PANCREATIC CANCER TREATMENT SYSTEMS AND METHODS

Embodiments herein relate to implantable systems and methods for treatment of pancreatic cancer. In an embodiment, a method of treating pancreatic cancer is included, the method including inserting an electrical stimulation lead through the inferior vena cava, a hepatic vein, and into the portal vein via a transjugular intrahepatic portosystem shunt (TIPS). The method can further include inserting the electrical stimulation lead into at least one of the superior mesenteric vein and the splenic vein. The method can further include positioning electrodes on the lead within at least one of the superior mesenteric vein and the splenic vein and delivering one or more electric fields through the electrodes to a treatment zone including at least a portion of the pancreas. The electric fields can be at frequencies and a field strength effective to prevent and/or disrupt cellular mitosis in a cell.

FIELD

Embodiments herein relate to implantable systems for cancer treatment and related methods. More specifically, embodiments herein relate to implantable systems and methods for treatment of pancreatic cancer.

BACKGROUND

According to the American Cancer Society, cancer accounts for nearly 25% of the deaths that occur in the United States each year. Cancerous tumors can form if one normal cell in any part of the body mutates and then begins to grow and multiply too much and too quickly. Cancerous tumors can be a result of a genetic mutation to the cellular DNA or RNA that arises during cell division, an external stimulus such as ionizing or non-ionizing radiation, exposure to a carcinogen, or a result of a hereditary gene mutation. Regardless of the etiology, many cancerous tumors are the result of unchecked rapid cellular division.

Surgery is a common first-line therapy for many cancerous tumors. However, not every tumor can be surgically removed. Pancreatic cancer is a type of cancer that originates in the pancreas, an organ that produces digestive enzymes and hormones such as insulin. Pancreatic cancer can be difficult to detect and treat because it often does not cause symptoms until it has spread limiting treatment options. For example, ingrowth into the superior mesenteric artery or celiac axis can cause the tumor to be unresectable, substantially limiting treatment options.

SUMMARY

Embodiments herein relate to implantable systems and methods for treatment of pancreatic cancer. In a first aspect, a method of treating pancreatic cancer is included, the method including inserting an electrical stimulation lead through the inferior vena cava, a hepatic vein, and into the portal vein via a transjugular intrahepatic portosystem shunt (TIPS). The method can further include inserting the electrical stimulation lead into at least one of the superior mesenteric vein and the splenic vein. The method can further include positioning electrodes connected to the lead within at least one of the superior mesenteric vein and the splenic vein and delivering one or more electric fields through the electrodes to a treatment zone including at least a portion of the pancreas. The electric fields can be at frequencies and a field strength effective to prevent and/or disrupt cellular mitosis in a cell.

In a second aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include implanting a medical device configured to generate the one or more electrical fields. The medical device can further include control circuitry and a therapy output circuit. The method can further include attaching the electrical stimulation lead to the medical device.

In a third aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the medical device can further include a conductive housing, wherein the conductive housing can be configured to serve as an electrode for use with delivering the one or more electrical fields.

In a fourth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, inserting the electrical stimulation lead can include inserting a first electrical stimulation lead into the superior mesenteric vein and inserting a second electrical stimulation lead into the splenic vein.

In a fifth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the one or more electric fields can be at a field strength of 1 V/cm to 10 V/cm within a treatment zone.

In a sixth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include selecting a patient with an unresectable pancreatic tumor.

In a seventh aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include selecting a patient with tumor ingrowth into the superior mesenteric artery or celiac axis.

In an eighth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, at least one the electrodes can have an axial length from 1.5 to 2.5 centimeters.

In a ninth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, at least one the electrodes can have a diameter of 0.8 to 1.2 millimeters.

In a tenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include selecting one or more pairs of electrodes forming a vector across which to deliver electrical fields.

In an eleventh aspect, a method of treating pancreatic cancer can be included. The method can include inserting an electrical stimulation lead into the inferior vena cava. The method can further include positioning electrodes on the lead within the inferior vena cava and adjacent to the pancreas. The method can further include delivering one or more electric fields through the electrodes to a treatment zone including at least a portion of the pancreas. The one or more electric fields can be at frequencies and field strengths effective to prevent and/or disrupt cellular mitosis in a cell.

In a twelfth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, can further include implanting a medical device configured to generate the one or more electrical fields, the medical device can include control circuitry and a therapy output circuit. The method can further include attaching the electrical stimulation lead to the medical device.

In a thirteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the medical device can further include a conductive housing, wherein the conductive housing can be configured to serve as an electrode for use with delivering the one or more electrical fields.

In a fourteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the one or more electric fields can be at a field strength of 1 V/cm to 10 V/cm within the treatment zone.

In a fifteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, can further include inserting a second electrical stimulation lead transversely across the abdomen, the second electrical stimulation lead can include a second set of electrodes disposed thereon.

In a sixteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include selecting a patient with an unresectable pancreatic tumor.

In a seventeenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include selecting a patient with tumor ingrowth into the superior mesenteric artery or celiac axis.

In an eighteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, wherein at least one the electrodes can have an axial length from 1.5 to 2.5 centimeters.

In a nineteenth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, wherein at least one the electrodes can have a diameter of 0.8 to 1.2 millimeters.

In a twentieth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include selecting one or more pairs of electrodes forming a vector across which to deliver electrical fields.

In a twenty-first aspect, a method of treating pancreatic cancer can be included. The method can include inserting electrical stimulation electrodes into a patient, positioning the electrodes into a ductal system of a pancreas of the patient, and delivering one or more electric fields through the electrodes to a treatment zone including at least a portion of the pancreas. The one or more electric fields can be at frequencies selected from a range of between 10 kHz to 1 MHz, wherein the electric fields can be effective to prevent and/or disrupt cellular mitosis in a cell.

In a twenty-second aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include positioning the electrodes in the main pancreatic duct of the pancreas of the patient.

In a twenty-third aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include inserting the electrodes through at least one of the minor duodenal papilla and the major duodenal papilla of the patient.

In a twenty-fourth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include implanting a medical device configured to generate the one or more electrical fields and attaching the electrodes to the medical device. The medical device can include control circuitry and a therapy output circuit.

In a twenty-fifth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the medical device further can include a conductive housing, wherein the conductive housing can be configured to serve as an electrode for use with delivering the one or more electrical fields.

In a twenty-sixth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the one or more electric fields can be at a field strength of 1 V/cm to 10 V/cm within the treatment zone.

In a twenty-seventh aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, at least one of the electrodes can have an axial length from 1.5 to 2.5 centimeters.

In a twenty-eighth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, at least one of the electrodes can have a diameter of 0.8 to 1.2 millimeters.

In a twenty-ninth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include selecting one or more pairs of electrodes forming a vector across which to deliver electrical fields.

In a thirtieth aspect, a method of treating pancreatic cancer can be included. The method can include inserting electrical stimulation electrodes into a patient, directly positioning the electrodes into or adjacent to a pancreas of the patient, and delivering one or more electric fields through the electrodes to a treatment zone including at least a portion of the pancreas. The one or more electric fields can be at frequencies selected from a range of between 10 kHz to 1 MHz, wherein the electric fields can be effective to prevent and/or disrupt cellular mitosis in a cell.

In a thirty-first aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include positioning the electrodes outside of the veinous system and outside of the ductal system of the pancreas of the patient.

In a thirty-second aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include implanting a medical device configured to generate the one or more electrical fields and attaching the electrodes to the medical device. The medical device can include control circuitry and a therapy output circuit.

In a thirty-third aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the medical device can further include a conductive housing, wherein the conductive housing can be configured to serve as an electrode for use with delivering the one or more electrical fields.

In a thirty-fourth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the one or more electric fields can be at a field strength of 1 V/cm to 10 V/cm within the treatment zone.

In a thirty-fifth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, at least one of the electrodes can have an axial length from 1.5 to 2.5 centimeters.

In a thirty-sixth aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, at least one of the electrodes can have a diameter of 0.8 to 1.2 millimeters.

In a thirty-seventh aspect, in addition to one or more of the preceding or following aspects, or in the alternative to some aspects, the method can further include selecting one or more pairs of electrodes forming a vector across which to deliver electrical fields.

DETAILED DESCRIPTION

Pancreatic cancer can be difficult to detect and treat because it often does not cause symptoms until it has spread, thereby limiting treatment options. For example, ingrowth into the superior mesenteric artery or celiac axis can cause the tumor to be deemed unresectable, substantially limiting treatment options.

However, embodiments of system and methods herein can be used to treat pancreatic cancer including, but not limited to, unresectable pancreatic cancer tumors. In an embodiment, a method of treating pancreatic cancer herein can include inserting an electrical stimulation lead through the inferior vena cava and then a hepatic vein, and into the portal vein via a transjugular intrahepatic portosystem shunt (TIPS). Then the electrical stimulation lead can be inserted into at least one of the superior mesenteric vein and the splenic vein. The method can further include positioning electrodes on the lead into at least one of the superior mesenteric vein and the splenic vein and delivering one or more electric fields through the electrodes to a treatment zone including at least a portion of the pancreas. The electric fields can be at frequencies and field strengths that are effective to prevent and/or disrupt cellular mitosis in a cell, but less than that used for tissue ablation. Further details regarding the electric fields are provided below.

In various other embodiments, a method of treating pancreatic cancer herein can include inserting an electrical stimulation lead into the inferior vena cava, positioning electrodes on the lead within the inferior vena cava and adjacent to the pancreas, and delivering one or more electric fields through the electrodes to a treatment zone including at least a portion of the pancreas. In some embodiments, another electrical stimulation lead can be inserted transversely across the abdomen and the electrodes thereon can be used in combination with electrodes of the first electrical stimulation lead and/or conductive housings of implanted devices serving as electrodes to deliver therapy.

Referring now toFIG.1, a simplified schematic view of the pancreas102is shown in accordance with various embodiments herein. Along with the pancreas102, the superior mesenteric vein108is shown. In this view, the duodenum104of a patient is also shown along with a portal vein106. The pancreas102can be divided into various portions. For example, the pancreas102includes the tail110, body112, neck114, head116, and uncinate process118.

Referring now toFIG.2, a simplified schematic view of a portion of anatomy including the pancreas102is shown in accordance with various embodiments herein. As before, along with the pancreas102, the superior mesenteric vein108, duodenum104, and portal vein106are shown. Additional anatomical features shown in this view include an inferior mesenteric vein208, splenic vein210, and liver202. The liver202is shown along with portions of the hepatic veinous system204and portions of the hepatic portal system206. Various of these anatomical features can be utilized in order to insert an electrical stimulation lead into a position so as to allow for treatment of a targeted zone that can be within or include at least a portion of the pancreas102.

Referring now toFIG.3, a schematic view of an exemplary lead insertion pathway302is shown in accordance with various embodiments herein. As before, the pancreas102is shown along with the superior mesenteric vein108, duodenum104, portal vein106, inferior mesenteric vein208, splenic vein210, and liver202. The liver202is shown along with portions of the hepatic veinous system204and portions of the hepatic portal system206. The lead insertion pathway302can include the inferior vena cava304, the hepatic veinous system204, a transjugular intrahepatic portosystem shunt (TIPS)306, the hepatic portal system206, portal vein106, and then into splenic vein210and/or superior mesenteric vein108. The inferior vena cava304can be surgically accessed in various ways including, but not limited to, jugular access and femoral access. In various embodiments, a stent-graft can be placed as part of forming the transjugular intrahepatic portosystem shunt306.

In various embodiments, a first electrical stimulation lead can be inserted into the superior mesenteric vein108and a second electrical stimulation lead can be inserted into the splenic vein210. Referring now toFIG.4, a schematic view of electrical stimulation leads and electrodes is shown in accordance with various embodiments herein. The pancreas102is shown along with a splenic vein210and a portal vein106.FIG.4shows an implantable medical device402. Attached to the implantable medical device402,FIG.4also shows a first electrical stimulation lead404including a first electrode408and a second electrode410(though it will be appreciated that various numbers of electrodes can be used on an electrical stimulation lead such as 1, 2, 3, 4, 4, 6, etc.).FIG.4shows a second electrical stimulation lead406which includes a third electrode412and a fourth electrode414disposed thereon. Pairs of electrodes can be used to form vectors across which electrical fields are delivered to a treatment site including at least a portion of the pancreas102. In some embodiments, at least one electrode can be positioned at least slightly above a mid-point of a target therapy zone (such as a position of a tumor to be treated). In some embodiments, at least one electrode can be positioned at least slightly below a mid-point of a target therapy zone (such as a position of a tumor to be treated). In some embodiments, at least one electrode can be positioned so that it is substantially centered within the target therapy zone (such as a position of a tumor to be treated).

The implantable medical device402further can include a conductive housing, wherein the conductive housing can be configured to serve as an electrode for use with delivering the one or more electrical fields. Further details of exemplary implantable medical devices are provided in greater detail below.

Other positioning for electrical stimulation leads in order to treat pancreatic cancer are also contemplated herein. For example, referring now toFIG.5, a schematic view of electrical stimulation lead placement is shown in accordance with various embodiments herein.FIG.5shows a patient502along with an implantable medical device402. The pancreas102of the patient502is schematically shown along with the duodenum104and the inferior vena cava304. In this example, the electrical stimulation lead506includes a first electrode508, a second electrode510, and a third electrode512. Pairs of electrodes can be used to form vectors across which electrical fields are delivered to a treatment site including at least a portion of the pancreas102. The positioning with in the inferior vena cava304shown inFIG.5provides a substantially vertical orientation to the electrodes. In some embodiments, at least one electrode (such as first electrode508) can be positioned at least slightly above a mid-point of a target therapy zone (such as a position of a tumor to be treated). In some embodiments, at least one electrode (such as third electrode512) can be positioned at least slightly below a mid-point of a target therapy zone (such as a position of a tumor to be treated). In some embodiments, at least one electrode (such as second electrode510) can be positioned so that it is substantially centered vertically within the target therapy zone.

In some embodiments, a second electrical stimulation lead can be implanted transversely across the abdomen, such as subcutaneously outside of the anterior abdominal muscles, inside of the abdominal cavity, etc. As such,FIG.5shows a second implantable device520along with a transverse abdominal electrical stimulation lead522. The transverse abdominal electrical stimulation lead522also includes a first abdominal electrode524and a second abdominal electrode526. Pairs of electrodes (on one or both leads) can be used to form vectors across which electrical fields are delivered to a treatment site including at least a portion of the pancreas102. In some embodiments, at least one electrode is disposed to one lateral side of a target therapy zone (such as a position of a tumor to be treated) and at least one electrode is disposed to the other lateral side of the target therapy zone.

In some embodiments, a single implantable device can be used, such that in this example both electrical stimulation leads can be connected to the same implantable medical device (e.g., one of medical device402and second implantable device520can be omitted with both leads connected to the remaining device). As such, placement of medical device402and second implantable device520can be thought of as alternatives in some embodiments. In addition, in some embodiments, only a single electrical stimulation lead (506or522) can be used as connected to one of the implantable devices (402or520).

In some embodiments, the ductal system of the pancreas can be used for the positioning of electrical stimulation leads herein. Referring now toFIG.6, a schematic view of electrical stimulation lead placement in accordance with various embodiments herein. In the view shown inFIG.6, the pancreas102is shown along with duodenum104. The pancreas102is shown along with main pancreatic duct602and accessory pancreatic duct604. The duodenum104is shown along with minor duodenal papilla608and major duodenal papilla610.

In this embodiment, there is a lead506that is connected to medical device402. The lead506passes through the interior of the duodenum104and into major duodenal papilla610. Access to the major duodenal papilla610can be achieved using techniques similar to that used with ERCP (endoscopic retrograde cholangiopancreatography). The lead506then passes through main pancreatic duct602. First electrode508and second electrode510on lead506are positioned within main pancreatic duct602in order to treat a site (such as a tumor) within or adjacent to pancreas102. However, it will be appreciated that the leads and/or electrodes thereof can be disposed within any portion of the ductal system of the pancreas. Further, in some embodiments, the minor duodenal papilla608can be used instead or in addition to the major duodenal papilla610(in some embodiments, one lead can be inserted into minor duodenal papilla608and a second lead can be inserted into major duodenal papilla610). In some embodiments, the electrode and/or a portion of the lead can take the form of a stent or other expanding structure to allow the duct to remain open while also allowing the electrode to remain in position for treatment. Electrodes of other embodiments herein can also take the form of a stent or stent like structure. Also, it will be appreciated that leads herein (such as lead506in the context ofFIG.6, but also applicable to other embodiments herein) can include structure that is sufficient to electrically connect therapy electrode with a device to generate the electrical therapy, such as medical device402. For example, the lead506can be as simple as one or more conductors (such as one or more insulated wires) in some embodiments, but in other embodiments can include a more complex structure such as that depicted with regard toFIG.8herein.

In some embodiments, electrical stimulation leads herein can be directed placed/inserted into a desired site and avoiding critical structures and/or ducts and veins. For example, a plunge lead/electrode(s) can be used to place the electrodes of a lead at a desired site to treat a site (such as a tumor) within or adjacent to pancreas102. Referring now toFIG.7, a schematic view of electrical stimulation lead placement in accordance with various embodiments herein. In this embodiment, lead506is connected to medical device402. The lead506passes to a desired treatment site such that first electrode508and second electrode510on lead506are positioned properly to treat a site (such as a tumor) within or adjacent to pancreas102. While two electrodes are shown in the example ofFIG.7, it will be appreciated that different numbers of electrodes can also be used. The electrodes can take the form of plunge electrodes and can be inserted such as using a catheter and/or insertion needle, such as with a lead over approach. The leads can be tunneled in from various points, such as being tunneled in from the abdomen. In various embodiments, multiple leads can be used. By way of example, multiple leads can be used to surround and/or triangulate around a desired treatment site, such as a tumor.

Cancer Therapy Stimulation Leads

Referring now toFIG.8, a schematic view of an exemplary cancer therapy stimulation lead506is shown in accordance with various embodiments herein. The cancer therapy stimulation lead506can include a lead body802with a proximal end804and a distal end806. In this example, a first electrode808and a second electrode809are coupled to the lead body802, as positioned near a distal end806thereof. In some embodiments, the electrodes808,809can include electric field generating electrodes (which can function as working electrodes or counter electrodes depending on the system configuration). In various embodiments, the electrodes808,809can include electric field sensing electrodes. The electrodes808,809can be internally connected or internally independent. The lead body802can define a lumen. The electrodes808,809can include various conductive materials such as platinum, silver, gold, iridium, titanium, and various alloys. In some embodiments, the cancer therapy stimulation lead506includes more than two electrodes. The electrodes can be of various sizes. In some embodiments, at least one of the electrodes has a diameter of 0.8 to 1.2 millimeters. In some embodiments, at least one the electrodes has an axial length from 1.5 to 2.5 centimeters.

In some embodiments, the cancer therapy stimulation lead506can include one or more therapy zone temperature sensors disposed along a length of the cancer therapy stimulation lead. In this example, a therapy zone temperature sensor811is positioned between the first electrode808and the second electrode809. However, the therapy zone temperature sensor811can also be positioned at various other points along or in the lead. In some embodiments, the therapy zone temperature sensor811can be positioned in the lead directly beneath an electrode. The therapy zone temperature sensor811can include an optical or electrical thermal sensor. For example, the therapy zone temperature sensor can include a thermistor. The therapy zone temperature sensor811can be used to measure the thermal heating about the cancer therapy stimulation lead to provide feedback to a clinician about the local thermal heating zone around the lead and provide a tissue temperature of the treatment site to the medical device.

In various embodiments, the therapy zone temperature sensor811can provide a tissue temperature at a site offset from a surface of the electrodes808,809. If a tissue temperature of a site offset from the electrodes808,809is measured, the medical device can compensate for the offset when measuring or estimating the temperature of the tissue. In some embodiments, the therapy zone temperature sensor811can measure or estimate the reference or core body temperature of the patient when the therapy is turned off or paused. While not intending to be bound by theory, in some scenarios it can be easier to get an accurate measurement of a reference or core body temperature when therapy is turned off or paused. In some embodiments, therapy zone temperature sensor data can be recorded and relayed to the clinician, patient, care provider, and/or medical record system.

The cancer therapy stimulation lead506can further include a terminal pin810for connecting the cancer therapy stimulation lead506to a medical device, such as a cancer treatment device. The terminal pin810can be compatible with various standards for lead-header interface design including the DF-1, VS-1, IS-1, LV-1 and IS-4 standards, amongst other standards.

In some embodiments, the cancer therapy stimulation lead506can further include a fixation element812, such as an element that can adhere to a portion of the subject's body to maintain the position of the cancer therapy stimulation lead506and/or the electrodes808. In various embodiments, the fixation element812can be disposed along the distal end806of the cancer therapy stimulation lead506. However, in some embodiments a fixation element812is omitted.

Referring now toFIG.9, a cross-sectional schematic view of a cancer therapy stimulation lead506as taken along line7-7′ ofFIG.8is shown in accordance with various embodiments herein. The cancer therapy stimulation lead506can include an outer layer900with an outer surface902. The outer layer900can be flexible and can be configured to protect other components disposed within the lumen of the outer layer900. In some embodiments, the outer layer900can be circular in cross-section. In some embodiments, the outer layer900includes a dielectric material and/or an insulator. In some embodiments, the outer layer900can include various biocompatible materials such as polysiloxanes, polyethylenes, polyamides, polyurethane and the like.

In various embodiments, the cancer therapy stimulation lead506can include one or more conductors, such as a first conductor904and a second conductor906. It will be appreciated that this is only by way of example and that the actual number of conductors within a lead can far exceed two. In some embodiments, the first conductor904and the second conductor906can be disposed within the lumen of the outer layer900. The first conductor904and a second conductor906can be configured to provide electrical communication between an electrode808and the proximal end804of the cancer therapy stimulation lead506. The first conductor904and a second conductor906can include various materials including copper, aluminum, silver, gold, and various alloys such as tantalum/platinum, MP35N and the like. An insulator908and910can surround the first conductor904and a second conductor906. The insulators908and910can include various materials such as electrically insulating polymers.

In some embodiments, each of the electrodes808can have individual first conductors904and second conductors906to electrically couple the electrode808to the proximal end804of the cancer therapy stimulation lead506. However, in some embodiments, each of the electrodes808only connects to a single conductor to electrically couple the electrode808to the proximal end804of the cancer therapy stimulation lead506. In some embodiments, the first conductor904and a second conductor906can be configured as a coil or a cable. Multiple conductors can be disposed within the lumen of the outer layer900. For example, a separate conductor or set of conductors can be in communication with each electrode disposed along the lead. In various embodiments, a first conductor904and a second conductor906can form a part of an electrical circuit by which the electric fields from the electric field generating circuit are delivered to the site of the cancerous tissue. Many more conductors than are shown inFIG.9can be included within embodiments herein. For example, the cancer therapy stimulation lead506can include 1, 2, 3, 4, 5, 6, 7, 8, 10, 15 or 20 or more conductors, or any number of conductors falling within a range between any of the foregoing.

In some embodiments, the cancer therapy stimulation lead506can include a central channel912. The central channel912can be configured for a guide wire, or other implanting device, to pass through, such as to aid in implanting the cancer therapy stimulation lead506and electrodes808. In some cases, additional channels (not shown) are disposed within the cancer therapy stimulation lead506.

Medical Device Components

Referring now toFIG.10, a schematic cross-sectional view of an exemplary medical device402is shown in accordance with various embodiments herein. The housing1062can define an interior volume1002that can be hollow and that in some embodiments is hermetically sealed off from the area1004outside of medical device402. In other embodiments the housing1062can be filled with components and/or structural materials such that it is non-hollow. The medical device402can include control circuitry1006, which can include various components1008,1010,1012,1014,1016, and1018disposed within housing1062. In some embodiments, these components can be integrated and in other embodiments these components can be separate. In yet other embodiments, there can be a combination of both integrated and separate components. The medical device402can also include an antenna1024, to allow for unidirectional or bidirectional wireless data communication, such as with an external device or an external power supply. In some embodiments, the components of medical device402can include an inductive energy receiver coil (not shown) communicatively coupled or attached thereto to facilitate transcutaneous recharging of the medical device via recharging circuitry.

The various components1008,1010,1012,1014,1016, and1018of control circuitry1006can include, but are not limited to, a microprocessor, memory circuit (such as random access memory (RAM) and/or read only memory (ROM)), recorder circuitry, controller circuit, a telemetry circuit, a power supply circuit (such as a battery), a timing circuit, and an application specific integrated circuit (ASIC), a recharging circuit, amongst others. Control circuitry1006can be in communication with an electric field generating circuit1020that can be configured to generate electric current to create one or more fields. The electric field generating circuit1020can be integrated with the control circuitry1006or can be a separate component from control circuitry1006. Control circuitry1006can be configured to control delivery of electric current from the electric field generating circuit1020. In some embodiments, the electric field generating circuit1020can be present in a portion of the medical device that is external to the body.

In some embodiments, the control circuitry1006can be configured to direct the electric field generating circuit1020to deliver an electric field via leads506and electrodes theron to the site of a cancerous tumor located within a bodily tissue. In other embodiments, the control circuitry1006can be configured to direct the electric field generating circuit1020to deliver an electric field via the housing1062of medical device402to the site of a cancerous tumor located within a bodily tissue. In other embodiments, the control circuitry1006can be configured to direct the electric field generating circuit1020to deliver an electric field between leads506and the electrodes thereon and the housing1062of medical device402. In some embodiments, one or more leads506and the electrodes thereon can be in electrical communication with the electric field generating circuit1020.

In some embodiments, medical device402can include an electric field sensing circuit1022configured to generate a signal corresponding to sensed electric fields. Electric field sensing circuit1022can be integrated with control circuitry1006or it can be separate from control circuitry1006.

In some embodiments, sensing electrodes (not shown in this view) can be disposed on or adjacent to the housing of the medical device, on one or more leads connected to the housing, on a separate device implanted near or in the tumor, or any combination of these locations. In some embodiments, the electric field sensing circuit1022can measure the electrical potential difference (voltage) between a first electrode and a second electrode, wherein the first and second electrodes are in any of the aforementioned locations. In some embodiments, the electric field sensing circuit can be configured to measure sensed electric fields and to record electric field strength in V/cm.

In some embodiments, the one or more leads506can be in electrical communication with the electric field generating circuit1020. The one or more leads506can include one or more electrodes. In some embodiments, various electrical conductors, such as electrical conductors1026and1028, can pass from the header1044through a feed-through structure1030and into the interior volume1002of medical device402. As such, the electrical conductors1026and1028can serve to provide electrical communication between the one or more leads506and control circuitry1006disposed within the interior volume1002of the housing1062.

In some embodiments, recorder circuitry can be configured to record the data produced by the electric field sensing circuit1022and record time stamps regarding the same. In some embodiments, the control circuitry1006can be hardwired to execute various functions, while in other embodiments the control circuitry1006can be directed to implement instructions executing on a microprocessor or other external computation device. A wireless communication interface can also be provided for communicating with external computation devices such as a programmer, a home-based unit, and/or a mobile unit (e.g., a cellular phone, personal computer, smart phone, tablet computer, smartwatch, and the like).

Elements of various embodiments of the medical devices described herein are shown inFIG.11. However, it will be appreciated that some embodiments can include additional elements beyond those shown inFIG.11. In addition, some embodiments may lack some elements shown inFIG.11. The medical devices as embodied herein can gather information through one or more sensing channels and can output information through one or more field generating channels. A microprocessor1102can communicate with a memory1104via a bidirectional data bus. The memory1104can include read only memory (ROM) or random-access memory (RAM) for program storage and RAM for data storage. The microprocessor1102can also be connected to a wireless communication interface1118for communicating with external devices such as a programmer, a home-based unit and/or a mobile unit (e.g., a cellular phone, personal computer, smart phone, tablet computer, and the like) or directly to the cloud or another communication network as facilitated by a cellular or other data communication network. The medical device can include a power supply circuit1120. In some embodiments, the medical device can include an inductive energy receiver coil interface (not shown) communicatively coupled or attached thereto to facilitate transcutaneous recharging of the medical device.

The medical device can include one or more electric field sensing electrodes1108and one or more electric field sensor channel interfaces1106that can communicate with a port of microprocessor1102. The medical device can also include one or more electric field generating circuits1122, one or more supply electrodes1112, and one or more supply channel interfaces1110that can communicate with a port of microprocessor1102. The medical device can also include one or more sensors1116(such as temperature sensors) and one or more sensor channel interfaces1114that can communicate with a port of microprocessor1102. The channel interfaces1106,1110, and1114can include various components such as analog-to-digital converters for digitizing signal inputs, sensing amplifiers, registers which can be written to by the control circuitry in order to adjust the gain and threshold values for the sensing amplifiers, source drivers, modulators, demodulators, multiplexers, and the like.

In some embodiments, one or more physiological sensors can also be included herein. In some embodiments, the physiological sensors can include sensors that monitor temperature, blood flow, blood pressure, and the like. In some embodiments, the respiration sensors can include sensors that monitor respiration rate, respiration peak amplitude, and the like. In some embodiments, the chemical sensors can measure the quantity of an analyte present in a treatment area about the sensor, including but not limited to analytes such as of blood urea nitrogen, creatinine, fibrin, fibrinogen, immunoglobulins, deoxyribonucleic acids, ribonucleic acids, potassium, sodium, chloride, calcium, magnesium, lithium, hydronium, hydrogen phosphate, bicarbonate, and the like. However, many other analytes are also contemplated herein. Exemplary chemical/analyte sensors are disclosed in commonly owned U.S. Pat. No. 7,809,441 to Kane et al., and which is hereby incorporated by reference in its entirety.

Although the temperature sensors1116are shown as part of a medical device inFIG.11, it is realized that in some embodiments one or more of the sensors could be physically separate from the medical device. In various embodiments, one or more of the can be within another implanted medical device communicatively coupled to a medical device via wireless communication interface1118. In yet other embodiments, one or more of the sensors can be external to the body and coupled to a medical device via wireless communication interface1118.

Electric Field Therapy Parameters

In some embodiments, medical devices herein can generate one or more electric fields between selected pairs of electrodes at frequencies selected from a range of between 10 kHz to 1 MHz. In some embodiments, the one or more electric fields can be effective to prevent and/or disrupt cellular mitosis in a cell. In some embodiments, the one or more electric fields can be effective to prevent and/or disrupt cellular mitosis in a cell, but not cause tissue ablation. In some embodiments, the system can be configured to deliver an electric field at one or more frequencies selected from a range of within 300 kHz to 500 kHz. In some embodiments, the system can be configured to deliver an electric field at one or more frequencies selected from a range of within 100 kHz to 300 kHz. In some embodiments, the system can be configured to periodically deliver an electric field using one or more frequencies greater than 10 kHz.

A desired electric field strength can be achieved by delivering an electric current between two electrodes. The specific current and voltage at which the electric field is delivered can vary and can be adjusted to achieve the desired electric field strength at the site of the tissue to be treated. In some embodiments, the system can be configured to deliver an electric field using currents ranging from 1 mAmp to 1000 mAmp to the site of a cancerous tumor. In some embodiments, the system can be configured to deliver an electric field using currents ranging from 20 mAmp to 500 mAmp to the site of a cancerous tumor. In some embodiments, the system can be configured to deliver an electric field using currents ranging from 30 mAmp to 300 mAmp to the site of a cancerous tumor.

In some embodiments, the system can be configured to deliver an electric field using voltages ranging from 1 Vrms to 50 Vrms to the site of a cancerous tumor. In some embodiments, the system can be configured to deliver an electric field using voltages ranging from 5 Vrms to 30 Vrms to the site of a cancerous tumor. In some embodiments, the system can be configured to deliver an electric field using voltages ranging from 10 Vrms to 20 Vrms to the site of a cancerous tumor.

In some embodiments, the system can be configured to deliver an electric field using one or more voltages including 1 Vrms, 2 Vrms, 3 Vrms, 4 Vrms, 5 Vrms, 6 Vrms, 7 Vrms, 8 Vrms, 9 Vrms, 10 Vrms, 15 Vrms, 20 Vrms, 25 Vrms, 30 Vrms, 35 Vrms, 40 Vrms, 45 Vrms, or 50 Vrms. It will be appreciated that the system can be configured to deliver an electric field at a voltage falling within a range, wherein any of the forgoing voltages can serve as the lower or upper bound of the range, provided that the lower bound of the range is a value less than the upper bound of the range.

In some embodiments, the system can be configured to generate one or more applied electric field strengths selected from a range of within 0.25 V/cm to 1000 V/cm, or 0.25 V/cm to 500 V/cm, or 0.25 V/cm to 100 V/cm, or 0.25 V/cm to 50 V/cm. In some embodiments, the system can be configured to generate one or more applied electric field with strengths of greater than 3 V/cm. In some embodiments, the system can be configured to generate one or more applied electric field strengths selected from a range of within 1 V/cm to 10 V/cm. In some embodiments, the system can be configured to generate one or more applied electric field strengths selected from a range of within 3 V/cm to 5 V/cm.

In some embodiments, an electric field can be applied to the site of a cancerous tumor or tumor resection at a specific frequency or constant frequency range.

Methods

Many different methods are contemplated herein, including, but not limited to, methods of treating pancreatic cancer, methods of treating unresectable tumors, methods of delivery cancer therapy, methods of placing electrical stimulation leads, and the like. Aspects of system/device operation described elsewhere herein can be performed as operations of one or more methods in accordance with various embodiments herein.

In some embodiments, operations described herein and method steps can be performed as part of a computer-implemented method executed by one or more processors of one or more computing devices. In various embodiments, operations described herein and method steps can be implemented instructions stored on a non-transitory, computer-readable medium that, when executed by one or more processors, cause a system to execute the operations and/or steps.

In an embodiment, a method of treating pancreatic cancer is included. The method can include inserting an electrical stimulation lead through the inferior vena cava, a hepatic vein, and into the portal vein via a transjugular intrahepatic portosystem shunt (TIPS). Then the electrical stimulation lead can be inserted into at least one of the superior mesenteric vein and the splenic vein. The method can also include positioning electrodes on the lead into at least one of the superior mesenteric vein and the splenic vein. The method can also include delivering one or more electric fields through the electrodes to a treatment zone including at least a portion of the pancreas. The electric fields can be effective to prevent and/or disrupt cellular mitosis in a cell.

In an embodiment, the method can further include implanting a medical device configured to generate the one or more electrical fields, the medical device including control circuitry and a therapy output circuit. The method can further include attaching the electrical stimulation lead to the medical device.

In an embodiment, the medical device further can include a conductive housing. The conductive housing can be configured to serve as an electrode for use with delivering the one or more electrical fields.

In an embodiment of the method, inserting the electrical stimulation lead can include inserting a first electrical stimulation lead into the superior mesenteric vein and inserting a second electrical stimulation lead into the splenic vein.

While cancers of various types can be treated, embodiments herein can be particularly useful to treat unresectable pancreatic cancer tumors. In an embodiment, the method can further include selecting a patient with an unresectable pancreatic tumor. In an embodiment, the method can further include selecting a patient with tumor ingrowth into the superior mesenteric artery or celiac axis.

In an embodiment, the method can further include selecting one or more pairs of electrodes forming a vector across which to deliver electrical fields so as to include a target treatment zone, such as including a pancreatic tumor.

In an embodiment, a method of treating pancreatic cancer is included herein that includes inserting an electrical stimulation lead into the inferior vena cava and positioning electrodes on the lead within the inferior vena cava and adjacent to the pancreas. The method can further include delivering one or more electric fields through the electrodes to a treatment zone including at least a portion of the pancreas, wherein the electric fields are effective to prevent and/or disrupt cellular mitosis in a cell.

In an embodiment, the method can further include implanting a medical device configured to generate the one or more electrical fields, the medical device can include control circuitry and a therapy output circuit. The method can further include attaching the electrical stimulation lead to the medical device.

In an embodiment, the method can further include inserting a second electrical stimulation lead transversely across the abdomen. The second electrical stimulation lead can include a second set of electrodes disposed thereon.

As used herein, the recitation of numerical ranges by endpoints shall include all numbers subsumed within that range (e.g., 2 to 8 includes 2.1, 2.8, 5.3, 7, etc.).

The headings used herein are provided for consistency with suggestions under 37 CFR 1.77 or otherwise to provide organizational cues. These headings shall not be viewed to limit or characterize the invention(s) set out in any claims that may issue from this disclosure. As an example, although the headings refer to a “Field,” such claims should not be limited by the language chosen under this heading to describe the so-called technical field. Further, a description of a technology in the “Background” is not an admission that technology is prior art to any invention(s) in this disclosure. Neither is the “Summary” to be considered as a characterization of the invention(s) set forth in issued claims.