1. Field of the Invention
The present invention relates to tumor and cancer cell treatment and more specifically to treatments involving the application of electromagnetic fields.
2. Description of the Related Art
Alternating Electric Fields, also referred to as Tumor Treating Fields (TTF's), can be employed as a type of cancer treatment therapy by using low-intensity electromagnetic fields. These low-intensity fields rapidly change direction, thousands of times per second. Since the TTF's are electric fields, they do not cause muscle twitching or severe adverse side effects on other electrically activated tissues. The growth rate of metastatic diseases is typically greater than the growth rate of normal, healthy cells. Alternating Electric Fields therapy takes advantage of this high growth-rate characteristic. TTF's act to disrupt a cancer cell's mitotic process and cytokinesis by manipulating the cell's polarizable intracellular constituents, namely tublins that form mitotic spindles that pull the genetic material in the nucleus into tow sister cells. TTF's interrupt mitotic spindle microtubule assembly thereby preventing cell division. The metastatic disease cells treated using TTF's will go into programmed cell death usually within 4 to 5 hours. The result is a significant reduction in tumor size and potential for full elimination of solid tumors. TTF's are tuned to treat specific cancer cells and thereby do not damage normal cells. TTF therapy can be used as a sole treatment method, or it can be combined with conventional drug delivery mechanisms.
TTF's are applied to patients using insulated electrodes adhered to the skin by a variety of methods including the use of medical adhesives, articles of clothing, etc. There are multiple configurations of insulated electrodes, but all have an insulated material with a high dielectric constant on one side and a thin metal coating on the other, usually silver. Insulated electrodes used to generate TTF's always come in pairs with both sides being similar, but not necessarily the same.
Referring now to FIG. 1, there is shown a typical insulated electrode array 10 used in the administration of TTF's. The insulated electrode array 10 includes a pair of arrays, 10A and 10B, which are made from smaller insulated electrode sub-elements 12. Because the insulated electrode 10 archetypically works in pairs, there is generally a Sub-array A and Sub-array B, respectively 10A and 10B. Each smaller insulated electrode 12 has an insulating material 14, typically a ceramic that is adhered to the patient. The leads 16 interconnect the smaller insulated electrodes 12 to a main lead line 18, which links to a generator (not shown).
Confusion arises in the prior art when the term insulated electrode is interchanged with the term “Isolect” or just “Electrode”. These terms are sometimes used to describe “elements of an array” or entire sets of arrays. It is often not disclosed in the prior art exactly what is meant by any of the above terms. It should be appreciated by persons skilled in the art that insulated electrodes or terms used in exchange for insulated electrodes are generally references to either fixed arrays of smaller dedicated insulated electrode sub-elements 12 as shown in FIG. 1 or to large solid insulated electrodes 20 as shown in FIG. 2.
There are many reasons small insulated electrodes 12 used individually will not work when producing TTF's, a non-exhaustive list includes:                1. Small elements used individually do not draw enough energy to form an electric field that will go through the human torso. For example, 4 amps over an area of approximately 1 square foot may be required to create an effective TT field strong enough to treat cancer tumors in the lungs. Small elements used individually cannot draw the required energy. In other words there is a minimum current density (amps/area) and a minimum area required to be effective. Single small insulated electrodes cannot meet these requirements. Placing small electrodes into an array close together and energizing them at the same time so that they act as one insulated electrode solves this problem.        2. If a small element was designed to carry enough energy to go through the lungs (e.g., 4 amps/sq. ft.), the resulting concentration of that much energy in a small area generally causes tingling on the patient's skin making treatment regimen unbearable.        3. If small elements were used individually to produce TTF's, their physical size and shape would create inefficiencies when treating massive areas like cancer spread throughout the pleura membranes. The pleurae, inside the thoracic cavity, generally extend from just below the clavicle area to the lower ribs. Using small individual insulated electrodes would increase the likelihood of gaps in field coverage, which in turn could allow cancer cells to persist.        
While large insolated electrodes 20, shown in FIG. 2, produce adequate fields, they have many disadvantages such as the inability to expand when a patient's skin stretches during bending or sitting. Large insulated electrodes 20 also tend to draw more energy at their center, causing tingling similar to that of over-powered smaller insulated electrodes. In contrast, insulated electrodes comprising arrays of smaller insulated electrode sub-elements can deliver energy in a more diffused manner and can adapt to the human body more easily.
Generally, in prior art references processes to choose insulated electrodes in groups, is referring to choosing a smaller group of elements from a larger group. What is typically shown in drawings and is done in practice, is that choosing a smaller number of electrodes from a larger group is for the purpose of wiring the smaller group together in a fixed, dedicated array. In the prior art processes of targeting TTF's from multiple sites to vector a treatment area, it is referring to targeting multiple fixed dedicated arrays or multiple large electrodes. When the prior art references mention sweeping through electrodes to target tumors from different angles, it is referring to energizing different fixed dedicated arrays in a sequential manner. It is generally understood that the prior art refers to fixed dedicated arrays or large electrodes when it discusses manipulating TTF's. Further, the prior art references disclose that insulated electrode sub-elements are dedicated for use in a single array and single power sub-array A or B. This is due to how array elements are wired (see FIG. 1). This creates serious drawbacks when treating patients with metastatic disease.
Referring collectively now to FIGS. 3 and 4, there is shown a typical prior art TTF treatment configuration on a patient with metastatic breast cancer. The metastatic cancer, illustrated as black spots 30, is shown to have spread throughout the pleura around the left lung (FIG. 3). These cancer cells are literally free floating in fluid within the pleura cavity, and are forming many new small tumors. Additionally, there are also small tumors located on the liver.
FIG. 4 shows an insulated electrode array 40 for the left lung and an insulated electrode array 42 for the liver, each including a respective pair, sub-array A and B. The left lung insulated electrode array 40 will fire its sub-array A array 40A with its sub-array B array 40B, and the liver insulated electrode 42 will fire its respective sub-array A array 42A with 42B. Typically, a cross firing of arrays will be programmed to target the cancer from different angles. In the case of cross firing, the front side A array 42A of the liver insulated electrode array 42 will fire with the back sub-array B array 40B of the left lung insulated electrode array 40A, and the front sub-array A array 40A of the lung insulated electrode array 40 will fire with the liver back sub-array B array 42B. However, in the above scenario cross firing may not be possible because of the significant difference in size between the lung and liver insulated electrodes, 40A and 40B. Of course, many other cross-firing combinations can be programmed. The significant limitation of the prior art is that each sub-element 12 of either array 40 or 42 is solely dedicated to its respective home insulated electrode array and to its home sub-array A or B array. In other words, a particular sub-element 12 is solely linked and devoted to its particular insulated electrode array and side and cannot be used except in the function of its home array.
FIG. 5 portrays how cancer cells 30 in the pleura and the liver are actually beginning to shrink, but new cancer cells 30 have appeared in the upper peritoneal cavity above the navel in between the left lung 40 and liver 42 insulated electrode arrays. Likewise, new cancer cells 30 have appeared near the lower peritoneal cavity.
As shown in FIG. 6, to combat the new cancerous growth in between the insulated electrodes, 40 and 42, there needs to be a new insulated electrode array 44 centering the tumors in the upper peritoneal cavity, region 45. This is not possible because it would require placing elements 12 on top of elements 12, as array 44 would overlap with the arrays 40 and 42, which would deny skin contact needed for proper field formation. This limitation in the prior art leads to treatment compromises, putting the patient at risk by failing to treat new tumors as the primary disease. Coplanar fields between the liver and lung are not desirable here because of the significant size difference between the two insulated electrodes, 40 and 42.
Referring now to FIG. 7, there is shown an illustration of a TT field where region 46A is the effective TTF area and region 46B is the ineffective TTF area. This portrays the importance of being able to target each area of tumor growth as a primary concern. TTF's vary in intensity throughout their shape, which can cause significant areas of a field to be below the effective strength. As shown by region 46B, it is possible for tumors to be covered by a field without actually having any beneficial effect because the intensity is not sufficient enough to prevent cell division. In addition, the extreme variance of tissue types and even air pockets within the body can create pockets where field formation is not possible if treatment is attempted from limited directions.
As shown in FIG. 8, continuing with the metastatic breast cancer example shown in FIGS. 4-6, a new insulated electrode array 48 is added to address the new tumor growth in the lower peritoneal cavity. The insulated electrode array 48 is designed to develop a co-planner field (half Moon), horizontally from left to right. In order to form a co-planner field, the array 48 pairs 48A, representing sub-array A, and 48B, representing sub-array B, together in the same front plane of the patient. In TTF best practices it is known that targeting a tumor from different angles increases the effectiveness of tumor reduction. However, prior art treatment with dedicated array elements is compromising the treatment of the patient in this example.
Prior art treatment with dedicated array elements does not have enough versatility to adequately address multiple disease locations. Creating a second co-planner field using the liver insulated electrode array 42 and the lower peritoneal cavity insulated electrode array 48 to create a vertical field cannot be done on the right side because both arrays are dedicated to the A sub-array. Further, multidirectional pairing is not possible because three of the four sub-arrays (40A, 42A and 48A) located on the front side of the patient are solely dedicated to sub-array A. A and B sides are required to establish coupling and field formation. In addition the differing sizes of the liver insulated electrode array 42 and the lower peritoneal cavity insulated electrode array 48 are too dissimilar to form the desired field. Undesired field concentration would occur (twenty-four elements 12 in array 42 to fifteen elements 12 in array 48). Also, the distance to the back liver and lung arrays are too far from the front peritoneal cavity to create an effective field.
In this example the prior art leaves the cancer in the upper peritoneal cavity untreated and the cancer in the lower peritoneal cavity under treated. Such short comings in the prior art can lead to a lack of tumor resolution, unnecessary pain and suffering in the patient, or even death. The prior art is inefficient in that new custom dedicated arrays need to be constantly designed and physically built to address changes in patients with metastatic disease. TTF treatment in the prior art fails the patient, as shown in FIGS. 4-6 and 8, and the patient will likely return to heavy chemotherapy, which can lead to days if not weeks of hospitalization and eventual death. At the time of this writing there does not exist a chemotherapy that does not eventually fail stage 4 patients who become reoccurring and non-responsive. As of 2014 the five year survival rate for stage 4 breast cancer, for example, is only 22% according to the American Cancer Society. A new TTF system needs to be applied in order to treat metastatic disease.
In general TTF treatment using prior art array shapes are determined before they are built. Then, for efficiency reasons, these minimalized array sizes are physically constructed. This however is inefficient when treating metastatic disease because the treatment areas continually change as the cancer spreads. Requiring frequent reconfiguring of arrays. What is needed in the art is the ability to quickly change the configurations of arrays.
When a patient is wearing TTF arrays it is important to ensure adequate warning if any overheating of the elements occurs. The prior art approach generally addresses this concern with temperature sensors that shut off the TTF device if overheating occurs. What is of equal concern is current leakage to the skin. Some patients, desiring the resolution of their disease, may have a tendency to endure warm spots that are actually current leaks. These leaks can cause blistering if not addressed quickly. The electric current levels per element are so low on TTF devices that current leakage can feel much like a warm heating pad. Of course adequately constructing elements to prevent leakage is the first line of defense for this issue. However, TTF arrays are expensive and in some cases can be worn for months at a time to save money. The electrode elements may experience various unknown types of stress during daily activity. It is conceivable that an insulated electrode array may be dropped, etc. The prior art systems lack a current monitoring system.
Array migration and overall warmth of the insulated electrodes can be an issue during TTF treatment. When working with patients with metastatic disease it is more likely that full body arrays will be worn to administer TTFs. When full body TTF arrays are worn during sleep and during other long periods of time it is a challenge to keep them from migrating to less optimal positions. For example, tossing and turning during sleep can exasperate this problem. In addition, warmth from the elements can cause sweating in some cases, which further enables slipping of the arrays as body movement occurs. The prior art has many methods of securing array elements to the skin including various shirts, medical adhesives, etc. These methods are not as successful when used on full-body arrays.
Metastatic disease can literally have dozens of tumor groupings throughout a patient's body. For example, metastatic breast cancer can spread to the lungs, liver, peritoneal cavity, and pancreas all at the same time. Large organs such as the liver can have tumor groupings very far apart. Metastatic disease in the pleura around the lungs and in the peritoneal cavity can pepper large areas of the abdomen with growing cancer cells. Using electric fields on metastatic disease has brought about the need for significant improvements in the application and generation of effective tumor treating fields (TTFs).
What is needed in the art, is a TTF system that enables the dynamic reassignment of array elements to thereby define any array needed and to apply the field from either sub-array A or B.
What is needed in the art is a modular system for adding and removing array elements.
What is needed in the art is a current monitoring sensor that sends a shut off signal to the control device if fluctuations in current, which may be caused by current leakage to the skin or the detachment of the electrode, is detected.
What is needed in the art is a method of adhering array elements to a material while also reducing the temperature of the array elements.