WO2021113359A1

WO2021113359A1 - Multichannel vaginal cylinder system for high dose rate brachytherapy of gynecologic cancers

Info

Publication number: WO2021113359A1
Application number: PCT/US2020/062886
Authority: WO
Inventors: Aaron H. WOLFSON; Elizabeth L. BOSSART
Original assignee: University of Miami
Current assignee: University of Miami
Priority date: 2019-12-03
Filing date: 2020-12-02
Publication date: 2021-06-10
Anticipated expiration: 2022-06-03

Abstract

Embodiments of multichannel vaginal cylinder systems and methods for high dose rate brachytherapy of gynecologic cancers are provided. A brachytherapy delivery system according to an embodiment comprises a cylinder structure comprising a proximal portion that abuts patient tissue when in a deployed state, a slot along a central longitudinal axis for receiving a tandem, and at least one channel. The at least one channel comprises a longitudinal segment extending longitudinally from an opening in a distal base of the cylinder structure toward the proximal portion, and a terminal segment extending at least partially transversely along the proximal portion. A radiation source can be positioned at one or more discrete positions within the at least one channel from a first position posterior to the slot to a second position anterior to the slot, when in the deployed state.

Description

MULTICHANNEL VAGINAL CYLINDER SYSTEM FOR HIGH DOSE RATE

BRACHYTHERAPY OF GYNECOLOGIC CANCERS

CROSS-REFERENCE TO RELATED APPLICATIONS

[1] This application claims priority to U.S. Provisional Patent App. No. 62/943,088, filed on December 3, 2019, which is hereby incorporated herein by reference as if set forth in full.

BACKGROUND

[2] Field of the Invention

[3] The embodiments described herein are generally directed to brachytherapy, and, more particularly, to a high-dose-rate brachytherapy delivery system for use in treating gynecologic cancers.

[4] Description of the Related Art

[5] Thousands of women in the United States are diagnosed with an invasive gynecologic malignancy every year. To treat such cancers, patients typically receive radiation as part or all of their treatment. In a majority of the patients treated with radiotherapy, brachytherapy (i.e., the placement radioactive sources into the body) is utilized to maximize control of the cancer, while minimizing long-term normal tissue complications from such treatment.

[6] Brachytherapy for gynecologic cancers, such as locally advanced cervical cancer, typically involves loading radioactive source materials (e.g., radionuclides) into special applicators that are surgically placed into the patient’s vagina, cervix, and/or uterus. For years, conventional brachytherapy delivery systems utilized for patients with cancers of the locally advanced cervix has involved either vaginal colpostats (e.g., ovoids) or a vaginal cylinder coupled to an intra-uterine tandem. Drawbacks of these conventional system include the inability to deliver a dose of radiation that is sufficient to treat tumors involving both the cervix and mid to lower (distal) portions of the vagina throughout the duration of the application without delivering excessive radiation dose to the healthy nearby pelvic organs, such as bladder or rectum.

[7] Another problem associated with conventional tandem and ovoid application systems pertains to requirement of ovoid stabilization during the implant procedure. Stabilization is usually achieved by a medical professional packing gauze into the vagina to prevent movement of the ovoids once in place. Due to clinician error during the implant attempt or to the narrowing of the vaginal apex from previous external beam irradiation, the vaginal ovoids may not rest directly in contact with the cervix, thereby resulting in dose heterogeneity and greater risk of tumor persistence or recurrence or greater risk of patient toxicity due to increased dwell time position of the radiation source in the tandem and/or ovoid application system at the expense of delivering excessive dose to the rectum and bladder

[8] U.S. Patent No. 6,641,518, which is hereby incorporated herein by reference as if set forth in full, discloses a multicomponent vaginal cylinder system for low dose rate (LDR) brachytherapy of gynecologic cancers. However, use of commercial tandem/ovoid systems or vaginal cylinders, such as that described in U.S. PatentNo. 6,641,518, for HDR brachytherapy applications can significantly increase the risk of damage to healthy tissue from radiation, and may still deliver an insufficient dose of radiation to target tumors, especially for cervical cancer, ultimately resulting in a reduced likelihood of long-term patient survival.

[9] Thus, there remains a need for improved brachytherapy delivery systems that are capable of administering HDR brachytherapy to effectively treat any type of gynecologic cancer, while minimizing damage to healthy tissue.

SUMMARY

[10] Accordingly, embodiments of an improved brachytherapy delivery system are disclosed. The following summary is not intended to define every aspect of the invention, and other features and advantages of the present disclosure will become apparent from the following detailed description, including the drawings. The present disclosure is intended to be related as a unified document, and it should be understood that all combinations of features described herein are contemplated, even if the combination of features are not found together in the same sentence, paragraph, or section of this disclosure. In addition, the disclosure includes, as an additional aspect, all embodiments of the invention narrower in scope in any way than the variations specifically mentioned herein.

[11] In an embodiment, the brachytherapy delivery system has an intracavitary deployed state and an extracorporeal inactive state, comprising a vaginal cylinder structure comprising

(i) a proximal portion that abuts patient tissue when the delivery system is in the deployed state,

(ii) a channel extending longitudinally from an opening formed in a distal base of the vaginal cylinder structure to the proximal portion, and a tandem slot located along a central longitudinal axis of the vaginal cylinder structure aligned for receiving a tandem for placement adjacent to or extending into the cervix, wherein the channel comprises a longitudinal segment and a terminal segment that extends at least partially transversely and along the proximal portion such that a radiation source can be positioned continuously within the channel from a location posterior to the tandem slot to a location anterior to the tandem slot, when in the deployed state.

[12] In an embodiment, a method of treating gynecological cancer in a patient is disclosed. The method may comprise deploying into the vagina of the patient a vaginal cylinder structure comprising a proximal portion that abuts the cervical tissue of the patient and a channel extending longitudinally from an opening formed in the distal base of the vaginal cylinder structure toward the proximal portion, inserting a radiation source into the channel, positioning the radiation source at any continuous position within the channel while the vaginal cylinder structure is deployed, and completely withdrawing the radiation source from the channel of the vaginal cylinder structure while the vaginal cylinder structure is deployed, thereby delivering a therapeutically effective amount of radiation to cancer cells.

[13] In an embodiment, the cancer to be treated is a gynecological cancer selected from the group consisting of cervical cancer, vaginal cancer, vulvar cancer, endometrial cancer, and combinations thereof.

[14] In an embodiment, a brachytherapy delivery system having an intracavitary deployed state and an extracorporeal inactive state is disclosed. The brachytherapy delivery system comprises a vaginal cylinder structure comprising a proximal portion that abuts patient tissue when the brachytherapy delivery system is in the intracavitary deployed state, a tandem slot located along a central longitudinal axis of the vaginal cylinder structure and aligned for receiving a tandem for placement adjacent to or extending into a cervix, and at least one channel. The at least one channel comprises a longitudinal segment extending longitudinally from an opening formed in a distal base of the vaginal cylinder structure toward the proximal portion, and a terminal segment that extends at least partially transversely and along the proximal portion. A radiation source can be continuously positioned at one or more discrete positions within the at least one channel from a first position of the one or more discrete positions posterior to the tandem slot to a second position of the one or more discrete positions anterior to the tandem slot, when the brachytherapy delivery system is in the intracavitary deployed state.

[15] In an embodiment, a method of treating a gynecological cancer in a patient is disclosed. The method comprises deploying into a vagina of a patient a vaginal cylinder structure. The vaginal cylinder structure comprises a proximal portion that abuts cervical tissue of the patient, a tandem slot located along a central longitudinal axis of the vaginal cylinder structure aligned for receiving a tandem for placement adjacent to or extending into a cervix of the vagina, and at least one channel comprising a longitudinal segment extending longitudinally toward the proximal portion from an opening formed in a distal base of the vaginal cylinder structure. The method also comprises inserting a radiation source into the channel and continuously positioning the radiation source at one or more discrete positions within the at least one channel while the vaginal cylinder structure is deployed, and completely withdrawing the radiation source from the channel of the vaginal cylinder structure while the vaginal cylinder structure is deployed, thereby delivering a therapeutically effective amount of radiation to cancer cells.

BRIEF DESCRIPTION OF THE DRAWINGS

[16] The details of the present invention, both as to its structure and operation, may be gleaned in part by study of the accompanying drawings, in which like reference numerals refer to like parts, and in which:

[17] FIG. 1 A illustrates a cross sectional side view of an example brachytherapy delivery system, according to embodiments of the present disclosure;

[18] FIG. IB illustrates another cross sectional side view of the example brachytherapy delivery system of FIG. 1A, according to various embodiments of the present disclosure;

[19] FIG. 1C illustrates a cross sectional top down view of the example brachytherapy delivery system of FIG. 1A, according to embodiments of the present disclosure;

[20] FIG. ID illustrates a schematic another cross sectional top down view of the example brachytherapy delivery system of FIG. 1A, according to embodiments of the present disclosure;

[21] FIG. 2 A illustrates a front view of the example brachytherapy delivery system of FIG. 1 A, according to embodiments of the present disclosure;

[22] FIG. 2B illustrates a side view of the example brachytherapy delivery system of FIG. 1 A, according to embodiments of the present disclosure;

[23] FIG. 2C illustrates a perspective view of the example brachytherapy delivery system of FIG. 1 A, according to embodiments of the present disclosure;

[24] FIG. 2D illustrates a top down view of the example brachytherapy delivery system of FIG. 1A, according to embodiments of the present disclosure;

[25] FIG. 2E illustrates a bottom up view of the example brachytherapy delivery system of FIG. 1A, according to embodiments of the present disclosure; [26] FIG. 2F illustrates a side view of another example brachytherapy delivery system, according to embodiments of the present disclosure;

[27] FIG. 2G illustrates a side view of another example brachytherapy delivery system, according to embodiments of the present disclosure;

[28] FIG. 2H illustrates a top down view of another example brachytherapy delivery system, according to embodiments of the present disclosure;

[29] FIG. 3 illustrates a schematic side view of another example brachytherapy delivery system comprising a plurality of radiation sources, a plurality of position members, and a processing device, according to embodiments of the present disclosure; and

[30] FIG. 4 is a block diagram illustrating an example wired or wireless processing system according to embodiments of the present disclosure.

DETAILED DESCRIPTION

[31] Embodiments of an improved brachytherapy delivery system for treating gynecologic cancers are disclosed. Embodiments disclosed herein provide for an improved brachytherapy delivery systems capable of administering HDR brachytherapy to effectively treat any type of gynecologic cancer while minimizing damage to healthy tissue. After reading this description, it will become apparent to one skilled in the art how to implement the invention in various alternative embodiments and alternative applications. However, although various embodiments of the present invention will be described herein, it is understood that these embodiments are presented by way of example and illustration only, and not limitation. As such, this detailed description of various embodiments should not be construed to limit the scope or breadth of the present invention as set forth in the appended claims.

[32] In an embodiment, embodiments of the brachytherapy delivery system and method described herein allow for effective treatment of all types of gynecologic cancers, including at high dose rates of radiation, while minimizing damage to adjacent healthy tissue. Instead of housing stationary, manually after-loaded radiation sources, the brachytherapy delivery system may comprise a vaginal cylinder structure comprising multiple channels that can accommodate remotely controlled mobile radiation sources. Thus, in an embodiment, the brachytherapy delivery system does not require vaginal packing, but still allows for a snug fit of the brachytherapy delivery system, with the radiation source(s) therein, against the cervix, and can also be used to treat vaginal extension of disease without needles. Orienting a radiation source so that the longitudinal axis of the radiation source is parallel to the target treatment area, and perpendicular to organs at risk, helps to spare the organs while treating the target. This can allow for a greater dose of radiation to be delivered to the target while keeping doses to organs at risk within a tolerance.

[33] Brachytherapy delivery devices for gynecologic cancers may involve placement of hollow applicators into the vagina, cervix and/or uterus that serve as a conduit for later insertion of radioactive sources, such as Iridium- 192 for example, that will deliver HDR brachytherapy to the high-risk clinical tumor volume (HR CTV) and maximize local control of the cancer, while minimizing long-term normal tissue complications from such treatment. In an embodiment of the present disclosure, the brachytherapy delivery system comprises one or more radiation sources within the channel(s) of the vaginal cylinder structure positioned parallel to the cervix, along with being positioned parallel to the vaginal mucosal surface, which provides optimized dose delivery to tumors and reduced radiation to nearly healthy tissue, such as bowel, bladder, rectum, and/or sigmoid colon. In contrast, commercially available devices only provide channels for delivery of radiation parallel to the vaginal mucosal surface. The ability of the mobile radiation sources to be inserted into the channel(s) of the vaginal cylinder structure, positioned at any location within the channel(s), and removed while the brachytherapy delivery system remains in the deployed state within the vagina of a patient (e.g., an intracavitary deployed state) allows for maximum control of a delivery of a dose of radiation to the cervix and/or proximal vaginal apex, as well as more distal regions of the vagina, and eliminates the need for multiple implantation procedures. Additionally, the dwell time of the radiation source within the patient is reduced, thereby preventing radiation damage to non-target tissues. In contrast, vaginal ovoids used in commercially available systems may not rest directly in contact with the cervix, for example, due to clinician error during the implant attempt or to the narrowing of the vaginal apex from previous external beam irradiation, thereby resulting in dose heterogeneity and greater increased risk of tumor persistence or recurrence or risk of patient toxicity due to increased dwell time position of the radioactive source in the tandem/ovoid application system to cover appropriately the HR CTV at the expense of delivering excessive dose to adjacent health tissue, such as the rectum and bladder.

[34] The following definitions may be useful in aiding the skilled practitioner in understanding the disclosure. Unless otherwise defined herein, scientific and technical terms used in the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art:

[35] “Brachytherapy” refers to internal radiation therapy in which a sealed radiation source is placed inside the body and/or next to the target treatment area. For example, brachytherapy includes the use of radionuclides or x-ray tubes (i.e., electronic brachytherapy) as the radiation source.

[36] “Distal” refers to the bottom portion of any structure for which it is used, which is closest to and/or abuts the vulva when the structure is inserted into the vagina.

[37] “Proximal” refers to the top portion of any structure for which it is used, which is closest to and/or abuts the ecto-cervix/vaginal apex when the structure is inserted into the vagina.

[38] “Intracavitary” refers to a position within the vagina of a patient. The disclosed brachytherapy delivery system is in a deployed state when it is intracavitary (i.e., following insertion of the vaginal cylinder structure into the vagina and until the vaginal cylinder structure is removed from the vagina).

[39] “Extracorporeal” refers to a position that is outside a patient. The disclosed brachytherapy therapy delivery system is in an undeployed or inactive state when it is extracorporeal (i.e., before insertion of the vaginal cylinder structure into the vagina or after removal of the vaginal cylinder structure from the vagina.

[40] “Therapeutically effective amount” and “effective amount” refer to an amount of a single radiation source or combination therapy that is effective to achieve a desired biological (e.g., clinical) effect. The therapeutically effective amount varies with the nature of the disease being treated, the length of time that activity is desired, and the age and condition of the subject. In an embodiment, a therapeutically effective amount is an amount that is effective to inhibit growth of cancer cells, prevent cancer cell metastasis, and/or result in cancer cell death (e.g., via apoptosis or necrosis).

[41] In an embodiment, the brachytherapy delivery system has an intracavitary deployed state and an extracorporeal inactive state, which are capable of delivering HDR brachytherapy, for example, to treat gynecologic cancers. FIGS. 1A-3 illustrate a brachytherapy delivery system, according to an embodiment. FIGS. 1A-1D depict longitudinal section views of the channels (left, FIG. 1 A depicting a longitudinal section view taken along cross-section line C- C’ shown in FIG. 2A) and tandem slot (right, FIG. IB depicting a longitudinal section view taken along cross-section line D-D’ shown in FIG. 2A) of an example brachytherapy delivery system. The proximal (top) 101, distal (bottom) 102, front, and back portions of the delivery system are labeled. Cross-section views of the proximal and distal portions taken along cross- sectional lines A-A’ and B-B’ are provided in the circular insets depicted in FIGS. 1C and ID, respectively. FIGS. 2A through 2E depict perspective views of the example brachytherapy delivery system of FIGS. 1A-1D. FIG 2A depicts a perspective view of the front of the brachytherapy delivery system. FIG. 2B depicts a perspective view of a side of the brachytherapy delivery system. FIG. 2C depicts a perspective view of the back of the brachytherapy delivery system. FIG. 2D depicts a perspective view of the top of the brachytherapy delivery system. FIG. 2E depicts a perspective view of the bottom of the brachytherapy delivery system. FIG. 2F depicts a perspective view of a side of an alternative embodiment the brachytherapy delivery system. FIG. 2G depicts a perspective view of a side of an alternative embodiment the brachytherapy delivery system. FIG. 2H depicts a perspective view of the top of an alternative embodiment of the brachytherapy delivery system. FIG. 3 depicts a brachytherapy system of the disclosure comprising a tandem and a radiation source and a second radiation source connected to a computer processing device.

[42] As illustrated, the brachytherapy delivery system comprises a vaginal cylinder structure 100 comprising a proximal portion 101, which abuts patient tissue when the delivery system is in the deployed state. Vaginal cylinder structure 100 also comprises one or more channels 103 (referred to herein as channels 103) that extend longitudinally from openings 104, which are formed in a distal base 102 of vaginal cylinder structure 100, toward proximal portion 101. The one or more channels 103 may comprise a cylindrical shape that extends from the respectively opening 104 toward an angled surface at the proximal portion 101. FIGS. 2 A and 2C depict two channels 103 comprised in the illustrative example vaginal cylinder structure 100. However, vaginal cylinder structures according to the embodiments herein within the scope of this disclosure may include one channel 103 (e.g., as shown in FIG. 2H and described in more detail below) or more than two channels 103 as desired. As such, the disclosure herein will be described with reference to a channel 103, but it will be appreciated that the various aspects and examples described in connection to one channel 103 may be equally applicable to the other channels 103. A radiation source (e.g., radiation source 109 of FIG. 3) is connected to a positioning member (e.g., positioning member 116 of FIG. 3). When the brachytherapy delivery system is in the deployed state, the radiation source can be inserted into at least one of channels 103, positioned at any continuous position within the channel 103, and completely withdrawn from the channel 103.

[43] The vaginal cylinder structure 100 may be molded from any material suitable for use in the human body and compatible with exposure to radiation. In some embodiments, the vaginal cylinder structure 100 comprises a biocompatible plastic. For example, the vaginal cylinder structure 100 may optionally comprise a transparent and/or disposable biocompatible plastic such as polystyrene crosslinked with divinylbenzene. Optionally, the vaginal cylinder structure 100 may further comprise at least one projection, e.g., a needle, extending exteriorly from the surface of the vaginal cylinder structure. The at least one projection may be configured to provide radiation interstitially, e.g., to parametrial tissue, when the brachytherapy delivery system is in the deployed state. In some embodiments, by positioning proximal ends of channel 107 and/or of the one or more additional channels adjacent to the proximal portion 101 (e.g., positioned up to the level of the ovoids), the brachytherapy delivery system, with radiation source(s) therein, and may provide for improved treatment of vaginal extension of disease without a projection (e.g., as described below in connection to FIG. 2F). For example, such embodiments may increase flexibility in appropriately covering the high risk clinical tumor volume (HR CTV). However, it will be appreciated that treatment of vaginal extension of disease may also be provided without a projection, where the proximal ends of channel 107 and/or the one or more additional channels terminate as illustrated in FIGS. 1 A-3.

[44] Optionally, the vaginal cylinder structure 100 may further comprise an external layer disposed on the outer surface of the vaginal cylinder structure 100 that is expandable and stabilizes the position of the vaginal cylinder structure 100 within the vagina without requiring conventional gauze packing. For example, as illustrated in FIG. 2G, the vaginal cylinder structure 100 may comprise an inflatable sheath 117 disposed about the external layer (or surface) of the vaginal cylinder structure 100. The sheath 117 may be attached at the proximal portion 101 and extend to the distal base 102. The sheath 117 may alternatively be attached to the external layer of the the vaginal cylinder structure 100 at any position between the proximal portion 101 and the distal base 102. The inflatable sheath wholly inflatable thereby expanding to meet the tissue of the patient and stabilize vaginal cylinder structure 100. Alternatively or in combination with a wholly inflatable sheath, the sheath may comprise one or more baffles 118. The inflatable sheath 117 and/or baffles 119 may be inflated when in the deployed state by liquid (e.g., water or other liquid) or gas (e.g., air or other gas) via fill/drain port 119. The sheath 117 and/or baffles 118 may be deflated via the fill/drain port 119 when the vaginal cylinder structure 100 is withdrawn. Each of the one or more baffles 119 may be disposed along the central longitudinal axis of the vaginal cylinder structure 100 and, where a plurality of baffles 119 are provided, each may be spaced apart from another of the one or more baffles. In one example, each baffle 119 may extend longitudinally along the central longitudinal axis of the vaginal cylinder structure 100, as shown in FIG. 2G. While in another embodiment, the one or more baffles 119 may surround the vaginal cylinder structure 100. The sheath 117 and/or baffles 119 may be inflatable to a predetermined distance extending radially from the central longitudinal axis vaginal cylinder structure 100. The predetermined distance may be selected to stabilize the position of the vaginal cylinder structure 100 within the vagina without requiring other restraining structures, such as conventional gauze packing. For example, each baffle 119 may be inflatable up to 5 mm in the radial direction. Alternatively or in addition, the vaginal cylinder structure 100 may be designed with a diameter selected to stabilize the position of the vaginal cylinder structure 100 within the vagina.

[45] Referring to FIG. 3, the brachytherapy delivery system may one or more radiation sources (collectively referred to as radiation sources) coupled to a processing device 113 via a corresponding position member of one or more positioning members (collectively referred to as positioning members). In various embodiments, each radiation source may be a tube housing one or more radionuclides or an x-ray tube. In the illustrative example shown in FIG. 3, the brachytherapy delivery system comprises a first radiation source 109 attached at its distal end to a proximal end of a positioning member 116. For example, the radiation source 109 may refer to a probe attached to the positioning member 116 at the distal end of the probe and having the source of radiation (such as a radionuclide or x-ray tube, for example) disposed at a proximal end of the probe. The positioning member 116 may be configured to control the movement of the radiation source into, within, and from channel 103 of the vaginal cylinder structure 100 when the brachytherapy delivery system is in the deployed state. In some embodiments, the positioning member 116 comprises an adjustable threading member connected to the radiation source 109 at the proximal end of the positioning member 116.

[46] The positioning member 116 may be coupled to a computer processing device 113 at the distal end of the positioning member 116. The processing device 113 may be configured to control the positioning of the positioning member 116. The computer processing device 113 may include at least one processor and at least one memory storing instructions that, when executed, cause the one or more processors to perform steps in accordance with the teachings herein. For example, the one or more memories may store instructions that provide precise control of the movement of one of more of the radiation sources into the vaginal cylinder structure 100, controlling threading a probe with a radioactive source at the proximal end of the probe to advance the radiation source within a channel into the proper position adjacent to the area within the vagina to be treated. In addition to the position, the processing device 113 may control the duration of the brachytherapy treatment before removal of the radiation source. In some examples, the processing device 113 may have a plurality of probes and radiation sources that may be aligned to move into each of the different delivery channels, depending on the treatment location and desired treatment protocol. The processing device 113 may be implemented as, for example, a processing device 400 of FIG. 4. In an embodiment, the position member 116 may also be controlled by a manual positioner for controlling the positioning of the positioning member 116 at its distal end.

[47] In various embodiments, channel 103 runs parallel to the longitudinal axis of the vaginal cylinder structure 100. The radiation source 109 can be positioned within the channel 103 so that the longitudinal axis of the radiation source 109 is parallel to the vaginal wall (not shown). Optionally, the channel 103 may extend to the proximal portion 101 of the vaginal cylinder structure 100. The channel 103 may comprises a terminal segment 106 adjacent to the proximal portion 101 and forming an angle with the preceding segment 106c (also referred to herein a longitudinal segment) of the channel 103. The angle formed between the terminal segment 106 and the preceding segment 106c of the channel 103 may be a right angle or an obtuse angle the angle of the terminal segment 106 may be formed such that, when the radiation source 109 is positioned within the terminal segment 106, the longitudinal axis of the radiation source 109 is parallel to the cervix. In some examples, the length of the terminal segment 106 may be greater than the radius of the vaginal cylinder structure 100. Furthermore, in some examples, the length of the terminal segment 106 may be greater than the radius of the vaginal cylinder. Accordingly, the length of the terminal segment 106 may allow for a single channel to be used to treat multiple target sites from the anterior side of the vaginal cylinder structure 100 to the posterior side.

[48] In the examples illustrated in FIGS. 1A-3, the terminal segment 106 may extend parallel to the angled top surface at the proximal portion 101 of the vaginal cylinder structure 100. In so doing, the terminal segment 106 traverses across a region that extends from an anterior region 106a, past a tandem slot 105, to a posterior region 106b. The development of a single channel (e.g., channel 103) capable of delivering radiation dosages over a path that traverses from the anterior to the posterior of the vaginal cylinder structure 100 allows for the treatment of multiple target sites without the need for multiple radiation sources or the use of multiple insertion channels. Whereas conventional systems can only position a radiation source on any one side of the tandem slot 105, thereby hindering treatment over the desired treatment area and requiring longer procedure times. Accordingly, the brachytherapy delivery systems and therapeutic methods of the present disclosure allow for uninterrupted continuous treatment over the entire longitudinal and transverse extent of the vaginal cavity (e.g., from the anterior side to the posterior side and from the proximal portion 101 to the distal base 102) and an inserted device using a single channel. In Figs. 2A-2E, two terminal segments 106 are shown, and it will be appreciated that additional terminal segments may be used. Furthermore, in some embodiments, a single terminal segment 106 may be used. [49] FIG. 2H illustrates another example embodiment of the brachytherapy delivery systems comprising a single terminal segment 106’. The brachytherapy delivery system of FIG. 2H is substantially the same as the brachytherapy delivery system shown in FIGS. 1 A-2E aside from the single terminal segment 106’. The single terminal segment 106’ is formed as a loop parallel to the angled top surface of the proximal portion 101 of the vaginal cylinder structure 100. That is, single terminal segment 106’ is arranged as a loop about an axis that is perpendicular to the angled top surface of the proximal portion 101. The single terminal segment 106’ may extend from a first channel 103 to a second channel 103 form the loop as to surround the tandem slot 105. This configuration may allow for a full or nearly full circumferential treatment path, such that radiation therapy can be applied at any site or sites along a continuous path that substantially, fully, or just partially, encircles the tandem slot 105, as shown in FIG. 2H. That is, a radiation source (e.g., radiation source 109 of FIG. 3) maybe inserted at any position along the continuous path of the single terminal segment 106’. Such treatment sites can be reached without the need for multiple radiation sources or multiple insertion channels. The single terminal segment 106’ may be an alternative embodiment or implemented in addition to the terminal segment 106 described in connection to FIGS. 1 A-2E. For example, a vaginal cylinder structure 100 may comprise a first channel 103 having single terminal segment 106’ and another channel 103 having a terminal segment 106.

[50] In various embodiments, the brachytherapy delivery system according to the present disclosure may also comprise a second channel 107. The second channel 107 extends longitudinally from a second opening 108 formed in the distal base 102 of the vaginal cylinder structure 100 toward the proximal portion 101. In various aspects, the brachytherapy delivery system further comprises one or more additional channels, for example, one, two, three, four, five, six, or more, additional channels, as depicted in FIGS. 1A-3. Each additional channel may extend longitudinally from an additional opening formed in the distal base 102 of the vaginal cylinder structure 100 and may be positioned at different radial locations about the central longitudinal axis In some embodiments, the channel 107 and/or one or more of the additional channels may extend longitudinally and terminate adjacent to the proximal portion 101. For example, as illustratively shown in FIG. 2F, a proximal end of channel 107’ terminates in alignment with the terminal segment 106 (e.g., along a virtual plane extending parallel with the terminal segment 106) of the channel 103, such that the proximal end of the channel 107’ is adjacent to the proximal portion 101. Channel 107’ is an example, and it will be appreciated that proximal ends of the channel 107 and/or of the one or more of the additional channels terminates in a similar manner, that is in alignment with the terminal segment 106 of the channel 103, such that the proximal end of the channel 107 and/or of the one or more of the additional channels is adjacent to the proximal portion 101. Proximal ends of the channels positioned as such provides for a radiation source situated therein to be positioned up to the level of the ovoids. In some embodiments, the channel 107 and/or one or more of the additional channels may comprise a terminal segment (e.g., such as terminal segment 106) that forms a right or obtuse angle with a preceding segment 106c of the respective channel.

[51] In various embodiments, the brachytherapy delivery system may comprise a second radiation source 114 attached at its distal end to a proximal end of a positioning member 115, as shown in FIG. 3. The radiation soured 14 can be inserted into the second channel 107 when the brachytherapy delivery system is in the deployed state. Similar to the radiation source 109 via positioning member 116, the radiation source 114 can be positioned at any continuous position within the second channel 107 via the positioning member 115, and can be completely withdrawn from the second channel 107. The configuration of the positioning member 115 and radiation source 114 may be substantially similar to that of radiation source 109 and positioning member 116, in that the positioning member 115 may each comprise an adjustable threading member connected to the radiation source 114 and connected to the computer processing device 113 at the distal end, which may be configured to control the positioning of the radiation source 114 into, within, and from the second channel 107 of the vaginal cylinder structure 100. In an embodiment, the position member 115 may also be controlled by a manual positioner for controlling the positioning of the positioning member 115 at its distal end.

[52] In various embodiments, the brachytherapy delivery system may include any number of additional radiation sources that may be inserted into additional channels and positioned via a respective positioning member under control by the processing device 113 and/or a manual positioner. For example, as illustrated in FIG. 3, a third radiation source 110 attached at its distal end to a proximal end of a positioning member 112. The radiation source 110 and the positioning member 112 may be substantially similar to radiation source 114 and positioning member 115. For example, the radiation source 110 can be inserted into any additional channel (e.g., an additional channel similar to second channel 107 and/or another one of channels 103) when the brachytherapy delivery system is in the deployed state via positioning member 112 under control by the processing device 113 and/or a manual positioner at the distal end of the positioning member 112. The brachytherapy delivery system may include one or more additional radiation sources and positioning members as desired. Thus, one or more additional radiation sources can be inserted into each additional channel, positioned at any continuous position within the additional channel, and completely withdrawn from the additional channel. Alternatively or in addition, an additional radiation source may be inserted into the tandem 111 and advanced into position by a respective positioning member.

[53] In various aspects, each radiation source (e.g., the radiation source 109, second radiation source 114 and/or additional radiation source(s)) may be positioned within the vaginal cylinder structure when the brachytherapy delivery system is in the deployed state to provide radiation to the cervix or any region of the vagina or to both the cervix and vagina simultaneously. The movement of each of radiation source 109, second radiation source 114, third radiation source 110, and any additional radiation source(s) can be coordinated and/or independently controlled by each respective positioning member under control by the processing device 113 and/or a manual positioner. Each of radiation source 109, second radiation source 114, third radiation source 110, and any additional radiation source(s) may comprise a radionuclide selected from iridium-192, iodine-125, palladium- 103, cesium-131, cesium- 137, cobalt-60, ruthenium- 106, radium -226, and any combinations thereof or an x-ray tube.

[54] In various embodiments, the brachytherapy delivery system may comprise a tandem slot 105 situated along the central longitudinal axis of the vaginal cylinder structure 100 arranged to receive a tandem 111 by insertion into the tandem slot 105, as illustrated in at least FIGS. 1 A, IB, and 2A-2C. For example, the tandem 111 may be inserted into the vagina of a patient and the vaginal cylinder structure 100 may then receive the tandem 111 upon insertion of the vaginal cylinder structure 100 into the vagina. The tandem 111 may be made of a biocompatible metal, such as stainless steel. The tandem 111 may be substantially hollow. Optionally, the tandem 111 may house a radionuclide, for example, iridium-192, iodine-125, palladium- 103, cesium-131, cesium-137, cobalt-60, ruthenium- 106, radium-226, and any combinations thereof, or an x-ray tube. The tandem 111 may be inserted into the tandem slot 105, positioned at any continuous position within the tandem slot 105, and/or completely withdrawn from the tandem slot 105, when the brachytherapy delivery system is in the deployed state. The tandem 111 may be inserted into the tandem slot 105 and fixed at a position within the slot, for example, by means of a fastener, when the brachytherapy delivery system is in the deployed state. Example fasteners may include a set screw, spring loaded latch, magnetic fasteners, and the like.

[55] The brachytherapy delivery system is capable of delivering HDR radiation, for example, radiation at a dose rate of at least about 12 gray per hour (Gy/h). In some embodiments, the brachytherapy delivery system delivers radiation at a dose rate of at least about 15 Gy/h, at least about 20 Gy/h, at least about 30 Gy/h, at least about 40 Gy/h, at least about 50 Gy/h, at least about 60 Gy/h, at least about 70 Gy/h, at least about 80 Gy/h, at least about 90 Gy/h, at least about 100 Gy/h, at least about 150 Gy/h, at least about 200 Gy/h, at least about 250 Gy/h, or at least about 300 Gy/h.

[56] The present disclosure also provides methods of treating a gynecological cancer using a brachytherapy delivery system described in connection to FIGS. 1 A-3. With reference to FIGS. 1 A-3, an example method of treating a gynecological cancer in a patient according to the disclosure comprises deploying into the vagina of the patient a vaginal cylinder structure 100 comprising a proximal portion 101 that abuts the cervical tissue of the patient. As described above, the vaginal cylinder structure 100 also comprises a tandem slot 105 located along a central longitudinal axis of the vaginal cylinder structure 100 arranged for receiving a tandem 111, thereby placing the tandem 111 adjacent to or extending into the cervix. The vaginal cylinder structure 100 also comprises at least one channel 103 extending longitudinally toward the proximal portion 101 from an opening 104 formed in the distal base 102 of the vaginal cylinder structure 100. The example method also includes inserting a radiation source 109 into the channel 103 and positioning the radiation source 109 at any continuous position within the channel 103, while the vaginal cylinder structure 100 is deployed. For example, the radiation source 109 may be positioned at a plurality of discrete positions within channel 103, such as a plurality of positions along preceding segment 106c and/or a plurality of positions between the anterior region 106a and posterior region 106b. Additionally, the method comprises completely withdrawing the radiation source 109 from the channel 103 of the vaginal cylinder structure 100, while the vaginal cylinder structure 100 is deployed. By executing the example method, a therapeutically effective amount of radiation can be delivered to cancer cells, for example at one or more of the discrete positions along channel 103.

[57] In various embodiments, the method may further comprise inserting a second radiation source 114 into a second channel 107 extending longitudinally toward the proximal portion 101 from a second opening 108 formed in the distal base 102 of the vaginal cylinder structure 100. The second radiation source 114 may be positioned at any continuous position within the second channel 107 while the vaginal cylinder structure 100 is deployed. The method may then also comprise completely withdrawing the second radiation source 114 from the channel 107 of the vaginal cylinder structure 100, while the vaginal cylinder structure is deployed.

[58] Optionally, the method may further comprises inserting an additional radiation source into an additional channel extending longitudinally toward the proximal portion 101 from an additional opening formed in the distal base 102 of the vaginal cylinder structure 100. The additional radiation source may be positioned at any continuous position within the additional channel, while the vaginal cylinder structure 100 is deployed. For example, a radiation source may be positioned at a plurality of discrete positions within a respective. Then the additional radiation source may be completely withdrawn from the channel of the vaginal cylinder structure while the vaginal cylinder structure is deployed. One or more additional radiation sources, for example, one, two, three, four, five, six, or more, may be inserted into a respective channel. In some embodiments, the movements of the radiation source, second radiation source, and additional radiation source(s) may be coordinated or controlled independently, for example, via the processing device 113 and/or manual positioner. By executing the example method, a therapeutically effective amount of radiation can be delivered to cancer cells, for example at one or more of the discrete positions along each respective channel.

[59] In various embodiments, the method may comprise positioning the radiation source 109, second radiation source 114, and/or additional radiation source(s) so that the longitudinal axis of the radiation source 109, second radiation source 114, and/or additional radiation source(s) are parallel to the vaginal wall and/or parallel to the cervix. By aligning the longitudinal axis as such radiation from the vaginal cylinder structure 100 may be delivered to the cervix, any region of the vagina, or to both the cervix and any region of the vagina simultaneously. Any of the channels (e.g., channel 103, second channel 107, and/or the additional channels) of the vaginal cylinder structure 100 may optionally comprises a terminal segment (e.g., terminal segment 106) formed at an angle (e.g., a right or obtuse angle) with respect to a preceding segment 106c of the channel 106. A radiation source (e.g., radiation source 109) can be positioned within the terminal segment 106 so that the longitudinal axis of the radiation source is parallel to the cervix, thereby providing an effective dose of radiation to the cervix at one or more discrete positions along the terminal segment 106. The method may further comprise inserting the radiation source 109 and/or second radiation source 114 into a respective channel and positioning the radiation source 109 and/or second radiation source 114 to deliver a therapeutically effective amount of radiation from a location that is posterior to the tandem slot 105 and a location anterior to the tandem slot 105, before withdrawing the radiation source 109 and/or second radiation source 114.

[60] The example method described herein may further comprise inserting a tandem 111 into a tandem slot 105 along the central longitudinal axis of the vaginal cylinder structure 100 so that the tandem 111 extends externally from the vagina of the patient. The tandem 111 may optionally houses a radionuclide selected from the group consisting of iridium- 192, iodine-125, palladium- 103, cesium-131, cesium- 137, cobalt-60, ruthenium- 106, radium-226, and combinations thereof or an x-ray tube.

[61] The example methods of the present disclosure may be executed to advantageously provide a therapeutically effective dose of radiation to cancer cells. A particular administration regimen for a particular patient will depend, in part, upon the cancer type, the radionuclide and/or other radiation source administered, along with the cause and extent of any side effects. The amount of radiation administered to a patient (e.g., a mammal, such as a human) in accordance with the present disclosure should be sufficient to effect the desired response over a reasonable time frame. Dosage may depend upon the timing and frequency of administration. Accordingly, a clinician titers the dosage and modifies the administration to obtain the optimal therapeutic effect. Use of a positioning member (e.g., positioning members 115, 112, and/or 116) coupled to a computer processing device (e.g., processing device 113) for controlling the positioning of the radiation source can minimize human error in administration of the radiation dosage.

[62] In various embodiments, the example methods disclosed herein comprises administering HDR brachytherapy. For example, the methods disclosed herein may comprise administering radiation to the tumor at a dose rate of at least about 12 gray per hour (Gy/h). The method may comprises delivering radiation to the tumor at a dose rate of at least about 15 Gy/h, at least about 20 Gy/h, at least about 30 Gy/h, at least about 40 Gy/h, at least about 50 Gy/h, at least about 60 Gy/h, at least about 70 Gy/h, at least about 80 Gy/h, at least about 90 Gy/h, at least about 100 Gy/h, at least about 150 Gy/h, at least about 200 Gy/h, at least about 250 Gy/h, or at least about 300 Gy/h. The dwell time of a radiation source (e.g., radiation source 109, second radiation source 114, and/or any additional radiation source(s)) may be reduced, because the radiation sources are mobile and may be inserted and removed from the vaginal cylinder structure 100 as needed. For example, the methods of the present disclosure may comprise delivering radiation, e.g., HDR radiation, to a patient over a period of about 1 minute to about 30 minutes. For example, radiation may be delivered to a patient over a period of about 1 minute, about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, or about 30 minutes. Purely by way of illustration, the methods of the present disclosure comprise administering a dose of radiation from, for example, about 1 Gy to about 15 Gy. For example, the method may include administering a dose of radiation of about 1 Gy, about 2 Gy, about 3 Gy, about 4 Gy, about 5 Gy, about 6 Gy, about 7 Gy, about 8 Gy, about 9 Gy, about 10 Gy, about 11 Gy, about 12 Gy, about 13 Gy, about 14 Gy, or about 15 Gy. Multiple fractions, for example, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fractions, each a dose of about 1 Gy to about 15 Gy, can be given to a patient over a treatment period of days or weeks, resulting in a total dose of radiation from about 5 Gy to about 150 Gy. For example, the total dose of radiation may be about 10 Gy, about 20 Gy, about 30 Gy, about 40 Gy, about 50 Gy, about 60 Gy, about 70 Gy, about 80 Gy, about 90 Gy, about 100 Gy, about 110 Gy, about 120 Gy, about 130 Gy, about 140 Gy, or about 150 Gy.

[63] In another embodiment, the methods of the present disclosure may comprise administering a minimal dose of radiation to healthy tissue adjacent to or close to a tumor, for example, bowel, bladder, rectum, or sigmoid colon tissue. In various examples, the method comprises administering a dose of radiation to healthy tissue at a dose rate of less than about 0.2 Gy/h. For example, a dose of radiation to health tissue may be less than about 0.1 Gy/h, less than about 0.05 Gy/h, less than about 0.01 Gy/h, less than about 0.005 Gy/h, or less than about 0.001 Gy/h. A total dosage may be less than about 0.05 Gy, less than about 0.02 Gy, less than about 0.01 Gy, less than about 0.005 Gy, less than about 1.2 Gy, less than about 0.001 Gy, less than about 0.0005 Gy, less than about 0.0002 Gy, or less than about 0.0001 Gy.

[64] Embodiments of the brachytherapy delivery systems disclosed herein are adapted to treat gynecological cancer selected from the group consisting of cervical cancer, vaginal cancer, vulvar cancer, endometrial cancer, and combinations thereof. One of ordinary skill will appreciate that treating a cancer does not require complete eradication of the cancer. Any beneficial physiologic response is contemplated, such as but not limited to tumor shrinkage, tumor cell death, reduction or halting of metastasis, reduction in cancer cell markers, alleviation of symptoms and the like.

Example

[65] The present disclosure will be more readily understood by reference to the following example, which is provided by way of illustration and is not intended to be limiting.

[66] A patient having a gynecologic cancer may be administered general anesthesia, and a tandem 111 is inserted into the vagina of the patent and into the uterus so that the tandem extends from the top of fundus of the uterus to the exterior of the patient’s vagina. The vaginal cylinder structure 100 may be inserted into the vagina so that the tandem is aligned with and situated within the tandem slot 105 of the vaginal cylinder structure 100. The vaginal cylinder structure may then be advanced until the proximal portion 101 abuts the cervix.

[67] To treat cervical tissue, a radiation source 109 comprising a closed tube containing, in this illustrative example, iridium-192 connected to a positioning member 116 may be inserted into a channel 103 via opening 104. The radiation source 109 may be advanced until the proximal end of the tube is positioned within the terminal segment 106 of the channel 103 adjacent to the proximal portion 101 of the vaginal cylinder structure 100, while and the positioning member 116 extends exteriorly from the channel 103 and the vagina. The radiation source 109 may be positioned in first the posterior region 106b for applying radiation therefrom and second in the anterior region 106a for applying radiation therefrom before withdrawing the radiation source 109 from the vaginal cylinder structure 100. Alternatively, the order may be reversed and the radiation source 109 may be positioned in the anterior region 106a first followed by the posterior region 106b. The longitudinal axes of terminal segment 106 and the closed tube comprising, in this illustrative example, iridium- 192 housed within are parallel to the cervix. To treat the vagina, the middle and/or distal portions of the tandem 111 is loaded with iridium- 192, either by insertion of a stationary cartridge housing the radionuclide or by inserting a closed tube containing a radionuclide attached to a threading member into the tandem 111 and advancing the portion containing the radionuclide to the desired position within the tandem 111. Alternatively or in addition, to treat vaginal mucosal tissue, a closed tube containing, in this illustrative example, iridium-192 connected to a positioning member 115 is inserted into a second channel 107 and advanced to the desired position within the channel 107. After the desired dose of radiation is delivered, each radiation source is withdrawn from the vaginal cylinder structure 100 without removing the vaginal cylinder structure 100 from the vagina.

[68] The brachytherapy delivery system and methods disclosed herein provided targeted delivery of radiation, including HDR radiation, to the cervix and/or vaginal tissue to treat gynecologic cancers. The ability to insert and withdraw the radiation sources while maintaining the vaginal cylinder structure deployed within the vagina and position a radiation source within a single channel at locations located in the proximal, distal, anterior, and posterior regions of the vaginal cylinder structure allow for specific dosing of radiation to target tissue and avoid damage to healthy tissue, as well as multiple implantation procedures.

[69] FIG. 4 is a block diagram illustrating an example wired or wireless system 400 that may be used in connection with various embodiments described herein. For example, system 400 may be used as or in conjunction with one or more of the mechanisms, processes, methods, or functions (e.g., to store and/or execute the application or one or more software modules of the application) described herein, and may represent components of the processing device 113 described in connection to FIG. 3. System 400 can be a server or any conventional personal computer, or any other processor-enabled device that is capable of wired or wireless data communication. Other computer systems and/or architectures may be also used, as will be clear to those skilled in the art. [70] System 400 preferably includes one or more processors, such as processor 410. Additional processors may be provided, such as an auxiliary processor to manage input/output, an auxiliary processor to perform floating point mathematical operations, a special-purpose microprocessor having an architecture suitable for fast execution of signal processing algorithms (e.g., digital signal processor), a slave processor subordinate to the main processing system (e.g., back-end processor), an additional microprocessor or controller for dual or multiple processor systems, or a coprocessor. Such auxiliary processors may be discrete processors or may be integrated with the processor 410. Examples of processors which may be used with system 400 include, without limitation, the Pentium® processor, Core i7® processor, and Xeon® processor, all of which are available from Intel Corporation of Santa Clara, California.

[71] Processor 410 is preferably connected to a communication bus 405. Communication bus 405 may include a data channel for facilitating information transfer between storage and other peripheral components of system 400. Furthermore, communication bus 405 may provide a set of signals used for communication with processor 410, including a data bus, address bus, and control bus (not shown). Communication bus 405 may comprise any standard or non-standard bus architecture such as, for example, bus architectures compliant with industry standard architecture (ISA), extended industry standard architecture (EISA), Micro Channel Architecture (MCA), peripheral component interconnect (PCI) local bus, or standards promulgated by the Institute of Electrical and Electronics Engineers (IEEE) including IEEE 488 general-purpose interface bus (GPIB), IEEE 696/S- 100, and the like.

[72] System 400 preferably includes a main memory 415 and may also include a secondary memory 420. Main memory 415 provides storage of instructions and data for programs executing on processor 410, such as one or more of the functions and/or modules discussed herein. For example, the main memory 415 may provide storage of instructions and data for programs for executing the example methods of treating gynecological cancer in a patient, as described above. It should be understood that programs stored in the memory and executed by processor 410 may be written and/or compiled according to any suitable language, including without limitation C/C++, Java, JavaScript, Perl, Visual Basic, .NET, and the like. Main memory 415 is typically semiconductor-based memory such as dynamic random access memory (DRAM) and/or static random access memory (SRAM). Other semiconductor-based memory types include, for example, synchronous dynamic random access memory (SDRAM), Rambus dynamic random access memory (RDRAM), ferroelectric random access memory (FRAM), and the like, including read only memory (ROM). [73] Secondary memory 420 may optionally include an internal memory 425 and/or a removable medium 430. Removable medium 430 is read from and/or written to in any well- known manner. Removable storage medium 430 may be, for example, a magnetic tape drive, a compact disc (CD) drive, a digital versatile disc (DVD) drive, other optical drive, a flash memory drive, etc.

[74] Removable storage medium 430 is a non-transitory computer-readable medium having stored thereon computer-executable code (e.g., disclosed software modules) and/or data. The computer software or data stored on removable storage medium 430 is read into system 400 for execution by processor 410.

[75] In alternative embodiments, secondary memory 420 may include other similar means for allowing computer programs or other data or instructions to be loaded into system 400. Such means may include, for example, an external storage medium 445 and a communication interface 440, which allows software and data to be transferred from external storage medium 445 to system 400. Examples of external storage medium 445 may include an external hard disk drive, an external optical drive, an external magneto-optical drive, etc. Other examples of secondary memory 420 may include semiconductor-based memory such as programmable read-only memory (PROM), erasable programmable read-only memory (EPROM), electrically erasable read-only memory (EEPROM), or flash memory (block- oriented memory similar to EEPROM).

[76] As mentioned above, system 400 may include a communication interface 440. Communication interface 440 allows software and data to be transferred between system 400 and external devices, networks, or other information sources. For example, computer software or executable code may be transferred to system 400 from a network server via communication interface 440. Examples of communication interface 440 include a built-in network adapter, network interface card (NIC), Personal Computer Memory Card International Association (PCMCIA) network card, card bus network adapter, wireless network adapter, Universal Serial Bus (USB) network adapter, modem, a network interface card (NIC), a wireless data card, a communications port, an infrared interface, an IEEE 1394 fire-wire, or any other device capable of interfacing system 400 with a network or another computing device. Communication interface 440 preferably implements industry -promulgated protocol standards, such as Ethernet IEEE 802 standards, Fiber Channel, digital subscriber line (DSL), asynchronous digital subscriber line (ADSL), frame relay, asynchronous transfer mode (ATM), integrated digital services network (ISDN), personal communications services (PCS), transmission control protocol/Internet protocol (TCP/IP), serial line Internet protocol/point to point protocol (SLIP/PPP), and so on, but may also implement customized or non-standard interface protocols as well.

[77] Software and data transferred via communication interface 440 are generally in the form of electrical communication signals 455. These signals 455 may be provided to communication interface 440 via a communication channel 450. In an embodiment, communication channel 450 may be a wired or wireless network, or any variety of other communication links. Communication channel 450 carries signals 455 and can be implemented using a variety of wired or wireless communication means including wire or cable, fiber optics, conventional phone line, cellular phone link, wireless data communication link, radio frequency (“RF”) link, or infrared link, just to name a few.

[78] Computer-executable code (i.e., computer programs, such as the disclosed application, or software modules) is stored in main memory 415 and/or the secondary memory 420. Computer programs can also be received via communication interface 440 and stored in main memory 415 and/or secondary memory 420. Such computer programs, when executed, enable system 400 to perform the various functions of the disclosed embodiments as described elsewhere herein.

[79] In this description, the term “computer-readable medium” is used to refer to any non-transitory computer-readable storage media used to provide computer-executable code (e.g., software and computer programs) to system 400. Examples of such media include main memory 415, secondary memory 420 (including internal memory 425, removable medium 430, and external storage medium 445), and any peripheral device communicatively coupled with communication interface 440 (including a network information server or other network device). These non-transitory computer-readable mediums are means for providing executable code, programming instructions, and software to system 400.

[80] In an embodiment that is implemented using software, the software may be stored on a computer-readable medium and loaded into system 400 by way of removable medium 430, EO interface 435, or communication interface 440. In such an embodiment, the software is loaded into system 400 in the form of electrical communication signals 455. The software, when executed by processor 410, preferably causes processor 410 to perform the features and functions described elsewhere herein.

[81] In an embodiment, I/O interface 435 provides an interface between one or more components of system 400 and one or more input and/or output devices. In various embodiments, the EO interface 435 provides an interface between the components of system 400 and one or more positioning members (e.g., positioning members 112, 115, and/or 116 and/or any additional position members as described in connection to FIG. 3.) Other example input devices include, without limitation, keyboards, touch screens or other touch-sensitive devices, biometric sensing devices, computer mice, trackballs, pen-based pointing devices, and the like. Examples of output devices include, without limitation, cathode ray tubes (CRTs), plasma displays, light-emitting diode (LED) displays, liquid crystal displays (LCDs), printers, vacuum fluorescent displays (VFDs), surface-conduction electron-emitter displays (SEDs), field emission displays (FEDs), and the like.

[82] System 400 may also include optional wireless communication components that facilitate wireless communication over a voice network and/or a data network. The wireless communication components comprise an antenna system 470, a radio system 465, and a baseband system 460. In system 400, radio frequency (RF) signals are transmitted and received over the air by antenna system 470 under the management of radio system 465.

[83] In one embodiment, antenna system 470 may comprise one or more antennae and one or more multiplexors (not shown) that perform a switching function to provide antenna system 470 with transmit and receive signal paths. In the receive path, received RF signals can be coupled from a multiplexor to a low noise amplifier (not shown) that amplifies the received RF signal and sends the amplified signal to radio system 465.

[84] In an alternative embodiment, radio system 465 may comprise one or more radios that are configured to communicate over various frequencies. In an embodiment, radio system 465 may combine a demodulator (not shown) and modulator (not shown) in one integrated circuit (IC). The demodulator and modulator can also be separate components. In the incoming path, the demodulator strips away the RF carrier signal leaving a baseband receive signal, which is sent from radio system 465 to baseband system 460.

[85] Baseband system 460 also codes digital signals for transmission and generates a baseband transmit signal that is routed to the modulator portion of radio system 465. The modulator mixes the baseband transmit signal with an RF carrier signal generating an RF transmit signal that is routed to antenna system 470 and may pass through a power amplifier (not shown). The power amplifier amplifies the RF transmit signal and routes it to antenna system 470, where the signal is switched to the antenna port for transmission.

[86] Baseband system 460 is also communicatively coupled with processor 410, which may be a central processing unit (CPU). Processor 410 has access to data storage areas 415 and 420. Processor 410 is preferably configured to execute instructions (i.e., computer programs, such as the disclosed example methods) that can be stored in main memory 415 or secondary memory 420. Computer programs can also be received from baseband processor 460 and stored in main memory 415 or in secondary memory 420, or executed upon receipt. Such computer programs, when executed, enable system 400 to perform the various functions of the disclosed embodiments. For example, data storage areas 415 or 420 may include various software modules.

[87] Various embodiments may also be implemented primarily in hardware using, for example, components such as application specific integrated circuits (ASICs), or field programmable gate arrays (FPGAs). Implementation of a hardware state machine capable of performing the functions described herein will also be apparent to those skilled in the relevant art.

[88] Furthermore, those of skill in the art will appreciate that the various illustrative logical blocks, modules, circuits, and method steps described in connection with the above described figures and the embodiments disclosed herein can often be implemented as electronic hardware, computer software, or combinations of both. To clearly illustrate the interchangeability of hardware and software, various illustrative components, blocks, modules, circuits, and steps are described herein generally in terms of their functionality. Whether such functionality is implemented as hardware or software depends upon the particular application and design constraints imposed on the overall system. Skilled persons can implement the described functionality in varying ways for each particular application, but such implementation decisions should not be interpreted as causing a departure from the scope of the invention. In addition, the grouping of functions within a component, block, module, circuit, or step is for ease of description. Specific functions or steps can be moved from one component, block, module, circuit, or step to another without departing from the invention.

[89] Moreover, the various illustrative logical blocks, modules, functions, and methods described in connection with the embodiments disclosed herein can be implemented or performed with a general purpose processor, a digital signal processor (DSP), an ASIC, FPGA, or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. A general-purpose processor can be a microprocessor, but in the alternative, the processor can be any processor, controller, microcontroller, or state machine. A processor can also be implemented as a combination of computing devices, for example, a combination of a DSP and a microprocessor, a plurality of microprocessors, one or more microprocessors in conjunction with a DSP core, or any other such configuration.

[90] Combinations, described herein, such as “at least one of A, B, or C,” “one or more of A, B, or C,” “at least one of A, B, and C,” “one or more of A, B, and C,” and “A, B, C, or any combination thereof’ include any combination of A, B, and/or C, and may include multiples of A, multiples of B, or multiples of C. Specifically, combinations such as “at least one of A, B, or C,” “one or more of A, B, or C,” “at least one of A, B, and C,” “one or more of

A, B, and C,” and “A, B, C, or any combination thereof’ may be A only, B only, C only, A and

B, A and C, B and C, or A and B and C, and any such combination may contain one or more members of its constituents A, B, and/or C. For example, a combination of A and B may comprise one A and multiple B’s, multiple A’s and one B, or multiple A’s and multiple B’s. [91] The above description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles described herein can be applied to other embodiments without departing from the spirit or scope of the invention. Thus, it is to be understood that the description and drawings presented herein represent a presently preferred embodiment of the invention and are therefore representative of the subject matter which is broadly contemplated by the present invention. It is further understood that the scope of the present invention fully encompasses other embodiments that may become obvious to those skilled in the art and that the scope of the present invention is accordingly not limited.

Claims

CLAIMS What is claimed is:

1. A brachytherapy delivery system having an intracavitary deployed state and an extracorporeal inactive state, comprising: a vaginal cylinder structure comprising: a proximal portion that abuts patient tissue when the brachytherapy delivery system is in the intracavitary deployed state, a tandem slot located along a central longitudinal axis of the vaginal cylinder structure and aligned for receiving a tandem for placement adjacent to or extending into a cervix, and a channel comprising: a longitudinal segment extending longitudinally from an opening formed in a distal base of the vaginal cylinder structure toward the proximal portion, and a terminal segment that extends at least partially transversely and along the proximal portion, wherein a radiation source is continuously positioned at one or more discrete positions within the channel from a first position of the one or more discrete positions posterior to the tandem slot to a second position of the one or more discrete positions anterior to the tandem slot, when in the intracavitary deployed state.

2. The brachytherapy delivery system of claim 1, further comprising the radiation source connected to a positioning member that, when the brachytherapy delivery system is in the intracavitary deployed state, is insertable into the channel, is continuously positioned at one or more discrete position within the channel, and completely removable from the channel.

3. The brachytherapy delivery system of claim 1 or 2, further comprising a tandem inserted into the tandem slot along the central longitudinal axis of the vaginal cylinder structure.

4. The brachytherapy delivery system of claim 3, wherein the tandem houses one of an x-ray tube and a radionuclide selected from a group consisting of iridium-192, iodine- 125, palladium- 103, cesium-131, cesium-137, cobalt-60, ruthenium- 106, radium-226, and combinations thereof.

5. The brachytherapy delivery system of any of claims 1-4, wherein the longitudinal segment of the channel is parallel to the longitudinal axis of the vaginal cylinder structure.

6. The brachytherapy delivery system of any of claims 1-5, further comprising a plurality of additional channels that extend longitudinally along the vaginal cylinder structure and are positioned at different radial locations from the central longitudinal axis.

7. The brachytherapy delivery system of any of claims 1-6, wherein the terminal segment forms one of a right or obtuse angle with the longitudinal segment of the channel.

8. The brachytherapy delivery system of any of claims 1-7, wherein the vaginal cylinder structure further comprises a second channel extending longitudinally toward the proximal portion from a second opening formed in the distal base of the vaginal cylinder structure; and the brachytherapy delivery system comprises a second radiation source is connected to a second positioning member that, when the brachytherapy delivery system is in the intracavitary deployed state, is insertable into the second channel, continuously positioned at one or more discrete position within the second channel, and completely removable from the second channel, wherein the positioning of the radiation source and the second radiation source are independently controlled by the second positioning member.

9. The brachytherapy delivery system of any of claims 1-8, wherein the one or more of the radiation source and the second radiation source is positioned within the vaginal cylinder structure when the brachytherapy delivery system is in the intracavitary deployed state to provide radiation from the vaginal cylinder structure to one or more of the cervix and a vaginal wall.

10. The brachytherapy delivery system of any of claims 1-9, further comprising at least one projection extending exteriorly from a surface of the vaginal cylinder structure.

11. The brachytherapy delivery system of claim 10, wherein the projection is a needle.

12. The brachytherapy delivery system of any of claims 1-11, wherein the positioning member comprises an adjustable threading member connected to the radiation source and to one of a computer processing device for controlling the positioning of the threading member and to a manual positioner for controlling the positioning of the threading member.

13. The brachytherapy delivery system of any of claims 1-12, wherein one or more of the radiation source and the second radiation source comprises one of an x-ray tube and a radionuclide selected from a group consisting of iridium-192, iodine-125, palladium- 103, cesium-131, cesium-137, cobalt-60, ruthenium- 106, radium-226, and combinations thereof.

14. The brachytherapy delivery system of any of claims 1-13, wherein the brachytherapy delivery system delivers radiation at a dose rate of at least about 12 gray per hour.

15. A method of treating a gynecological cancer in a patient comprising: deploying into a vagina of a patient a vaginal cylinder structure of a brachytherapy delivery system according to any of claims 1-14; inserting the radiation source into the channel of the vaginal cylinder structure; positioning the radiation source at one or more of the discrete positions within the channel while the vaginal cylinder structure is deployed; and completely withdrawing the radiation source from the channel of the vaginal cylinder structure while the vaginal cylinder structure is deployed, thereby delivering a therapeutically effective amount of radiation to cancer cells.

16. A method of treating a gynecological cancer in a patient comprising: deploying into a vagina of a patient a vaginal cylinder structure comprising, the vaginal cylinder structure comprising: a proximal portion that abuts cervical tissue of the patient, a tandem slot located along a central longitudinal axis of the vaginal cylinder structure aligned for receiving a tandem for placement adjacent to or extending into a cervix of the vagina, and a channel comprising a longitudinal segment extending longitudinally toward the proximal portion from an opening formed in a distal base of the vaginal cylinder structure; inserting a radiation source into the channel; continuously positioning the radiation source at one or more discrete positions within the channel while the vaginal cylinder structure is deployed; and completely withdrawing the radiation source from the channel of the vaginal cylinder structure while the vaginal cylinder structure is deployed, thereby delivering a therapeutically effective amount of radiation to cancer cells.

17. The method of claim 15 or 16, further comprising inserting a tandem into the tandem slot so that the tandem extends externally from the vagina of the patient, wherein the tandem houses one of an x-ray tube and a radionuclide selected from a group consisting of iridium-192, iodine-125, palladium- 103, cesium-131, cesium-137, cobalt-60, ruthenium- 106, radium-226, and combinations thereof.

18. The method of any of claims 15-17, further comprising: inserting a second radiation source into a second channel extending longitudinally from a second opening formed in the distal base of the vaginal cylinder structure toward the proximal portion; continuously positioning the second radiation source at one or more discrete positions within the second channel while the vaginal cylinder structure is deployed; and completely withdrawing the second radiation source from the channel of the vaginal cylinder structure while the vaginal cylinder structure is deployed.

19. The method of claim 18, wherein the positioning of the radiation source and second radiation source are controlled independently.

20. The method of any of claims 15-19, comprising positioning one or more of the radiation source and the second radiation source to deliver a therapeutically effective amount of radiation from the vaginal cylinder structure to at least one of the cervix and a vaginal wall of the vagina.

21. The method of any of claims 15-20, further comprising: inserting one or more of the radiation source and the second radiation source into the channel; and continuously positioning the one or more of the radiation source and the second radiation source to deliver a therapeutically effective amount of radiation from a first position of the one or more discrete positions posterior to the tandem slot and a second position of the one or more discrete positions anterior to the tandem slot, before withdrawing the one or more of the radiation source and the second radiation source.

22. The method of any of claims 15-21, wherein the gynecological cancer is selected from a group consisting of cervical cancer, vaginal cancer, vulvar cancer, endometrial cancer, and combinations thereof.

23. The method of any of claims 15-22, comprising administering radiation at a dose rate of at least about 12 gray per hour.

24. The method of any of claims 15-23, comprising administering a dose of radiation to cancer cells of at least about 1 gray.

25. The method of any of claims 15-24, comprising administering a dose of radiation to adjacent healthy tissue of less than about 0.2 gray.

26. The method of claim 25, wherein the adjacent healthy tissue is selected from a group consisting of bowel, bladder, rectum, sigmoid colon, and combinations thereof.