Abstract:
The present disclosure relates to an implant comprising at least two sheets of a biocompatible material, and at least one radioactive seed disposed between said sheets of material. The disclosure also relates to a method for treating a patient, comprising fixing to the tissue of the patient at least one implant comprising at least two sheets of a biocompatible material, and at least one radioactive seed disposed between said sheets of material.

Description:
BACKGROUND 
       [0001]    Bodily cancers are commonly treated using radiation therapy. Radiation therapy employs high energy radiation to kill cancer cells. One type of radiation therapy is brachytherapy, in which a source of radiation is in direct contact with an afflicted tissue. A common brachytherapy treatment, transperineal seed implantation, involves placing radioactive seeds in the prostate gland to kill prostate gland cancer cells. A physician employs tools such as ultrasound, computerized tomography (“CT”) scans, and X-ray images in concert with dose-planning computer software programs to evaluate the medical condition of a patient. The physician constructs an optimal treatment plan to evenly distribute radiation throughout the afflicted tissue. Radioactive seeds of discrete radioactive strengths are inserted through multiple implantation needles at positions in the prostate gland corresponding to the treatment plan. Multiple implantation needles are required to insert the radioactive seeds into multiple locations in the afflicted tissue, with each needle containing a specified arrangement of the radioactive seeds. 
         [0002]    Although brachytherapy is perhaps most often effected by needle implantation, other implantation methods have also been used. One example is a configuration employing seeds and sutures. To make such a configuration, the physicians have utilized a seed product (e.g., Seed in Carrier, manufactured by Oncura) that consists of seeds disposed within a suture material. The sutures are weaved through a piece of bioabsorbable fabric to yield a planar array of seeds. This array is then used to irradiate a tumor bed, most commonly following a lung resection, by sewing the array to the wall of the tumor bed. 
         [0003]    Gross surgical removal of tumorous tissue can leave behind traces of cancerous tissue which can result in mestatasis or recurrence of the tumor. Thus, the site of removal of a tumor is often treated postoperatively in an attempt to destroy any such diseased tissue left behind by the surgery. Conventional techniques for treating the site of surgical removal of a tumor include post-operative administration of radiation, chemotherapy, and/or heat. Another method is disclosed in U.S. Pat. No. 5,030,195, the disclosure of which is incorporated by reference herein. In accordance with that disclosure, seeds can be threaded into a mesh, and the mesh embedded in a nonabsorbable silicone compound. Once the exact location and extent of a tumor is determined, the tumor is removed, and the mesh/silicone material is embedded in a region where residual tumor cells may exist. 
         [0004]    Proper seed placement and seed retention at the implantation site strongly influence the success or failure of a brachytherapy procedure. As described above, seed implantation devices may contain a plurality of seeds that may be separated by spacers. Prior implantation devices and methods do not reliably maintain proper seed spacing during and after implantation. Therefore, a device and/or method of reliably maintaining proper seed spacing during and after implantation would be of great benefit to brachytherapy patients. 
         [0005]    Loose seeds implanted in the prostate, especially those that are extra-capsular (located outside the capsule of the prostate), may possibly migrate within the patient. Because extra-capsular tissue is less dense than tissue within the capsule of, e.g., the prostate, prior brachytherapy seed implantation devices and methods cannot effectively maintain the location of seeds in the extra-capsular material. These seeds may migrate and fail to provide radiation where needed. Migrating radioactive seeds not only fail to provide needed radiation therapy at the treatment site, but may cause damage to other radiation-sensitive areas of the body. Therefore, a device and/or method of preventing migration of radioactive seeds in tissues and/or fluids of varying densities and consistencies would be of great benefit to brachytherapy patients. 
         [0006]    In view of the above, it would be desirable to have an implant, whether standard or custom, that is capable of delivering radiation to a patent in need thereof without the above-mentioned disadvantages. 
       SUMMARY 
       [0007]    According to one aspect of the present disclosure, there is provided an implant comprising at least two sheets of a biocompatible material, and at least one radioactive seed disposed between said sheets of material. 
         [0008]    According to another aspect of the present disclosure, there is provided a method for treating a patient, comprising fixing to the tissue of the patient at least one implant comprising at least two sheets of a biocompatible material, and at least one radioactive seed disposed between said sheets of material. 
         [0009]    According to yet another aspect of the present disclosure, there is provided a method for treating a patient, comprising surgically excising at least a portion of a tumor from surrounding tissue, and providing at least one implant at the locus of said surrounding tissue, wherein the implant comprises at least two sheets of a biocompatible material, and at least one radioactive seed disposed between said sheets of material. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0010]    The disclosed embodiments can be better understood with reference to the following drawing. The components in the drawing are not necessarily to scale. 
           [0011]      FIG. 1 , according to various embodiments, is an illustration of an implant in accordance with the present disclosure. 
           [0012]      FIG. 2 , according to various embodiments, is a detailed illustration of an implant having radioactive seeds in accordance with the present disclosure. 
           [0013]      FIG. 3 , according to various embodiments, is an overall illustration of an implant having radioactive seeds in accordance with the present disclosure. 
           [0014]      FIG. 4 , according to various embodiments, is a detailed illustration of an alternative embodiment of an implant having radioactive seeds in accordance with the present disclosure. 
           [0015]      FIG. 5 , according to various embodiments, is an overall illustration of an alternative embodiment of an implant having radioactive seeds in accordance with the present disclosure. 
           [0016]      FIG. 6 , according to various embodiments, is an overall illustration of an implant having radioactive seeds in a predetermined pattern in accordance with the present disclosure. 
           [0017]      FIG. 7 , according to various embodiments, is an overall illustration of an implant having radioactive seeds in another predetermined pattern in accordance with the present disclosure. 
       
    
    
     DESCRIPTION 
       [0018]    According to various embodiments, the present disclosure relates to an implant comprising at least one seed in a carrier. For example, the implant comprises a plurality of seeds. The implant can comprise an array, for example a planar array, of seeds. The seeds can be disposed in an array on the material, based on horizontal and vertical separation of the seeds. The implant can also comprise seeds arranged in a three dimensional construction. For example, the seeds can be disposed in a flexible mass (such as a sphere) of mesh that could be collapsed, inserted into a body cavity and allowed to naturally expand to fill the cavity. According to various embodiments, the mass could be flexible enough to conform to an area that would not be perfectly spherical. According to various embodiments, the mass could be expanded and/or compressed to a shape by natural stresses or forces. 
         [0019]    According to various embodiments of the disclosure, the array can be provided pre-made, or standardized, with definite spacing between the seeds. This known array allows calculation of dosimetry to the treated area. The array could be constructed with a standard spacing, or be customized to a seed pattern desired by the end user. For example, the carrier could be provided without radioactive seeds and with provisions in the carrier, such as pouches or slits, to allow for loading of individual seeds by the end user. In this manner, the seeds can be disposed in the carrier with either standardized or customized spacing. A discrete seed spacing could be advantageous in that the end user would not have to weave a suture containing seeds into a mesh. This could provide a time savings, and could ensure that the seeds would have a definite spacing (independent of the skill of the end user in weaving a filament of seeds) and provide reproducible and calculable dosimetry. 
         [0020]    According to various embodiments, the implant comprises a bioabsorbable or permanent carrier. Alternatively, the implant can comprise both bioabsorbable and permanent components in the carrier. The use of either a bioabsorbable or permanent carrier allows the physician to tailor the mechanical properties of the implant to fit the tumor type or location of the tumor/tumor bed. 
         [0021]    There is a variety of radioactive seeds that can be used in accordance with the present disclosure. Suitable non-limiting examples of such seeds include, for example, I 125 , Pd 103 , Cs 131 , Au 198 , Co 60 , and Ir 192 . Those of ordinary skill in the art will appreciate that any seed or radioactive particle capable of providing a therapeutic dose of radiation can be used. Seeds can be made of a number of different materials known to the ordinary practitioner. For example, the seeds can be in the form of a metallic capsule, a polymer, a ceramic, a ribbon, or can be particulate in nature. Any form capable of providing the desired dose of radiation can be used. 
         [0022]    The implant can comprise a variety of materials (in addition to the seeds). For example, the seeds can be entrained within a non-absorbable mesh. Suitable non-absorbable meshes are well-known, and include those disclosed in, for example, U.S. Pat. No. 6,971,252 (the disclosure of which is incorporated by reference herein). The meshes can be constructed of at least one of polypropylene, polyester, stainless steel, titanium, carbon fiber, nitinol, and other materials. According to various embodiments, the seeds can be entrained in a non-absorbable material, such as a non-absorbable polymeric sheet. Suitable non-limiting examples of polymeric sheets include polyurethane and silicone. 
         [0023]    According to various embodiments, the seeds can be entrained within an absorbable mesh or sheet. Absorbable materials are well-known to those of ordinary skill in the art, and can be constructed of, for example, polydioxanone, polylactide, polyglycolic acid, and collagen, etc. 
         [0024]    The seeds can be disposed in the carrier via a number of different mechanisms. For example, the seeds can be attached to the carrier via adhesives, welding, sewing, entrainment between two sheets of material, or placement into formed pockets on the material. The entrainment between two sheets of material can be accomplished by heat staking around the seeds to affix the two sheets together. The heat staking technique could be advantageous in that a second chemical and/or material would not necessarily need to be added to affix the seeds, and the tedious task of sewing with radioactive materials could be avoided. The original properties of the entrainment material, most importantly the ability of tissue to grow into the pores of the material, could also be maintained with minimal disruption during the staking process. 
         [0025]    According to various embodiments, the carrier materials can be homogeneous, or can be constructed of layers or areas of dissimilar materials (e.g., a polypropylene mesh welded to a polyester mesh, with the seeds trapped between). This construction can be used to adjust physical and performance qualities, including but not limited to flexibility, degree of tissue in-growth, tensile or flexural strength, avenues for sterilization or processing, degree of seed retention, visibility by medical imaging modalities, attachment method to tissue or bone, degradation time, and control of tissue erosion. 
         [0026]    The carrier material can incorporate additional elements for a variety of purposes. Suitable non-limiting examples of such elements include fiducial markers for visualization/localizing by medical imaging modalities (ultrasound, fluoroscopy, MRI, CT, etc.); visual markings indicating alignment, seed placement, seed placement distances, and/or tissue attachment points; and coatings to increase/reduce adhesion, promote/retard in-growth, cause coagulation of blood, provide tumoricidal activity, increase biocompatibility, reduce microbiological growth, etc. In addition, the carrier material can have incorporated therein, or attached thereon, features to ease attachment to tissue such as, for example, loops, arms, filaments, sutures, and staples. 
         [0027]    According to various embodiments, the implant can comprise a radiation shielding backing material to afford a directional radiation dose. Suitable non-limiting examples of such materials include bismuth- or barium-loaded polymers. This backing material can be in the form of a solid sheet, or have open areas to allow selective dose transmission. Such a backing material could be useful to direct the dose towards areas of interest while shielding healthy or sensitive tissues or organs. 
         [0028]    The above-described features of the various embodiments of the present method and apparatus are depicted in  FIGS. 1-7 . 
         [0029]      FIG. 1 , according to various embodiments, is an illustration of an implant in accordance with the present disclosure. In this embodiment a first sheet of material  101  may be operatively coupled to a second sheet of material  102 . The second sheet of material  102  may have formed pockets  103  which hold seeds  103 . The first and second sheets of material  101 ,  102  may be adhered to one another by heat staking around the seeds in areas  105 . 
         [0030]      FIG. 2 , according to various embodiments, is a detailed illustration of an implant  201  having radioactive seeds  203  in accordance with the present disclosure. The seeds  203  may be held in pockets  202  by staking areas  204 . In this embodiment each pocket  202  may be surrounded by one common staking area  204 . 
         [0031]      FIG. 3 , according to various embodiments, is an overall illustration of an implant  301  having radioactive seeds  303  in accordance with the present disclosure. The seeds  303  may be held in pockets  302  by staking area  304 . The seeds  303  in the pockets  302  may be arranged in a predetermined pattern  305 . The pattern  305  may be constructed with a standard spacing as depicted, or may be customized to a seed pattern desired by the end user. 
         [0032]      FIG. 4 , according to various embodiments, is a detailed illustration of an alternative embodiment of an implant  401  having radioactive seeds  403  in accordance with the present disclosure. The seeds  403  may be held in pockets  402  by staking areas  404 . In this embodiment each pocket  402  is surrounded by its own respective staking area  404 . 
         [0033]      FIG. 5 , according to various embodiments, is an overall illustration of an alternative embodiment of an implant  501  having radioactive seeds  503  in accordance with the present disclosure. The seeds  503  may be held in pockets  502  by individual staking areas  504 . The seeds  503  in the pockets  502  may be arranged in a predetermined pattern  505 . The pattern  505  may be constructed with a standard spacing as depicted, or may be customized to a seed pattern desired by the end user. 
         [0034]      FIG. 6 , according to various embodiments, is an overall illustration of an implant  601  having radioactive seeds  603  in a predetermined pattern  605  in accordance with the present disclosure. The seeds  603  may be held in pockets  602  by individual staking areas  604 . The implant  601  may incorporate additional elements for a variety of purposes, such as, fiducial markers  606 , visual markings  607 , coatings  608 , and attachment elements  609 . 
         [0035]      FIG. 7 , according to various embodiments, is an overall illustration of an implant  701  having radioactive seeds  703  in another predetermined pattern  705  in accordance with the present disclosure. The seeds  703  may be held in pockets  702  by individual staking areas  704 . 
         [0036]    The implants can be attached to tissue using a variety of different methods. For example, the implants can be affixed to tissue via at least one of sutures, staples, tacks, adhesives, physical entrapment (chevrons), or other standard tissue-anchoring means. The implants can be permanently flexible, or can be rigid and formed into particular rigid shapes using heat and/or pressure based on the particular application. The implants could be constructed of materials that would change physical properties when contacted with body fluids or exposed to body temperature. 
         [0037]    According to various embodiments, the implants can be applied externally or internally. For example, the implants can be inserted laproscopically or by open surgery. The implants can be used in the body, or externally (i.e., a skin patch). The implant can be inserted into a tumor bed. For example, a tumor can be excised from a body cavity and the implant can be fixed to the locus thereof. The implant can be fixed to the tumor bed by a variety of different methods, including suturing, stapling, and adhesion. In the case of a spherical or semispherical implant, the implant can be inserted into the cavity and permitted to expand, thereby filling at least a portion of the cavity. 
         [0038]    According to various embodiments, the implant can be provided simultaneously or sequentially with an adjunctive therapy. For example, the implant can comprise a slow-release chemotherapeutic agent. Such agents and their release profiles are well-known to those of ordinary skill in the art of, inter alia, oncology. In addition, external beam radiation can be provided as an adjunct to seed radiation. 
         [0039]    For the purposes of this specification and appended claims, unless otherwise indicated, all numbers used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. 
         [0040]    Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Moreover, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein. For example, a range of “1 to 10” includes any and all subranges between (and including) the minimum value of 1 and the maximum value of 10, that is, any and all subranges having a minimum value of equal to or greater than 1 and a maximum value of equal to or less than 10, e.g., 5.5 to 10. 
         [0041]    It is noted that, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the,” include plural referents unless expressly and unequivocally limited to one referent. Thus, for example, reference to “a mesh” includes two or more meshes. 
         [0042]    Other various embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.