Abstract:
The invention relates to a device for radiation treatment of proliferative tissue surrounding a cavity in an animal body comprising a radiation delivering means for placing at least one energy emitting source at a desired position within the cavity for performing radiation treatment. The device includes at least one permanent implant element for placement in the body cavity that is made from a non-deformable material and has an outer surface around which the inner surface of the body cavity will adapt or conform itself. The invention aims to provide a device and method for radiation treatment of proliferative tissue surrounding a cavity in an animal body, wherein the radiation treatment is performed in a far more accurate and reproducible manner and wherein the device causes far less discomfort to the patient.

Description:
BRIEF SUMMARY OF THE INVENTION 
   The invention relates to a device for radiation treatment of proliferative tissue surrounding a cavity in an animal body comprising radiation delivering means for placing at least one energy emitting source at a desired position within said cavity for performing said radiation treatment. 
   The invention also relates to an implant element to be implanted into a cavity in an animal body for radiation treatment of proliferative tissue surrounding said cavity. 
   The invention also relates to a method for performing radiation treatment of proliferative tissue surrounding a cavity in an animal body comprising the steps of:
     A removing in a first surgical step a tumour from said animal body thereby creating said cavity;   B placing a brachytherapy applicator within said cavity;   C inserting at least one energy emitting source in said brachytherapy applicator at a desired position relative to said cavity for performing said radiation treatment;   D after a predetermined time removing said at least one energy emitting source after performing said radiation treatment.   

   A device according to the preamble is also indicated as a brachytherapy applicator and is for example known from the U.S. Pat. No. 5,492,582. In U.S. Pat. No. 5,492,582 a method and apparatus are described for treating tissue surrounding a surgically excised tumour with radioactive emission to kill any cancer cells that may be present in the margins surrounding the excised tumour. Following surgical removal of a tumour, say in the brain or breast, a supportive probe having an inflatable chamber connected at a distal end thereof is introduced into the cavity caused by the removal of the tumour. 
   A significant drawback of the known so-called “inflatable” devices is that the inflatable chamber or balloon is deformable adversely affecting the desired (read: correct) radiation dose distribution to the tissue to be treated. 
   Furthermore after the treatment the device is deflated and removed from the cavity of the patient. The removal of the device requires a second discomforting surgical procedure, which can be painful. Also the part of the device extending outside the patients body causes much discomfort to the patient in between subsequent treatment sessions. 
   The invention aims to obviate the above known drawbacks and to provide a device and method for radiation treatment of proliferative tissue surrounding a cavity in an animal body, wherein the radiation treatment is performed in a far more accurate and reproducible manner and wherein the device causes far less discomfort to the patient. 
   According to the invention said device comprises at least one permanent implant element for placement in said body cavity, said at least one element being made from a non-deformable material and having an outer surface being conformal to the inner surface of said body cavity. 
   Due to the permanent implant of the element into the cavity surrounding the tissue to be treated by radiation no discomfort is caused to the patient as subsequent removal and reintroduction in the cavity. 
   As the implant element is non-deformable and the outer surface has a shape/dimension that is conformal to that of the inner surface of the cavity (being the tissue layer to be treated) deformation of the surface of balloon system of the device is avoided and hence the radiation dose distributions will correspond with the intended, preplanned distribution and will be identical during subsequent treatment sessions. 
   According to an embodiment of the device according to the invention said non-deformable element is provided with at least one insertion hole for guiding said at least one energy emitting source inside said cavity. As stated above this will allow the positioning of an energy emitting source in an accurate, reproducible manner during subsequent treatment sessions improving the overall radiation treatment significantly. 
   More in particular said at least one insertion hole serves to accommodate a hollow guiding tube having a distal end to be inserted into said insertion hole and a proximal end remaining exposed outside said animal body. 
   An accurate positioning of the energy emitting sources within the cavity is further improved as according to the invention said device comprises fixating means for fixating said proximal end of said guiding tube relative to said animal body. 
   The device may also comprise further fixating means for fixating the device inside the cavity to the tissue surrounding the cavity. This latter fixating step is performed following surgical removal of the tumour. 
   According to the invention the device is further characterized in that said at least one guiding tube serves to accommodate a hollow catheter tube having a distal end to be inserted into said guiding tube and a proximal end to be connected to an afterloader apparatus, wherein moreover said at least one energy emitting source is contained in said afterloader apparatus and guided through said hollow catheter tube toward said cavity using a source wire having a distal end connected to said energy emitting source. 
   According to a embodiment of the implantable element said element consists of an outer shell part surrounding an inner core part. In one preferred embodiment at least said inner core part is manufactured from a non-absorbable, bio-compatible material, for example from a filling material, for example from expandable poly-vinyl-alcohol (PVA), poly-ethylene-glycol, a saline solution, silicone gel or stabilized semisolid fibrin. 
   In another embodiment said outer shell part can be made from a resilient material, for example from silicon. 
   In yet another embodiment said outer shell part and/or inner core part of said non-absorbable, bio-compatible element can be manufactured from a porous poly-ethylene material and more in particular from expanded polytetra-fluoroethylene (e-PTEE). 
   The implant elements made from such porous poly-ethylene material are flexible and soft. It is also possible to use as a material a “mesh structure” commercially available by Atrium Medical Corporation. The implant element made from a porous material encourages the body&#39;s tissue to grow into the implant element thereby improving the recovery of the patient. Moreover the need for a second painful, discomforting surgery procedure in order to remove the implant element after treatment is herewith obviated. 
   Another embodiment of the element according to invention is characterized in that at least said outer shell part is manufactured from a bio-absorbable material, for example from poly-lactide, wherein the inner core part is made from one of the materials listed above. In this embodiment the outer shell part is allowed to be absorbed by the patient&#39;s body, whereas a non-absorbable, bio-compatible inner core part remains inside the patient&#39;s body. In the case of an inner core part of a porous material like stabilized semisolid fibrin of a porous material, like poly-ethylene the body&#39;s tissue grow into the implant element is encouraged. 
   Also both the outer shell part and inner core part can be made from a bio-absorbable material. In this latter example the whole element is allowed to be absorbed by the patients body after treatment leaving no non-body materials behind in the patient. 
   A specific embodiment of the element according to the invention consists of an outer shell part surrounding an inner open core part. 
   Both the bio-absorbable and the non-absorbable, bio-compatible implant element may in a specific embodiment consist of at least two separate interconnected element parts, this in order to facilitate the implant of the element in the cavity to be treated. In a specific embodiment said implant element parts may be semi-spherical or ovoid. 
   Furthermore said separate element parts are each provided with cooperating connection means, wherein said connection means may comprise multiple protrusions and corresponding openings provided on said element parts. This guarantees the preservation of the outer dimensions of the implant element after implant within the cavity even during subsequent radiation treatment, thereby maintaining a reproducible radiation dose distribution. 
   According to another, beneficial embodiment according to the invention said device is composed from two or more permanent implant elements, which two or more permanent implant elements are interconnected to each other using interconnecting means. 
   Said interconnecting means may comprise elongated shaped interconnecting elements having a first and second end, which first and second ends fit in corresponding openings present in the outer surface of said permanent implant elements. 
   According to one embodiment said elongated shaped interconnecting elements exhibit a straight configuration, whereas in another embodiment said elongated shaped interconnecting elements exhibit a bent configuration, for example shaped as a 90° degree arc. 
   The method according to the invention is further characterized in that step B consists of the step of
     E positioning an implant element according to anyone of the preceding claims into said cavity; and   F leaving said implant element into said cavity after performing step C.   

   The guiding tubes, which to be inserted into the insertion holes of the permanent implant element can be likewise be manufactured from one of said non-absorbable, bio-compatible materials mentioned above. The guiding tubes can also be manufactured from a bio-absorbable material, for example from poly-lactide. 

   
     BRIEF DESCRIPTION OF THE DRAWINGS 
     The invention will be now described with reference to the accompanying drawings, which drawings show in: 
       FIGS. 1   a - 1   d  a first embodiment of a device according to the invention shown in subsequent steps of the method according to the invention; 
       FIGS. 2   a - 2   b  a second embodiment of a device according to the invention; 
       FIGS. 3   a - 3   b  a third and fourth embodiment of a device according to the invention; 
       FIG. 4  a fifth embodiment of a device according to the invention; 
       FIG. 5  an embodiment of a device according to the invention connected to an after loader device. 
   

   For the sake of clarity the corresponding parts in the different embodiments will be denoted with identical reference numerals. 
   DETAILED DESCRIPTION OF THE INVENTION 
     FIGS. 1   a - 1   b  disclose a first embodiment of the device according to the invention as shown in subsequent steps of the method according to the invention. 
   The device and method according to the invention will now be described by means of the radiation treatment of proliferative tissue surrounding a cancer tumour for example in a women&#39;s breast. 
   In an known first step of the method according to the prior art the cancer tumour is removed by surgery from the patient&#39;s body (the women&#39;s breast  1 ) thereby creating a surgical incision wound  4  and a cavity  3  where the tumour is excised from ( FIG. 1   a ). In the next step of the method according to the invention a non-deformable element  10  is placed via said surgical incision wound  4  into said body cavity  3  after which the surgical incision wound  4  is closed. The implant element  10  being part of the device according to the invention is intended for permanent placement in the patient&#39;s body  1  and is made of a non-deformable material containing an outer surface  10   a  being conformal to the inner surface of the body cavity  3 . 
   As shown in  FIG. 1   b  said non-deformable element  10  is provided with at least one insertion hole  11 , which serves to accommodate a hollow guiding tube  12 . The hollow guiding tube  12  exhibits a distal end  12   b  for insertion into said insertion hole  11  and a proximal end  12   a  which remains exposed outside the patient&#39;s body  1 . 
   As the implant element  10  is made of a non-deformable material an exact orientation of the guiding tube  12  in the corresponding insertion hole  11  is accurately maintained. The accurate position or orientation of the hollow guiding tube  12  within the insertion hole  11  of the implant element  10  is further assured as according to the invention the device comprises fixating means  13  for fixating the proximal end  12   a  of the guiding tube  12  relative to the skin  2  of the patient&#39;s body  1 . The fixating means  13  may comprise a clamping element, which clamping element, after shifting it over the proximal end  12   a  against the skin surface  2 , can be clammed against the circumferential surface of the proximal end  12   a . The clamping element  13  can also be adhered against the skin surface  2  using a glue or adhesive film. 
   All guiding tubes  12  to be used with the intended radiation treatment are placed in the corresponding insertion holes  11  present in the outer surface  10   a  of the permanent implant element  10  prior to the implant of said implant element  10  in said body cavity. Hence once the cancer tumour is removed by surgery from the patient&#39;s body (the women&#39;s breast  1 ) the assembly of permanent implant element  10  with pre-positioned guiding tubes  12  is placed via the surgical incision wound  4  into the body cavity  3  where the tumour is excised from (see  FIG. 1   a ). 
   The proximal ends  12   a  of each guiding tube  12  remain exposed outside the patient&#39;s body  1  once the surgical incision wound  4  is closed. Subsequently one or more hollow catheter tubes  19  are inserted with their distal end  19   b  via the proximal end  12   a  of a corresponding guiding tube  12  until said distal end  19   b  reaches the distal end  12   b  of the guiding tube  12 . This situation is depicted in  FIG. 1   c.    
   Each hollow catheter tube  19  comprises also a proximal end  19   a , which is to be connected to an after loader apparatus (not shown in  FIG. 1   c ). For performing the radiation treatment of the proliferative tissue now surrounding the implant element  10  a source wire  14  is advanced from said after loader apparatus through the hollow catheter tube  19  and the hollow guiding tube  12  towards the distal end  12   b  thereof within the implant element  10 . See again  FIG. 1   c.    
   An energy emitting source  15  is connected to the distal end  14   b  of the source wire  14  and is advanced by said source wire  14  from the after loader apparatus until within the implant element  10 . The energy emitting source may be a radioactive source emitting radiation according to a natural decay sequence. However the energy emitting source  15  can also be a High Dose Rate or Pulse Dose Rate source, for example an Ir-192 source. The energy emitting source can also be a miniature X-ray source. 
   Once the radiation treatment session has been performed after a specific preplanned time the source wire  14  is retracted together with the energy emitting source  15  through the hollow guiding tube  12  and the hollow catheter tube  19  back into the after loader apparatus. The hollow catheter tube(s)  19  is (are) then also retracted from the guiding tube(s)  12 . 
   The guiding tube  12  remains within the patient&#39;s body and the implant element  10  in between subsequent radiation treatment sessions and during that prolonged period of time the patient is allowed to move freely, even outside the hospital, whereas the guiding tube  12  remains within the implant element  10 . As the guiding tube  12  is fixed by means of the fixating means  13  to the skin  2  of the patient an accurate and reproducible orientation of the guiding tube  12  relative to the patient&#39;s body is maintained, allowing subsequent radiation treatment sessions to be performed. As the patient is allowed to move freely between subsequent radiation treatments, even outside the hospital the implant element  10  within the cavity of the patient&#39;s body and the guiding tube  12  being exposed outside the patient&#39;s body  1  discomforts the patient to a minimum. 
   As the repositioning of the energy emitting source can be accurately reproduced identical subsequent radiation treatment sessions can be performed, resulting in a very precise overall radiation treatment where the actual radiation dose being administrated accurately conforms the desired, preplanned radiation dose. 
   Once the overall radiation treatment has been performed the guiding tube  12  is removed from the implant element  10  and the implant element  10  together with the empty insertion hole  11  remains within the body cavity  3 . Once the insertion wound created by the guiding tube  12  is healed the presence of the implant element  10  will become invisible from the outside. This stage of the method step according to the invention is shown in  FIG. 1   d.    
     FIGS. 1   a - 1   d  also disclose a specific embodiment of the implant element  10  according to the invention. The implant element  10  is composed of an outer shell part  10   a  surrounding an inner core part  10   b . Preferably the outer shell part is made from a resilient material, for example from silicon, whereas the inner core part is made from a filling material, for example from expandable poly-vinyl-alcohol (PVA), poly-ethylene-glycol, a saline solution, silicone gel. 
   In another embodiment the implant element  10  is manufactured from a bio-absorbable material, for example from poly-lactide. Once the radiation treatment has been performed and the implant element  10  is left inside the patient&#39;s body  1 , the element  10  being made from poly-lactide will be gradually absorbed by the patient&#39;s body until the whole implant element has disappeared. 
   In the embodiment of  FIG. 2   a  the implant element  10  is provided with multiple insertion holes  11 - 11 ′- 11 ″ for accommodating corresponding hollow guiding tubes  12 - 12 ′- 12 ″. Also in the embodiment as shown in  FIG. 2   a  each guiding tube  12 - 12 ′- 12 ″ is fixated to the skin  2  of the patient&#39;s body  1  by using suitable fixating means  13 - 13 ′- 13 ″. 
   As stated above it is preferred to place the assembly of permanent implant element  10  with pre-positioned guiding tubes  12  via the surgical incision wound  4  into the body cavity  3  where the tumour is excised from (see  FIG. 1   a ). 
   According to the invention and as shown in  FIG. 2   b  the implant element  10  has a spherical shape with one or more insertion holes  11  present in the surface  10   a  and extending until the interior of the implant element  10 . Into the insertion holes  11  corresponding guiding tubes  12  are to be inserted. 
   An advantageous embodiment of the implant element  10  according to the invention is shown in  FIGS. 3   a  and  3   b , wherein the implant element  10  is composed of two more or less identical parts  10 ′- 10 ″, which element parts are constructed as semi-sphericals. Each element part  10 ′- 10 ″ comprises a surface or outer shell part  10   a ′- 10   a ″ and an open inner core part  10   b ′- 10   b ″ (hence where no implant element material is present). 
   However the element parts  10 ′- 10 ″ can also exhibit other spatial shapes, like an ovoid shape or other geometrical shapes. 
   Additionally the outer surface of the element parts  10 ′- 10 ″ can be perforated or otherwise be provided with holes. 
   The separate semi-spherical element parts  10 ′- 10 ″ allows an easy insertion into the cavity  3  via the surgical incision wound  4  as created in order to remove the cancerous tumour from the patient&#39;s body  1  (see  FIG. 1   a ). In order to compose the implant element  10  from both implant parts  10 ′- 10 ″, both semi-spherical element parts are provided with a circular contact surface  16 . When the implant element  10  is composed of both element parts  10 ′- 10 ″ both element parts abut against each other a long said contact surfaces  16 . In order to maintain the abutment of both element parts  10 ′- 10 ″ both abutment surfaces  16  are provided with interacting connection means  17 - 18 . 
     FIG. 3   a  shown a first embodiment of said connection means, wherein the first element part  10 ′ is provided with multiple openings  18  present within said abutment surface  16 , whereas the other implant element  10 ″ is provided with corresponding protrusions  17  which are also present on the abutment surface  16 . When composing the implant element  10  from both element parts  10 ′- 10 ″ the protrusions  17  fit in said corresponding openings  18  and the connection between both element parts  10 ′- 10 ″ is assured as the protrusions  17  are provided with a click mechanism preventing an unintentional and undesired detachment of both element parts  10 ′- 10 ″ for example due to abrupt movements of the patient&#39;s body or impacts on said patient&#39;s body. 
   Another embodiment as shown in  FIG. 3   b  discloses two element parts  10 ′- 10 ″ which are identical as they both comprise openings  18  and protrusions  17  which engage with each other when both element parts  10 ′- 10 ″ are placed against each other. 
     FIGS. 4   a - 4   b  disclose other embodiments of the device according to the invention. In  FIGS. 4   a - 4   b  the device is composed as a kit-assembly of a plurality (two or more) permanent implant elements  100 - 100 ′- 100 ″-etc. The kit-assembly of multiple permanent implant elements  100 - 100 ′- 100 ″-etc. are interconnected with each other by means of interconnecting means  40 - 41 - 42 . The interconnecting means comprise different elongated shaped interconnection elements  40 - 41 , each having a first and a second end  40   a - 40   b  respectively  41   a - 41   b , which first and second ends fit in corresponding openings  30 - 30 ′- 30 ″ present in the outer surface of said permanent implant elements  100 - 100 ′- 100 ″. 
   As depicted in  FIG. 4   a , one embodiment of said elongated shaped interconnecting elements exhibit a straight configuration and is depicted with reference numeral  40 . Another embodiment of the elongated shaped interconnecting elements exhibit a bent configuration and more particular said bent shaped interconnecting element  41  is shaped as an arc of 90°. When fitting multiple permanent implant elements  100 - 100 ′- 100 ″-etc. any three dimensional configuration can be constructed using the interconnecting means  40  (straight) or  41  (90° degree arc). The three dimensional shaped constructions using multiple permanent implant elements can be spheres, cylinders or other angular geometrical shapes. 
   Like the permanent implant devices also the interconnecting elements  40 - 41  can be manufactured from bio-compatible, non-absorbable materials or from bio-absorbable materials as discussed in this application. 
   Using suitable fixation elements  42  the interconnecting elements  40 - 41  can be held in place when inserted into the connecting openings  30 - 30 ′- 30 ″ present in the permanent implant elements  100 - 100 ′- 100 ″. As each permanent implant element  100 - 100 ′- 100 ″ is provided with one or more insertion holes  11 - 11 ′- 11 ″ in which the guiding tubes  12  (not depicted) are to be inserted a well defined three dimensional orientation of the positions where the energy emitting sources are to be placed (using the catheter tubes and the source wires as discussed previously in this application) can be obtained depending on the radiation therapy treatment to be performed on the proliferative tissue surrounding the cavity. 
   Preferably each permanent implant element  100 - 100 ′- 100 ″ is in this specific three-dimensional constructional embodiment shaped as a sphere and provided with 1-6 openings or holes  30 - 30 ′- 30 ″ located at certain angles on the outer surface of the permanent implant elements  100 - 100 ′- 100 ″ in order to allow the unambiguous construction of variable three dimensional geometries like letters structures, or imitations of carbon allotropes, like diamond, graphite, buckeyballs, buckeytubes, etc. 
   An example of a kit-assembly of the device according to the invention is disclosed in  FIG. 4   b , wherein multiple implant elements  100  are interconnected with the use of straight interconnecting elements  40  and 90° arc-shaped interconnecting elements  41 , thus creating a spherical assembly of an implant device according to the invention. 
   Likewise, the guiding tubes  12 , which to be inserted into the insertion holes  11  of the permanent implant element  10  according to the invention can be likewise be manufactured from one of said non-absorbable, bio-compatible materials mentioned above. The guiding tubes  12  can also be manufactured from a bio-absorbable material, for example from poly-lactide. 
   Besides eliminating the need for a second, painful, discomforting surgical procedure (for removing the implant element after treatment) the use of the bio-degradable or bio-absorbable materials offers other advantages. The use of bio-degradable polymers for manufacturing the implant element  10  (and the guiding tubes  12 ) stimulates tissue growth around the implant element after placement into the body cavity. The bio-degradable polymers exhibit a certain degree of porosity and form a matrix on which the cell growth of the tissue surrounding the implanted elements and guiding tubes is stimulated. The polymer matrix may represent the device itself, and it serves also as a “scaffold” for cell growth. 
   Also the use of non-absorbable but bio-compatible materials especially expanded polytetrafluro-ethylene (e-PTFE) stimulate tissue growth around, but especially inside the implant elements. These implants are flexible and soft. The implants are thin-walled tubes consisting of a soft, high-porosity center that is surrounded by a smooth medium porosity outer layer. This tube shape encourages the body&#39;s tissue to grow into the implants. 
   In  FIG. 5  an application of the device according to the invention is disclosed wherein the implant element  10  is provided with three insertion holes  11 ′- 11 ″ in which corresponding guiding tubes  12 ′- 12 ″ are accommodated. To their proximal ends being exposed outside the patient&#39;s body  1  hollow catheter tubes  19  are connected with their proximal ends  19   b , which catheter tubes  19  are connected to an after loader apparatus  20  with their proximal ends  19   a.    
   As disclosed in  FIG. 1   c  through said plurality of catheter tubes  19  a source wire  14  is advanced to which distal end  14   b  an energy emitting source  15  is connected. With the after loader apparatus  20  one or more energy emitting sources  15  can be advanced through the hollow catheter tubes  19 - 19 ′- 19 ″ and through the corresponding guiding tube  12 - 12 ′- 12 ″ towards different positions within the implant element  10  and relative to the proliferative tissue  3  to be treated by radiation and surrounding the implant element  10 . 
   With the device according to the invention having multiple insertion holes  11 - 11 ′- 11 ″-etc. it is possible to position several energy emitting sources  15  at the same time and at different locations within the implant element  10  and relative to the proliferative tissue  3  to be treated by radiation. The exact position of each energy emitting source in each guiding tube  12  relative to the proliferative tissue  3  is controlled by the after loader apparatus  20  based on a preplanned desired radiation dose distribution. 
   It is also possible to use one single energy emitting source which is advanced in succession through the several hollow catheter tubes  19 - 19 ′- 19 ″ towards different positions within the implant element  10 . The position of the single energy emitting source within each insertion hole  11 - 11 ′- 11 ″-etc. as well as its dwell time at said location is again controlled by the after loader apparatus  20  based on a radiation therapy pre-plan. 
   As the orientation of the implant element and the guiding tubes  12 - 12 ′- 12 ″ is maintained during the overall radiation treatment the single energy emitting source or multiple energy emitting sources are inserted in a reproducible manner into each guiding tube  12 - 12 ′- 12 ″ towards their desired position within the implant needle  10  during subsequent radiation treatment sessions, which are therefore identical, resulting in a very precise overall radiation treatment.