 706), the green zone system temperature process will be followed (at box 708). If the temperature value is in the yellow zone (at box 710), the subsequent yellow zone system temperature process will be followed (at box 712). If the temperature value is in the red zone (at box 714), the red zone system temperature process will be followed (at box 716). If the temperature value is in the blue zone (at box 718), the subsequent blue zone system temperature process will be followed (at box 720). If the measured temperature value is in the non-zone (at box 722), method 700 may disconnect the array element (at box 724). Method 700 may then store the address of the element with the temperature sensor fault for reporting to a local computer or mobile device (at block 726). The method may then determine if an alternative acceptable subarray configuration is available (at block 728). If so, method 700 may load the new subarray configuration for the affected array element (at block 732). Appropriate alarm indicators, tones, or both may then be activated (at block 734). If not, method 700 may disconnect all array elements (at block 730). Thereafter, alarm indicators, tones, or both may be activated to reflect the appropriate alarm, and the alarm may be appropriately issued via text, voice, email, computer or mobile application, or other electronic device (at block 734). Method 700 may then proceed to the next system process (at block 736).

[0126] Method 800 describes the green zone temperature measurement process ( Figure 8). The method 800 may cause the SC to check the array element address in memory to determine whether the address is stored in memory with a green, yellow, red, or blue temperature flag (at block 802). Green zone flag: If yes, continue with the existing sub-array configuration (at block 804); or, if no, 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 timestamp (at block 806). Thereafter, the method 800 may determine whether an alternative acceptable sub-array configuration is available (at block 808). If yes, the new sub-array configuration for the affected array elements may be loaded (at block 810). If a device (e.g., a fan, cooling pad, cooling suit, or other similar device) is connected wired or wirelessly so that it can 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 812). The patient and / or caregiver may be instructed via an alarm indicator, via text, email, computer or mobile application, or other electronic device, about actions they can take to reduce the temperature of the affected array element, as indicated in the training (at block 814). Method 800 may record the instructions, alarms, and state changes in memory for reporting purposes (at block 816). If not, method 800 may disconnect all array elements, record the timestamp and action (at block 820). Method 800 may then activate an alarm indicator, an audible tone, or both to reflect the appropriate alarm, and issue an alarm via text, email, computer or mobile application, or other electronic device, as appropriate (at block 822). If a device (e.g., a fan, cooling pad, cooling suit, or other similar device) is connected, either wired or wirelessly, so that it can be triggered / controlled by the Lifebridge 10000SC to change state, the SC communicates with the device or devices to take appropriate actions (at block 824). The method may record the instructions, alarms, and state changes in memory for reporting purposes (at block 826). The method 800 may then proceed to the next system process (at block 736).

[0127] Method 1100 describes the yellow zone temperature measurement process ( Figure 11). Method 1100 may cause the SC to 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 at the same yellow zone increment as the previous measurement (at block 1104)? If so, method 1100 will continue with the current sub-array configuration (at block 1106). If not, is the temperature measurement at a higher increment or a lower increment (at block 1108)? If higher, is an alternative acceptable sub-array configuration available (at block 1110)? If so, method 1100 will load the new sub-array configuration of the array element (at block 1112). If a device (e.g., a fan, cooling pad, cooling suit, or other similar device) is connected, either wired or wirelessly, so that it can 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 may then determine whether the system will activate an alarm indicator, tone, and / or voice (at block 1116). The alarm indicator may indicate to the patient and / or caregiver, via text, email, computer or mobile application, or other electronic device, the actions they can take to reduce the temperature of the affected array element as indicated in the training (at block 1118). The instructions and state changes sent to the connected device may be recorded in memory for reporting purposes (at block 1120). Method 1100 may then proceed to the next system process (at block 736). If not, method 1100 may disconnect all array elements (at block 1122). Method 1100 may then activate an alarm indicator, tone, or both to reflect the appropriate alarm (at block 1124). If a device (e.g., a fan, cooling pad, cooling suit, or other similar device) is connected, either wired or wirelessly, so that it can be triggered / controlled by the Lifebridge 10000SC to change state, the SC communicates with the device or devices to take appropriate action (at block 1126). The patient and / or caregiver may be instructed via an alarm indicator, via text, email, computer or mobile application, or other electronic device, about actions they can take to reduce the temperature of the affected array element as indicated in the training (at block 1128). The instructions and state changes sent to the connected device may be recorded in memory for reporting purposes (at block 1130). Method 1100 may then proceed to the next system process (at block 736). If the temperature delta is lower, is an alternative acceptable subarray configuration available (at block 1132)? If so, a new subarray configuration for the affected array element is loaded (at block 1134).If a device (e.g., a fan, cooling pad, cooling garment, or other similar device) is connected, either wired or wirelessly, so as to be triggerable / controllable 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 1136). Method 1100 may then determine whether the system will deactivate an alarm indicator, audible tone, and / or voice notification (at block 1138). The success of the action taken to reduce the temperature of the affected array element may be indicated to the patient and / or caregiver via an alarm indicator via text, email, computer or mobile application, or other electronic device (at block 1140). The instruction and state change may be recorded in memory for reporting purposes (at block 1142). Method 1100 may then proceed to the next system process (at block 736). If no acceptable alternative sub-array configuration is available, method 1100 may deactivate all array elements (at block 1122). Alarm indicators, audible tones, or both may then be activated to reflect the appropriate alarm (at block 1124). If a device (e.g., a fan, cooling pad, cooling suit, or other similar device) is connected, either wired or wirelessly, so as to be capable of being triggered / controlled by the Lifebridge 10000SC to change state, the SC communicates with the device or devices to take appropriate action (at block 1126). The patient and / or caregiver may be instructed via an alarm indicator, text message, email, computer or mobile application, or other electronic device, on actions they can take to reduce the temperature of the affected array element as indicated in the training (at block 1128). The instructions and state changes sent to the connected device may be recorded in memory for reporting purposes (at block 1130). Method 1100 may then proceed to the next system process (at block 736). If the address is not already marked as yellow zone, method 1100 may store the green, red, or blue zone designation from the array element and record the element address with the new yellow zone designation at the correct increment (at block 1144). Is an alternative acceptable subarray configuration available (at block 1146)? If so, the new subarray configuration for the array element address may be loaded (at block 1148). If a device (e.g., a fan, cooling pad, cooling garment, or other similar device) is connected, either wired or wirelessly, so as to be triggerable / controllable 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 1150. If the previous flag was green, the patient and / or caregiver may be instructed via an alarm indicator, via text, email, computer or mobile application, or other electronic means, at block 1152, on actions they can take to reduce the temperature of the affected array element as indicated in the training.Alternatively, if the previous flag was red or blue, the success of the action taken to reduce the temperature of the affected array element can be indicated to the patient and / or caregiver via an alarm indicator, text, email, computer or mobile application, or other electronic device (at block 1152). Method 1100 can then activate an alarm indicator, an audible tone, or both to reflect the appropriate alarm, and issue an alarm via text, email, computer or mobile application, or other electronic device as appropriate (at block 1154). The instruction and state change can be recorded in memory for reporting purposes (at block 1156). Method 1100 can then proceed to the next system process (at block 736). If not, method 1100 can disconnect all array elements (at block 1158). Method 1100 can then activate an alarm indicator, an audible tone, or both to reflect the appropriate alarm (at block 1160). If a device (e.g., a fan, cooling pad, cooling suit, or other similar device) is connected, either wired or wirelessly, so as to be capable of being triggered / controlled by the Lifebridge 10000SC to change state, the SC communicates with the device or devices to take appropriate action (at block 1162). If the previous flag was green, the patient and / or caregiver can be instructed via an alarm indicator, text, email, computer or mobile application, or other electronic device, on actions they can take to reduce the temperature of the affected array element as indicated in the training (at block 1164). The instructions and state change can then be recorded in memory for reporting purposes (at block 1166). Method 1100 can continue to monitor temperature measurements of all array elements. Method 1100 can then proceed to the next system process (at block 736).

[0128] Method 900 describes the red zone temperature measurement process ( Figure 9). The method 900 may cause the SC to check the array element address in memory to determine whether the address is stored in memory with a yellow, red, or blue temperature flag (at block 902). Red zone flag: If yes, continue with the existing sub-array configuration (at block 904); if no, disconnect the array element (at block 906). The method 900 may remove the green zone, yellow zone, or blue zone flag from the array element address and record the element address with the red zone flag (at block 908). The method 900 may then determine whether an alternative acceptable sub-array configuration is available (at block 910). If yes, the method 900 may load the new sub-array configuration for the affected array element (at block 912). If a device (e.g., a fan, cooling pad, cooling suit, or other similar device) is connected wired or wirelessly so that it can 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). Method 900 may activate an alarm indicator, an audible tone, or both to reflect the appropriate alarm, and may issue an alarm via text, email, computer or mobile application, or other electronic device, as appropriate (at block 916). The patient and / or caregiver may be instructed via the alarm indicator, via text, email, computer or mobile application, or other electronic device, on actions they can take to reduce the temperature of the affected array element, as indicated in the training (at block 918). The instructions, alarm, and state change may be recorded in memory for reporting purposes (at block 920). If not, method 900 may disconnect all array elements (at block 922). Method 900 may activate an alarm indicator, an audible tone, or both to reflect the appropriate alarm (at block 924). If a device (e.g., a fan, cooling pad, cooling suit, or other similar device) is connected, either wired or wirelessly, so that it can be triggered / controlled by the Lifebridge 10000SC to change state, the SC communicates with the device or devices to take appropriate action (at block 926). If the previous flag was a green or yellow zone, the patient and / or caregiver may be instructed via an alarm indicator, via text, email, computer or mobile application, or other electronic device, at block 928, on actions they can take to reduce the temperature of the affected array element as indicated in the training. Instructions, alarms, and status changes may be recorded in memory for reporting purposes at block 930. Method 900 may then proceed to the next system process at block 736.

[0129] According to another aspect of the present invention, the system can operate in the blue zone as follows. Array elements that fail to efficiently or fully couple to the generated electric field typically operate at a lower temperature (in the blue temperature zone) than array elements that efficiently couple to the electric field, provided that these array elements are part of the same transmitting subarray. Conditions that may affect array element coupling include poor adhesion to the skin surface or electrical breakdown in the insulation of the array elements or wiring that causes current to flow to the skin, as well as other similar fault conditions in the array elements.

[0130] By comparing the temperature of an array element with its surrounding array elements (included in the same sub-array transmission), low temperature conditions can be detected and appropriate action can be taken.

[0131] The system stores a database containing the address of each isolated array element on the patient, along with a list of neighboring subarray elements. The temperature of each individual array element is compared to other array elements in the same subarray. The list of suitable neighbor elements for comparison can contain from one to the entire subarray of elements with the same voltage polarity. The number and location of suitable neighbors for comparison will vary based on location, current temperature status, and active or inactive status assignment within the active subarray. This process can be used to track and compare other variables, such as voltage, element switch status, and so on.

[0132] The system compares the subarray element to the mean and median temperatures calculated for the group of neighbor subarray elements identified in the neighbor database.

[0133] If the temperature of an array element is 0.5 to 10 degrees cooler than its neighbor list calculation (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 valid subarray configurations, marked with a blue zone temperature indicator in system memory, and the SC will determine whether the alternative subarray configuration is acceptable or the system will enter safe mode.

[0134] Method 1000 describes the Blue Zone Temperature Test and Process ( Figure 10). Method 1000 may create a blue zone to read array element temperatures. Method 1000 may measure array element temperatures and report them to the SC, and calculate and store average and median neighbor list array element temperatures (at block 1002). Method 1000 may appropriately include scaling factors in the comparison algorithm (adaptive optimization). The 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 may include a step of determining if the array element is in the blue zone (at block 1004)? If not, method 1000 may continue with the current subarray configuration (at block 1008). If yes, does the address have a blue zone flag (at block 1006)? If yes, method 1000 may continue with the existing subarray configuration (at block 1008). Method 1000 may then proceed to the next system process (at block 736). If not, method 1000 may disconnect the array element (at block 1010). Method 1000 may then remove the green, yellow, or red zone designation from the array element address and record the element address with the blue zone designation (at block 1012). Is an alternative acceptable subarray configuration available (at block 1014)? If so, the new configuration for the affected array element may be loaded (at block 1016). If a device (e.g., a fan, cooling pad, cooling suit, or other similar device) is connected, either wired or wirelessly, so as to be triggerable / controllable 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. Method 1000 may record the instructions and state changes sent to the connected devices (at block 1018). Method 1000 may activate an alarm indicator, tone, and / or voice to reflect the appropriate alarm (at block 1020). The alarm indicator may indicate to the patient and / or caregiver, via text, email, computer or mobile application, or other electronic device, the actions they can take to reattach or isolate the affected array element as instructed in the training (at block 1022). The method 1000 may record the instructions, alarms, and state changes in memory for reporting purposes (at block 1024). The method 1000 may then proceed to the next system process (at block 736). If an alternative acceptable subarray is not available, the method 1000 may disconnect all array elements and record the action in memory (at block 1026). The method 1000 may activate an alarm indicator, an audible tone, or both to reflect the appropriate alarm (at block 1028). If a device (e.g., a fan, cooling pad, cooling suit, or other similar device) is connected, either wired or wirelessly, so that it can 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 1030).The patient and / or caregiver may be instructed via an alarm indicator, via text, voice, email, computer or mobile application, or other electronic device, as to the actions they can take to reattach or isolate the affected array element as instructed in the training (at block 1032). Instructions, alarms, and status changes may be recorded in memory for reporting purposes (at block 1034). Method 1000 may then proceed to the next system process (at block 736).

[0135] Although the present invention has been described with respect to at least one embodiment, the present invention may be further modified within the spirit and scope of the present disclosure. Therefore, this application is intended to cover any variations, uses, or modifications of the present invention using its general principles. Further, this application is intended to cover departures from the present disclosure that come within known or customary practice in the art to which the invention pertains and that are claimed.

Claims

1. A tumor treatment field device comprising an array of insulated electrode elements coupled to a control device; characterized in that: The apparatus is configured to: i) determining a spatial relationship between at least two tumor-filled regions on a scan of the patient; ii) determining and / or implementing at least two sub-array transmit configurations of said array of insulated electrode elements for targeting said at least two tumor-filled regions, said at least two sub-array transmit configurations being dependent at least in part on said spatial relationship between said at least two tumor-filled regions.

2. The device according to claim 1, wherein The control device is configured to: i) determining a spatial relationship between at least two tumor-filled regions on a scan of the patient; ii) determining and / or implementing at least two sub-array transmit configurations of said array of insulated electrode elements for targeting said at least two tumor-filled regions, said at least two sub-array transmit configurations being dependent at least in part on said spatial relationship between said at least two tumor-filled regions.

3. The device according to claim 1 or 2, wherein: Also included is a field generator.

4. The device according to claim 1, wherein Also included are one or more sensors for sensing the real-time temperature of the insulated electrode element.

5. The device according to claim 1, wherein Also includes a scanner.

6. The device according to claim 5, wherein The scanner is a 3D scanner.

7. The device according to claim 1, wherein The device is configured to perform a method of a tumor treating field device configured to deliver a tumor treating electric field to a patient, the method comprising the steps of: a) receiving a scan of the patient's body; b) identifying on the scan at least two tumor-filled regions, each having at least one tumor in the respective tumor-filled region; Characterized in that the method further comprises: c) determining a spatial relationship between at least two tumor-filled regions; and d) determining at least two sub-array transmit configurations of an array of insulated electrode elements for targeting the at least two tumor-filled regions, the at least two sub-array transmit configurations being dependent at least in part on the spatial relationship between the at least two tumor-filled regions.

8. The device according to claim 7, wherein The method further includes assigning respective groups of insulated electrode elements of the array of insulated electrode elements to respective sub-array transmit configurations.

9. The device according to claim 7, wherein The method further comprises: classifying the tumors in the at least two tumor-filled regions to obtain a classification strategy; and wherein The determining or implementing of at least two sub-array transmit configurations of the insulated electrode element array depends at least in part on the spatial relationship between the at least two tumor-filled regions and the classification strategy; wherein, optionally, the classification includes assigning a priority value to the at least one tumor in each tumor-filled region.

10. The device according to claim 7, wherein The method also includes optimizing one or more of the total amount of treatment time, duration of field strength, and number of angles of electric field delivery dedicated to at least one tumor in each tumor-filled region based on the assigned priority values of the tumors in the at least two tumor-filled regions.

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