APPARATUS FOR THERMAL THERAPY TREATMENT OF A SELECTED REGION OF THE BODY OF A HUMAN OR OF AN ANIMAL AND METHOD OF OPERATING SAID APPARATUS

Abstract

The invention relates to a device and method for thermal therapy of a selected region of a human or animal body, particularly for treating tissue damage after surgery, injuries, inflammation, chronic rheumatic conditions, and for supporting chemotherapy. The system includes a temperature control device that circulates a temperature-controlled fluid through a heat transfer unit configured for uniform skin contact, and a pressure device to optimize thermal transfer. During chemotherapy, the device maintains the selected region, such as hands or feet, at a target temperature to prevent or reduce chemotherapy-induced polyneuropathy (CIPN). Sensors monitor temperature and pressure, enabling feedback control for consistent therapy. Methods include fitting the device to the patient, adjusting pressure, and maintaining even skin cooling throughout chemotherapy, thereby improving patient comfort, reducing adverse side effects, and supporting adherence to treatment. The invention provides improved outcomes in thermal therapy applications.

Claims

1. A method of treating or preventing chemotherapy induced polyneuropathy (CIPN) in a patient receiving chemotherapy treatment, the method comprising: providing thermal therapy to a selected region of a body of the patient, wherein the thermal therapy comprises: fitting a thermal therapy device to uniformly contact a skin surface of the selected region of the body; and supplying the thermal therapy device with a temperature control fluid which is maintained at a temperature of between about 15 C. and 17 C. for duration of the chemotherapy treatment, such that even tempering of the skin surface is achieved.

2. The method according to claim 1, wherein the temperature of the skin surface during the thermal therapy is no more than 22 C.

3. The method according to claim 1, wherein the temperature of the skin surface during the thermal therapy is no more than 20 C.

4. The method according to claim 1, wherein the thermal therapy is provided for at least 20 minutes after starting the chemotherapy treatment.

5. The method according to claim 1, wherein the selected region of the body comprises a hand.

6. The method according to claim 1, wherein the selected region of the body comprises a foot.

7. A method of treating or preventing chemotherapy induced polyneuropathy (CIPN) in a patient receiving chemotherapy treatment, the method comprising: providing thermal therapy to a selected region of a body of the patient, the thermal therapy being delivered using a thermal therapy device, the thermal therapy device comprising: a heat transfer unit provided to be brought into contact with the selected region of the body, the heat transfer unit being configured to receive a temperature control fluid; a pressure device configured to generate, or to increase, a contact pressure of the heat transfer unit on the selected region of the body, to improve thermal transfer between the heat transfer unit and the selected region of the body; and a temperature control device provided to control a temperature of the temperature control fluid; and cooling the selected region of the body to a target skin temperature, using a temperature control fluid that is no more than 7 C. cooler than the target skin temperature.

8. The method of claim 7, wherein the thermal therapy comprises cooling the selected region of the body to a target skin temperature, using a temperature control fluid that is no more than 5 C. cooler than the target skin temperature.

9. The method of claim 7, wherein the temperature control fluid is between about 15 C. and 17 C.

10. The method according to claim 7, wherein the selected region of the body comprises a hand.

11. The method according to claim 7, wherein the selected region of the body comprises a foot.

12. A method of increasing adherence to chemotherapy treatment, the method comprising: administering chemotherapy to a patient in need thereof; and providing thermal therapy to a selected region of a body of the patient to prevent CIPN thereby increasing treatment adherence, wherein the thermal therapy comprises fitting a thermal therapy device to uniformly contact a skin surface of the selected region of the body and supplying the thermal therapy device with a temperature control fluid which is maintained at a temperature of between about 15 C. and 17 C. for a duration of the chemotherapy treatment, such that even tempering of the skin surface is achieved.

13. The method according to claim 12, wherein the temperature of the skin surface during the thermal therapy is no more than 22 C.

14. The method according to claim 12, wherein the temperature of the skin surface during the thermal therapy is no more than 20 C.

15. The method according to claim 12, wherein the selected region of the body comprises a hand.

16. The method according to claim 12, wherein the selected region of the body comprises a foot.

17. The method according to claim 1, wherein the temperature control fluid is water-based.

18. The method according to claim 7, wherein the temperature control fluid is water-based.

19. The method according to claim 12, wherein the temperature control fluid is water-based.

Description

[0115] Further advantageous embodiments of the invention are explained in the following description in connection with the accompanying drawings. In the drawings:

[0116] FIG. 1 shows a device in accordance with the invention for use in thermal therapy treatment;

[0117] FIG. 2 shows a glove-shaped heat transfer unit in accordance with the invention in the unfolded state;

[0118] FIG. 3 shows a pressure device in accordance with the invention in the unfolded state;

[0119] FIG. 4 shows a heat transfer unit in accordance with the invention in accordance with FIG. 1, in combination with a pressure device in accordance with the invention in accordance with FIG. 3; and

[0120] FIG. 5 shows a flow diagram of a method of operating the device in accordance with the invention.

[0121] FIG. 1 shows a device for use in the thermal therapy treatment of a selected region of the body of a human or of an animal, and in particular for use in the treatment of tissue damage after surgical interventions, of injuries, of inflammations and of chronic diseases of the rheumatic type, and in particular for the support of chemotherapeutic treatments, with a temperature control device 1, which is provided for tempering a temperature control fluid. The temperature control device 1 is connected, in a fluid conducting manner, to a heat transfer device 2, which is arranged for the transfer of heat to the selected region of the body, and which is further arranged to temper the heat transfer device 2 with a heat transferring temperature control fluid flowing through the heat transfer device 2. Furthermore, a control device 3 is connected to the temperature control device 1 and the heat transfer device 2, whereby the control device 3 is arranged to control the temperature control device 1 in order to cause the heat transfer device 2 to have at least partially an approximately uniform temperature in the region of a contact surface between the heat transfer device 2 and the selected region of the body to be tempered.

[0122] In this context, the heat transfer device 2 comprises at least one heat transfer unit 4, which is provided to be brought into contact with the selected region of the body, whereby the heat transfer unit 4 consists of a substantially flexible material, in which one or more temperature control fluid chambers 5 are arranged, through which the temperature control fluid can flow.

[0123] In this context, the heat transfer device further comprises a pressure device 10 which is adjacent to the heat transfer unit 4, wherein the pressure device 10 comprises at least one pressure unit 11 and a support device 12.

[0124] The pressure unit 11 is in communication with the support device 12, and the pressure unit 11 is provided in order to at least partially subject the heat transfer unit 4 to a pressure, which is then absorbed by the portion of the body to be treated as a contact pressure of the heat transfer device 2. For this purpose, the pressure unit 11 comprises at least one pressure chamber 13 with a predetermined or a variable internal pressure, and it is arranged to at least partially increase a contact pressure of the heat transfer device 2 on the selected region. In this context, the at least one pressure chamber 13 comprises a chamber which is filled with a pressure fluid, wherein the at least one chamber filled with a pressure fluid is formed by a flexible material. In this context, the pressure fluid in the at least one pressure chamber filled with a pressure fluid can be subjected to pressure via a pressure line which is connected to the at least one chamber filled with a pressure fluid, either manually via muscle power and/or with the help of a compressor 17, in order to change an internal pressure in the at least one chamber filled with a pressure fluid.

[0125] The support device 12 of the pressure device 10 further comprises a connecting device 14 which has at least one fixing element, and the connecting device 14 is constructed in such a way that it at least partially extends around the pressure device 10 and that it exerts supporting forces on the pressure device 10 in this surrounding position, which supporting forces at least partially contribute to fixing the pressure device 10 to the selected region of the body of a human or of an animal in a deployed for use condition.

[0126] Further, at least one sensor device 15 is provided, which is connected to the control device 3. The sensor device 15 is set up to measure a sensor signal between the selected region of the body and the skin contact surface. Here, the sensor signal can be present in optical, acoustic or digital form. In the example embodiment shown in FIG. 1, the sensor device 15 is mounted between the heat transfer unit 4 and the portion of the body to be treated, but other positions are also possible.

[0127] Further, at least one display device 16 is provided, wherein the display device 16 is connected to the control device 3 and is set up to output, to a user via the display device 16, the sensor signal which has been measured by the sensor device 15. The sensor signal can also be used for control with feedback, so that a region of a contact surface between the heat transfer device 2 and the portion of the body to be tempered has, at least in one region, an approximately uniform, preselected temperature.

[0128] FIG. 2 shows a heat transfer unit 4 which is provided to be brought into contact with the selected region of the body, wherein the heat transfer unit 4 consists of a substantially flexible material in which one or more temperature control fluid chambers 5 (not shown) are arranged through which the temperature control fluid can flow.

[0129] In this context, the heat transfer unit 4 comprises: [0130] at least a first flexible material layer 6 having at least a first skin contact surface which faces at least partially towards a selected region of the body of a human or of an animal, and having at least a first temperature control fluid contact surface which faces away from the first skin contact surface, [0131] at least a second flexible material layer 7 having at least a second temperature control fluid contact surface, which, between itself and the first temperature control fluid contact surface of the first flexible material layer 6, at least partially delimits one or more temperature control fluid chambers through which a heat transferring temperature control fluid can flow, [0132] wherein the heat transfer unit 4 further comprises: [0133] at least a first connecting line 8 for supplying a heat transferring temperature control fluid to the heat transfer unit 4, [0134] at least a second connecting line 9 for discharging a heat transferring temperature control fluid from the heat transfer unit 4.

[0135] The use of flexible material layers 6, 7 is necessary because the region of the body to be tempered is not flat, but comprises concave and/or convex regions, and the flexibility of the material layers 6, 7 makes it possible to keep the distance between the heat transfer unit 4 and the region to be tempered as small as possible over the entire three-dimensional surface, whereby the heat transfer unit 4 preferably rests directly on the skin surface.

[0136] In this context, the heat transfer unit 4 has at least a first shape or can assume such a first shape in which it at least partially encloses the selected region of the body of a human or of an animal.

[0137] In a preferred variant, the heat transfer unit 4 has one of the following shapes, or can assume one of these shapes: [0138] the shape of a cover enclosing the hand without subdivisions of the interior space; [0139] the shape of a glove with partially separated covers for at least one finger, in particular the shape of a mitten with a partially separated cover for the thumb, as is shown in FIG. 2; [0140] the shape of a finger glove with partially separated covers for each finger; [0141] the shape of an at least partially fingerless glove, in which at least one finger is not enclosed.

[0142] However, the portion of the body to be treated can also be a foot or any other body part, in which case the heat transfer unit 2 has, or can assume, the shape of a shoe or stocking, or any other shape adapted to the respective body part.

[0143] FIG. 3 shows the pressure device 10, wherein the pressure device 10 comprises at least one pressure unit 11 and a support device 12, which is provided for building up a contact pressure. The pressure unit 11 is attached to the support device 12 and is provided for at least partially subjecting the heat transfer unit 4 to a pressure. For this purpose, the pressure unit 11 comprises at least one pressure chamber 13, which has a predetermined or a variable internal pressure and which is arranged to at least partially increase the contact pressure of the heat transfer device 2 on the selected region by means of the internal pressure. In this context, according to one embodiment, the pressure unit 11 may comprise a pressure chamber 13 in the form of a chamber which is filled with a pressure fluid, wherein the at least one chamber filled with a pressure fluid is delimited by a flexible material. In a further preferred embodiment, the at least one pressure unit 11 is made of an elastic material, such as preferably a type of foam rubber, a type of rubber, or a combination of these or similar materials, whereby the pressure unit 11 and the pressure chamber 13 are to be considered as the same component in this embodiment.

[0144] FIG. 4 again shows the heat transfer device 2 from FIG. 1 and the pressure device 10 from FIG. 3 with slightly different dimensions. Here, the right-hand figure represents a section A-A through the section plane coming out of the plane of the drawing, along the dashed straight line A-A in the left-hand figure. In the left-hand figure, the heat transfer unit 4 of FIG. 2 is also indicated by dashed lines. Here, the heat transfer device 2 comprises at least one heat transfer unit 4, in which one or more temperature control fluid chambers 5 are arranged. A pressure device 10 is connected to the heat transfer unit 4, wherein the pressure device 10 comprises at least one pressure unit 11 and a support device 12. The support device 12 is attached to the pressure unit 11 and is provided so as to at least partially build up, via the heat transfer unit 4, a contact pressure of the heat transfer device 2 on the portion of the body to be treated. For this purpose, the pressure unit 11 comprises at least one pressure chamber 13. The pressure chamber 13 is arranged for at least partially increasing, by means of an internal pressure, the contact pressure of the heat transfer device 2 on the selected region. The pressure device 10 further comprises a support device 12, whereby the pressure device 10 is attached to the support device 12, and the pressure unit 11 is provided to at least partially subject the heat transfer unit 4 to a pressure. In this embodiment, the pressure device has three connecting devices 14, although preferably more, or fewer, connecting devices are conceivable. In this embodiment, each of the connecting devices 14 shown is of a one-piece construction; in a preferred embodiment, the connecting device is constructed in a circumferential manner, for example in the form of a zipper or a similar mechanism. In the embodiment shown in FIG. 4, the pressure unit 11 occupies a larger area, in a plan view, than the heat transfer unit 4, as well as being of one-piece construction, but, in relation to the heat transfer unit, smaller dimensions and multi-part pressure units are preferably also conceivable, which can be filled individually or jointly, through a common fluid connection, or can be controlled individually or jointly, with the help of a control device 3.

[0145] FIG. 5 shows a flowchart of a method of operating a device for thermal therapy treatment of a selected region of the body of a human or of an animal in accordance with the invention. The method illustrated in FIG. 5 may use any of the devices previously described herein, it being appreciated that the invention is not limited solely to the use of such devices.

[0146] As shown in step 101 of FIG. 5, a heat transfer device 2 with a pressure device 10 is brought into contact with the selected region of the body in a deployed for use condition.

[0147] Step 102 illustrates applying, via the pressure device 10, a contact pressure acting on the selected region of the body.

[0148] Step 103 illustrates tempering, via a temperature control device 1 connected to the heat transfer device 2, the selected region of the body by causing a heat transferring heat control fluid to flow through a heat transfer unit 4 of the heat transfer device 2.

[0149] In this way, the region of a contact surface between the heat transfer device 2 and the portion of the body to be tempered has an approximately uniform temperature in at least one region.

[0150] In some embodiments, the selected region of the body may include, for example, hands and/or feet, as well as other regions of the body such as the arms, legs, chest, back, abdomen, and/or head. Additionally, the method may include fitting the thermal therapy device to uniformly contact a skin surface of the selected region, such as the hands and/or feet.

[0151] Further, in some embodiments, the pressure device 10 may be configured to generate or increase the contact pressure on the selected region of the body, for example, to improve thermal transfer to a skin surface of the selected region of the body.

[0152] Further, in some embodiments, the heat control fluid may be supplied to the heat transfer device 2 and may be maintained at a temperature of between about 15 C. and 17 C., or other suitable temperature, for the duration of the chemotherapy treatment, such that even tempering of the skin surface is achieved. In some embodiments, the heat control fluid may be water-based.

[0153] Further, in some embodiments, the temperature of the skin surface during the thermal therapy may be no more than 22 C., and in other embodiments, no more than 20 C.

[0154] In a preferred embodiment, the method of operating a device for thermal therapy treatment further comprises a step 104 of adjusting an internal pressure of a pressure unit 11 of the pressure device 10, wherein the pressure unit 11 comprises at least one chamber filled with a pressure fluid, wherein the internal pressure of the at least one chamber filled with a pressure fluid can be adjusted manually by means of muscle power of a user and/or by means of an external pressure source.

[0155] In a further preferred embodiment, the method of operating a device for thermal therapy treatment further comprises the step 105 of measuring a sensor signal by means of a sensor device 15 which is connected to the heat transfer device 2, and the step 106 of controlling, by means of a control device 3, the pressure device 10 which is connected to the control device 3, on the basis of the measured sensor signal.

[0156] In this context, the control device 3 is preferably set up in such a way that, together with the heat transfer device 2 and the temperature control device 1, it forms a control loop using the sensor signal measured by the sensor device 15, so that an approximately uniform, preselected temperature is feedback controlled in at least one region in the region of a contact surface between the heat transfer device and the portion of the body to be tempered. In this context, by avoiding thermally insulating air pockets between the heat transfer unit and the region of the body to be tempered, the heat transfer is significantly improved.

CLINICAL STUDY RESULTS/EXAMPLES

[0157] A number of studies have been carried out by, or on behalf of, the present applicant, details of which are given below. All of the studies were carried out in a confidential setting. The ambient temperature was at room temperature (about 22 C.).

Example 1

[0158] A device (a temperature control device, a heat transfer unit generally in the form of a hand cuff, as well as connecting hoses) in accordance with an embodiment of the present invention was used to cool a human hand. A temperature sensor was attached to the hand using several layers of adhesive tape. This way of attaching the temperature sensor to the hand was chosen so as to ensure, as far as reasonably possible, that the sensor measures the temperature of the skin of the hand rather than a temperature prevailing within a space between the skin and the hand cuff.

[0159] First, the skin temperature at different locations of the hand was measured without any cooling and without the hand being inserted in the hand cuff. The average temperature was about 29 C., with slight variations depending on the location on the hand (palm of the hand, back of the hand, or between fingers). All measurements were between 27 C. and 30 C.

[0160] Next, the hand was inserted in the hand cuff. Cooling fluid, in this case water, was cooled by the temperature control device and circulated between the temperature control device and the hand cuff. The target temperature of the cooling fluid was set to 10 C. on the temperature control device. The temperature control device kept the temperature of the cooling fluid stable at about 10 C.0.5 C. (within the temperature control device). Due to thermal losses between the temperature control device and the hand cuff, the average temperature of the cooling fluid arriving at the hand cuff was about 11 C. Initially, no pressure (using a pressure device, as described above) was applied to generate an (additional) contact pressure between the hand cuff and the hand. After about 7 minutes, the hand temperature had gradually dropped to about 25 C. and remained approximately stable at that temperature.

[0161] Pressure was then applied by the pressure device so as to increase the contact pressure and to achieve a better (thermal) contact between the hand cuff and the hand. As a result, the temperature of the hand dropped more steeply than when the hand was first placed in the hand cuff without additional pressure. About 7 minutes after the beginning of the application of pressure, the hand temperature had gradually dropped to about 18 C. Eventually, the hand temperature settled at about 15 C. This was achieved approximately 18minutes after the beginning of the application of pressure.

[0162] The pressure (as generated by the pressure device) was then removed but the hand cuff remained in place, and cooling fluid continued to be circulated. The hand temperature slowly increased again, by about 1 C. over the course of about 6 minutes. Once the hand cuff was removed completely, the temperature of the cooled hand increased only slowly, by about a further 3 to an average of about 19 (between 17 and 21, depending on the location on the hand) over the course of a further 8 minutes.

[0163] Example 1 shows (inter alia) the following results: [0164] a) The target temperature set on the temperature control device can differ significantly from the actual temperature measured at the skin temperature, in particular dependent on the contact pressure. [0165] b) Even without the application of (additional) pressure, a reasonable degree of cooling can be achieved. A higher degree of cooling can be achieved through the application of (additional) pressure. [0166] c) As the therapeutic effect is dependent on the temperature of the tissue to be cooled, certain embodiments of the present invention seek to ensure that the skin is actually cooled down to a target skin temperature. This produces better results than a therapy which merely ensures that the temperature of the cooling fluid (while still in the temperature control device) is cooled to a particular temperature whilst ignoring the actual skin temperature. The same applies if the therapy seeks to heat the tissue.

Example 2

[0167] The setup and the principle of the experiment in Example 2 corresponded in essence to that of Example 1, except that the experiment was carried out on a human foot instead of a human hand.

[0168] A device (a temperature control device, a heat transfer unit generally in the form of a slipper, as well as connecting hoses) in accordance with an embodiment of the present invention was used to cool a human foot. A temperature sensor was attached to the foot using several layers of adhesive tape. This way of attaching the temperature sensor to the foot was chosen so as to ensure, as far as reasonably possible, that the sensor measures the temperature of the skin of the foot rather than a temperature prevailing within a space between the skin and the slipper.

[0169] First, the skin temperature at different locations of the foot was measured without any cooling and without the foot being inserted in the slipper. The average temperature was about 31 C., with slight variations depending on the location on the foot (sole of the foot, back of the foot or between toes, here between the big toe and the second toe). All measurements were between 30 C. and 32 C.

[0170] Next, the foot was inserted in the slipper. Cooling fluid, in this case water, was cooled by the temperature control device and circulated between the temperature control device and the slipper. The target temperature of the cooling fluid was set to 10 C. on the temperature control device. The temperature control device kept the temperature of the cooling fluid stable at about 10 C.0.5 C. (within the temperature control device). Due to thermal losses between the temperature control device and the slipper, the average temperature of the cooling fluid arriving at the slipper was about 11 C. Initially, no pressure (using a pressure device, as described above) was applied to generate an (additional) contact pressure between the slipper and the foot. After about 7 minutes, the foot temperature had gradually dropped to about 27 C. and remained approximately stable at that temperature.

[0171] Pressure was then applied by the pressure device so as to increase the contact pressure and to achieve a better (thermal) contact between the slipper and the foot. As a result, the temperature of the foot dropped. Depending on the location on the foot, this drop was slightly steeper than when the foot was first placed in the slipper without additional pressure. Between about 7 and 20 minutes (depending on the location on the foot) after the beginning of the application of pressure, the foot temperature had gradually dropped to about 22 C. Eventually, the foot temperature settled at about 17 C. (with some variation, depending on the location on the foot). This was achieved approximately 40 to 45 minutes after the beginning of the application of pressure.

[0172] The pressure (as generated by the pressure device) was then removed but the slipper remained in place, and cooling fluid continued to be circulated. The foot temperature slowly increased again, by about 1 C. over the course of about 6 minutes. Once the slipper was removed completely, the temperature of the cooled foot increased only slowly, by about a further 2 to an average of about 19 (between 17 and 20.5, depending on the location on the foot) over the course of a further 8 minutes.

[0173] Example 2 shows similar results as Example 1, albeit with somewhat different rates of cooling and slightly different amounts of temperature variation depending on the location on the foot/hand.

Example 3

[0174] This clinical trial concerned 130 female patients with breast cancer, who underwent a taxane-based chemotherapy, in particular using Paclitaxel or Docetaxel. Before, during and after each chemotherapy treatment, their hands and feet were continuously cooled to about 10 to 12 C. (skin temperature) using a method/device according to an embodiment of the present invention. Cooling started 30 minutes before the chemotherapy treatment and continued for 30 to 60 minutes after the end of each chemotherapy treatment.

[0175] The occurrence of side-effects (adverse events, AE) resulting from the chemotherapy was then recorded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. This uses clinical descriptions to define five grades depending on the severity of adverse events, plus a Grade 0, as follows:

[0176] Grade 0 No AE observed.

[0177] Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

[0178] Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL (Activities of Daily Living). Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.

[0179] Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Self care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.

[0180] Grade 4 Life-threatening consequences; urgent intervention indicated.

[0181] Grade 5 Death related to AE.

[0182] In this clinical trial, examples of Grade 2 AE were tingling, moderate numbness, reddening of the skin or other painful sensations. Examples of Grade 3 AE were extensive numbness, reduced ability of using arms and legs, the formation of blisters, skin flakes, bleeding of the skin, ulcerations or detachment of one or more fingernail or toenail, as well as strong pain.

[0183] In this clinical trial, the highest grade of AE reported during the entire course of the chemotherapy was: [0184] Grade 0: 51 patients [0185] Grade 1: 70 patients [0186] Grade 3: 1 patient [0187] Grade 4: 0 patients [0188] Grade 5: 0 patients

[0189] In other words, using a method/device in accordance with an embodiment of the present invention, 93% of the patients (n=121) had no symptoms or only non-limiting symptoms (Grades 0 and 1), 6.2% (n=8) had Grade 2 symptoms and less than 1% (n=1) had Grade 3 symptoms. None of the patients had Grade 4 or 5 symptoms.

[0190] By way of contrast, in studies (involving a large number of patients) reported in scientific journals without the use of a method/device in accordance with an embodiment of the present invention, CIPN was reported in 60% of all patients, with one study reporting 4.1% and another study reporting 6-20% of patients with Grade 3 or 4 symptoms. Other studies reported that 50% of patients undergoing taxane-based chemotherapy (without the use of a method/device in accordance with an embodiment of the present invention) showed Grade 2 or 3 symptoms.

[0191] A comparison between, on the one hand, the clinical trial using a method/device in accordance with an embodiment of the present invention, and on the other hand, the studies reported in scientific journals, demonstrates that the methods/devices in accordance with the present invention significantly reduce the prevalence of AE from chemotherapy, and in particular the prevalence of AE in higher grades according to CTCAE v5.0.

Example 4

[0192] This clinical trial was based on the clinical trial of Example 3, i.e. the clinical trial of example 3 was followed by further treatments using a method/device in accordance with an embodiment of the present invention at four different points in time after the last chemotherapy treatment. These four points in time were chosen to be: 4 weeks, 4 months, 7 months and 10 months after the last chemotherapy treatment.

[0193] Whilst at the end of the chemotherapy treatment, 93% of the patients had no symptoms or only non-limiting symptoms (see example 3), this percentage increased to 98% at 10 months after the last chemotherapy treatment.

Example 5

[0194] This clinical trial was similar to the clinical trial of Example 3. This clinical trial concerned 38 female patients with breast cancer, who underwent a taxane-based chemotherapy, in particular using Paclitaxel or Docetaxel. However, initially they did not use a method/device in accordance with an embodiment of the present invention when they started their chemotherapy, and only did so once they developed symptoms of CIPN and/or HFS. They then carried on using the method/device in accordance with an embodiment of the present invention for all subsequent chemotherapy treatments and until 4 weeks after the last such treatment.

[0195] The prevalence of the symptoms according to CTCAE v5.0 was recorded at the time of the last chemotherapy treatment, and four weeks thereafter, i.e. the percentage of patients having symptoms of Grade 0, 1, 2 etc. In addition, the highest grade encountered during the period of observation was recorded. This produced the following results:

TABLE-US-00001 Grade 0 Grade 1 Grade 2 Grade 3 Highest 0% 50% 45% 5% Grade Grade at last 16% 59% 22% 3% therapy Grade at 4 31% 50% 17% 2% weeks after last therapy

[0196] The above results demonstrate a clear shift from symptoms in Grades 2 and 3 towards symptoms in Grade 0 (i.e. no symptoms) or in Grade 1 (non-limiting symptoms) during the time when a method/device in accordance with an embodiment of the present invention was used.

Example 6

[0197] The clinical trial of Example 5 was continued, i.e. a therapy in accordance with an embodiment of the present invention was provided at 4, 7, 10 and 14 months after the last chemotherapy treatment. The trend towards Grade 0 (no symptoms) or Grade 1 (non-limiting symptoms) continued during this additional period of observation.

Example 7

[0198] Further clinical trials similar to those of Examples 3 to 6 were carried out with patients undergoing chemotherapy to treat a variety of types of cancer, including breast, gynecological, and pancreatic cancer, and using a variety of chemotherapeutic agents such as those listed above. The results in terms of AE, in particular the shift towards lower grades (according to CTCAE v5.0) as a result of the treatment in accordance with an embodiment of the present invention), were generally similar to those of Examples 3 to 6.

Example 8

[0199] The setup and the principle of the experiment in Example 8 corresponded in essence to that of Examples 1 and 2. However, the temperature control device was set to a higher target temperature of between about 15 C. and 17 C. (instead of about 10 C.). It has been found that a skin temperature (hands and feet) of between about 20 C. and 22 C. is sufficient to significantly reduce the likelihood of negative (chemotherapy-related) effects developing (such as CIPN, for example). Using the higher target temperature of about 15 C. and 17 C. (as set on the temperature control device) was found to be sufficient to result in skin temperatures of between about 20 C. and 22 C. Subjects participating in this experiment reported that cooling the skin to about 20 C. and 22 C. (using a target temperature of about 15 C. and 17 C. as set on the temperature control device) feels more pleasant than cooling the skin to the somewhat lower temperature range used in Examples 1 and 2 (target skin temperature of about 15 C. and 17 C., using a target temperature of about 10 C. as set on the temperature control device).

Example 9

[0200] The following study is being conducted:

[0201] In this trial, patients receiving Taxan-based chemotherapy regimen e.g. paclitaxel, nab-paclitaxel or docetaxel in gynecological malignancies such as ovarian cancer, breast cancer, endometrial cancer or cervical cancer will either receive cooling of hands and feet during the application of above-mentioned substances or not. The cooling will be provided by a machine called Hilotherm ChemoCare unit and will be administered constantly at a temperature of 15-17 C. Randomization will be 50:50. [0202] if a patient is randomized in the non-interventional arm, no cooling is allowed during the application of the chemotherapy.

[0203] To assess the occurance and the extent of peripheral neuropathy, a neurological examination will take place before the start of chemotherapy, in the middle of the planned cycles of chemotherapy and after the completion of the regimen.

[0204] Quality of life and the subjective impacts of peripheral neuropathy will be evaluated via questionnaires.

Inclusion Criteria:

[0205] Written consent for participation in this trail [0206] Age 18 years [0207] Female [0208] Breast or genital cancer of the woman [0209] Planned application of a Taxan-based chemotherapy regimen (Paclitaxel, Nab-Paclitaxel, Docetaxel) independent of the therapy line [0210] Taxan- and Platin-naivity [0211] Sufficient knowledge of the German language to assure an adequat survey of patient's history

Exclusion Criteria:

[0212] pre-existing peripheral polyneuropathy [0213] chemotherapy with taxan- and/or carboplatin-based regimens in a preceding therapy

[0214] Existence of one of the following diseases: Diabetes mellitus (of any type), neurological diseases that are involving peripheral nerve damage (e.g. Multiple Sclerosis, Amytrophic lateral sclerosis, Parkinson's disease), chronic pain syndrome, Cryoglobulinemia, cold hemagglutination, cold hives/cold contact hives, Raynaud's disease, significant peripheral artery disease, [0215] Lack of knowledge of German [0216] Males
Primary Outcome measures:

TABLE-US-00002 Outcome Measure Measure Description Time Frame incidence of The primary endpoint of this study is Up to one peripheral the comparison of the incidence of a year after polyneuropathy peripheral polyneuropathy (clinical the end of Total Neuropathy Score cTNS 11) in chemotherapy. patients with gynecologic malignoma that are undergoing Taxan-based chemotherapy regimen with or without a preventive hilotherapy of hands and feet.
Secondary Outcome measures:

TABLE-US-00003 Outcome Measure Measure Description Time Frame Changes in the Changes in the result of From the beginning to the result of electrophysical examinations end of chemotherapy, electrophysical before and after chemotherapy. exact time frame examinations depending on the chemotherapy regimen, assessed up to 30 weeks. Adverse effects of Adverse effects of hilotherapy Up to one year after the hilotherapy documented as any adverse end of chemotherapy. event. Tolerance of Tolerance of chemotherapy From the beginning to the chemotherapy measured as the proportion of end of chemotherapy, patient with dose reduction or exact time frame premature end of chemotherapy. depending on the chemotherapy regimen, assessed up to 30 weeks. Patient reported Quality of Life of patients Up to one year after the Quality of Life measured with the EORTC QLQ- end of chemotherapy. C30 questionnaire Residual Symptoms Comparison of the time of Up to one year after the of Chemotherapy- regression, cTNS score of end of chemotherapy. induced persisting symptoms and amount polyneuropathy of patients without residues after end of chemotherapy and follow- up between patients with and without preventive hilotherapy. Subjective extent of Subjective extent of CIPN as Up to one year after the CIPN measured with the EORTC QLQ- end of chemotherapy. CIPN20 (quality of life questionnaire regarding chemotherapy-induced peripheral neuropathy with 20 questins) questionnaire. The qustionnaire consits of 20 items on 3 scales. The minimum is 0, the maximum is 100 points. The higher the score, the worse the CIPN. Acceptance of Acceptance of hilotherapy From the beginning to the hilotherapy measured as the amount of end of chemotherapy, patients that have to stop local exact time frame cold application during a session depending on the (up to 5 minutes) or terminate chemotherapy regimen, earlier or stop the treament assessed up to 30 weeks. completely for the rest of chemotherapy.

[0217] The device is operated as follows:

Preparation

[0218] 1. Check the device for visible damage and ensure it's clean. [0219] Place the device on a stable, flat surface near the patient. [0220] Ensure cuffs (hand and foot) are available and clean. [0221] 2. Filling the Water Tank [0222] Open the water tank compartment. [0223] Fill with distilled water up to the indicated level. [0224] Close the compartment securely. [0225] 3. Powering On [0226] Connect the device to a power source. [0227] Press the power button to switch on. [0228] Wait for the system to initialize. [0229] 4. Setting the Temperature [0230] Use the menu navigation buttons to access the temperature settings. [0231] Set the desired temperature (typically 15-17 C. for CIPN prevention). [0232] Confirm the setting. [0233] 5. Connecting the Cuffs [0234] Attach the hand and foot cuffs to the designated ports on the device. [0235] Ensure connections are secure to prevent leaks. [0236] Position the cuffs on the patient's hands and feet. [0237] 6. Starting the Therapy [0238] Press the start button to begin cooling. [0239] Monitor the display to ensure the temperature remains stable. [0240] Therapy duration typically matches the chemotherapy infusion time. [0241] 7. Ending the Session [0242] Press the stop button to end the cooling session. [0243] Carefully remove the cuffs from the patient. [0244] Disconnect the cuffs from the device. [0245] 8. Post-Use Maintenance [0246] Empty and clean the water tank if needed. [0247] Disinfect cuffs according to hygiene guidelines. [0248] Store the device and accessories in a clean, dry place.

Further Findings

[0249] Common to all of the above examples was that the vast majority of patients (about 75%) felt that the cold applied by the device in accordance with an embodiment of the present invention did not result in any particular discomfort. 89 patients were asked how did you feel about the cold?; their answers were: [0250] Very comfortable: 33 patients [0251] A bit cold: 33 patients [0252] Cold: 14 patients [0253] Very cold: 7 patients [0254] Too cold: 2 patients

[0255] This contrasts with previous treatments in which ice packs, ice buckets or similar were used to cool hands and/or feet, which is considered to be very uncomfortable by patients. In addition, and perhaps more importantly, such treatments often resulted in skin and tissue damage (frost burn/paralysis) and reactive hyperemia, whereas these side effects did not occur in the clinical trials in which a method/device in accordance with an embodiment of the present invention was used.

[0256] Further, the use of a method/device in accordance with an embodiment of the present invention did not appear to affect the efficacy of the chemotherapy treatment.

LIST OF REFERENCE SIGNS

[0257] 1 temperature control device [0258] 2 heat transfer device [0259] 3 control device [0260] 4 heat transfer unit [0261] 5 temperature control fluid chamber [0262] 6 first flexible material layer [0263] 7 second flexible material layer [0264] 8 first connecting line [0265] 9 second connecting line [0266] 10 pressure device [0267] 11 pressure unit [0268] 12 support device [0269] 13 pressure chamber [0270] 14 connecting device [0271] 15 sensor device [0272] 16 display device [0273] 17 compressor [0274] 101 bringing into contact [0275] 102 applying [0276] 103 tempering [0277] 104 adjusting [0278] 105 measuring [0279] 106 controlling