Apparatus and method for optimizing and tailoring the treatment of multiple tumors in patients with metastatic disease with electric fields - Patents.com

Abstract

The present invention relates to a method for applying a tumor treatment electric field to a patient's body, the method including scanning the patient's body to identify at least two tumor fill regions. The method further includes determining a spatial relationship between the at least two tumor fill regions. The method further includes positioning an insulated electrode element array on the patient's body. The method further includes implementing at least two subarray firing configurations of the insulated electrode element array to treat the at least two tumor fill regions in response at least in part to the spatial relationship between the at least two tumor fill regions, such that each subarray firing configuration treats a respective tumor fill region. The present invention also relates to a tumor treatment electric field device including an insulated electrode element array coupled to a control device, and a method for configuring a tumor treatment electric field device.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application is based on U.S. Provisional Patent Application No. 62 / 948,600, entitled “APPARATUS AND METHOD FOR OPTIMIZING AND ADAPTING TREATMENT OF MULTIPLE TUMORS IN PATIENTS WITH METASTATIC DISEASE BY ELECTRIC FIELD,” filed December 16, 2019, which is incorporated herein by reference.

[0002] The present invention relates to the selective destruction of multiple solid tumors in large areas, including the entire torso, of metastatic cancer patients. More specifically, the present invention relates to an apparatus and method for optimizing the destruction of multiple tumors without damaging normal cells, and for 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 technology]

[0003] Alternating electric fields, also called Tumor Treating Fields (TTF's), can be employed as a type of cancer treatment therapy by using low-intensity electromagnetic fields. These low-intensity electromagnetic fields change direction rapidly, thousands of times per second. Because TTF's are electric fields, they do not cause muscle spasms or other severe harmful side effects in electrically activated tissues. The growth rate of metastatic disease is typically faster than that of normal, healthy cells. Alternating electric field therapy exploits this high growth rate property. TTF's act to disrupt the mitotic process and cytokinesis of cancer cells by manipulating the polarizable intracellular components of cells, namely tubulin, which forms the mitotic spindle that pulls the genetic material in the nucleus into two sister cells. TTF's prevent cell division by disrupting the assembly of mitotic spindle microtubules. Metastatic disease cells treated with TTF typically undergo programmed cell death within 4-5 hours. This results in a significant reduction in tumor size and potentially complete elimination of solid tumors. TTF is tailored to treat specific cancer cells, without harming normal cells. TTF therapy can be used as the sole treatment method or in combination with traditional drug delivery mechanisms.

[0004] Below we explain how electric fields selectively kill cancer cells. The fundamental physics of using electric fields to trigger an immunogenic response and selectively kill cancer cells involves commonly known properties of charged particles: like charges repel and opposite charges attract. Key proteins essential for mitosis have high dipole moments; one negative and the other positive.

[0005] In a constant electric field, charged particles move towards the opposite charge. When exposed to an alternating electric field, dipole proteins essential to mitosis rotate back and forth with the alternating charge of the field.

[0006] Electric fields that lead to cancer cell death are generated through solid tumors at frequencies between 100kHz and 300kHz, depending on the size of the cancer cell. The first question to answer is what is it within the cancer cell that interacts with the electric field to disrupt tumor growth.

[0007] The main protein complex involved in mitosis is septin, which has a very high dipole moment. Septin has many functions and is involved in the structural support of the cell. In the presence of an alternating electric field, at optimal frequencies, the localization necessary for septin to perform its function is suppressed. As a result of exposure to an electric field during mitosis, it does not prevent the formation of tumor daughter cells, but causes their malformation. The foreign nature of the daughter cells developed under optimal electric fields is to trigger an immune response. Immunogenic cell death occurs and the tumor is reduced.

[0008] The mechanism of action of using Septin is to treat patients with compromised immune systems who are undergoing electric field therapy for glioblastoma (CD8 cell counts <144 cells / mm 2 This is further supported by the fact that patients with a CD4 / CD8 ratio <1.09) who have a lower response to electric field therapy than those with a healthy immune system, and therefore may not benefit from the therapy.

[0009] Of course, the outcome of this therapy may depend on a properly tuned electric field that can penetrate the cell wall. Whether an electric field can penetrate a cancer cell wall depends on the relationship between the frequency of the electric field and the size of the cell.

[0010] There is an inverse relationship between effective electric field frequency and the size of the cancer cells. 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 penetrate its cell wall. In fact, the effectiveness of electric fields in reducing solid tumors depends on frequency, and each cancer cell type may have a specific frequency at which the inhibitory effect is greatest. This allows the selection of metastatic cancers to be treated with applicable electric field therapy to be determined in part by the range of cell sizes. Since the mechanism of action of electric field therapy is based on disrupting mitosis, the most universal process of all cancer cells, there is no attribute that indicates that electric fields should be used for one cancer over another. The cancers selected for treatment need only be effectively treated within the frequency range of 100kHz to 300kHz, which has been shown not to harm normal cells.

[0011] The secondary mechanism of action of sending a selective electric field through a solid tumor is called dielectrophoresis. The electric field may push polarizable macromolecules and / or organelles toward the mitotic furrow during late mitosis, often causing the cleavage furrow to rupture and cell destruction. This secondary killing effect is achieved when the electric field lines are parallel to the cleavage furrow lines. When the electric field lines and the cleavage furrow lines are perpendicular, dielectrophoresis does not occur. Because the cleavage axis (the line of the cleavage furrow) may be random in cancer tumors, if only one angled electric field is applied, only a portion of the cells may be exposed to possible dielectrophoresis. It may not be possible to achieve an angle sufficient to cause this phenomenon at the level required to eliminate the tumor. Nevertheless, adding angles in therapy can promote tumor reduction.

[0012] In addition to the frequency and number of angles of application (dielectrophoresis), there are other variables that can affect the success of electric field therapy to reduce tumors, among them the strength of the electric field, the speed of switching from one angle to the next, and patient compliance.

[0013] Known devices and methods for treating tumors focus on localized tumors, and thus prior art treatments using dedicated array elements may not be sufficiently diverse to adequately address multiple disease sites.

[0014] What is needed in the art are devices and methods that take a more comprehensive and adaptive approach to treating late-stage widespread cancers over time. Summary of the Invention

[0015] 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 elicited by specially tailored electric fields.

[0016] The present invention provides a solution to optimize the immunogenic response to reduce multiple / diffuse solid tumors, thereby focusing on diffuse disease, or disease at multiple sites in advanced cancer patients. The device achieves this in the following way: 1. Treat multiple TTFs (two or more strategic areas treated simultaneously and / or in rotation). 2. The spatial relationships between multiple tumors and vital organs may allow for the application of multiple electric fields or simultaneous application of electric fields. 3. Track and vary the electric field strength as it changes with changes in other variables (angle, frequency, interactions with other electric fields, etc.) to optimize its effectiveness. 4. Maximum number of applied angles (to reduce the duty cycle of the array elements). 5. When the frequency of the tumor treatment field is changed, all other variables are adapted. 6. Adapt therapy to patient compliance. 7. Use predictive data, such as predictive blood tests or predictive modeling, to design preventative treatment regimens that minimize the chance of relapse after remission is achieved.

[0017] By allowing each of these variables to be applied more effectively, the devices and methods of the present invention make electric field therapy for treating solid tumors accessible to metastatic cancer patients with diffuse disease or disease at two or more sites.

[0018] The invention in another form relates to a method of applying a tumor treating electric field to a patient's body, the method including scanning the patient's body to identify at least two tumor filling regions. The method further includes determining a spatial relationship between the at least two tumor filling regions. The method further includes positioning an insulated electrode element array on the patient's body. The insulated electrode element array is coupled to a control device. The method further includes implementing at least two subarray firing configurations of the insulated electrode element array to treat the at least two tumor filling regions in response at least in part to the spatial relationship between the at least two tumor filling regions, such that each subarray firing configuration treats a respective tumor filling region.

[0019] The present invention further provides a method of configuring a tumor treating electric field apparatus to apply a tumor treating electric field to a patient, the apparatus including an array of insulated electrode elements coupled to a control device, the method comprising: a) receiving a scan of a patient's body; b) identifying at least two tumor-filled regions in the scan, each having at least one tumor; c) determining a spatial relationship between at least two tumor filled regions; and d) determining at least two subarray firing configurations of the insulated electrode element array that target the at least two tumor filling regions, the at least two subarray firing configurations being at least partially dependent on a spatial relationship between the at least two tumor filling regions.

[0020] The invention in another form relates to a method of applying a tumor treating electric field to a patient's body, the method including scanning the patient's body to identify at least two tumor filling regions, each tumor filling region having at least one tumor. The method further includes determining a spatial relationship between the at least two tumor filling regions. The method further includes disposing an insulated electrode element array on the patient's body. The insulated electrode element array is coupled to a control device. The method further includes triaging tumors in the at least two tumor filling regions to obtain a triage strategy. The method further includes implementing at least two subarray firing configurations of the insulated electrode element array such that each subarray firing configuration treats a respective tumor filling region to treat the at least two tumor filling regions in response at least in part to the spatial relationship between the at least two tumor filling regions and the triage strategy.

[0021] The invention in yet another form relates to a method of applying a tumor treating electric field to a patient's body, the method including scanning the patient's body to identify at least two tumor filling regions, each tumor filling region having at least one tumor. The method further includes determining a spatial relationship between the at least two tumor filling regions. The method further includes positioning an insulated electrode element array on the patient's body. The insulated electrode element array is coupled to a control device. The method further includes determining at least two subarray firing configurations of the insulated electrode element array in response at least in part to the spatial relationship between the at least two tumor filling regions. Each subarray firing configuration is configured to treat a respective tumor filling region. The method further includes determining whether the at least two subarray firing configurations can be performed simultaneously or sequentially. The method further includes performing the at least two subarray firing configurations for treating the at least two tumor filling regions simultaneously or sequentially.

[0022] The invention in yet another form relates to a method of applying a tumor treating electric field to a patient's body, the method including scanning the patient's body to identify at least one tumor filling region, each tumor filling region having at least one tumor. The method further includes positioning an insulated electrode element array on the patient's body. The insulated electrode element array is coupled to a control device. The method further includes implementing at least one initial subarray firing configuration of the insulated electrode element array to treat the at least one tumor filling region. The method further includes sensing a temperature of an insulated electrode element of the insulated electrode element array. The method further includes implementing at least one alternative subarray firing configuration of the insulated electrode element array in response to the sensed temperature to treat the at least one tumor filling region.

[0023] The present invention further provides a tumor treating electric field apparatus including an array of insulated electrode elements coupled to a control device, the apparatus comprising: i) determining a spatial relationship between at least two tumor filled regions in a scan of a patient; ii) configured to determine and / or implement at least two subarray firing configurations of the array of insulated electrode elements targeting at least two tumor fill regions, the at least two subarray firing configurations depending at least in part on a spatial relationship between the at least two tumor fill regions. The apparatus may be configured to perform the method of the present invention.

[0024] An advantage of the present invention is that the insulated electrode system and method allows for simultaneous treatment of multiple, spatially separated tumors or clusters thereof in two or more firing configurations using different electrode elements.

[0025] The above and other features and advantages of the present invention, as well as the manner in which they are accomplished, will become more apparent and the invention will be better understood by referring to the following description of the embodiments of the invention taken in conjunction with the accompanying drawings. [Brief description of the drawings]

[0026] [Figure 1A(1)]1 shows a flow chart of a method for applying an adaptive tumor treatment electric field. [Figure 1A(2)] 1 shows a flow chart of a method for applying an adaptive tumor treatment electric field. [Figure 1B] 1 shows a flow chart of a method for applying an adaptive tumor treatment electric field. [Diagram 2] 1 shows a flow chart of a method for increasing patient compliance. [Figure 3A(1)] 1 shows a flow chart of a method for optimizing electric field therapy when all tumors are of equal threat. [Figure 3A(2)] 1 shows a flow chart of a method for optimizing electric field therapy when all tumors are of equal threat. [Figure 3B(1)] 1 shows a flow chart of a method for optimizing electric field therapy when all tumors are of equal threat. [Figure 3B(2)] 1 shows a flow chart of a method for optimizing electric field therapy when all tumors are of equal threat. [Figure 3C] 1 shows a flow chart of a method for optimizing electric field therapy when all tumors are of equal threat. [Figure 4A(1)] 1 shows a flow chart of a method for optimizing electric field therapy when all tumors are of unequal threat. [Figure 4A(2)] 1 shows a flow chart of a method for optimizing electric field therapy when all tumors are of unequal threat. [Figure 4B(1)] 1 shows a flow chart of a method for optimizing electric field therapy when all tumors are of unequal threat. [Figure 4B(2)] 1 shows a flow chart of a method for optimizing electric field therapy when all tumors are of unequal threat. [Figure 4C] 1 shows a flow chart of a method for optimizing electric field therapy when all tumors are of unequal threat. [Figure 5(1)] 1 shows a method flow chart for a configuration procedure of the system. [Figure 5 (2)] 1 shows a method flow chart for a system configuration procedure. [Figure 6]1 shows a method flow chart for the operating procedure of the system. [Figure 7] 13 shows a flow chart of a method for an adaptive tumor treatment electric field procedure of the system. [Figure 8] 1 shows a flow chart of a method for a green zone temperature measurement procedure of a system. [Figure 9] 1 shows a flow chart of a method for a red zone temperature measurement procedure of the system. [Figure 10(1)] 1 shows a method flow chart for a Blue Zone temperature measurement procedure of the system. [Figure 10(2)] 1 shows a method flow chart for a Blue Zone temperature measurement procedure of the system. [Figure 11(1)] 13 shows a method flow chart for the yellow zone temperature measurement procedure of the system. [Figure 11 (2)] 13 shows a method flow chart for the yellow zone temperature measurement procedure of the system. [Figure 11 (3)] 13 shows a method flow chart for the yellow zone temperature measurement procedure of the system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0027] Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set forth herein are illustrative of embodiments of the present invention, and such exemplifications should not be construed as limiting the scope of the present invention in any manner.

[0028] 1A-1B, a flow chart is shown outlining a process for applying Adaptive Tumor Treating Fields (ATTF). The isolated electrode system (or tumor treating field device) may include a control device, an array of isolated electrode elements, an electric field generator, and one or more sensors for sensing real-time temperature of the isolated electrode elements. The isolated electrode system may further include a scanner, such as a 3D scanner. A multi-layer flex circuit may couple the isolated electrode elements, the control device, and the electric field generator together. The control device may be programmed to send signals to the electric field generator including the frequency ranges to be sent to the array electrode elements, as well as which array electrode elements are to be used in which firing configuration and sequence.

[0029] 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 subarray firing configurations of the insulated electrode element array. Alternatively, the control device may receive at least two subarray firing configurations from the 3D simulator. Here, the control device may evaluate real-time system conditions and determine which preloaded firing configuration to implement. Such calculations may depend on the spatial relationship between two or more tumor-filled regions, triage strategies, 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 electric field generator of the insulated electrode system, and / or time constraints to maintain optimal therapeutic effect, e.g., 1-3 seconds of the electric field firing process. The control device may determine the peak and / or total power consumption. For example, firing more electrode elements simultaneously will draw more power from the electric field generator, and a particular firing configuration may not exceed the power rating or total power limit of the electric field generator. If the isolated electrode system is operating on battery power, the power limit may be determined by the available battery life. The control device may track the time spent on battery power in order to modify the firing configuration.

[0030] As used herein, a tumor fill region is a region of a patient's body in which one or more tumors reside. The tumor fill regions may be spaced apart from one another by a distance such that a single electric field from a given firing configuration cannot be used to treat two tumor fill regions. The spatial relationship between tumors or clusters thereof thereby necessitates the use of two or more electrode elements to apply an optimized treatment electric field to each of the tumors or clusters thereof.

[0031] The control device may implement the firing configurations simultaneously and / or sequentially throughout a treatment session. The control device may optimize the treatment process by treating as many tumor-filled regions as possible simultaneously. The control device may also assign a respective isolated electrode element group to each sub-array firing configuration. The groups may be composed of different electrode elements such that they do not share the exact same electrode elements. For example, the groups may share some common electrode elements between them or may be composed of completely different electrode elements.

[0032] The process of treating diffuse tumors may include scanning the patient's body. The scanner may or may not be a component of the insulated electrode system. The control device may thus identify the tumors and their spatial relationship to one another. The control device may integrate the scan of the tumor into a phantom to map the location. The control device may run firing simulations and / or mathematical algorithms to determine the number of separate firing configurations required to create a treatment field that optimally treats the tumor-filled region. The control device may then triage the tumor or clusters thereof. The control device may also determine which tumors or clusters thereof may be treated together with a single disk firing configuration, with separate firing configurations applied simultaneously, and / or with separate firing configurations applied sequentially. The control device may incorporate any desired limiting characteristics in determining the firing configurations. For example, the control device may incorporate limitations on the duty cycle of the target array elements and / or the power available from the electric field generator. Alternatively, the control device may receive information about the tumor, such as the spatial relationship of the tumor and a tumor triage strategy. For example, the control device may receive and store tumor locations, firing configurations, triage strategies, etc., which may be pre-determined by the simulator and / or a medical professional.

[0033] The control device may also optimize the overall treatment plan. For example, the control device may determine which firing configurations should be included in each treatment session (i.e., which tumors to treat each day) and which tumors to treat on a less frequent schedule to optimize the overall TTF therapy. It may not be possible or necessary to treat all tumors or clusters thereof with every firing sequence due to tumor location, fever, power consumption, triage strategies, etc. The control device may optimize the overall therapy depending on the overall situation of the patient and adapt or change the treatment plan as the situation changes. Advantageously, the insulated electrode element array can be placed on the patient's body every time, but the control device software changes the treatment, e.g., reconfigures the firing configurations of the independently programmable electrode elements, to optimize the treatment session. For example, firing configurations and sequences can occur during a day or change from one day to the next, since some tumors are treated every time, while some tumors are treated less frequently on some days of the week or month depending on factors described herein, results seen from body scans, blood tests, etc. Based on all the aforementioned parameters, an overall plan can be created that varies by hour, day, time of day (sleep time vs wake time), week, month. Another way to optimize the overall treatment plan may include treating low priority tumors during periods when the temperature of the electrode elements used to treat high priority tumors needs to be cooled. In other words, downtime that overheats a first, e.g., high priority array element group, allows the use of other array elements in a second, e.g., low priority array element group, used to treat low priority tumors that can lower the temperature of the high priority disk.

[0034] 3D Simulation: Scans (CT scans, MRIs, etc.) showing the patient's diseased area are loaded into a 3D simulation program (block 102) that uses finite element methods or other physics solvers to determine the characteristics of the electric field through the human body. Such programs use mathematical algorithms, phantoms, or avatars to simulate the patient. A phantom, selected to closely match the patient, can then be morphed 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 location of the tumors can be precisely determined, and by importing them into the simulator, their spatial distance from one another can be precisely determined. It is to be understood that the control device may or may not include a simulation program.

[0035] Establish Frequency: A biopsy of the patient's tumor is used to determine the absolute average cell size of the cancer. If a biopsy is not available, the cell size of the cancer type is referenced using database knowledge of cell size by cancer type. The most effective frequency for the patient's cancer is selected based on cell size. This step can be repeated if the initial therapy is not successful (block 104).

[0036] Spatial Relationship of Tumors: Using the 3D simulation, establish the mutual spatial relationship of multiple tumors to the variables of the tumor treatment electric field. For example, an advanced patient may have 14 different tumors. The following types of questions are asked and answered throughout the simulation run (block 106): If the initial therapy is not successful, this step can be repeated. It should be understood that the spatial relationship of 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. Will any of the 14 tumors be clustered together until the cluster can be treated with one fire configuration (a fire configuration is a sequence of tumor treatment electric fields applied to a given area at different angles, frequencies and timing)? Or will 14 separate, different fire sequences be needed for the tumors? · Will it be possible to demonstrate that either distant tumors or clusters of tumors in the body can be used simultaneously with minimal interaction between the two electric fields? · Are the tumors positioned so that the duty cycle of the array electrode elements is not strained to the point of overheating, and all tumors are treated the first time? Or should tumors be triaged and treated according to priority? Some tumors are triaged and treated now and some tumors are triaged and treated later because tumors that are treated early are either removed or brought under control. Does tumor placement require special firing configurations such as co-planner fields or non-uniform array pairs? · Answer additional similar questions.

[0037] Triage Strategy: In the above example, once the spatial relationship between the tumors is understood, the tumors may be triaged to obtain a triage strategy. The triage strategy outlines which tumors should be treated more than others. Each tumor or cluster of tumors should be graded or assigned a priority value according to how life-threatening it is to the patient. If some tumors are particularly life-threatening, they are prioritized. Adding additional firing sequences from different angles to the same area has been shown to accelerate tumor reduction, so the electric field is applied at more angles to the high priority tumors. This means that low grade tumors, which are less life-threatening, may have to wait to receive therapy until the more life-threatening tumors are removed. If the initial therapy is not successful, this step can be repeated (block 108). It is understood that the control device may or may not determine the triage strategy. For example, the control device may receive a triage strategy determined by a medical professional. Additionally, for example, the control device may determine a triage strategy, alone or in conjunction with a medical professional, by ranking tumors according to one or more characteristics. After one or more rounds of treatment, the control device and / or medical professional may re-triage the tumors to obtain an updated triage strategy. Thus, the triage ranking of tumors may change over time as new information is obtained, such as relative growth, growth vs. expectation, new tumors, success rates, patient compliance, etc. The control device and / or medical professional may change treatment priorities via the array firing configuration during or across several treatment sessions.

[0038] Interactive optimization process: Design an initial firing sequence based on the spatial relationship between tumors and the triage grade of each tumor. Then, optimize the initial firing sequence using 3D simulation. The optimization considers all variables and their interactions that contribute to the efficacy of the therapy. The optimization is performed for all firing angles and considers the duty cycle of the entire array electrode elements when the firing sequence occurs (block 110).

[0039] For example, it may be determined that the primary frequency for a certain type of cancer is 150 kHz, and that the optimal intensity through this target tumor is 2.5 V / cm. This frequency and intensity combination may prove achievable when applied at a first angle. However, application at a second angle may indicate a drop in intensity to 1.5 V / cm, which is less than optimal. This is because the path of travel at the second angle may be a different distance and pass through a different organ. The optimization process then begins testing changes in frequency and power output to see if the optimal intensity can be achieved at the second angle. For example, the frequency may be changed to 140 kHz or 160 kHz. Since frequency results in differences in intensity when passing through organs with different dielectric constants, relatively modest adjustments to these frequencies may return the intensity to the desired 2.5 V / cm. This represents an optimization, as it is believed that maintaining intensity is more important than moderate variations in frequency.

[0040] In a similar manner, the optimization process tests whether the power output of the second firing can be increased without raising the temperature of the array electrode elements above a safe level. Assume that it is determined that increasing the power level is successful in maintaining the intensity at 2.5 V / cm, but can raise the temperature of the array electrode elements above the desired level. The optimization process then begins testing to decrease the duty cycle of the array electrode elements to maintain the new power level without increasing the temperature. Ultimately, the optimization requires that all target tumors are exposed to the electric field of the optimized frequency and intensity every 1-3 seconds.

[0041] The above are just a few examples of how the optimization process takes into account how all of the variables of the electric field therapy interact to generate an optimal firing sequence. This allows for the most effective therapy for treating multiple tumors. It should be understood that not all variables are outlined here, but are included in the iterative optimization process.

[0042] Once electric field therapy is initiated, the adaptation process requires periodic blood draws to look for tumor markers and periodic scans to see if any changes have occurred that require adaptation (block 112).

[0043] This close monitoring determines whether therapy should continue unchanged or if adaptations are necessary. Adaptations may be made to both positive and negative results. If a negative result occurs, a new biopsy may be requested to see if the frequency needs to be changed. Alternatively, reoptimization may be required if new cancers develop. If successful results are observed, low priority untreated tumors may be placed under treatment (block 114).

[0044] Predictive tools to guide preventive treatment: Once remission or significant improvement is observed, predictive tools are used to create a preventive treatment plan. The predictive tools determine the areas most likely for the next recurrence, such as the lungs, liver, or abdominal cavity. Predictive tools work in a variety of ways. Some use genetic markers collected from blood tests or biopsies. Some use aggregated databases from many cancer patients with different types of disease. Statistical probabilities and algorithms are used to predict the areas most likely for recurrence. Other predictive tools not mentioned can be used as well (block 116).

[0045] Once the likely areas of recurrence are determined, an initial prophylactic firing sequence is deployed. The initial firing sequence is then subjected to the optimization process described above. This process determines the optimal firing sequence for the prophylactic treatment. Different prophylactic treatments are scheduled depending on the patient and the severity of their disease. Prophylaxis may span alternating periods (e.g., monthly, bimonthly), or annual, semi-annual, or quarterly regimens. Periodic blood tests and scans tracking tumor markers are performed to monitor the prophylactic treatment. Adjustments are prescribed or the entire optimization process is repeated as needed. Maintenance therapy may further include scanning previously unaffected areas of the body to remove undetectable tumors (block 118).

[0046] Patient Compliance: It is well known that the success of electric field therapy depends heavily on patient compliance. Electric field therapy is an ON-OFF therapy; that is, it works in the ON state, but the therapeutic effect stops in the OFF state. Patient compliance has been demonstrated to be high, but improvements are needed. Process 200 can be performed constantly to increase patient compliance (FIG. 2). A control device, e.g., a wave generator, may record daily variables (block 202). The control device may also create an activity report (block 204). A master report can then be generated (block 206). A survey may then be deployed and the patient may be interviewed regarding their treatment experience (block 208). If a challenge exists, process 200 may include a problem solving the challenge to improve the patient's treatment experience (block 210).

[0047] In yet another invention, optimization of electric field therapy is prioritized when all tumors or groups of tumors (T groups) are of equal threat. In such cases, it is not possible to optimize all T groups inclusively using a 50% duty cycle of the array elements and for each T group to be treated within 1-3 seconds. In such cases, certain T groups are selected to be excluded from treatment based on how their absence enhances the optimization of other T groups that remain in treatment (Figures 3A-3C).

[0048] The method 300 may include loading the scan into a simulator (block 302). The scan may be calibrated to a phantom (block 304). The tumors may be triaged (block 306). The tumors may then be grouped by distance and triage strategy (block 308). The tumor groups may then be triaged (block 310). It may then be queried whether the tumor groups are equal threats (block 312). If so, the firing sequence may be designed accordingly (block 314). If not, an alternative process such as method 400 may be initiated (block 316). The method 300 may then include removing firing angles that produce intensities below 2.35V / cm (block 318). If moderate frequency adjustments can add sweepback angles at 2.35V / cm, such angles are added back (block 320). The aforementioned steps 318, 320 are then repeated for all tumor groups (block 322). A test may then be performed with an optimal switching rate (block 324). Then, a query may be made as to whether each group is treated within 1-3 seconds (block 326). If not, the particular firing sequence may be removed (block 328). If so, a query may be made as to whether all remaining T groups have three or more treatment angles (block 330). If so, the method 300 may continue by determining the duty cycle characteristics (block 338). If not, a query may be made as to whether two T groups are sufficiently spaced apart to fire simultaneous electric fields (block 332). If not, the method 300 may allow two angles for the least threatening group (block 334). If so, the firing sequence may be redesigned using simultaneous groups (block 336). If the duty cycle of each array element is less than or equal to 50%, a firing configuration may be prepared (block 348). If the duty cycle of each array element is not less than or equal to 50%, the method may determine if a change in the firing sequence would reduce the duty cycle (block 340). If so, the launch configuration may be prepared (block 348).If not, the group may be removed that allows the remaining group to have a maximum applied angle while still having a duty cycle less than 50% (block 342). The method 300 may then query whether the duty cycle goal has been achieved for at least two angles per group (block 344). If so, a fire configuration may be prepared (block 348). If not, the particular fire sequence may be removed (block 346). A fire configuration may then be subsequently prepared (block 348).

[0049] In yet another embodiment, optimization of electric field therapy is prioritized when all tumors are of unequal threat. In such cases, it is not possible to optimize all T groups including using a 50% duty cycle of the array elements and treat each T group within 1-3 seconds. In such cases, certain T groups are selected to be excluded from treatment based on how life threatening they are compared to the other T groups (Figures 4A-C).

[0050] The method 400 may include loading the scan into a simulator (block 402). The scan may be calibrated to a phantom (block 404). The tumors may be triaged (block 406). The tumors may then be grouped by distance and triage strategy (block 408). The tumor groups may then be triaged (block 410). The method 400 may then query whether the tumor groups are equal threats (block 412). If not, the firing sequence may be designed accordingly (block 414). If so, an alternative process such as method 300 may be initiated (block 416). The method 400 may then include removing firing angles that produce intensities below 2.35V / cm (block 418). If moderate frequency adjustments can add sweepback angles at 2.35V / cm, such angles are added back (block 420). The aforementioned steps 418, 420 are then repeated for all tumor groups (block 422). Next, the method 400 may perform a firing test with an optimal switching rate (block 424). Then, it may query whether each group is treated within 1-3 seconds (block 426). If so, the method 400 may continue by determining a duty cycle characteristic, where the method 400 determines whether each array element has a duty cycle of 50% or less (block 442). If not, the particular firing sequence may be removed (block 428). Next, the method 400 may query whether all remaining T groups have three or more treatment angles (block 430). If so, the method 400 may continue to step 442. If not, it may query whether two T groups are spaced apart enough to fire simultaneous electric fields (block 432). If not, the method 400 may remove firing sequences of angles from three to two until the entire firing sequence can be completed within 1-3 seconds for the given tumor group (block 434). If so, the method 400 may redesign the firing sequence using simultaneous groups with the maximum angle at the optimal frequency (block 436).After method 400 eliminates a particular firing sequence in step 434, method 400 may query whether the 1-3 second timing goal can be achieved at at least two angles for each tumor group (block 438). If so, method 400 may proceed to step 442. If not, method 400 may exclude the least life threatening group until the timing goal is achieved (block 440). To determine which group to exclude, method 400 may incorporate current tumor triage strategies and / or predictive threat analysis. Next, method 400 proceeds to step 442 and determines whether each array element has a duty cycle of 50% or less. If the duty cycle of each array element is 50% or less, a firing configuration may be prepared (block 450). If the duty cycle of each array element is not 50% or less, method 400 may determine whether a change in the firing sequence would reduce the duty cycle (block 444). If so, the sequence may be changed (block 446). A fire configuration may then be prepared (block 450). If not, the method 400 may begin removing the fire sequence of angles from three to two until the entire sequence can be accomplished within one to three seconds at a 50% duty cycle (block 448). The method 400 may then proceed to step 450 and prepare a fire configuration.

[0051] In yet another invention, daily electric field therapy begins at a low power and is slowly increased to allow the patient time to adjust.

[0052] In yet another embodiment, the wave generator includes wireless and / or remote monitoring / reporting, reprogramming, or updating of the system via a wireless modem, which may include cellular, Wi-Fi, Bluetooth, or other wireless technologies.

[0053] Yet another invention involves adapting or modifying the array elements with different characteristics to increase efficiency based on the frequency used.

[0054] Yet another invention uses a process for minimizing peripheral nerve stimulation (PNS): Place a test array on a patient; Slowly adjust the power level upward to determine the patient's PNS sensitive areas; Load the PNS sensitive areas into a 3D simulator; When designing a firing configuration, avoid the PNS sensitive areas; Design a compensating firing configuration.

[0055] The present invention is comprised of a master array of insulating array elements placed on a patient's body. The master array is comprised of individual insulating array elements. Each array element is electronic. Each array element has a unique address. The master array is divided into subarray pairs comprised of two or more array elements that are activated together to apply a low frequency electric field through the body. These electric fields have been shown to reduce cancer tumors. The subarray elements are software configured to be activated in an advantageous sequence based on a treatment simulation performed for each patient. However, the initial subarray configuration can be overridden by the introduction of an alternate configuration that is activated based on variables affecting the subarray elements (temperature, adhesion, voltage, failure, etc.), real-time monitoring of the patient's condition, and the results of actions taken on the patient or caregiver that affect the beneficial subarray configuration during treatment. For example, the control device may select an initial firing configuration and then reselect an alternate firing configuration based on real-time conditions. This is done to optimize a therapy beneficial to the patient. Additionally, the control device may select an alternate firing configuration optimized to treat potential tumor regions based on a prophylactic treatment regimen.

[0056] Definition: 1. Subarray Configurations: The LifeBridge system utilizes output from an external computational model that simulates the human body using a variety of physical and electrical (size, tissue type, organ placement, thermal, electrical) properties. These properties allow the LifeBridge 10000 to simulate the effects of numerous array element subarray configurations. These simulations inform the assignment of variables for subarray configurations. a. The addresses of the array elements that are activated together b. The phase assigned to each array element address or group of addresses c. The voltage applied to each array element or group of addresses d. The sequence in which each array or group of array elements is activated e. The duration for which each array or group of array elements is activated The frequency at which each array or group of array elements operates, although there may be periods during which the array elements are not activated. 2. Adaptive Tumor Treatment Electric Field: Arrays within a subarray are activated together to form a desired treatment electric field at the target region. Array elements can be dynamically (adaptively) reassigned to new subarray configurations as determined by the LifeBridge 10000 system algorithms. 3. Adaptive Optimization: A more optimal subarray configuration, subarray sequence, and subarray duration are obtained, determined by a combination of weightings for applying the therapeutic electric field and the duty cycle of the array elements for a given state of the subarray elements (current temperature, expected voltage vs. measured voltage, communication state, etc.). The control device can determine whether each electrode element is in any of the following zones, and then perform a corresponding temperature process to optimize the insulated electrode system: 4. Blue Zone: Temperature measurements substantially lower than the temperature measurements of adjacent array elements. 5. Green Zone: Temperature measurements of array elements that are within the tolerance range that does not require changes to the initial subarray configuration values. 6. Yellow Zone: Temperature measurements above the Green Zone value and below the Red Zone value. The Yellow Zone has increments from 2 to 25. These increments are used to distinguish the absolute value and direction of change (increase or decrease) of the temperature of the array elements. 7. Red Zone: A temperature measurement above which an element is deactivated and cannot be reactivated until the measured temperature is within the values ​​assigned by the LifeBridge 10000 system to the Yellow or Green Zones. 8. System Controller or Control Device: A control system for implementing the tumor treatment electromagnetic field by independently and / or individually controlling the electrode elements. The control system may consist of computational and storage elements included in the LifeBridge 10000 system. These elements may be located in an electrical system physically integrated in the wave generator and / or connected to the wave generator via an external communication port and / or a computer or mobile device, or may be located completely or partially in a server or cloud service. Some or all of the system control functions are performed in a distributed computing environment. The control system or device may include a wave generator, a simulator, and / or a controller with memory.

[0057] In accordance with one aspect of the invention, the controller, or more specifically, the software in the memory of the controller, may or may not perform the following procedures.

[0058] Outline of the subarray configuration procedure: 1) Input data and images, such as those found in MRI, X-ray, or other medical images, into a medical computational model, which creates a "phantom" torso with a cancerous tumor in a location similar to that found in a patient. 2) Run various simulations to determine the optimal array element activation program. This program determines which array elements are activated in what order, at what voltages, and for what duration for each step of the systematic treatment program. This creates a subarray configuration list. Arrays activated in a given period (usually 0.5-3 seconds) are assigned in the program to the same subarray for that period. 3) The subarray configuration program is then loaded into the system controller (i.e., the wave generator).

[0059] Method 500 describes the configuration procedure for the LifeBridge 10000 system (FIG. 5). First, the System Controller (SC) is activated by the power switch and performs self-diagnostics and hardware checks, including temperature, current, voltage, communication ports, valid program load, system ID operation authentication, etc. (block 502). If the SC passes the diagnostic check, it proceeds to the next step (block 504). If a fault is detected, the system stops the start-up sequence, stores diagnostic values ​​in memory, and reports immediately and / or delayed to local and / or remote computer or mobile databases / displays. The software triggers a local warning indicator and / or voice or tone (block 518). Once the diagnostics are checked and all values ​​are within tolerance, the SC assigns a unique software address to each master array element physically present in the system and / or to each slave array element logically present (block 506). Next, the SC runs a diagnostic sequence with each array element (block 508). It performs diagnostic checks such as program rods, voltage, temperature sensor status, relay machine status (open or closed), etc. If the element passes the diagnostic check, proceed to the next step (block 510). If a major fault is detected, the system stops the start-up sequence, stores diagnostic values ​​in memory, and reports immediately and / or delayed to local and / or remote computer or mobile databases / displays. The software triggers a local warning indicator and / or voice or tone (block 518). If no major fault is detected, the SC loads the array activation program (subarray configuration) into the memory of each array or master array (block 512) if the master / slave arrangement is appropriate for a given physical and / or logical array element array. The program stored in the array element is then verified against the master copy of the program by checksum, hash, or other bit-perfect verification method (block 514).If a fault is detected, the system stops the start-up sequence, stores diagnostic values ​​in memory, and reports immediately and / or delayed to local and / or remote computer or mobile databases / displays. The software triggers a local warning indicator and / or a sound or tone (block 518). Once the array program load is verified by the SC, the SC places the LifeBridge 10000 system in a system ready state (block 516). At any point during this sequence, the stop button is activated (block 520). The system stops the start-up sequence, stores the event in memory, and reports immediately and / or delayed to local and / or remote computer or mobile databases / displays. The software triggers a local warning indicator and / or a sound or tone (block 518).

[0060] Method 600 describes the operation procedure of the LifeBridge 10000 system (FIG. 6). The system is in a ready state (block 602). A start button or switch 606 is physically engaged on the SC to begin execution of the subarray configuration sequence steps (block 604). The SC communicates the start of the subarray sequence to all arrays (block 622) and to the wave generators (block 608), which set the appropriate wave generator parameters and element phases controlled by the element switches. During execution of the system subarray program, wave generator diagnostics are performed by the SC (blocks 610-624). If an undercurrent condition is found in the wave generator (i.e., below expected current values), the SC activates an alert and changes the patient and caregiver that the array elements may not be adequately attached (blocks 618-620). If the diagnostics find a major fault in the wave generator (overheat, overcurrent, overvoltage, etc.), the system shuts down, stores diagnostic values ​​in memory, and reports immediately and / or delayed to local and / or remote computer or mobile databases / displays. The software triggers a local warning indicator and / or voice or tone (block 644). Concurrently, during execution of the system subarray program, diagnostics of the array elements are performed by the array elements and / or SC (blocks 632-638). If the diagnostics find a fault in the array element or array elements, the program shuts down the element, stores diagnostic values ​​in memory, and reports immediately and / or delayed to local and / or remote computer or mobile databases / displays (block 640). Depending on the severity and type of array element fault, the SC may issue additional warnings and notifications, perform a system shutdown, and activate appropriate alerts (block 644). The system response is adaptive to the severity of the fault, and the system determines the fault handling procedure based on a set of algorithms. If no faults are detected during execution of the subarray configuration, the system program issues a "step subarray" at time increments determined by the system program (block 642).This continues if the stop button / switch is actuated (block 646), if the diagnostics detect an SC wave generator fault (under / over voltage, under / over temperature, under / over current, array communication fault) (blocks 612-628), or if an array fault is detected (under / over voltage, under / over temperature) (blocks 632-638).

[0061] In addition to method 600, as described above, the LifeBridge 10000 system may have enhanced procedures for processing temperature measurements to optimize delivery of therapy. The generation of the tumor treatment electric field causes some heating of the array elements due to the generation of an alternating electric field through the patient. Some heat is also generated by the circuitry of the array, as well as the resistance of the wires and other resistive elements. Some heating is expected, but heating that causes the temperature of the elements and the patient's skin to exceed 105° F. is not tolerated.

[0062] Additionally, the temperature of the elements may be monitored such that appropriate mitigating measures are taken to minimize, stabilize, or reduce heat generated in the elements, thereby slowing or stopping the temperature rise of the elements and the patient's skin before an unacceptable temperature is reached. Thus, the control device may monitor the temperature of the electrode elements by means of a temperature sensor associated with each electrode element dependent on the sensed temperature, and the control device may reselect and implement another alternative firing configuration using one or more different electrode elements to allow cooling of an overheated electrode element.

[0063] The present invention has adaptive tumor treatment capabilities that include extensive preventative steps taken to modify the treatment program (subarray configurations) while allowing disk temperatures to stabilize or decrease before they reach unacceptable levels. This can be achieved by implementing alternative subarray configurations that change one or more of the following parameters: 1. Duty cycle: real-time or predicted heating of addressable array elements, duration and timing that elements are activated, time / duration that elements are not activated, number of times that elements are activated in a programmed sequence, applied voltage, electric field strength generated in the body when activated, etc. 2. Voltages assigned to subarray configurations of addressable array elements. 3. Control of external devices that help cool or stabilize the temperature of the element (fans, chill pads, etc.). 4. Suggested actions for the patient and / or caregiver to take, such as shifting body position in chair or bed, loosening clothing or outerwear, increasing ambient air conditioning, adjusting or turning on fans, etc. Reference is now made to the following inventions:

[0064] Further to method 600, as described above, the LifeBridge 10000 system may provide reinforcement to the LifeBridge 10000 ATTF system with recommended actions and positive progress notifications for the patient and / or caregiver. For out-of-tolerance conditions (e.g., overheating, under-temperature, voltage, or out-of-tolerance communication with an array element, etc.) that may be remedied or resolved by an action the patient and / or caregiver can take, reinforcement notifications with recommended actions and progress toward remedying or resolving the out-of-tolerance condition are provided. These actions may include moving position in chair or bed, loosening or removing clothing, reseating loose connections, turning on a fan or other cooling device, pointing the array element toward a cooling device when in an out-of-tolerance condition, checking that the insulating array is properly attached to the skin, etc.

[0065] The system notifies the patient and / or caregiver of the recommended action directly from the system via a display, tone, voice command, and / or via a computer or mobile device notification via text, voice, email, or computer or mobile application selected by the patient and / or caregiver.

[0066] The system monitors for out-of-tolerance conditions and provides feedback periodically (at intervals of 0.5-10 minutes depending on the severity of the out-of-tolerance condition, the type of out-of-tolerance condition, the recommended action, etc.) indicating that actions taken are improving or have resolved the out-of-tolerance condition until the out-of-tolerance condition is resolved or a preset limit on the number of notifications is reached.

[0067] The system notifies the patient and / or caregiver of the outcome (improvement, no change, or worsening of an out-of-tolerance condition) directly from the system via similar display, tone, voice command, and / or via computer or mobile device notification via text, voice, email, or computer or mobile application selected by the patient and / or caregiver. These notification settings can be changed, muted, or stopped based on the time of day (i.e., silent or do not disturb mode settings). The patient and / or caregiver can stop these notifications via a button or switch on the system or via a website, text, computer or mobile application command.

[0068] According to another aspect of the present invention, the system, for example the LifeBridge 10000 system, may also perform the following procedures. 1. Are there recommended actions that the patient and / or caregiver can take to alleviate and / or correct the out-of-tolerance condition? 2. YES a. Activating an indicator / display, tone or voice prompt, and / or sending a notification via electronic means to a computer or mobile device stored in system memory. b. Monitor for any out-of-tolerance conditions and report improvements; and there is no change or deterioration of the condition as described above. c. Repeating the appropriate notification for a set number, duration of the notification time limit, start of a do not disturb period, or until a stop command is received by the system or computer or mobile communication from the caregiver or patient. d. Record the time and duration of notifications sent and interactions initiated by the patient and / or caregiver. 3. NO a. In the case of an out-of-tolerance condition, follow the notification process.

[0069] According to another aspect of the invention, a system, for example, a LifeBridge 10000 system, may also execute the following method 700 (FIG. 7). Method 700 may be considered as an adaptive tumor treatment electric field procedure controlled by temperature measurements of the array elements. Method 700 may include: Measure the temperature of the array elements and report the value to a system controller (block 702). Method 700 may then determine whether the temperature is in the green zone, yellow zone, red zone, blue zone, or no color zone (block 704). If the temperature value is in the green zone (block 706), the green zone system temperature process is followed (block 708). If the temperature value is in the yellow zone (block 710), the yellow zone system temperature process is followed (block 712). If the temperature value is in the red zone (block 714), the red zone system temperature process is followed (block 716). If the temperature value is in the blue zone (block 718), the next blue zone system temperature process is followed (block 720). If the measured temperature value is in the colorless zone (block 722), the method 700 deactivates the array element (block 724). The method 700 may then store the element address with the temperature sensor failure for local, computer or mobile reporting (block 726). The method then determines whether an alternative acceptable sub-array configuration is available (block 728). If so, the method 700 loads the new sub-array configuration into the affected array element (block 732). Then, the method 700 activates an appropriate warning indicator, tone, or both (block 734). If not, the method 700 may deactivate all array elements (block 730). Then, the method 700 activates an alert indicator, tone, or both to reflect the appropriate alert and issue an alert via text, voice, email, computer or mobile application, or other electronic means as appropriate (block 734). The method 700 then proceeds to the next system procedure (block 736).

[0070] Method 800 describes a Green Zone temperature measurement procedure (FIG. 8). Method 800 has the SC check memory for an array element address to determine if the address is stored in memory with a Green Zone, Yellow Zone, Red Zone, or Blue Zone temperature flag (block 802). Green Zone Flag: If so, continue with existing sub-array configuration (block 804); if not, remove Yellow Zone, Red Zone, or Blue Zone flag where the array was placed and record element address with Green Zone flag along with timestamp (block 806). Method 800 may then determine if an alternative acceptable sub-array configuration is available (block 808). If so, the new sub-array configuration may be loaded into the affected array element (block 810). If devices such as fans, chill pads, cooling suits, or other similar devices are connected wired or wirelessly so that they can be triggered / controlled by the LifeBridge 10000 system to change state, the system switches or communicates with one or more devices to take appropriate action (block 812). The patient and / or caregiver may be instructed via text, email, computer or mobile application, or other electronic means on actions that can be taken to reduce the temperature of the affected array element as indicated by the training and by the warning indicator (block 814). The method 800 may record the instructions, warnings, and status changes in memory for reporting (block 816). If not, the method 800 may deactivate all array elements and record the timestamp and action (block 820). The method 800 may then activate warning indicators, tones, or both to reflect the appropriate warning and issue a warning via text, email, computer or mobile application, or other electronic means as appropriate (block 822).If devices such as fans, chill pads, cooling suits, or other similar devices are connected, wired or wirelessly, such that they can be triggered / controlled by the LifeBridge 10000SC to change state, the SC communicates to one or more devices to take appropriate action (block 824). The method may also record instructions, warnings, and state changes in memory for reporting (block 826). The method 800 then proceeds to the next system procedure (block 736).

[0071] Method 1100 describes a yellow zone temperature measurement procedure (FIG. 11). Method 1100 has the SC check memory for an array element address to determine if the address is stored in memory with a yellow zone temperature flag (block 1102). If so, is the temperature at the same yellow zone increment as the previous measurement (block 1104)? If so, method 1100 continues with the current subarray configuration (block 1106). If not, is the temperature measurement taken at a high increment or a low increment (block 1108)? If so, is an alternative acceptable subarray configuration available (block 1110)? If so, method 1100 loads the new subarray configuration into the array element (block 1112). If devices such as fans, chill pads, cooling suits, or other similar devices are connected, wired or wirelessly, such that they can be triggered / controlled by the LifeBridge 10000 system to change state, the system switches or communicates with one or more devices to take appropriate action (block 1114). The method 1100 then determines whether the system should activate warning indicators, tones, and / or sounds (block 1116). The patient and / or caregiver may be instructed by the warning indicator via text, email, computer or mobile application, or other electronic means on actions that can be taken to reduce the temperature of the affected array element, as indicated in the training (block 1118). The instructions sent to the connected devices and the state change may be recorded in memory for reporting (block 1120). The method 1100 then proceeds to the next system procedure (block 736). If not, the method 1100 may deactivate all array elements (block 1122). Next, the method 1100 may activate a warning indicator, a tone, or both to reflect the appropriate warning (block 1124).If devices such as fans, chill pads, cooling suits, or other similar devices are connected, wired or wirelessly, such that they can be triggered / controlled by the LifeBridge 10000 SC to change state, the SC communicates to one or more devices to take appropriate action (block 1126). The patient and / or caregiver may be instructed via text, email, computer or mobile application or other electronic means, by a warning indicator, as indicated in the training, as to actions that can be taken to reduce the temperature of the affected array element (block 1128). The instructions sent to the connected device and the state change may be recorded in memory for reporting (block 1130). The method 1100 then proceeds to the next system procedure (block 736). If the temperature increment is lower, is an alternative acceptable subarray configuration available (block 1132)? If so, the new subarray configuration is loaded into the affected array element (block 1134). If devices such as fans, chill pads, cooling suits, or other similar devices are connected, wired or wireless, such that they can be triggered / controlled by the LifeBridge 10000 system to change state, the system switches or communicates with one or more devices to take appropriate action (block 1136). The method 1100 may then determine whether the system should deactivate warning indicators, tones, and / or audio notifications (block 1138). The patient and / or caregiver may be instructed by the warning indicators via text, email, computer or mobile application, or other electronic means, as to the success of actions that can be taken to reduce the temperature of the affected array elements (block 1140). Instructions and state changes may be logged in memory for reporting (block 1142). The method 1100 then proceeds to the next system procedure (block 736). If no alternative acceptable sub-array configurations are available, the method 1100 may deactivate all array elements (block 1122).An alert indicator, tone, or both may then be activated to reflect the appropriate alert (block 1124). If devices such as fans, chill pads, cooling suits, or other similar devices are connected, wired or wireless, such that they can be triggered / controlled by the LifeBridge 10000SC to change state, the SC communicates to one or more devices to take appropriate action (block 1126). The patient and / or caregiver may be instructed by the alert indicator via text, email, computer or mobile application, or other electronic means as to actions that can be taken to reduce the temperature of the affected array element, as indicated in the training (block 1128). The instructions sent to the connected device and the state change may be recorded in memory for reporting (block 1130). The method 1100 then proceeds to the next system procedure (block 736). If the address is not already yellow zone flagged, the method 1100 may store the green, red, or blue zone flag from the array element and record the element address with the new yellow zone flag in the correct increment (block 1144). Is an alternative acceptable subarray configuration available (block 1146)? If so, the new subarray configuration may be loaded into the array element addresses (block 1148). If devices such as fans, chill pads, cooling suits, or other similar devices are connected, wired or wireless, such that they can be triggered / controlled by the LifeBridge 10000 system to change state, the system switches or communicates with one or more devices to take appropriate action (block 1150). If the previous flag was a green zone flag, the patient and / or caregiver may be instructed via text, email, computer or mobile application or other electronic means as to actions that can be taken to reduce the temperature of the affected array element, as indicated in the training, by a warning indicator (block 1152).Alternatively, if the previous flag was a red zone or blue zone flag, the patient and / or caregiver may be instructed by a warning indicator via text, email, computer or mobile application, or other electronic means on the success of the action that can be taken to reduce the temperature of the affected array element (block 1152). The method 1100 may then activate a warning indicator, tone, or both to reflect the appropriate warning and issue a warning via text, email, computer or mobile application, or other electronic means as appropriate (block 1154). The instruction and status change may be recorded in memory for reporting (block 1156). The method 1100 then proceeds to the next system procedure (block 736). If not, the method 1100 may deactivate all array elements (block 1158). The method 1100 may then activate a warning indicator, tone, or both to reflect the appropriate warning (block 1160). If devices such as fans, chill pads, cooling suits, or other similar devices are connected, wired or wirelessly, so that they can be triggered / controlled by the LifeBridge 10000SC to change state, the SC communicates to one or more devices to take appropriate action (block 1162). If the previous flag was a green zone flag, the patient and / or caregiver may be instructed via text, email, computer or mobile application, or other electronic means on actions that can be taken to reduce the temperature of the affected array element, as indicated in the training, by the warning indicator (block 1164). The instructions and state change may then be recorded in memory for reporting (block 1166). The method 1100 may continue to monitor temperature measurements of all array elements. The method 1100 then proceeds to the next system procedure (block 736).

[0072] Method 900 describes a red zone temperature measurement procedure (FIG. 9). Method 900 has the SC check memory for an array element address to determine if the address is stored in memory with a yellow zone, red zone, or blue zone temperature flag (block 902). Red zone flag: if yes, continue with existing sub-array configuration (block 904); if not, deactivate the array element (block 906). 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 (block 908). Method 900 may then determine if an alternative acceptable sub-array configuration is available (block 910). If yes, method 900 loads the new sub-array configuration into the affected array element (block 912). If devices such as fans, chill pads, cooling suits, or other similar devices are connected, wired or wirelessly, such that they can be triggered / controlled by the LifeBridge 10000 system to change state, the system switches or communicates with one or more devices to take appropriate action (block 914). The method 900 may activate an alert indicator, tone, or both to reflect the appropriate alert and issue an alert via text, email, computer or mobile application, or other electronic means as appropriate (block 916). The patient and / or caregiver may be instructed by the alert indicator via text, email, computer or mobile application, or other electronic means as to actions that can be taken to reduce the temperature of the affected array element, as indicated in the training (block 918). Instructions, alerts, and state changes may be logged in memory for reporting (block 920). If not, the method 900 may deactivate all array elements (block 922). The method 900 may activate a warning indicator, a tone, or both to reflect the appropriate warning (block 924).If devices such as fans, chill pads, cooling suits, or other similar devices are connected, wired or wirelessly, so that they can be triggered / controlled by the LifeBridge 10000SC to change state, the SC communicates to one or more devices to take appropriate action (block 926). If the previous flag was a green zone or yellow zone flag, the patient and / or caregiver may be instructed via text, email, computer or mobile application or other electronic means on actions that can be taken to reduce the temperature of the affected array element, as indicated by the training, by the warning indicator (block 928). Instructions, warnings and state changes may be logged in memory for reporting (block 930). The method 900 then proceeds to the next system procedure (block 736).

[0073] According to another aspect of the invention, the system may operate in the blue zone as follows: Array elements that are unable to efficiently or completely couple to the electric field being generated will typically operate at a lower temperature (operating in the blue temperature zone) than array elements that are part of the same subarray launch configuration and that efficiently couple to the provided electric field. Conditions that may affect array element coupling include poor adhesion to the surface of the skin, electrical breakdown of the insulation of the array element or wiring that allows current to flow to the skin, and other similar fault conditions within the array elements.

[0074] By comparing the temperature of an array element with its surrounding array elements (which are in the same subarray firing configuration), a cold condition can be detected and appropriate action taken.

[0075] The system stores a database containing the addresses of all the isolated array elements on the patient and a list of adjacent subarray elements. The temperature of each array element is compared to the temperatures of other array elements in the same subarray. The appropriate neighbor comparison list can include anything from one element with the same voltage polarity to an entire subarray of elements. The number and location of appropriate neighbors for comparison varies depending on the location in the active subarray, the current temperature state, and the assignment of active or inactive status. This process may also be used to track and compare other variables such as voltage, element switch state, etc.

[0076] The system compares the temperature of the subarray element to the average temperature and median temperature calculated for a set of adjacent subarray elements identified in the adjacent database.

[0077] If an array element's temperature is 0.5 to 10 degrees cooler than its neighbor list calculated value (the value varies depending on the primary array element's location, system sub-array configuration factors (duty cycle, operating voltage, number of active secondary array elements, etc.)), the array element is removed from all active sub-array configurations, flagged with a Blue Zone temperature indicator in system memory, and the SC determines whether an alternate sub-array configuration is acceptable or whether the system should enter safe mode.

[0078] Method 1000 describes a blue zone temperature test and procedure (FIG. 10). Method 1000 may create a blue zone where the temperature of the array elements is read. Method 1000 may measure and report the temperature of the array elements to the SC, and may calculate and store the average temperature and median temperature of the array elements in the neighbor list (block 1002). Method 1000 may optionally include a scaling factor in the comparison algorithm (adaptive optimization). The scaling factor may be derived from the duty cycle, subarray configuration parameters, the location of the element in the physical array, the location of the primary array on the body, etc. Method 1000 may include a step of determining (block 1004) whether the array element is in a blue zone. If not, method 1000 may continue with the current subarray configuration (block 1008). If so, does that address have a blue zone flag (block 1006)? If so, method 1000 may continue with the existing subarray configuration (block 1008). The method 1000 then proceeds to the next system procedure (block 736). If not, the method 1000 may deactivate the array element (block 1010). The method 1000 may then remove the green zone, yellow zone, or red zone flag from the array element address and record the element address with the blue zone flag (block 1012). Is an alternative acceptable sub-array configuration available (block 1014)? If so, the new sub-array configuration may be loaded into the affected array element (block 1016). If devices such as fans, chill pads, cooling suits, or other similar devices are connected wired or wirelessly so that they can be triggered / controlled by the LifeBridge 10000 system to change state, the system switches or communicates with one or more devices to take appropriate action. The method 1000 may record the commands sent to the connected devices and the state changes (block 1018). The method 1000 may activate warning indicators, tones and / or sounds to reflect appropriate warnings (block 1020).The patient and / or caregiver may be instructed by the alert indicator via text, email, computer or mobile application, or other electronic means on actions that can be taken to reconnect or disconnect the affected array element as indicated in the training (block 1022). The method 1000 may record the instructions, alerts, and status changes in memory for reporting (block 1024). The method 1000 then proceeds to the next system procedure (block 736). If no alternative acceptable subarrays are available, the method 1000 may deactivate all array elements and record the actions in memory (block 1026). The method 1000 may deactivate the alert indicator, tone, or both to reflect the appropriate alert (block 1028). If devices such as fans, chill pads, cooling suits, or other similar devices are connected, wired or wirelessly, such that they can be triggered / controlled by the LifeBridge 10000 system to change state, the system switches or communicates with one or more devices to take appropriate action (block 1030). The patient and / or caregiver may be instructed via text, voice, email, computer or mobile application, or other electronic means as to actions that can be taken to reconnect or disconnect the affected array elements as indicated in the training by the alert indicator (block 1032). Instructions, alerts, and state changes may be logged in memory for reporting (block 1034). The method 1000 then proceeds to the next system procedure (block 736).

[0079] While the present invention has been described with respect to at least one embodiment, it 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 invention using its general principles. Further, this application is intended to cover such departures from the disclosure as come within known or customary practice in the art to which this invention pertains and as fall within the scope of the appended claims.

Claims

1. 1. A method of configuring a tumor treatment electric field device for applying a tumor treatment electric field to a patient, the tumor treatment electric field device including an array of insulated electrode elements coupled to a control device, the method comprising: a) receiving a scan of the patient's body; b) a simulator identifying at least two tumor-filled regions in said scan, each having at least one tumor; c) the simulator determining a spatial relationship of the at least two tumor filled regions; and step d) the simulator determining at least two subarray firing configurations of the insulated electrode element array targeting the at least two tumor filling regions, the at least two subarray firing configurations depending at least in part on the spatial relationship between the at least two tumor filling regions.

2. The method of claim 1, further comprising a step of the simulator assigning each group of insulated electrode elements of the insulated electrode element array to each subarray firing configuration.

3. The method of claim 2 , wherein each of the groups of insulated electrode elements share some common insulated electrode elements of the array of insulated electrode elements.

4. The method of claim 2 , wherein each of the groups of insulated electrode elements does not share any common insulated electrode elements of the array of insulated electrode elements.

5. 2. The method of claim 1, further comprising the step of the simulator determining the at least two sub-array firing configurations in response to one or more of a triage strategy, a duty cycle of each insulated electrode element, a peak power consumption of the insulated electrode element array, and a total power consumption of the insulated electrode element array.

6. The method further includes the step of the simulator triaging tumors within the at least two tumor-filled regions to obtain a triage strategy; 2. The method of claim 1, wherein the step of the simulator determining at least two subarray firing 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 triage strategy.

7. The method of claim 6 , wherein triage comprises assigning a priority value to at least one tumor within each tumor-filled region.

8. The method of claim 7, further comprising the step of the simulator optimizing one or more of the total treatment time, duration of electric field strength, and several electric field application angles spent on at least one tumor in each tumor-filled region according to assigned priority values ​​of the tumors in the at least two tumor-filled regions.

9. 7. The method of claim 6, further comprising the step of the simulator determining the at least two subarray firing configurations in response to one or more of a duty cycle of each insulated electrode element, a peak power consumption of the insulated electrode element array, and a total power consumption of the insulated electrode element array.

10. The method of claim 6, further comprising, after the step of the simulator determining the at least two subarray firing configurations, determining at least two alternative subarray firing configurations in response to a preventive treatment regimen.

11. The method of claim 1, further comprising the step of the simulator determining whether the at least two subarray firing configurations can be implemented simultaneously or sequentially.

12. The method of claim 11, wherein the step of the simulator determining whether the at least two subarray firing configurations can be performed simultaneously or sequentially depends on one or more of the electric field interaction of the at least two subarray firing configurations, power availability of the insulated electrode system, duty cycle of each insulated electrode element, triage strategy, peak power consumption of the insulated electrode element array, total power consumption of the insulated electrode element array, and time constraints to maintain optimal therapeutic effect.

13. 1. A tumor treating electric field apparatus comprising an array of insulated electrode elements coupled to a control device, i) determining a spatial relationship between at least two tumor filled regions in a scan of a patient; ii) a tumor treating electric field device configured to determine and / or implement at least two subarray firing configurations of the insulated electrode element array targeting the at least two tumor filling regions, the at least two subarray firing configurations being at least partially dependent on the spatial relationship between the at least two tumor filling regions.

14. The control device comprises: i) determining said spatial relationship between at least two tumor filled regions in a scan of a patient; ii) configured to determine and / or implement at least two subarray firing configurations of the insulated electrode element array that target the at least two tumor filling regions, the at least two subarray firing configurations depending at least in part on the spatial relationship between the at least two tumor filling regions.

15. 15. The tumor treating electric field device of claim 13 or 14, further comprising an electric field generator.

16. The tumor treating electric field device of any one of claims 13 to 15, further comprising one or more sensors for sensing real-time temperature of the insulated electrode elements.

17. The tumor treating electric field device of any one of claims 13 to 16, further comprising a scanner, such as a 3D scanner.

18. A tumor treating electric field device according to any one of claims 13 to 17, configured to carry out the method according to any one of claims 1 to 12.

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