Application of tumor treatment field (TTField) via electrodes embedded in skull implant

Abstract

A tumor treatment field (TTField) is applied via an electrode embedded in a skull implant. By positioning capacitively coupled electrodes on opposite sides of the tumor and applying an AC voltage between the electrodes, a tumor treatment field (TTField) may be used to treat a tumor (e.g., a brain tumor) within a human's head. Unlike conventional methods, in which all electrodes are located on the scalp of a person, at least one of the electrodes is implemented using an implanted device. The implanted device includes a rigid substrate that is shaped and dimensioned to replace a section of the skull of a person. At least one conductive plate is secured to the inside of the rigid substrate, and a dielectric layer is disposed on the inside of the one or more conductive plates. The conductive lead is used to apply an AC voltage to the one or more conductive plates.

Description

[0001] Cross-references to related applications This application claims the benefit of U.S. Provisional Application 62 / 880,893, filed July 31, 2019, which is incorporated herein by reference in its entirety. Background Technology

[0002] A tumor therapeutic field, or TTField, is a low-intensity (e.g., 1-3 V / cm) alternating electric field in the mid-frequency range (e.g., 100-500 kHz) that inhibits the growth of cancer cells. This non-invasive treatment targets solid tumors and is described in U.S. Patent 7,565,205, which is incorporated herein by reference in its entirety. A 200 kHz TTField is FDA-approved for the treatment of glioblastoma (GBM) and can be used, for example, via Optune. TM System delivery. Optune TM It includes a generator and two pairs of transducer arrays (i.e., electrode arrays) placed on the patient's shaved head. One pair of arrays is located on the left and right sides of the tumor, and the other pair of arrays is located on the front and back sides of the tumor. Summary of the Invention

[0003] One aspect of the invention relates to a first device. The first device includes a rigid substrate shaped and sized to replace a segment of the skull. The substrate has an inner side and an outer side. The first device also includes a conductive plate having an inner side and an outer side. The outer side of the plate is fixed to the inner side of the substrate. The first device also includes a dielectric layer disposed on the inner side of the plate; and a conductive lead having an inner end and an outer end. The inner end of the lead is configured to make electrical contact with the plate, the lead passes through the substrate, and the outer end of the lead is configured to receive an electrical signal from an external device.

[0004] Some embodiments of the first device also include a temperature sensor located adjacent to the dielectric layer. Optionally, these embodiments may further include at least one wire passing through the substrate and terminating at the temperature sensor, wherein the wire is configured to transmit an electrical signal from the temperature sensor to an external device. Optionally, in these embodiments, the temperature sensor includes a thermistor.

[0005] In some embodiments of the first device, the dielectric layer comprises a ceramic layer with a dielectric constant of at least 10,000. In some embodiments of the first device, the dielectric layer comprises a flexible thin layer of a high-dielectric polymer.

[0006] Another aspect of the invention relates to a second device. The second device includes a rigid substrate shaped and sized to replace a segment of the skull. The substrate has an inner side and an outer side. The second device also includes a plurality of conductive plates, each having an inner side and an outer side. The outer side of each plate is fixed to the inner side of the substrate. The second device further includes a dielectric layer disposed on the inner side of each plate; and a first conductive lead having an inner end and an outer end. The inner end of the first lead is configured to make electrical contact with a first plate in the plate, the first lead passes through the substrate, and the outer end of the first lead is configured to receive an electrical signal from an external device.

[0007] Some embodiments of the second device further include a second conductive lead having an inner end and an outer end. The inner end of the second lead is configured to make electrical contact with a second plate in the board, the second lead passes through the substrate, and the outer end of the second lead is configured to receive electrical signals from an external device.

[0008] Some embodiments of the second device also include additional conductive leads configured to electrically connect the first plate in the board to the second plate in the board.

[0009] Some embodiments of the second device also include a temperature sensor located adjacent to the dielectric layer. Optionally, these embodiments may further include at least one wire passing through the substrate and terminating at the temperature sensor, wherein the wire is configured to transmit an electrical signal from the temperature sensor to an external device. Optionally, in these embodiments, the temperature sensor includes a thermistor.

[0010] In some embodiments of the second device, the dielectric layer comprises a ceramic layer with a dielectric constant of at least 10,000. In some embodiments of the second device, the dielectric layer comprises a flexible thin layer of a high-dielectric polymer.

[0011] Another aspect of the present invention relates to a first method for treating a tumor in the head of a person. The first method includes positioning a first set of electrodes on a first side of the tumor, inside a first skull implant; positioning a second set of electrodes on a second side of the tumor opposite to the first side; and applying an AC voltage between the first set of electrodes and the second set of electrodes to generate an alternating electric field through the tumor.

[0012] In some instances of the first method, the second set of electrodes is positioned on the inner side of the first skull implant. In some instances of the first method, the second set of electrodes is positioned on the inner side of the second skull implant. In some instances of the first method, the second set of electrodes is positioned on the outer surface of the human head. Attached Figure Description

[0013] Figure 1 An embodiment incorporating a transducer array into four skull implants is depicted.

[0014] Figure 2 Describes the methods used to achieve Figure 1 The first embodiment of any of the skull implants depicted herein.

[0015] Figure 3 Describes the methods used to achieve Figure 1 A second embodiment of any of the skull implants depicted herein.

[0016] Figure 4 Describes the methods used to achieve Figure 1 The third embodiment of any of the skull implants depicted herein.

[0017] Various embodiments are described in detail below with reference to the accompanying drawings, wherein the same reference numerals denote the same elements. Detailed Implementation

[0018] In patients with glioblastoma, when Optune TM When a transducer array is placed on a patient's shaved head, the electric field must pass through the patient's scalp and skull twice to reach the tumor. This situation introduces two problems. First, the presence of the skull between the transducer array and the tumor makes it more difficult to target the field to the desired location in the brain (i.e., the tumor bed). And second, due to the attenuation of the electric field introduced by the skull and scalp, the voltage and current applied to the transducer array must be relatively high (e.g., on the order of 50 VAC and 1 A) in order to obtain an electric field with therapeutically effective values ​​in the tumor bed.

[0019] Figure 1 An embodiment is depicted that improves these two problems by incorporating a transducer array into one or more cranial implants. In the illustrated embodiment, cranial implants 10L and 10R are located on the left and right sides of the patient's skull 15, respectively; and cranial implants 10A and 10P are located on the anterior and posterior sides of the patient's skull 15, respectively. An AC field generator 11 (a) applies an AC voltage between electrodes in cranial implant 10A and cranial implant 10P during a first time interval (e.g., 1 second); then (b) applies an AC voltage between electrodes in cranial implant 10L and cranial implant 10R during a second time interval (e.g., 1 second); and then repeats the two-step sequence (a) and (b) for the duration of treatment.

[0020] Figure 2 Describes the methods used to achieve Figure 1 The first embodiment of any of the cranial implants 10 A / P / L / R depicted herein. In this embodiment, a rigid substrate 20 is shaped and sized to replace a segment of the skull. The substrate 20 has an inner and outer side and can be formed using any of a variety of conventional methods for forming cranial implants, including but not limited to 3D printing. In some preferred embodiments, the substrate 20 has a diameter of at least 5 cm.2 The area.

[0021] A conductive plate 22 is fixed to the inner side of the substrate 20. The plate 22 is preferably metal (e.g., copper, steel, etc.), but alternative conductive materials can also be used. The shape of the plate 22 can be customized to match the contour of the substrate 20, and the outer side of the plate 22 can be fixed to the substrate 20 using any of a variety of conventional methods, including but not limited to 3D printing and adhesives. A dielectric layer 24 is disposed on the inner side of the plate 22.

[0022] In many cases, it is preferable to capacitively couple the electric field to the target region. The conductive plate 22 and the dielectric layer 24 form a capacitor, and using higher capacitance improves the coupling of the electric field to the tumor. One method to achieve high capacitance is to implement the dielectric layer 24 using a ceramic dielectric material with a dielectric constant of at least 10,000, similar to conventional Optune. TM The method used in the system. An alternative method to increase capacitance is to use a flexible thin layer of a high-dielectric polymer as the dielectric layer 24.

[0023] Any portion of the conductive plate 22 not covered by the dielectric 24 should be covered by a suitable insulator (e.g., medical-grade silicone) to prevent non-capacitive coupling between the conductive plate 22 and the tissue in the patient's head.

[0024] The inner end of the conductive lead 26 (e.g., a wire) is configured to make electrical contact with the plate 22. The lead 26 passes through the substrate 20, and the outer end of the lead 26 is configured to receive signals from an external device (e.g., an external device). Figure 1 The electrical signal of the field generator 11) depicted in the figure. This can be achieved, for example, by providing a terminal at the outer end of the lead 26.

[0025] For example, suppose Figure 2 The four sets of devices 10 depicted are located on all four sides of the patient's head (i.e., left, right, front, and back, respectively), as shown in the image. Figure 1 As depicted above, field generator 11 generates AC voltages on the wires leading to implants 10A and 10P, and then on the wires leading to implants 10L and 10R (in a repeating and alternating sequence as described above). The corresponding AC current propagates through wires 26 until it reaches the conductive plate 22 in each implant 10A / B / L / R. Due to the presence of dielectric layer 24, the desired electric field is imposed in the tumor bed via capacitive coupling.

[0026] Preferably, at least one temperature sensor (e.g., a thermistor, not shown) is integrated into each implant 10 A / P / L / R to reduce the risk of overheating any part of the patient's brain. In some embodiments, appropriate wiring (not shown) passes through the substrate 20 and is used to route signals from the temperature sensor to the system's controller (which may be located, for example...). Figure 1 (As shown in field generator 11). In an alternative embodiment, the system can be configured to communicate wirelessly with the temperature sensor using any of a variety of conventional methods.

[0027] Figure 3 Similar to Figure 2 In embodiments, in addition to using multiple smaller conductive plates 32 and smaller dielectric layers 34 instead of using a single conductive plate 22 and a single dielectric layer 24 (as in...), Figure 2 In addition to the embodiments described above. Optionally, each of these smaller conductive plates 32 may be circular. Optionally, each of the smaller dielectric layers 34 may be a ceramic coating disposed on the smaller conductive plate 32.

[0028] exist Figure 3 In one embodiment, a single lead 36 passes through the substrate 20 to one of the conductive plates 32, and internal wiring 37 is used to route current to other conductive plates. Alternatively, as Figure 4 As depicted, if each of the conductive plates 32 is provided with its own lead 36 passing through the substrate 20, the internal wiring can be omitted.

[0029] It is worth noting that, since the electric field does not need to penetrate the scalp or skull, the voltage and current used in this embodiment can be significantly lower than those of conventional Optune for any given desired field strength at the tumor site. TM The voltage and current used in the system. (This is because in traditional Optune...) TM In the system, the electrodes are all located on the patient's shaved scalp, which means that the electric field must pass through the scalp and skull twice to reach the tumor.

[0030] Furthermore, when transducer arrays are incorporated into cranial implants, treatment planning can be simplified, allowing the desired field to appear in the tumor bed because the electrical path between transducer arrays on opposite sides of the tumor is simplified. Finally, locations of surgical wounds or skin abnormalities may hinder the application of conventional optune. TM When a transducer array is applied to a specific location on the patient's skin surface, incorporating the transducer array into a cranial implant can improve the treatment plan.

[0031] Notice, Figure 1The diagram depicts all electrodes being incorporated into the respective cranial implants 10A / P / L / R. However, in an alternative embodiment, only some groups of electrodes are incorporated into the cranial implant, and the remaining groups of electrodes are located outside the patient's skull (as in the case of Optune). TM (In traditional TTField treatment). For example, one set of electrodes can be located in the skull implant 10A on the front of the patient's head, and multiple sets of electrodes on the right, left and back sides can all be located outside the patient's skull.

[0032] In other alternative embodiments, two or more sets of electrodes are incorporated into a single cranial implant. For example, a single, generally hemispherical cranial implant may be placed on the patient's head, replacing the upper hemisphere of the patient's skull, and all four sets of electrodes may be incorporated into this single cranial implant (i.e., on the left, right, front, and back inner walls of the implant).

[0033] While the invention has been disclosed with reference to certain embodiments, many modifications, alterations, and variations of the described embodiments are possible without departing from the scope and meaning of the invention as defined in the appended claims. Therefore, it is intended that the invention be limited to the described embodiments, but rather has the full scope defined by the language of the appended claims and their equivalents.

Claims

1. A system for treating a tumor or tumor bed in the head of a patient, comprising: One or more cranial implants (10L, 10R, 10A, 10P), wherein each of the one or more cranial implants (10L, 10R, 10A, 10P) includes a rigid substrate (20) which is shaped and sized to replace a segment of the skull, wherein the substrate (20) has an inner side and an outer side, and one or more electrodes, each electrode including a conductive plate (22; 32) having an inner side and an outer side, wherein the outer side of each plate (22; 32) is fixed to the inner side of the substrate (20); Field generator (11), which is configured to generate AC voltage and is located outside the patient's head; and Conductive leads (26; 36) having inner and outer ends, wherein the inner end of the lead (26; 36) is configured to make electrical contact with a plate (22; 32) of one of the electrodes and pass through a substrate (20), wherein the outer end of the lead (26; 36) is electrically connected to a field generator (11).

2. The system according to claim 1, further comprising: At least one temperature sensor is integrated into each cranial implant (10L, 10R, 10A, 10P).

3. The system of claim 2, wherein the at least one temperature sensor is configured for wireless communication.

4. The system according to claim 1, wherein the substrate (20) has a depth of at least 5 cm. 2 The area.

5. The system according to claim 1, further comprising: Controller; At least one temperature sensor is integrated into each cranial implant (10L, 10R, 10A, 10P); as well as Wiring through the substrate (20) to route signals from the at least one temperature sensor to the controller.

6. The system according to claim 5, wherein the controller is located in the field generator (11).

7. The system according to claim 2 or 5, wherein the at least one temperature sensor comprises a thermistor.

8. The system of claim 1, wherein all electrodes of the system are incorporated into one or more cranial implants (10L, 10R, 10A, 10P).

9. The system according to claim 1, further comprising: Electrodes that can be positioned outside the patient's skull.

10. The system of claim 1, wherein the one or more cranial implants (10L, 10R, 10A, 10P) comprise a single cranial implant (10L, 10R, 10A, 10P).

11. The system of claim 10, wherein the individual cranial implant (10L, 10R, 10A, 10P) is hemispherical.

12. The system of claim 1, wherein each of the one or more electrodes further comprises a dielectric layer (24; 34) disposed on the inner side of the respective plate (22; 32).

13. The system of claim 12, wherein the dielectric layer (24; 34) is a flexible thin layer of ceramic or high dielectric polymer having a dielectric constant of at least 10,000.

14. The system of claim 1, wherein the conductive lead (26; 36) is the first conductive lead (36), and further comprises: A second conductive lead (36) having an inner end and an outer end, wherein the inner end of the second lead (26; 36) is configured to make electrical contact with a plate (32) of another electrode of one or more electrodes and pass through a substrate (20), wherein the outer end of the second lead (36) is electrically connected to a field generator (11).

15. The system according to claim 1, further comprising: Additional conductive leads (37) are configured to electrically connect the plate (32) of one electrode to the plate (32) of another electrode among one or more electrodes.

Images