Anchored brachytherapy device

Aspects herein are directed to an anchorable brachytherapy device configured to be permanently implanted in a tumor bed at the time of operative removal of the tumor. In exemplary aspects, the brachytherapy device may comprise a plurality of hollow tubes that form a spherical or ellipsoid shape. Protrusions or grooves may be formed on an outer surface of the tubes to help anchor the brachytherapy device in the tumor bed. Radioactive seeds or strands may be positioned within the tube channels to provide radiation to the tumor bed.

TECHNICAL FIELD

Aspects herein relate to an anchored, permanently implantable brachytherapy device.

BACKGROUND

Radiation therapy, or brachytherapy, is a known modality for treating certain types of tumors such as, for example, breast tumors, brain tumors, lung tumors, sarcomas, and the like and has been shown to result in good tumor control. Brachytherapy may be used by itself or in combination with other therapies such as surgical resection, and/or chemotherapy. Radiation therapy has traditionally been administered using external beam radiation and/or by temporarily delivering a radioactive source to a tumor site via, for example a catheter. Both of these treatment modalities take days to weeks to complete and can be expensive, inconvenient to the patient, time-consuming to the patient and the treatment staff, and potentially painful to the patient. For example, catheter-based partial breast radiation may take five to eight days, and the patient has to be treated twice a day, six hours apart, and the catheter stays in the patient for two to three weeks. During this time, the catheter tail protrudes outside of the patient causing pain and a possible infection risk. Moreover, catheter-based radiation requires planning prior to each treatment which is time-consuming and expensive. Because of this, some patients may opt for more radical, but sometimes unnecessary, treatment options such as, for example, mastectomy instead of lumpectomy and adjuvant radiation with respect to breast cancer.

SUMMARY OF INVENTION

Aspects herein are directed to an implantable and anchorable brachytherapy device. Aspects herein may also be directed to an implantable and anchorable stereotactic marker device. With respect to the implantable and anchorable brachytherapy device, aspects herein contemplate a bioabsorbable or biocompatible, three-dimensional (3-D) or two-dimensional (2-D) device that can be, for instance, permanently introduced into a tumor bed at the time of surgical resection of the tumor and which does not need to be removed. As such, the brachytherapy devices described herein provide a convenient and cost-effective alternative to traditional catheter-based and/or external beam radiation options. Moreover, because the device is enclosed within the tumor bed, there are no catheter tails protruding from the patient, which lowers the risk of pain, bleeding, and infection. Further, because the device is anchored within the tumor bed, the risk of device rotation and/or migration is reduced. Additionally, in some instances, filling the void caused by surgical removal of the tumor with one of the devices described herein may be associated with a better cosmetic outcome as described below.

In one exemplary aspect, the device comprises a plurality of grooves, a plurality of projections, and, optionally, one or more central channels extending through the device body. Prior to placement within the tumor bed, one or more low-dose radioactive sources (e.g., seeds or strands) are secured in the grooves. As well, one or more low-dose radioactive sources and/or high-dose radioactive sources may be secured in the central channels. Once placed within the surgical site, the projections help to anchor the device to prevent or minimize shifting, migration, rotation, or movement of the device during radiation delivery. This, in turn, enables a more accurate radiation delivery to the intended area of the patient's body.

In another exemplary aspect, the device comprises one or more hollow tubes having grooves and/or projections. In one configuration, the device comprises a single, continuous hollow tube formed into a helical shape having a vacancy or space at its center. Radioactive seeds or strands may be loaded into the tube channel before intra-operative placement. The grooves and/or projections may be used to anchor the device once placed within the tumor bed. In a second configuration, the device comprises a plurality of hollow tubes formed into, for example, a spherical or ellipsoid shape having a vacancy at its center. Radioactive seeds or strands may be loaded into one or more of the tube channels prior to intra-operative placement. The grooves and/or projections may be used to anchor the device after placement.

Continuing with respect to the hollow tube configurations, because each of these configurations has a vacancy at its center, it can be considered a non-space (or minimally space-) occupying device making it useful in closed-space locations such as, for example, the brain to avoid increases in intracranial pressure. Further, the vacancy at the center of the device may allow for migration or influx of any blood, secretions, or other inflammatory fluids produced by the tumor bed thereby minimizing the opportunity for these fluids to accumulate between the tumor bed and the device wall which may decrease the effectiveness of the radiation treatment.

The brachytherapy devices as contemplated herein provide a customizable, accurate, and sustained delivery of radiation while requiring minimal physician and patient intervention after placement. Further, the brachytherapy devices as contemplated herein may help minimize side effects due to, for instance, infection or radiation damage. As well, in cases such as placement after a breast lumpectomy, the insertion of a 3-D brachytherapy device may provide a pleasing cosmetic effect to the breast.

The 2-D or 3-D device as described herein may also be used as a stereotactic marker device. Stereotactic marker devices typically comprise one more radiopaque markers, and, once positioned within a tumor site, the device may be used to guide, for example, external beam radiation. In one exemplary aspect, the devices described herein may comprise both a brachytherapy device and a stereotactic marker device. With respect to this aspect, both radioactive seeds/strands and radiopaque markers can be placed in the device grooves, the device central channels, or in the device tube channels. In other exemplary aspects, the devices described herein may be used as just a brachytherapy device or as just a stereotactic marker device. As such, the term “brachytherapy device” as used herein may comprise both a device used to deliver therapeutic radiation and/or a device that is useable as a stereotactic marker.

DETAILED DESCRIPTION

As described above, aspects herein are directed to a bioabsorbable and/or biocompatible implantable brachytherapy device and/or stereotactic marker device having a plurality of protrusions and/or grooves useable for anchoring the device within a tumor bed. In one exemplary aspect, radioactive seeds may be positioned within one or more grooves and/or one or more central channels on the brachytherapy device to deliver customizable amounts of radiation to the tumor bed. In an alternative aspect, the radioactive seeds may be positioned within channels of one or more hollow tubes that form the brachytherapy device. When used as a stereotactic marker, radiopaque markers may be positioned within the grooves, central channels, or the tube channels. A description of the brachytherapy devices and/or stereotactic marker devices is provided below with reference to the figures.

As used throughout this disclosure, the term “biocompatible device” means compatible with living tissue such that the biocompatible device is not toxic, is not physiologically reactive and generally does not cause an immunological reaction. The term “bioabsorbable device” as used herein generally means a device that is biocompatible as defined above and that is capable of being absorbed into the patient's body over time.

In exemplary aspects, the brachytherapy devices described herein may be formed from a silicone (polysiloxane) polymer, silastic (polydimethylsiloxane), polyether ether ketones (PEEK), or mixtures of polysiloxane, polydimethylsiloxane, and PEEK. As well, the brachytherapy device described herein may be formed from polyglycolic acid, L polylactic acid, D polylactic acid, or mixtures of L and D polylactic acid. In general, polysiloxane, polydimethylsiloxane, and PEEK may be used to form devices which are biocompatible, and polyglycolic acid and L and/or D polylactic acid may be used to form bioabsorbable devices. The brachytherapy devices described herein may be formed by, for example, 3-D printing, using complementary molds, injection molding, and the like. When the devices are configured to be bioabsorbable, materials may be selected and/or the devices may be configured such that the device absorbs at a rate that is at least four times the half-life of any radioactive seeds/strands positioned on or in the device. For instance, Palladium 103 has a half-life of 17 days. In this instance, materials for the device would be selected and/or the device may be configured so that the device does not completely absorb for at least 68 days. In one example, the amount of the L-isomer of polylactic acid may be increased and the amount of the D-isomer may be decreased to slow the rate of bioabsorption. Conversely, the amount of the L-isomer of polylactic acid may be decreased and the amount of the D-isomer may be increased to increase the rate of bioabsorption.

The term “radioactive seed” as used herein refers to a single radiation source that is positioned within a brachytherapy device. The term “radioactive strand” as used herein refers to multiple radiation sources positioned within a brachytherapy device, where the “strand” may be in the form of an actual strand or tube. Radioactive seeds or strands may comprise low-dose and/or high-dose radiation sources such as, for example, palladium-103, iodine-125, cesium-131, gold-198, radium-223, yttrium-90, iridium-192, and the like. It is contemplated herein that other active elements may be used in association with the brachytherapy devices described herein. An active element is an element that has therapeutic properties for the treatment of a patient, such as, for example, pharmaceutical, nuclear, or radioactive properties. Any and all aspects, and any variation thereof, are contemplated as being within the scope herein.

With reference first toFIG. 1A, a brachytherapy device100is illustrated having a generally solid, three-dimensional (3-D) shape. The brachytherapy device100is configured to be permanently placed within a tumor bed at the time of surgical resection of a tumor. The particular shape shown inFIG. 1Ais a sphere but it is contemplated herein that the 3-D shape may comprise an ellipsoid shape, a cylindrical shape, and variants thereof. The brachytherapy device100may be formed in a number of predetermined sizes such as, for example, about 2 cm, 3 cm, 5 cm, or 7 cm as measured across the maximum diameter of the device100; the use of different sizes better accommodates different sizes of tumor beds. A brachytherapy device having a 3-D shape, such as the device100, may be particularly useful in cancers such as breast or brain where the tumor bed generally comprises a three-dimensional shape. Further, because the brachytherapy device100comprises a solid 3-D shape, it can be considered a space-occupying device. This may make the device100especially useful following a breast lumpectomy. In this case, the placement of a solid, 3-D device having a size corresponding to the size of the tumor bed may help to provide a pleasing aesthetic to the breast following lumpectomy surgery by helping to fill the tumor cavity and preventing or minimizing depressions on the exterior of the breast.

The materials described above for forming the brachytherapy devices described herein may cause the resulting brachytherapy device, such as the brachytherapy device100, to exhibit a degree of elastic deformability (i.e., a temporary shape change that is self-reversing after a stress is removed). In other words, the device100, in exemplary aspects, may not be completely rigid. By forming the device100to have a degree of elastic deformability, the brachytherapy device100may be better adapted to adjust to external pressures. This may be particularly useful when the brachytherapy device100is used in breast cancer patients. For example, because the breast is often subject to external pressures, using a device that exhibits some degree of elastic deformability allows the breast to more comfortably adapt to external pressures as opposed to using a rigid device. This, in turn, improves the patient's comfort.

The brachytherapy device100comprises a plurality of protrusions110extending in a positive z-direction with respect to the surface plane of the device100. As shown inFIG. 1Awith reference to the Cartesian coordinate system, the surface plane of the device100at any one location may be thought of as extending in an x direction and a y direction (both positive and negative). The protrusions110extending in a positive z-direction would extend outward from the surface plane of the device100. In exemplary aspects, the protrusions110are useable to anchor the brachytherapy device100in the tumor bed thereby minimizing or eliminating problems due to migration, motion, rotation, or shift in position after intra-operative placement of the device100. In one exemplary aspect, the protrusions110are uniformly distributed over the surface of the device100. However, it is contemplated herein that the protrusions110may be localized to one or more discrete areas of the device100. Any and all aspects, and any variation thereof, are contemplated as being within aspects herein.

Continuing with respect to the protrusions110, and with reference toFIG. 1Cwhich depicts a cross-section of a protrusion110taken along cut line1C-1C ofFIG. 1A, the protrusions110may be integrally formed with the brachytherapy device100. In other words, they are formed of the same material as the brachytherapy device100. However, it is also contemplated herein that the protrusions110may be formed by adding an additional biocompatible and/or bioabsorbable treatment to the surface of the device100. Each protrusion110has a conical shape with a base width or diameter124from about 0.9 mm to about 5.5 mm, or from about 1.0 mm to about 5.0 mm. Further, each protrusion110may have a height126from about 0.4 mm to about 5.1 mm, or from about 0.5 mm to about 5.0 mm. As used herein, the term “about” means within ±10% of a designated value.

With respect toFIG. 1A, the protrusions110, in one exemplary aspect, are arranged in rows with each row extending from a first pole of the device100to a second opposite pole of the device100. As such, the protrusions110are generally uniformly distributed across the surface of the device100. Each protrusion110may be spaced apart from an adjacent protrusion110in a particular row by a distance of from about 1 mm to about 14 mm or from about 2 mm to about 12 mm. It is contemplated herein that the rows of protrusions110may not extend all the way from the first pole of the device100to the second opposite pole of the device100(i.e., the rows of protrusions110may extend only partially between the poles of the device100). It is further contemplated herein that the protrusions110may be not be configured in rows but may be randomly positioned on the device100, and/or arranged in some other pattern other than linear rows (e.g., curvilinear rows, zig-zag rows, sinusoidal rows, and the like). Any and all aspects, and any variation thereof, are contemplated as being within aspects herein.

With continued reference toFIG. 1Aand with further reference toFIG. 1B, which depicts a cross-section of a groove taken along cut line1B-1B ofFIG. 1A, the brachytherapy device100further comprises a plurality of grooves114extending in a negative z-direction with respect to the surface plane of the device100. That is, the grooves114extend inwardly with respect to the surface plane of the device100. As shown inFIG. 1B, the grooves114are useable to hold in place loose radioactive seeds, radioactive strands, radiopaque markers, and/or other active elements120. For example, the seeds, strands, markers, or active elements120may be positioned within the grooves114and held in place through the use of a medical adhesive such as n-2-butyl-cyanoacrylate. As well, because the device100may exhibit some elastic deformability, the seeds, strands, markers, or active elements120may be biased or tensioned into the grooves114and held in place through the elastic tension created by the biasing process. This may eliminate the need to use a medical adhesive in some exemplary aspects.

In general, loose radioactive seeds have a diameter of about 0.8 mm, while radioactive strands (radioactive seeds positioned within a tube of bioabsorbable material) have a diameter of about 0.99 mm. With this as context, and with respect toFIG. 1B, the grooves114may have a width116from about 0.75 mm to about 0.9 mm and a depth118from about 1.0 mm to about 1.2 mm when configured for use with loose radioactive seeds. Alternatively, the grooves114may have a width116from about 0.95 mm to about 1.1 mm and a depth118from about 1.0 mm to about 1.2 mm when configured for use with radioactive strands. It is contemplated herein that the brachytherapy device100may have some grooves114configured for loose radioactive seeds and some grooves114configured for radioactive strands. Any and all aspects, and any variation thereof, are contemplated as being within aspects herein.

Continuing, the grooves114, in one exemplary aspect, are configured to extend from the first pole of the device100to the second opposite pole of the device100. As such, the grooves114, like the protrusions110, are generally uniformly distributed across the surface of the device100. In one exemplary aspect, the rows of protrusions110alternate with the grooves114to form a repeating pattern of “row of protrusions-groove-row of protrusions-groove,” and the like. However, it is contemplated herein that there may be other patterns such as two grooves separated by a row of protrusions, two rows of protrusions separated by a groove, and the like. It is contemplated herein that the grooves114may not extend all the way from the first pole of the device100to the second opposite pole of the device100(i.e., the grooves114may extend only partially between the poles of the device100). It is further contemplated herein that the grooves114may be randomly positioned on the device100, and/or arranged in some other pattern than that shown inFIG. 1A(e.g., curvilinear, zig-zag, sinusoidal, and the like). Any and all aspects, and any variation thereof, are contemplated as being within aspects herein.

As shown inFIG. 4A, which depicts the device100without any protrusions or grooves for illustrative purposes, and as further shown inFIG. 4B, which depicts a cross-section of the device100taken across cut line4B-4B ofFIG. 4A, the device100may optionally comprise one or more central channels410that extend through the body of the device100. With respect toFIG. 4Ain particular, a central channel, such as central channel416, may extend from a first surface location412on one side the device100, through the body of the device100, to a second surface location414on the device100where the second surface location414is opposite the first surface location412. The central channels410thereby form through passages in the device100as shown inFIG. 4B. In one exemplary aspect, one or more of the central channels410may be configured to pass through a maximum diameter of the device100. The central channels410may number from about 1 to 12 and may have a diameter418from about 0.7 mm to about 1.2 mm, or from about 0.8 mm to about 1.1 mm.

The central channels410are useable for additional seed, strand, radiopaque marker, and/or active element placement. Similar to the grooves, the radioactive seeds/strands/markers/elements may be held in the central channels410via a medical adhesive, or the radioactive seeds/strands/markers/elements may be biased into the central channels410and held in place via the elastic tension created by the biasing process. In one exemplary aspect, high dose radiation seeds, such as seed415inFIG. 4A, may be placed in one or more of the central channels410while low dose radiation seeds may be positioned in the grooves114. Because the central channels410are positioned further away from the tumor bed as compared to the grooves114, some of the damaging effects of the higher dose radiation seeds may be lessened based on the inverse-square law which generally states that the intensity of the radiation is inversely proportional to the square of the distance from the radioactive source. It is also contemplated herein that low dose radiation seeds may also be placed in the central channels410. Any and all aspects, and any variation thereof, are contemplated as being within aspects herein.

FIG. 2Aillustrates another exemplary brachytherapy device200in accordance with aspects herein. The device200shares the same features as the device100including grooves212and protrusions210and optionally central channels. The main difference between the device200as compared to the device100is that the protrusions210have a generally cylindrical shape as opposed to a conical shape as inFIG. 1. In this exemplary aspect, and as shown inFIG. 2Bwhich represents a cross-section of a protrusion210taken along cut line2B-2B ofFIG. 2A, the protrusions210may have a uniform width or diameter214from about 0.9 mm to about 5.5 mm, or from about 1.0 mm to about 5.0 mm and a height216from about 0.4 mm to about 5.1 mm, or from about 0.5 mm to about 5.0 mm.

It is contemplated herein that the device100or the device200(or any of the other devices described herein) may have other shape configurations for the protrusions.FIGS. 3A-3Cillustrate some additional exemplary shapes. For example,FIG. 3Adepicts a protrusion310having a semi-hemispherical shape.FIG. 3Bdepicts a protrusion312having a planar distal surface that comprises a greater surface area than the base of the protrusion312(i.e., the protrusion312expands outward), whileFIG. 3Cdepicts a protrusion314having a planar distal surface that comprises a smaller surface area than the base of the protrusion314(i.e., the protrusion314tapers as it extends outward). Additional shape configurations beyond those shown are contemplated as being within aspects herein.

Turning now toFIGS. 5A and 5B, a brachytherapy device500is shown as having a generally two-dimensional (2-D) planar shape comprising a first planar surface510shown inFIG. 5A, and a second planar surface512opposite the first planar surface510shown inFIG. 5B. The device500further comprises one or more sides514extending between, and generally perpendicular to, the first planar surface510and the second planar surface512. In exemplary aspects, the sides514may have a height from about 2.0 mm to about 4.0 mm. In other words, the device500may have a thickness from about 2.0 mm to about 4.0 mm. The use of a device having a 2-D planar shape may be especially useful in tumors such as sarcomas where the tumor bed generally comprises a one-dimensional planar surface.

Although the brachytherapy device500is shown in a rectangular form, the device500may also comprise a square form. When the device500is in the form of a square, the device500may be formed in a number of predetermined sizes such as about 2×2 cm, 4×4 cm, 6×6 cm, 8×8 cm, or 10×10 cm. When the device500is in the form of a rectangle, the device500may be formed in a number of predetermined sizes such as about 2×4 cm, 2×6 cm, 4×6 cm, 4×8 cm, 4×10 cm, 6×8 cm, or 6×10 cm. It is also contemplated herein that the device500may be formed into other shapes such as a 2-D planar circle, a 2-D planar ellipse, and the like. It is further contemplated herein that the device500may be cut to shape or formed to shape at the time of intra-operative placement. This may be useful for tumor beds having an irregular shape. Any and all aspects, and any variation thereof, are contemplated as being within aspects herein.

In one exemplary aspect, the device500may comprise a plurality of protrusions516useable for anchoring the device500in a tumor bed. The plurality of protrusions516may extend in a positive z-direction from, for example, the first planar surface510, the sides514, and the second planar surface512of the device500and may be integrally formed from the same materials used to form the device500. Alternatively, the protrusions516may be formed by adding an additional biocompatible or bioabsorbable treatment to the surface of the device500. The protrusions516may be conical in shape and may have similar dimensions as those described for the protrusions110of the device100. Alternatively, the protrusions516may have a cylindrical shape such as that shown for the device200or may have one of the shape configurations shown inFIGS. 3A-3C. In one exemplary aspect, the protrusions516may be arranged in linear rows along the first planar surface510, along the sides514, and along the second planar surface512, where the rows extend from a first end of the device500to a second end of the device500. Although linear rows of protrusions516are shown for the device500, it is contemplated herein that the protrusions516may be randomly positioned on the device500or may assume other patterns than those shown (e.g., curvilinear rows, zig-zag rows, sinusoidal rows, and the like). Moreover, it is contemplated herein that the rows of protrusions516may not extend all the way to the first and second ends of the device500. Any and all aspects, and any variation thereof, are contemplated as being within aspects herein.

The device500may further comprise a plurality of grooves518having similar dimensions as those described for the grooves114of the device100where the grooves518are useable for securing radioactive seeds, strands, radiopaque markers, and/or active elements. Although only two grooves518are shown, it is contemplated herein that the device500may comprise any number of grooves. In exemplary aspects, the grooves518may be positioned on just the first planar surface510, where the first planar surface510is configured to be positioned adjacent to the tumor bed when placed intra-operatively. It is also contemplated herein that the grooves518may be positioned on the second planar surface512and/or along one or more of the sides514of the device500. In one exemplary aspect, the grooves518extend from a first end of the device500to a second end of the device500along its longitudinal axis. However, it is contemplated herein that the grooves518may extend only partially between the first and second ends of the device500or may extend widthwise across the device500when the device500comprises a rectangular shape. Although the grooves518are shown as being linear in form, it is contemplated herein that the grooves518may comprise other shapes such as curvilinear, sinusoidal, zig-zag, and the like. Any and all aspects, and any variation thereof, are contemplated as being within aspects herein. Similar to the device100, a particular groove518may alternate with a row of protrusions516to form a repeating pattern. It is contemplated herein that the grooves518and the protrusions516may assume other patterns as well such as, for example, groove-groove-row of protrusions, and the like.

FIG. 6Aillustrates another brachytherapy device600in accordance with aspects herein. The device600comprises a single, continuous, hollow tube610formed into a helix having a spherical shape as shown. It is also contemplated herein that the tube610may be formed into other shapes such as a cylindrical shape, an ellipsoid shape, a disc shape, and the like. The device600may come in a number of predetermined sizes such as sizes having a diameter of about 2 cm, 3 cm, 5 cm, or 7 cm.

As described above, features of the device600such as material composition or device configuration may be altered to increase or decrease the time it takes for the device600to bioabsorb. In one example, a thickness of the walls forming the tube610may be increased to slow the rate of bioabsorption, and a thickness of the walls may be decreased to increase the rate of bioabsorption. Additionally, or alternatively, the percentage of, for instance, the D-isomer of polylactic acid or the L-isomer of polylactic acid may be increased or decreased to alter the rate of bioabsorption.

Continuing, because of its helical form, the device600has a vacancy at its center. That is, the device600is generally a non-space occupying (or minimally-space occupying) device. Since it generally occupies less space as compared to, for instance, the device100, this configuration may be useful for placement in tumor beds where an increase in pressure is generally avoided (e.g., brain tumors). Moreover, the vacancy at the center of the device600may also act as a repository for any accumulation of bloods, secretions, and inflammatory fluids thereby preventing or minimizing the buildup of these materials in the space between the device600and the tissue of the tumor bed. This may help to improve the efficacy of the device600by allowing the radioactive seeds/strands to be positioned closer to the tumor bed.

In exemplary aspects, the tube610has a continuous, central channel (i.e., bore)711extending at least partially or completely along the length of the tube610where the channel711is useable for receiving radioactive seeds, strands, radiopaque markers, and/or active elements. This aspect is shown inFIGS. 7 and 8whereFIG. 7depicts a cross-section of the tube610taken along cut line7-7ofFIG. 6A, andFIG. 8depicts a longitudinal cross-section of the tube610. As shown inFIGS. 7 and 8, the outer diameter710of the tube610may be from about 3.0 mm to about 9.0 mm, or from about 4.0 mm to about 8.0 mm. And a diameter712of the channel711located in the tube610is from about 1.1 mm to about 1.5 mm, or from about 1.2 mm to about 1.4 mm.

Continuing, the tube610may have at least one open end in which radioactive seeds, radioactive strands, radiopaque markers, and/or active elements may be placed and secured using, for example, a medical adhesive at the time of placement in the tumor bed. With respect to this aspect, the open end of the tube610may be secured using, for example, a clip, a plug, a medical adhesive, and the like. Alternatively, the tube610may be pre-loaded with radioactive seeds, strands, radiopaque markers, and/or active elements during manufacturing. When pre-loaded, the tube ends may be sealed prior to shipping. With respect toFIG. 8, the channel711extends along at least a portion of the length of the tube610and is useable for receiving seeds, strands, markers, and/or active elements as shown by reference numeral810inFIG. 8. It is also contemplated herein that the channel711extends along an entire length of the tube610. Any and all aspects, and any variation thereof, are contemplated as being within aspects herein.

Returning toFIG. 6A, in one exemplary aspect, the device600comprises a plurality of conical protrusions612extending in a positive z-direction with respect to the surface plane of the tube610. The protrusions612have similar dimensions as to those described for the device100or the device500. Alternatively, the protrusions612may have a cylindrical form as depicted for the device200, or the protrusions612may comprise other configurations such as those shown inFIGS. 3A-3C. In exemplary aspects, the protrusions612are configured to extend away from the center of the device600. To describe this differently, the protrusions612may be positioned on just one side of the tube610—the side that faces away from the center of the device600(also known as the outer-facing surface of the tube610). It is also contemplated herein that the protrusions612may be positioned on the tube610such that they extend both away from the center of the device600and toward the center of the device600. Any and all aspects, and any variation thereof, are contemplated as being within aspects herein. Similar to the devices already described, the protrusions612are configured to anchor the device600in, for example, a tumor bed to minimize migration, rotation, or shifting of the device600.

FIG. 6Bdepicts a brachytherapy device650having a similar configuration as the brachytherapy device600but having grooves652instead of protrusions, where the grooves652are useable for anchoring the brachytherapy device650. As shown in the magnified view, the grooves652extend in a negative z-direction with respect to the surface plane of the tube610. Each groove652may have a width from about 0.1 mm to about 2.0 mm, and each groove652may have a depth from about 0.1 mm to about 2.0 mm. In exemplary aspects, the grooves652may be rotationally positioned along the tube610. To state it differently, the grooves652may extend in a helical fashion or a corkscrew manner along the length of the tube610. However, it is contemplated that the grooves652may be arranged in other patterns on the tube610and may extend only partially along the length of the tube610. The grooves652contribute to making the outer surface of the tube610irregular or rough which, in turn, helps to anchor the device650in the tumor bed. For example, the grooves652may help to promote tissue ingrowth thereby helping to anchor the device650. It is further contemplated herein that other features besides grooves may be used to create a rough outer surface of the tube610. For example, the outer surface of the tube610may be molded or formed to have ridges, braids, or some other type of texture. In another aspect, an additional bioabsorbable or biocompatible treatment may be applied to the outer surface of the tube610to create the rough surface. Any and all aspects, and any variation thereof, are contemplated as being within aspects herein.

FIG. 9Aillustrates a brachytherapy device900in accordance with aspects herein. The device900comprises a plurality of hollow tubes910that are formed into a spherical shape having a first pole912and a second opposite pole916. Although shown in a spherical shape, it is contemplated herein that the device900may comprise other shapes such as a 3-D ellipsoid shape, a 3-D cylindrical shape, a 2-D disc shape, and the like. Similar to the device600, the device900may be formed in such a way as to increase or decrease the time it takes for the device900to bioabsorb. For example, a thickness of the walls forming the tubes910may be increased to slow the rate of bioabsorption, and a thickness of the walls may be decreased to increase the rate of bioabsorption. Additionally, or alternatively, the percentage of, for instance, the D-isomer of polylactic acid or the L-isomer of polylactic acid may be increased or decreased to alter the rate of bioabsorption.

The device900may be formed using the same materials as described with respect to the devices100,200,500,600, or650and, as such, may be biocompatible and/or bioabsorbable and may exhibit a degree of elastic deformation. Similar to the devices600and650, the device900has a vacancy at its center. That is, the device900is generally a non-space occupying (or minimally-space occupying) device. Because of this, the device900may have the same functional advantages as detailed for the devices600and650.

The device900may be manufactured in a number of predetermined sizes having diameters such as about 2 cm, 3 cm, 5 cm, or 7 cm. With respect to the device900, each tube910, such as tube911, comprises a first end913and a second end915, and an intervening portion extending between the first end913and the second end915. In exemplary aspects, the respective first ends of the tubes910are interconnected at the first pole912, and the respective second ends of the tubes910are interconnected at the second pole916. This may be accomplished through, for example, a molding process or a 3-D printing process. In exemplary aspects, the intervening portions of the tubes are spaced apart from one another by a predetermined distance such as from about 0.05 mm to about 11 mm, or from about 1 mm to about 10 mm.

Each of the tubes910has a continuous, central channel (i.e., bore) extending at least partially along or completely along the length of the respective tube910. A cross-section of one of the tubes910would be similar to that shown inFIG. 7, and a longitudinal cross-section of one of the tubes910would be similar to that shown inFIG. 8. In exemplary aspects, the outer diameter of the tubes910is from about 3.0 mm to about 9.0 mm, or from about 4.0 mm to about 8.0 mm. And the diameter of the channel located in the respective tubes910is from about 1.1 mm to about 1.5 mm, or from about 1.2 mm to about 1.4 mm. The tubes910may have at least one open end in which radioactive seeds, radioactive strands, radiopaque markers, and/or active elements may be placed and secured using, for example, a medical adhesive at the time of intra-operative placement. Similar to the devices600and650, the open ends of the tubes910may be secured using, for example, a clip. Alternatively, the tubes910may be pre-loaded with radioactive seeds, strands, radiopaque markers, and/or active elements during manufacturing and the open ends of the tubes910may be sealed prior to shipping.

In exemplary aspects, one or more of the tube channels may be left empty (i.e., not loaded with a radioactive seed or strand) to protect nearby structures once the brachytherapy device900is implanted in the tumor bed. For instance, when used after a breast lumpectomy, tube channels not containing a radioactive seed or strand may be positioned in the tumor bed so as to be adjacent to, for instance, the chest wall, as opposed to the tumor bed. This may help to lessen the effects of radiation on these structures.

In one exemplary aspect and as shown inFIG. 9A, the device900comprises a plurality of conical protrusions914extending in a positive z-direction with respect to the surface plane of the tubes910. The protrusions914have similar dimensions as to those described for the device100. Alternatively, the protrusions914may have a cylindrical form as depicted for the device200or may assume other shape configurations such as those shown inFIGS. 3A-3C. In exemplary aspects, the protrusions914are configured to extend away from the center or middle of the device900. Similar to the devices already described, the protrusions914are configured to anchor the device900in, for example, a tumor bed to minimize migration or shifting of the device900.

An alternative configuration where grooves are used instead of protrusions is shown inFIG. 9B.FIG. 9Billustrates a device925with grooves927that are useable for anchoring the brachytherapy device925. Similar to what was discussed with respect to the device650, the grooves927extend in a negative z-direction with respect to the surface plane of the tubes910. Each groove927may have a width from about 0.1 mm to about 2.0 mm, and each groove927may have a depth from about 0.1 mm to about 2.0 mm. In exemplary aspects, the grooves927may be rotationally positioned along the tubes910. To state it differently, the grooves927may extend in a helical fashion or a corkscrew manner along the length of the tubes910. However, it is contemplated that the grooves927may be arranged in other patterns on the tubes910or may extend only partially along the length of the tubes910. The grooves927contribute to making the outer surface of the tubes910irregular or rough which, in turn, helps to anchor the device925in the tumor bed. For example, the grooves927may help to promote tissue ingrowth thereby helping to anchor the device925. It is further contemplated herein that other features besides grooves may be used to create a rough outer surface of the tubes910. For example, the outer surface of the tubes910may be molded or formed to have ridges, braids, or some other type of texture. In another aspect, an additional bioabsorbable or biocompatible treatment may be applied to the outer surface of the tubes910to create the rough surface. Any and all aspects, and any variation thereof, are contemplated as being within aspects herein.

Yet another alternative exemplary configuration is shown inFIG. 9Cin accordance with aspects herein. Similar to the devices900and925, the device950comprises a plurality of hollow tubes952that are formed into a spherical shape having a first pole954and a second opposite pole956. The device950further comprises a central column957that extends through the center of the device950and terminates in a first planar hub958at the first pole954and a second planar hub960at the second pole956. In exemplary aspects, the central column957provides additionally stability to the device950.

Continuing, in a first aspect, the central column957may comprise a continuous channel or bore extending partially or completely along the length of the central column957. A cross-section of the central column957in accordance with the first aspect would be similar to that shown inFIG. 7(minus the protrusion612), and a longitudinal cross-section of the central column957would be similar to that shown inFIG. 8(minus the protrusions612). With respect to this aspect, the channel may be useable for receiving a radioactive seed, radioactive strand, radiopaque marker, and/or active element. In a second aspect, the central column957may be solid (i.e., not comprising a channel). Any and all aspects, and any variation thereof, are contemplated as being within aspects herein. In exemplary aspects, the central column957has a length generally equal to or slightly greater than the diameter of the device950. For instance, if the diameter of the device comprises about 3 cm, the central column may have a length from about 3.0 cm to about 3.5 cm, from about 3.0 cm to about 3.3 cm, or from about 3.0 cm to about 3.1 cm. Further, in exemplary aspects, the central column957may be capped with or may terminate in an optional protrusion959at each respective end of the column957, where the protrusion959is useable for helping to anchor the device950.

Continuing, each of the tubes952has a continuous, central channel (i.e., bore) extending at least partially or completely along the length of the respective tube952. A cross-section of one of the tubes952would be similar to that shown inFIG. 7(minus the protrusion612), and a longitudinal cross-section of one of the tubes952would be similar to that shown inFIG. 8(minus the protrusions612). In exemplary aspects, the outer diameter of the tubes952is from about 3.0 mm to about 9.0 mm, or from about 4.0 mm to about 8.0 mm. And the diameter of the channel located in the respective tubes952is from about 1.1 mm to about 1.5 mm, or from about 1.2 mm to about 1.4 mm. The channel of the tubes952is useable to receive a radioactive seed and/or strand, a radiopaque marker, and/or an active element.

Instead of having protrusions extending from the surface of the tubes952as described for the device900, the tubes952may instead comprise grooves962similar to the brachytherapy device925. The grooves962extend in a negative z-direction with respect to the surface plane of the tubes952. In exemplary aspects, the grooves962may be rotationally positioned along the tubes952. To state it differently, the grooves962may extend in a helical fashion or a corkscrew manner along the length of the tubes952. However, it is contemplated that the grooves962may be arranged in other patterns on the tubes952and may extend only partially along the length of the tubes952. The grooves962contribute to making the outer surface of the tubes952irregular or rough which, in turn, helps to anchor the device950in the tumor bed. For example, the grooves962may help to promote tissue ingrowth thereby helping to anchor the device950. It is further contemplated herein that other features besides grooves may be used to create a rough outer surface of the tubes952. For example, the outer surface of the tubes952may be molded or formed to have ridges, braids, or some other type of texture. In another aspect, an additional bioabsorbable or biocompatible treatment may be applied to the outer surface of the tubes952to create the rough surface. Any and all aspects, and any variation thereof, are contemplated as being within aspects herein.

With respect to the first planar hub958and the second planar hub960, aspects herein contemplate a number of different configurations for the hubs958and960as shown byFIGS. 10A and 10B.FIG. 10Adepicts an exemplary hub1000having a first surface1010, a second surface1012opposite the first surface1010, and a side wall1014extending therebetween. The exemplary hub1000may comprise the first planar hub958and/or the second planar hub960. The side wall1014of the hub1000further comprises a plurality of receiving holes1016evenly spaced around the circumference of the hub1000. Each receiving hole1016extends a predetermined distance towards the center of the hub1000(shown by the dashed lines). Exemplary distances may comprise, for example, from about 2 mm to about 10 mm, from about 2 mm to about 8 mm, or from about 2 mm to about 5 mm. In general, the number of receiving holes1016is equal to the number hollow tubes952forming the brachytherapy device950(excluding the central column).

In use, the tubes952may be loaded with radioactive seeds or strands, radiopaque markers, and/or active elements and the tube ends may be fed into the receiving holes1016and secured using, for instance, a medical adhesive. This step may occur at, for instance, the manufacturing facility making the brachytherapy device950or may occur at the time of intra-operative placement.

FIG. 10Bdepicts an alternative configuration for the planar hubs958and/or960in accordance with aspects herein.FIG. 10Bdepicts a hub1050having a first surface1052, a second surface1054opposite the first surface1052, and a side wall1056extending therebetween. The side wall1056of the hub1050further comprises a plurality of receiving holes1058evenly spaced around the circumference of the hub1050. Each receiving hole1058extends to the center of the hub1050(shown by the dashed lines). To describe this differently, each hole1058extends to the central column957. In general, the number of receiving holes1058is equal to the number hollow tubes952forming the brachytherapy device950(excluding the central column).

Similar to the planar hub1000, in use the tubes952may be loaded with radioactive seeds or strands, radiopaque markers, and/or active elements and the tube ends may be fed into the receiving holes1058and secured using, for instance, a medical adhesive. This step may occur at, for instance, the manufacturing facility making the brachytherapy device950or may occur at the time of intra-operative placement.

Turning now toFIG. 11, aspects herein further contemplate a brachytherapy kit1100. In exemplary aspects, the kit1100includes a plurality of brachytherapy devices1110such as the device100, the device200, the device300, the devices600and650, and/or the devices900,925, and950in a number of predetermined sizes as described above. The kit1100further includes loose radioactive seeds (high dose and low dose)1112, radioactive strands (high dose and low dose)1114, radiopaque markers (not shown), and/or other types of active elements (not shown). The kit1100may optionally include a medical adhesive1116, computer software useable for determining an appropriate radiation dose and/or an appropriate device configuration to use (not shown), and/or Babcok forceps with long arms for placement of the loaded brachytherapy device in the tumor bed (not shown). The brachytherapy kit1100would come in a sterile form and is meant to be used in the operating room during the resection of a tumor.

In a use scenario, a surgeon and a radiation oncologist would be present in the operating room. After the tumor is removed and a preliminary reading is received from the pathologist, the radiation oncologist would determine the appropriate type, shape and size of the brachytherapy device depending on the size and shape configuration of the tumor bed and where the tumor bed is located. For instance, when the tumor is located in the brain, the radiation oncologist may select the brachytherapy device600,650,900,925, or950since these are non-space occupying (or minimally-space occupying) devices, and these devices would generally not increase pressure in the organ in which they are placed (an important consideration in the brain). In another example, when the tumor is located in the breast, the radiation oncologist may select the brachytherapy device100or200. By using a solid, space-occupying device with this type of tumor, the device may help to fill the tumor bed and produce a better visual aesthetic to the breast after lumpectomy. In yet another example, when the tumor is a sarcoma or other similar types of tumor, the radiation oncologist may select the brachytherapy device300. By using a 2-D shape with grooves and seeds located on just one planar surface, the device can be positioned such that the radioactive seeds are next to the tumor bed and not adjacent to healthy tissue.

Continuing, the radiation oncologist would also determine an appropriate radiation dose depending on the grade of the tumor. Based on this, the radiation oncologist would load the selected brachytherapy dose with the appropriate dose of radiation using the seeds1112and/or strands1114in the kit1100. The loaded brachytherapy device would then be positioned within the tumor bed by the surgeon, and the surgeon would proceed with closing the surgical wound.

It is also contemplated herein that the kit1100may come with a variety of pre-loaded brachytherapy devices in one or more sizes and shape configurations. In other words, the radioactive seeds/strands/markers/elements would be positioned in or on the brachytherapy device at the time of manufacture and the pre-loaded devices would then be shipped. It is also contemplated herein, that brachytherapy kits may be customized based on tumor type. For instance, there may be a breast brachytherapy kit having devices such as device100and/or device200in a number of predetermined sizes. There may be a brain brachytherapy kit having devices600,650,900,925, and/or950in a number of predetermined sizes. As well, there may be a sarcoma brachytherapy kit having device300in a number of predetermined sizes. These are just illustrative examples, and it is contemplated that brachytherapy kits may be customized for any number and type of tumors.

Aspects herein further contemplate a method of manufacturing a brachytherapy device as shown inFIG. 12.FIG. 12depicts a flow diagram of an exemplary method1200of manufacturing a brachytherapy device, such as any of the brachytherapy devices100,200,500,600,650,900,925, or950in accordance with aspects herein. At a step1210, a material is provided. The material may comprise a silicone (polysiloxane) polymer, silastic (polydimethylsiloxane), PEEK, polyglycolic acid, L or D polylactic acid, or any combination thereof.

Continuing, in one exemplary aspect and as indicated at a step1212, the material is formed into a brachytherapy device having grooves, protrusions, and optional central channels such as illustrated for the brachytherapy devices100,200, and500. In another exemplary aspect, and as indicated at a step1214, the material is formed into a brachytherapy device having one or more hollow tubes with grooves or protrusions on the outer surface of the tubes such as illustrated for the brachytherapy devices600,650,900,925, and950. The material may be formed into a brachytherapy device using complementary molds, injection molding, 3-D printing, and the like. The steps1212and1214may further comprise an optional curing step. In one exemplary aspect, the steps1210,1212or1214may take place at a manufacturing facility. When done at a manufacturing facility, the brachytherapy device may be formed into one of the device configurations shown for the devices100,200,500,600,650,900,925, and950and may be further formed into one of a predetermined number of sizes as described above.

Continuing, in another exemplary aspect, the steps1210,1212or1214may take place in an operating room setting at the time a tumor is being removed. This may be particularly useful for when the tumor bed has an irregular shape that does not correspond to the shapes/configurations associated with the devices100,200,500,600,650,900,925, and950. Exemplary tumors that may fall within this category include, for example, sacral convexity tumors, paraspinal tumors, and irregular shaped brain tumors. To provide effective radiation delivery for these types of tumors, a brachytherapy device having a customized shape may be useful. In exemplary aspects, the tumor bed may be scanned using for example, known laser scanning techniques, and the information inputted into a 3-D printer. The 3-D printer would be utilized to form a brachytherapy device having a shape corresponding to the shape of the tumor bed and having one or more of the features describes for the brachytherapy devices100,200,500,600,650,900,925, or950.

The method1200may further comprise, at a step1216, positioning one or more radioactive seeds, strands, radiopaque markers, and/or active elements within one or more grooves of the brachytherapy device or within one or more channels when the brachytherapy device is formed using hollow tubes. In one exemplary aspect, the formed and loaded brachytherapy device may be packaged separately or as part of a kit and shipped to its destination end point. In an alternative step, the formed brachytherapy device may not be pre-loaded and, instead, may be packaged separately or as part of a kit and shipped to its destination end point. With respect to this aspect, the brachytherapy device may be loaded with radioactive seeds/strands or radiopaque markers at the time of intra-operative placement. Any and all aspects, and any variation thereof, are contemplated as being within aspects herein.

Aspects of the present disclosure have been described with the intent to be illustrative rather than restrictive. Alternative aspects will become apparent to those skilled in the art that do not depart from its scope. A skilled artisan may develop alternative means of implementing the aforementioned improvements without departing from the scope of the present invention.