A system for treatment using photodynamic therapy

Abstract

A photodynamic therapy treatment of a body cavity bounded by cells bearing a photosensitizer to provide a predetermined amount of light energy, comprising an outer hollow rod (12), an inner hollow rod inserted inside the outer rod, an inflatable balloon (18) fixed to the outer rod and in fluid communication with the interior of the outer rod, and a handle (20) made in a single piece. The handle receives an irradiation device (16) for irradiating the balloon to activate the photosensitizer. The handle and the rod are hermetically fixed to each other with a single screwing action. The irradiation time is determined by a transfer function relating each volume of the balloon to at least one of a corresponding light power distribution on its outer surface and a corresponding irradiation time for providing that amount of energy.

Description

Technical Field

[0001] The present invention relates to a system for the treatment of a patient's body cavity by photodynamic therapy, and a method of providing such a system.

[0002] Without being limited thereto, the present invention finds particular use in neurosurgery, particularly in the surgical resection of glioblastoma.

Background Art

[0003] Glioblastoma is the most frequent malignant primary brain tumor in adults, and the incidence rate in France is 4 per 10,000 people. However, this is considered a rare disease. In particular, with conventional treatments including surgery and radiotherapy / chemotherapy, the median survival period is 14.5 months. The infiltrative nature of glioblastoma somewhat explains why recurrence is inevitable. Even with a radiologically complete resection, tumor cells infiltrating adjacent healthy tissues are not adequately treated with adjuvant radiotherapy / chemotherapy, and recurrence occurs in more than 80% of cases adjacent to the resection cavity. Many studies have shown that the quality of surgical resection is often an important prognostic factor.

[0004] Therefore, optimizing local control of the quality of surgical resection is a major challenge in order to improve the survival rate without tumor progression and thereby improve the overall survival rate.

[0005] Regarding such optimization, an association with photodynamic therapy (PDT) delivered to the edge of the resection cavity has been investigated. Photodynamic therapy depends on the interaction of three elements: a photosensitizing compound, oxygen in the tissue, and light having characteristics suitable for the activation of the photosensitizing compound. The photosensitizing compound injected into the patient's body is absorbed by all cells, but remains in tumor cells for a longer time. When the photosensitizing compound is activated by light, a photochemical reaction occurs and the tumor cells are destroyed.

[0006] An example of photodynamic therapy for glioblastoma is disclosed in Lyons et al., “The effects of PDT in primary malignant brain tumours could be improved by intraoperative radiotherapy”, Photodiagnosis and Photodynamic Therapy, 2012, 9(1):40-45. Known systems for photodynamic therapy are of the type that include an irradiation device intended to irradiate the body cavity to be treated. This irradiation device includes an irradiation member extending along a central axis between opposing proximal and distal ends. This irradiation member is - A core having a light-emitting surface for emitting light adapted to activate a photosensitizing compound, the light-emitting surface being located at the distal end of the irradiating member, - A hollow sheath having a balloon positioned at the distal end of the irradiating member, and adapted to receive a core having a light-emitting surface positioned inside the balloon, The balloon is equipped with walls having an inner and outer surface that define the internal space, the walls being flexible and adapted to diffuse the light emitted by the light-emitting surface, the balloon exhibiting rotational symmetry about the central axis, an expanded state in which the internal space is filled with a light-diffusing solution to diffuse the light emitted by the light-emitting surface, and a contracted state in which the internal space is empty.

[0007] However, known systems have not been able to significantly improve survival rates. In particular, such systems require a fluence (J / cm²). 2 ) or the delivery of standardized and controlled treatments in terms of efficient pattern exposure has not been achieved globally. [Overview of the project] [Problems that the invention aims to solve]

[0008] The present invention aims to solve the above-mentioned problems in providing a system that is easier to set up and assemble than systems of the latest technology, and therefore safer.

[0009] The present invention further aims to provide a convenient, accurate, easy-to-assemble, and easy-to-handle system for doing so. Such a system reduces the time required for surgery and, therefore, significantly reduces the risks associated with anesthesia. The easy-to-handle system further reduces the risks of manipulation and the risk of sterilization failure. [Means for solving the problem]

[0010] Therefore, the present invention provides a system for photodynamic therapy of a patient's body cavity, configured to provide a predetermined amount of light energy to the patient's body cavity, which is demarcated by tissue containing cells that have absorbed a photosensitizing compound or its precursor, ○ An outer hollow rod extending along the central axis and having a distal end, ○ An inner hollow rod, configured to be inserted into the outer hollow rod, extending along its central axis and having at least a partially transparent distal end, ○ An inflatable balloon fixed to the distal end of an outer hollow rod, with its interior fluid-connected to the interior of the outer hollow rod, exhibiting rotational symmetry about its central axis, and designed to be evacuated in a controlled manner or filled with fluid to a given volume, ○Having two openings, the first opening connected to the inside of the inner hollow rod and the second opening connected to the inside of the outer hollow rod, the handle and Regarding systems that include this.

[0011] In this system, the interior of the inner hollow rod is separated from the interior of the outer hollow rod, the handle is made from a single piece, the first opening of the handle is designed to receive in a sealed state an irradiation device intended to irradiate an inflatable balloon, the irradiation device is designed to emit light adapted to activate a photosensitizing compound, the second opening of the handle is designed to connect to a pump device, the handle, outer rod and inner rod are designed to be locked together in a sealed state with a single screwing action, and a given irradiation time is determined by a transfer function that associates each given volume of the inflatable balloon with at least one of the corresponding light output distribution on the outer surface of the inflatable balloon and the corresponding irradiation time to provide a predetermined amount of light energy.

[0012] In this way, this solution can treat any type of body cavity. The volume of the inflatable balloon can be adapted to the size of any body cavity, and since the light output distribution corresponding to the volume of the inflatable balloon is known, it is possible to deliver the appropriate amount of light energy completely and uniformly.

[0013] The system according to the present invention may be equipped with one or more of the following features, either separately or in combination with each other: - The inflatable balloon can be adapted to diffuse the light emitted by the irradiation device. - An inflatable balloon can have a variable volume, is elastic, reversibly inflatable, and exhibits multiple inflated states depending on the amount of fluid contained inside the inflatable balloon. - The transfer function can relate the volume of each inflated state of an inflatable balloon to at least one of the corresponding light output distribution on the outer surface of the inflatable balloon and the corresponding irradiation time for providing a predetermined amount of light energy. - Inflatable balloons can have an elongated shape. - The distal end of the inner hollow rod can be designed to be in permanent contact with the inflatable balloon. - The inner hollow rod may be equipped with a sliding element that can slide along the central axis to allow permanent contact between the inflatable balloon and the distal end of the inner hollow rod. - The handle, outer rod, and inner rod are designed to be locked together in a sealed state with a single screwing motion. - The inner hollow rod may be equipped with a positioning device adapted to lock the distal end of an irradiation device inserted inside the inner hollow rod at a desired distance from the tip of the distal end of the inner hollow rod. - The inner hollow rod can be made flexible. - The inner hollow rod may have a centering means configured to center the inner hollow rod with respect to its central axis.

[0014] The present invention further relates to a kit for photodynamic therapy of a patient's body cavity, configured to provide a predetermined amount of light energy to the patient's body cavity, comprising a system relating to any one of the above-described technical features, an irradiation device configured to be inserted into the system, and a control unit configured to control the irradiation device.

[0015] The present invention further relates to a method for preparing a system for treatment by photodynamic therapy relating to one or more of the features described above, - The step of inserting the inner hollow rod into the outer hollow rod, - Steps include connecting the handle to the outer hollow rod, - The step of inserting the irradiation device into the inner hollow rod through the first opening of the handle, - A step of positioning and / or locking the irradiation device at a predetermined distance from the tip of the distal end of the inner hollow rod, - A step of securing the handle, the inner hollow rod, and the outer hollow rod in a sealed state, - The step of connecting the second opening of the handle to the pump device, - To enable the inflatable balloon to be completely emptied and the size of the emptied balloon to be accurately determined to set a reference value, a step of evacuating the inflatable balloon by a pump device; - A step of filling the inflatable balloon with a given volume of fluid by a pump device; - A step of determining an irradiation time by a transfer function; relates to a method including repeatedly executing the above.

[0016] The present invention also relates to a method for treating cancer in a patient who needs it by photodynamic therapy, - A step of administering a photosensitizing compound or a precursor thereof to the patient; - A step of providing a system according to any one of the features listed above or preparing a system according to the method described above; - A step of positioning the inflatable balloon of the system in the body cavity of the patient; - A step of operating an irradiation device; - A step of deactivating the irradiation device; - Optionally, a step of repeating the previous two steps once or several times; relates to a method including the above.

[0017] According to this method, the inflatable balloon can be contracted between two operations of the irradiation device, and this method can further include a step of treating the patient by immunotherapy before, simultaneously with, and / or after photodynamic therapy.

[0018] By reading one or some detailed descriptions of embodiments of the present invention given as examples below, the present invention will be better understood, and other objects, details, features, and advantages will become clearer. These are examples, not merely exemplary limitations, referring to the attached schematic diagrams.

Brief Description of the Drawings

[0019] [Figure 1]This is a schematic diagram of one embodiment of the system according to the present invention, inserted into a patient's body cavity. [Figure 2] This is a schematic diagram of one embodiment of the system according to the present invention being used in a patient's body cavity. [Figure 3a] This is a schematic diagram of the outer hollow rod according to the present invention. [Figure 3b] This is a schematic diagram of the internally hollow rod according to the present invention. [Figure 4] This is a perspective view detail of one embodiment of the system according to the present invention. [Figure 5] This is a longitudinal cross-sectional view of one embodiment of the system according to the present invention. [Figure 6] This is a graph of the transfer function of the system according to the present invention. [Modes for carrying out the invention]

[0020] As can be seen from Figure 1, the system 10 for treating a patient's body cavity 100 by photodynamic therapy according to the present invention is - Outer hollow rod 12 (see Figure 3a) and, - Inner hollow rod 14 (see Figure 3b) and, - Irradiation device 16, - Inflatable balloon 18, - Handle 20 and, Includes.

[0021] The system 10 according to the present invention is intended to be connected to a pump device 22 and a fluid reservoir 23.

[0022] In one embodiment, the patient's body cavities 100 are natural cavities, i.e., spaces or compartments that house organs and other structures. Natural cavities also include so-called “latent spaces” or “serosalic spaces,” i.e., spaces between two adjacent structures that are normally more or less pressed against each other (in other words, directly juxtaposed) and open during physiological or pathophysiological events. Examples of natural cavities include, but are not limited to, the dorsal cavities (including the cranial and spinal cavities) and the ventral cavities (including the thoracic, abdominal, and pelvic cavities). Examples of latent spaces include, but are not limited to, the two pleural cavities (right and left), the superior mediastinum, the pericardial cavity, and the peritoneal cavity. Each cavity and latent space may be subdivided into subcavities or subspaces that are well known to those skilled in the art.

[0023] In one embodiment, the patient's body cavity 100 is a surgically formed resection cavity, i.e., the space remaining after the surgical removal of a part of the body such as tissue, organ or part thereof, or a tumor, particularly a solid tumor.

[0024] "Solid tumors" means tumors and / or metastases (wherever they are located) other than lymphoma, for example: tumors of the brain and other central nervous system (tumors of the meninges, brain, spinal cord, cranial nerves, or other parts of the central nervous system, such as glioblastoma or medulloblastoma); head and / or neck cancers; breast tumors; circulatory system tumors (tumors of the heart, mediastinum, pleura, or other intrathoracic organs, as well as vascular tumors); excretory system tumors (tumors of the kidneys, renal pelvis, ureters, bladder, or other urinary organs); gastrointestinal tumors (tumors of the esophagus, stomach, small intestine, colon, colorectal, rectosigmoid junction, rectum, anus, or anal canal); liver tumors (hepatocellular carcinoma, etc.); intrahepatic bile duct tumors, gallbladder tumors, biliary tract tumors, pancreatic tumors, and tumors of other digestive organs; head and neck tumors; oral tumors (tumors of the lips, tongue, gums, floor of the mouth, palate, or other parts of the mouth). Tumors include, but are not limited to, tumors of the parotid gland, salivary gland, tonsils, oropharynx, nasopharynx, piriform sinus, hypopharynx, or lips, oral cavity, or other parts of the pharynx; tumors of the genital system (tumors of the vulva, vagina, cervix, uterine body, uterus, ovaries, or other parts associated with the female reproductive organs, as well as tumors of the penis, prostate, testes, or other parts associated with the male reproductive organs); tumors of the respiratory system (tumors of the nasal cavity, middle ear, sinuses, larynx, trachea, bronchi, pleura, or lung, such as small cell lung cancer, non-small cell lung cancer, or malignant pleural mesothelioma); tumors of the skeletal system (tumors of bone, articular cartilage of the limbs, or osteoarticular cartilage); and tumors of the skin (malignant melanoma of the skin, non-melanoma skin cancer, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, mesothelioma, Kaposi's sarcoma, etc.).

[0025] Some of the tumors listed above develop within natural body cavities, and these are called "serous carcinomas" in this field. Examples of such serosal carcinomas include, but are not limited to, nasal cancer, oral cancer, mesothelioma, malignant pleural mesothelioma, pleural metastasis, bladder cancer, uterine cancer, pancreatic cancer, esophageal cancer, gastric cancer, and peritoneal dissemination.

[0026] In one embodiment, photodynamic therapy may be performed intraoperatively, that is, during the same medical procedure as the removal of a part of the body or a tumor, or postoperatively, that is, during another medical procedure after the removal of a part of the body or a tumor.

[0027] In a particular embodiment, the solid tumor is a glioblastoma, and the patient's body cavity 100 is the result of the excision of the glioblastoma.

[0028] In a particular embodiment, the solid tumor is a malignant pleural mesothelioma, and the patient's body cavity 100 is the pleural cavity.

[0029] In certain embodiments, the solid tumor is hepatocellular carcinoma, and the patient's body cavity 100 is the result of resection of hepatocellular carcinoma, or alternatively, the patient's body cavity 100 is the abdominal cavity, for example, the space on the mesentery of the colon.

[0030] In a particular embodiment, the solid tumor is a pancreatic tumor, and the patient's body cavity 100 is the result of the resection of the pancreatic tumor.

[0031] As can be seen from Figures 3a and 5, the outer hollow rod 12 extends along the central axis X and has a proximal end 12P and a distal end 12D. The outer hollow rod 12 is preferably made of a biocompatible material, particularly a transparent or translucent material, which allows for the diffusion of light emitted by the light-emitting device 16. The outer hollow rod 12 is preferably rigid. The outer hollow rod 12 may be a device similar to a trocar, which is intended to be used by an operator to insert and guide an inflatable balloon 18 through the patient's body into and into the body cavity 100. The outer hollow rod 12 is connected to a fluid reservoir 23 and configured to be in fluid communication with the fluid reservoir 23 by a pump device 22. The pump device 22 may be a passive or active pump device 22. It may be manually or electronically actuated. It may be, for example, a syringe-type (e.g., 50 mL) pump device.

[0032] As can be seen from Figures 3b, 4, and 5, the inner hollow rod 14 also extends along the central axis X and likewise has a proximal end 14P and a distal end 14D. The inner hollow rod 14 may be made of polypropylene. The distal end 14D of the inner rod 14 is at least partially transparent and therefore comprises a transparent portion 24. The transparent portion may be made of, for example, styrene methyl methacrylate. The length of the at least partially transparent portion 24 of the distal end 14D of the inner rod 14 is 50 to 100 mm. The inner rod 14 is configured to be inserted inside the outer hollow rod 12. Both the outer rod 12 and the inner rod 14 have a length of 50 to 150 cm. The outer hollow rod has a width of 7 to 12 cm, while the inner hollow rod 14 has a width of 2 to 4 cm. The outer hollow rod 12 has a certain length.

[0033] The inner hollow rod 14 may be made of polypropylene and therefore flexible. To ensure the centering of the inner hollow rod 14 along the central axis X inside the outer hollow rod 12, the inner hollow rod 14 has a centering means 25 configured to center the inner hollow rod 14 with respect to the central axis X.

[0034] The interior of the inner hollow rod 14 is configured to receive at least a portion of the irradiation device 16 and is therefore isolated from the interior of the outer hollow rod 12 to seal the irradiation device 16 from any possible fluid circulating inside the outer hollow rod 12. The system 10 according to the present invention includes a positioning device 15. This positioning device 15 is intended to properly position the irradiation device 16 inside the inner hollow rod 14 in order to maximize the efficiency of the system 10. In some embodiments, the positioning device is located inside the handle 20. In other embodiments, the positioning device is located inside the inner hollow rod 14. In this embodiment, the positioning device 15 is adapted to lock the distal end 16D of the irradiation device 16 inserted inside the inner hollow rod 14 at a desired distance from the tip T of the distal end 14D of the inner hollow rod 14. In this embodiment, the positioning device 15 may be, for example, a graduated scale that allows adjustment of the position of a contact piece located at a specific distance from the tip of the inner hollow rod 14 inside the inner hollow rod 14, or the position of the distal end 16D of the irradiation device 16, and then locking it in place by a pinch element on, for example, the handle 20. The positioning device 15 is intended to lock the irradiation device 16 in order to optimize its position with respect to the partially transparent portion 24 of the distal end 14D of the inner rod 14 (to be checked).

[0035] The irradiation device 16 is designed to emit light. In one embodiment, as can be seen from Figure 2, the light is adapted to activate a photosensitizer that has been absorbed by tissues defining the boundaries of the patient's body cavities 100, or otherwise metabolized from a photosensitizer precursor within these tissues. As already mentioned above, treatment by photodynamic therapy (PDT) relies on the activation of a photosensitizer, the photosensitizer (or its precursor) being administered to the patient in advance and absorbed by cells in tissues defining the boundaries of the patient's body cavities 100. This activation requires specific light, which has physical properties that allow for the destruction of tumor cells into which the photosensitizer preferentially accumulates. Thus, the system 10 according to the present invention is configured to deliver a predetermined amount of light energy to the patient's body cavities 100, which are defined by tissues containing cells that have absorbed the photosensitizer.

[0036] Examples of photosensitizing compounds and their precursors are well known in the art. These include, but are not limited to, porphyrins, chlorines, and dyes. Specific examples include, but are not limited to, 5-aminolevulinic acid (ALA), verteporfin, etiopluprin, tetra(m-hydroxyphenyl)chlorine (mTHPC), motexafin lutetium, 9-acetoxy-2,7,12,17-tetrakis-(β-methoxyethyl)-porphycene (ATMPn), zinc phthalocyanine, naphthalocyanine, sodium porfimer, meso-tetrahydroxyphenylchlorine, methyl aminolevulinate, hexyl aminolevulinate, mono-L-aspartylchlorine e6 (NPe6), 2-(1-hexyloxyethyl)-2-devinylpyropheophorbide-a (HPPH), aluminum phthalocyanine sulfonate, azadipyrrometene, silicon phthalocyanine (Pc4), and their salts, prodrugs, and derivatives.

[0037] In one embodiment, the precursor of the photosensitizing compound is 5-aminolevulinic acid, which is commercially available under the trademark names Gliolan® (Medac GmbH), Gleolan® (NX Development Corp), Levulan® (DUSA Pharmaceuticals, Inc.), or Ameluz® (Biofrontera Bioscience GmbH).

[0038] In one embodiment, where photodynamic therapy is performed intraoperatively, that is, during the same medical procedure as the removal of a part of the body or a tumor, the photosensitizing compound can first be administered to the patient before the medical procedure, allowing the surgeon to visually predict the prognosis of the tumor within the body cavity 100, and then, once metabolized, to be used as a photosensitizer for photodynamic therapy.

[0039] More precisely, the irradiation device 16 is intended to irradiate the inflatable balloon 18. The irradiation device 16 may be an optical fiber connected to a laser light source. The light source may be a front light source, a cylindrical light source, or a spherical light source. It may comprise one or more ring light diffusion chips.

[0040] The irradiation device 16 may be operated for an extended period (for example, up to 2 hours continuously), or it may be operated and deactivated continuously for a shorter period, thus providing a variable irradiation time. This enables the following two different types of treatment: - Continuous treatment type ("always on" irradiation) that allows the irradiation device 16 to operate continuously for several minutes or several hours. - A fractional treatment type comprising a series of "on time" and "off time" periods in which the irradiation device 16 is activated and deactivated (on / off irradiation), with each "on time" and "off time" lasting independently for several seconds or several minutes.

[0041] More specifically, each given irradiation time is determined by a transfer function that relates any given volume V of the balloon 18 to at least one of the following: a corresponding light output distribution on the outer surface of the inflatable balloon 18 and a corresponding irradiation time to provide a predetermined amount of light energy.

[0042] The irradiation time is within the range of each value of the volume V of the inflatable balloon 18. ○Setting of light output values ​​on the outer surface of the inflatable balloon 18, ○Irradiation time to provide a predetermined amount of light energy, It can be manually controlled by an operator based on a transfer function associated with at least one of the following:

[0043] In a modified example, the irradiation time can be automatically controlled by the control unit 26. For example, in the case of a volume of 53 mL, the control unit 26 controls a predetermined amount of light energy, for example, 25 J / cm³. 2 The corresponding irradiation time is calculated. The typical amount of energy required to activate a photosensitizing compound is well known in the art and is approximately 1 J / cm². 2 ~About 40J / cm 2 It could be within the range of.

[0044] An example of a transfer function is shown in Figure 6, where the irradiation time (minutes) (axis A2) is expressed as a function of the volume V (mL) of the injected light-diffusing solution (axis A1). The volume V of the injected fluid corresponds to the volume V of the inflatable balloon 18. As can be seen from Figure 6, each volume of the light-diffusing solution is related to the corresponding irradiation time for providing a given amount of light energy.

[0045] The inflatable balloon 18 is fixed to the distal end 12D of the outer hollow rod 12. The inside of the inflatable balloon 18 is in fluid communication with the inside of the outer hollow rod 12, and therefore any fluid flowing through the inside of the outer hollow rod 12 can enter the inflatable balloon 18.

[0046] The inflatable balloon 18 is adapted by the irradiation device 16 to diffuse the light emitted more specifically by at least the partially transparent portion 24 of the distal end 14D of the inner rod 14.

[0047] The inflatable balloon 18 exhibits elastic properties and has a variable capacity, and therefore a variable volume V. Thus, it can be filled with any type of fluid from the fluid reservoir 23 and inflated to any given volume up to or below its maximum capacity of 1.5 L. In connection with the present invention, the inflatable balloon 18 is preferably filled with a light-diffusing solution. In particular, a 0.1% light-diffusing solution can be prepared by injecting 5 mL of intralipide® solution, such as the 20% intralipide solution developed by Fresenius Kabi France, into 1 L of physiological serum to form a mixture, which is then stirred until a homogeneous solution is obtained.

[0048] Since the inflatable balloon 18 is reversibly inflatable, it exhibits multiple inflated states depending on the amount of fluid injected into its interior. Therefore, the inflatable balloon 18 can be controlled by evacuating or filling it with fluid to control its volume V, and thus to fit the volume V to the patient's body cavity 100. Thus, the transfer function relates the volume V of each inflated state to at least one of the corresponding light output distribution on the outer surface of the inflatable balloon 18 and the corresponding irradiation to provide a predetermined amount of light energy. Each given volume V or inflated state is determined by the size of the patient's body cavity 100. More precisely, during operation, the inflatable balloon 18 conforms to the patient's body cavity 100 by filling its entire internal space. Thus, the inflatable balloon 18 is filled with fluid and inflates (bulges) until its walls contact the tissue defining the boundary of the body cavity 100.

[0049] The inflatable balloon 18 is inflated manually or by a pump device 22. A given volume V of the inflatable balloon 18 is recorded by the operator or stored by a control unit 26. The pump device 22 can also be controlled by the control unit 26.

[0050] To ensure regular and uniform light diffusion within the body cavity, the inflatable balloon 18 exhibits rotational symmetry about a central axis X. The inflatable balloon 18 is preferably made of transparent or translucent silicone.

[0051] To facilitate movement through the patient's body into the body cavity 100, the inflatable balloon 18 preferably has an elongated shape.

[0052] To improve the stability of the inflatable balloon 18 and maintain centering and a fully expanded state during inflation, the distal end 14D of the inner hollow rod 14 is designed to be in permanent contact with the balloon 18 by a sliding element 27 (see Figure 5) connected to either the proximal end 14P or the distal end 14D of the inner hollow rod 14. This sliding element 27 is slidable along the central axis X and allows for permanent contact between the inflatable balloon 18, preferably the tip of the inflatable balloon 18, and the distal end 14D of the inner hollow rod 14.

[0053] The handle 20 allows the operator to safely operate the system 10 during operation. The handle 20 further allows the system 10 to be securely fixed to conventional transport devices commonly found in operating rooms. These transport devices are commonly known as “instrument holding arms”. With respect to the operation, the handle 20 has an ergonomic shape to facilitate the operator's grip. In some embodiments, the handle 20 further includes a circular gripping zone 29 (see Figure 3b) specially designed for an articulated arm to securely grasp it, thus enabling the system 10 to be securely held in a given position during the operation of the irradiation device 16. In some embodiments (see Figure 4), the handle 20 is made from a single piece and connects to the proximal end 12P of the outer hollow rod 12 and the proximal end 14P of the inner hollow rod 14. Thus, a handle 20 made from a single piece can be used and fixed to the outer hollow rod 12 and the inner hollow rod 14 without the need to add sealing elements or joints to achieve liquid tightness, thus improving the practicality and efficiency of the handle 20 and, therefore, the system 10. Since the handle 20 is manufactured from a single piece, it is further possible to secure the handle 20 to the outer rod 12 and inner rod 14 with a simple manual "one-gesture". Because the handle 20 is manufactured from a single piece, it is directly possible to secure the handle 20, the outer rod 12, and the inner rod 14 to each other in a sealed state with a single screwing operation. In some embodiments, the handle 20 may comprise several parts 20A, 20B, 20C that may be movable relative to each other. However, in these embodiments, since these different parts 20A, 20B, 20C are not removable from each other, the handle 20 is still considered a single piece, and the handle 20 is still operated as a single independent technical element without the need to add sealing elements or joints to achieve liquidtightness.

[0054] Alternatively, in the embodiment shown in Figure 3b, the handle 20 comprises three parts 20A, 20B, and 20C that are movable relative to each other. All three parts 20A, 20B, and 20C are aligned along a central axis X. The central part 20B is firmly fixed to the inner hollow rod 14, and the distal part 20A and proximal part 20C are both rotatable in opposite directions around the central part 20B. As the distal part 20A and proximal part 20C rotate in a first direction around the central part 20B, the distal part 21A and proximal part 20C are screwed in / screwed out, respectively, around the central part 20B. As the distal part 20A and proximal part 20C rotate in a second direction around the central part 20B, the distal part 21A and proximal part 20C are screwed in / screwed out, respectively, around the central part 20B. To screw in / unscrew out both the distal component 21A and the proximal component 20C, they must be rotated in opposite directions. By screwing in the distal component 20A, the irradiation device 16 can be secured. By screwing in the proximal component 20C, the outer rod 12 can be secured.

[0055] The handle 20 further comprises two openings 28, 30 (see Figures 3b, 4, and 5), the first opening 28 being connected to the interior of the inner hollow rod 14, and the second opening 30 being connected to the interior of the outer hollow rod 12.

[0056] The first opening 28 of the handle 20 is designed to receive the irradiation device 16 in a sealed state in order to introduce the irradiation device 16 at least partially into the interior of the inner hollow rod 14. This can be recovered by the septum. The second opening 30 of the handle 20 is designed to connect to the pump device 22 in order to circulate the fluid both in the direction toward the inflatable balloon 18 and toward the inflatable balloon 18 from the fluid reservoir 23 through the outer hollow rod 12.

[0057] The second opening 30 is equipped with a valve 32 (see Figures 3b, 4, and 5) to control the flow of fluid either manually or by a control unit 26, either from the fluid reservoir 23 to the inflatable balloon 18 or from the inflatable balloon 18 to the fluid reservoir 23. When the valve 32 is operated manually, it is equipped with elements such as wings or handles to allow the operator to open / close it with a simple movement. In some specific embodiments, the valve 32 is a spontaneous non-automatic valve, meaning it is operated purely by mechanical means and does not require intervention from the control unit 26 or the operator. In one of these embodiments, the valve is equipped with a piece of flexible, deformable material fully inserted into the second opening 30, which forms a so-called tight plug and thus closes the second opening 30. To allow fluid to pass through the second opening 30, the flexible, deformable plug is provided with a central slit that allows the operator to push the syringe needle through the plug without having to manually open or close the valve 32, thus reducing the movement required to operate the system 10. When the syringe is withdrawn, the surfaces of the slits come together and the plug becomes tight again. A known valve corresponding to this description is the “needle-free swabable valve” by Nordson Medical.

[0058] In some embodiments, system 10 is partially or entirely disposable.

[0059] For convenience, speed, and ease of use, the handle 20, the outer hollow rod 12, and the inner hollow rod 14 are designed to be locked together in a sealed state with a single screwing motion. More precisely, the operator can easily place one hand around the handle 20 and the other hand around the distal end 12D of the outer hollow rod 12, and the elements can be sealed together when two opposing rotational movements are applied. System 10 according to the present invention is a method for preparing for treatment by photodynamic therapy, - The step of inserting the inner hollow rod 14 into the outer hollow rod 12, - Steps include connecting the handle 20 to the outer hollow rod 12, - The step of inserting the irradiation device 16 at least partially into the interior of the inner hollow rod 14 through the first opening 28 of the handle 20, - A step of positioning and / or locking the irradiation device 16 at a predetermined distance from the tip T of the distal end 14D of the inner hollow rod 14, - A step of securing the handle 20, the inner hollow rod 14, and the outer hollow rod 12 in a sealed state, - The steps include connecting the second opening 30 of the handle 20 to the pump device 22 and the fluid reservoir 23, preferably a light-diffusing solution reservoir, - The step of connecting the irradiation device 16 to the laser light source, - The steps include completely emptying the inflatable balloon 18 and using a pump device 22 to evacuate the inflatable balloon 18 so that the size of the empty inflatable balloon 18 can be accurately determined and a reference value can be set, - A step of filling the inflatable balloon 18 with a given volume V of fluid, preferably a light-diffusing solution, using a pump device 22 and a fluid reservoir 23 until the outer surface of the inflatable balloon 18 reaches and presses against the tissue defining the boundary of the patient's body cavity 100, - The transfer function (see Figure 6) is approximately 1 J / cm². 2 ~About 40J / cm 2 The steps include determining the irradiation time required to provide a predetermined amount of light energy within a given range, This enables the implementation of methods that include [this].

[0060] The present invention also relates to a method for treating cancer in patients in need by photodynamic therapy using system 10 according to the present invention.

[0061] In one embodiment, this method is - The steps include administering the photosensitizing compound or its precursor as defined above to the patient, thereby causing the cells of the tissue defining the boundaries of the patient's body cavity 100 to absorb the photosensitizing compound or its precursor, - A step of preparing the system 10 according to the method of providing the system 10 described above, - A step of positioning the inflatable balloon 18 of system 10 within the patient's body cavity 100, - Preferably, the steps include operating the irradiation device 16 for a predetermined irradiation time to provide a predetermined amount of light energy, - The step of deactivating the irradiation device 16, - Optionally, if necessary, repeat the previous two steps once or several times over a predetermined amount of time, Includes.

[0062] In one embodiment, the photosensitizing compound or its precursor may be administered orally (i.e., via an oral route) or parenterally, such as by injection via arterial, intra-articular, intracardiac, intramuscular, intraperitoneal, or intravenous injection.

[0063] An example of the implementation of both cancer treatment methods is "always-on" irradiation.

[0064] Further examples of implementing both cancer treatment methods include a series of on / off irradiations, such as a 2-minute irradiation period followed by a 2-minute period without irradiation, and then another 2-minute irradiation period.

[0065] The inflatable balloon 18 can be deflated between two operations of the irradiation device 16 to release the pressure applied to the tissue defining the boundaries of the patient's body cavity 100 by the inflated balloon 18. Therefore, when the irradiation device is not operating, the inflatable balloon 18 does not press against the tissue defining the boundaries of the patient's body cavity 100. This is made possible by the pump device 22.

[0066] The system 10 according to the present invention enables the delivery of the required amount of energy independently of the volume V of the inflatable balloon 18, that is, independently of the size of the patient's body cavity 100. Therefore, it is possible to treat body cavities 100 of all possible sizes. The irradiation time can also be adjusted to match the output of the laser light source, making it possible to use the system 10 under any kind of conditions. The light source can be controlled by a control unit 26, which may be a computer.

[0067] Furthermore, thanks to the simple and reliable control of the amount of light energy delivered provided by the system 10 according to the present invention, the treatment can be easily reproduced. This increases the efficiency of treatment by photodynamic therapy.

[0068] Furthermore, the system according to the present invention is very easy to assemble and, moreover, has a minimal number of parts, making it easy to seal together, thus improving the efficiency of use of the system 10 around the operating table and during surgery. The system 10 is operated entirely manually and does not require any additional systems to assemble and use it. Once the light source is programmed (for example by the control unit 26), the system 10 is configured to be operated entirely manually by the operator.

[0069] In one embodiment, the method for treating cancer may be performed only once, or it may be performed more than once with delays of several weeks, months, or years between each photodynamic therapy session.

[0070] In one embodiment, cancer treatment by photodynamic therapy may be further combined with immunotherapy. Such a combination is known in the art as photoimmunotherapy (PIT).

[0071] The present invention also includes a kit, in particular, - System 10 and, - At least one photosensitizing compound, - Optionally, refer to the instruction manual and This relates to a kit suitable for performing photodynamic therapy, including the following.

Claims

1. A system (10) for photodynamic therapy of a patient's body cavity (100), configured to provide a predetermined amount of light energy to the patient's body cavity (100) whose boundaries are defined by tissue containing cells that have absorbed a photosensitizing compound or a precursor thereof, An outer hollow rod (12) extending along the central axis (X) and having a distal end (12D) and a proximal end (12P), An inner hollow rod (14) is configured to be inserted into the outer hollow rod (12), extends along a central axis (X), and has a proximal end (14P) and at least partially transparent distal end (14D), An inflatable balloon (18) is fixed to the distal end (12D) of the outer hollow rod (12), its interior is in fluid communication with the interior of the outer hollow rod (12), it exhibits rotational symmetry about a central axis (X), and is designed to be evacuated in a controlled manner or filled with fluid to a given volume (V), A handle (20) having two openings, the first opening (28) connected to the inside of the inner hollow rod (14) and the second opening (30) connected to the inside of the outer hollow rod (12), Includes, The interior of the inner hollow rod (14) is separated from the interior of the outer hollow rod (12). The inside of the inner hollow rod (14) is configured to receive at least a portion of an irradiation device (16) intended for irradiating an inflatable balloon (18), thereby isolating the irradiation device (16) from any fluid that may circulate inside the outer hollow rod (12), The first opening (28) of the handle (20) is designed to receive the irradiation device (16) in a sealed state so as to be introduced at least partially into the interior of the inner hollow rod (14), and the irradiation device (16) is designed to emit light adapted to activate the photosensitizing compound. The second opening (30) of the handle (20) is designed to be connected to the pump device (22). The handle (20) consists of a single member comprising a central component (20B), a proximal component (20C), and a distal component (20A) arranged along a central axis (X), wherein the central component (20B) is firmly fixed to the proximal end (14P) of the inner hollow rod (14), the distal component (20A) is rotatable around the central component (20B) to seal and secure the irradiation device (16), and the proximal component (20C) is rotatable around the central component (20B) to seal and secure the proximal end (12P) of the outer hollow rod (12). The handle (20), the outer hollow rod (12), and the inner hollow rod (14) are designed so that the distal part (20A) and the proximal part (20C) are sealed and fixed to the central part (20B) in a single screwing operation. A given irradiation time is determined by a transfer function that associates each given volume (V) of the inflatable balloon (18) with at least one corresponding light output distribution on the outer surface of the inflatable balloon (18) and a corresponding irradiation time for providing a predetermined amount of light energy. System (10).

2. The system (10) according to claim 1, wherein the inflatable balloon (18) is adapted to diffuse the light emitted by the irradiation device (16).

3. The system (10) according to claim 1 or 2, wherein the inflatable balloon (18) has a variable volume, is elastic, is reversibly inflatable, and exhibits multiple inflated states depending on the amount of fluid contained inside the inflatable balloon (18).

4. The system (10) according to claim 3, wherein the transfer function relates the volume (V) of each inflated state of the inflatable balloon (18) to at least one of a corresponding light output distribution on the outer surface of the inflatable balloon (18) and a corresponding irradiation time for providing a predetermined amount of light energy.

5. The system (10) according to claim 1 or 2, wherein the inflatable balloon (18) has an elongated shape.

6. The system (10) according to claim 1 or 2, wherein the distal end (14D) of the inner hollow rod (14) is designed to be in permanent contact with the inflatable balloon (18).

7. The system (10) according to claim 6, wherein the inner hollow rod (14) comprises a sliding element (27) that is slidable along a central axis (X) to enable permanent contact between the inflatable balloon (18) and the distal end (14D) of the inner hollow rod (14).

8. The system (10) according to claim 1 or 2, wherein the inner hollow rod (14) comprises a positioning device (15) adapted to position and lock the distal end (16D) of an irradiation device (16) inserted inside the inner hollow rod (14) at a desired distance from the tip (T) of the distal end (14D) of the inner hollow rod (14).

9. The system (10) according to claim 1 or 2, wherein the inner hollow rod (14) is flexible.

10. The system (10) according to claim 1 or 2, wherein the inner hollow rod (14) has a centering means (25) for the purpose of centering the inner hollow rod (14) with respect to a central axis (X).

11. A kit for photodynamic therapy of a patient's body cavity (100), configured to provide a predetermined amount of light energy to the patient's body cavity (100), comprising: a system (10) according to claim 1 or 2; an irradiation device (16) configured to be inserted into the system (10); and a control unit (26) configured to control the irradiation device.

12. A method for preparing a system (10) for treatment by photodynamic therapy according to claim 1 or 2, - The step of inserting the inner hollow rod (14) into the outer hollow rod (12), - The step of connecting the handle (20) to the outer hollow rod (12), - The step of inserting the irradiation device (16) into the interior of the inner hollow rod (14) through the first opening (28) of the handle (20), - A step of positioning and / or locking the irradiation device (16) at a predetermined distance from the tip (T) of the distal end (14D) of the inner hollow rod (14), - A step of fixing the handle (20), the inner hollow rod (14), and the outer hollow rod (12) in a sealed state, - The step of connecting the second opening (30) of the handle (20) to the pump device (22), - A step of evacuating the inflatable balloon (18) with a pump device (22) in order to completely empty the inflatable balloon (18), to accurately determine the size of the empty balloon (18), and to set a reference, - A step of filling an inflatable balloon (18) with a given volume (V) of fluid using a pump device (22), - A step of determining the irradiation time by the transfer function, A method that involves repeatedly performing the same action.

Images