RU235474U1 - Prostate Cancer Repeat Brachytherapy Implant - Google Patents

Abstract

An implant (30) for repeated brachytherapy of prostate cancer comprises successively arranged radiopaque sources (32) of radioactive radiation, essentially the same as the radiopaque sources of radioactive radiation of implants intended for use in the first stage of brachytherapy, wherein radiopaque markers (33) are placed between adjacent sources (32) of radioactive radiation. 2 c.p. f-ly, 9 fig.

Description

AREA OF TECHNOLOGY

The utility model relates to the field of medicine, in particular to intra-tissue radiation therapy, carried out using radioactive radiation sources introduced into the body, and can be used to treat prostate cancer.

LEVEL OF TECHNOLOGY

One of the effective modern methods of treating prostate cancer is interstitial low-dose radiation therapy - brachytherapy. This method involves implanting radioactive radiation sources (the so-called "seeds") into the prostate gland. Unlike radical prostatectomy, which can often result in negative urological side effects, or high-dose radiation therapy, both external and interstitial, in which a large volume of tissue is exposed to radiation, interstitial brachytherapy is the most gentle both in terms of the implantation procedure and the effect of ionizing radiation, the sources of which are implanted "targeted" relative to the cancerous tumor, irradiating it with small doses over a long period of time.

In general, the method of brachytherapy for prostate cancer is described, for example, in the article: Zyryanov A.V. et al. Recommendations for the treatment of prostate cancer using low-dose permanent interstitial radiation therapy (brachytherapy) Expert meeting of the Association of Brachytherapists of Russia (ABRR), October 4, 2014, Moscow // Experimental and Clinical Urology. 2015. No. 2. P. 37-64. These recommendations describe in detail all stages of brachytherapy: preimplantation planning, direct implantation of sources, including visualization methods and preparation of sources for implantation, and postimplantation dosimetry.

The radioactive substance used to treat prostate cancer is usually the iodine isotope I-125, placed in a sealed capsule - container. The half-life of the isotope I-125 is about 60 days.

One of the first descriptions of such a source of radioactive radiation for prostate cancer brachytherapy can be found in patent US 3351049 (published 07.11.1967). This source is made in the form of a cylindrical container with hermetically sealed ends, inside which a substrate with the iodine isotope I-125 applied to it is placed. The container is made of a material with a low atomic weight, for example, stainless steel or titanium, which has a low absorption coefficient of ionizing radiation. To control the spatial position of the source in the patient's body, the substrate is equipped with a longitudinal wire - a marker made of radiopaque material, for example, gold, which makes the source a contrast object in the image obtained using a computer tomograph - a CT image.

A similar source of radioactive radiation is described in patent US 4323055 (published 06.04.1982). It is made in the form of a cylindrical container with hermetically sealed ends, inside which a substrate with the iodine isotope I-125 applied to it is placed. The substrate is made of silver or coated with a layer of silver, which is a radiopaque material that provides visualization of the source both during the implantation procedure and after it. In addition, radioactive iodine is easily deposited on silver using known electrochemical methods. The substrate also has an elongated shape, allowing one to see the spatial orientation of the implanted source on a CT image. The container is made of titanium for reasons of low radiation absorption, as well as corrosion resistance, non-toxicity and satisfactory compatibility with biological tissue.

Another example of an implantable radioactive radiation source for brachytherapy is described in RU 2238121 C2 (published 20.10.2004). This source includes a substrate in the form of a tube with a radioactive substance applied to its outer surface, placed in a sealed container. At least one radiopaque marker, in particular made of silver, is placed inside the tube. Preferably, for determining the spatial orientation of the implanted source, the markers can be placed at the ends of the tube.

In practice, one of the most common sources of radioactive radiation used for brachytherapy of prostate cancer are sources from the company OOO BEBIG (see "Microsources based on iodine 125 for the treatment of prostate cancer". URL: https://bebig.ru/products/mikroistochniki-dlya-lecheniya-raka-predstatelnoy-zhelezy/ - accessed 12/29/2024).

This source of radioactive radiation is a cylinder made of medical titanium measuring 4.5 x 0.8 mm, inside which is a gold wire - a radiopaque marker and the radionuclide I-125 in the form of silver iodide, located in a porous alumina ceramic.

These and similar sources of radioactive radiation can be implanted into the prostate tissue separately, for example, as described in US Patent No. 5,860,909 (published on January 19, 1999), using a needle with a stylet. First, the stylet is fully extended through the distal opening of the needle, which is inserted into the tissue where the sources are planned to be implanted. Then the stylet is removed from the needle, the source of radioactive radiation is inserted into the needle from the proximal side, after which the stylet is pressed through the needle into the tissue. After implantation of the first source, the needle is removed from the tissue to a specified distance so that the next source, similarly advanced by the stylet, is implanted at this distance from the first source, etc. As a result, all sources of radioactive radiation are implanted into the tissue along the "path" made by the needle.

However, this method of successive implantation of single radiation sources has a number of significant limitations. Thus, after the needle is removed, the sources tend to move along this track, and some of them, held by the tissue, may migrate from the initial implantation site. Such migration is undesirable from a clinical point of view, since it changes the radiation distribution planned in accordance with the dosimetric scheme and may lead, for example, to an overdose or insufficient dose of radiation of the affected tissue, as well as to irradiation of healthy tissue. Free radiation sources may rotate relative to their initial orientation, which is also undesirable for the same clinical reasons. In addition, the individual implantation of radiation sources takes a lot of time.

A solution that significantly simplifies the process is described in US patent 5938583 (published 17.08.1999), where, before implanting the radioactive radiation sources, all of them are simultaneously loaded into the needle through separating elements in the form of a chain.

At present, when the task is to implant multiple sources of radioactive radiation, they are assembled in advance in the form of a chain, forming an implant for insertion into the prostate gland. Various design solutions are known that allow individual sources of radioactive radiation to be assembled into a single implant.

Thus, patent US 4697575 (published 06.10.1987) describes an implant consisting of a set of radioactive radiation sources assembled in a chain one after another. The sources include cylindrical containers with a radioactive substance, encapsulated in a cylindrical body made of bioresorbable material. The body at the ends has elements of axial articulation with other source bodies, ensuring their connection into a single rigid rod in the form of a needle for insertion into the prostate gland tissue. After inserting the rod into the tissue to the required depth, it is broken off, leaving the appropriate number of radioactive radiation sources implanted in the tissue.

A simpler and more convenient to use implant design is described in patent US 6264600 B1 (published 24.07.2001). It is a hollow tube made of suture material, inside which alternating sources of radioactive radiation and separating elements (spacers) between them are loaded in the form of a chain. The separating elements maintain a given distance between the sources of radioactive radiation, provide sufficient axial rigidity of the implant and prevent warping of the supporting suture material when the implant is pulled out of the needle during its installation in the prostate gland.

International application WO 2019171308 A1 (published 12.09.2019) describes a brachytherapy implant comprising a flexible hollow tube made of a biocompatible material, onto which radioactive radiation sources are strung on the outside in the form of a chain, each of which is made in the form of a tubular body, on the surface of which a radioactive substance is applied.

International application WO 2003039463 A2 (published 15.05.2003) describes a brachytherapy implant comprising radioactive radiation sources in the form of tubular bodies with a through axial opening through which suture material - thread - is inserted. After stringing the required number of radioactive radiation sources on the thread and placing them at a given distance from each other, the thread is heated, which leads to its local expansion and fixation of the radioactive radiation sources on it. As a result, a sufficiently rigid in the axial direction and flexible in the transverse direction implant design is obtained. Rigidity ensures the ability to push the implant out of the needle while maintaining a given distance between the radioactive radiation sources, and flexibility - to move along with the tissue in which it is installed.

International application WO 2003039655 A2 (published 15.05.2003) describes a brachytherapy implant made in the form of a section of polymer monofilament made of bioresorbable material, inside which radioactive radiation sources are encapsulated in a chain at a given distance from each other. The implant is manufactured by compression molding, in which radioactive radiation sources placed in a mold are filled with molten polymer.

International application WO 2009097408 A1 (published 06.08.2009) describes a brachytherapy implant made in the form of a section of a polymer monofilament or a hollow tube made of bioresorbable material, inside which radioactive radiation sources are encapsulated in a chain at a given distance from each other. Moreover, each source is made in the form of a hollow cylinder made of bioresorbable material, with the radioactive substance applied to its outer surface, and the radiopaque (marker) - on the inner. Such an implant does not have any metal or plastic elements that would remain in the patient's tissues for an indefinitely long time after the radiation sources lose their radiation activity.

Thus, various design solutions for implants assembled in the form of a chain of radioactive radiation sources are known, which can be used for prostate cancer brachytherapy. In any case, the implants form chains of radioactive radiation sources held together in a single whole, sequentially located and spaced at some distance from each other.

For prostate cancer brachytherapy, an average of 18-25 such implants are used, which together include about 65 sources of radioactive radiation. The implants are installed using a corresponding number of needles, in which they are pre-positioned. The needles are inserted through a special plate, for example, as described in international application WO 2004101026 A2 (published 25.11.2004) or in patent US 7527593 B2 (published 05.05.2009), which has a plurality of guide holes and which allows positioning the implants in the prostate tissue relative to each other and the area of the prostate gland being irradiated.

The so-called dosimetric planning precedes the installation of implants, when the number of implants and sources is determined based on the required distribution of ionizing radiation in the prostate gland. Specialists are familiar with such planning methods, including those performed using computed tomography, for example, those described in the article: Dosimetric planning of brachytherapy / [Andreeva Yu.V., Kravets O.A., Maryina L.A. et al.] // Proceedings of the V Congress of Oncologists and Radiologists of the CIS, Tashkent, May 14-16, 2008. - P. 488. The software for low-dose brachytherapy systems PSID currently used is registered by Roszdravnadzor in the State Register of Medical Devices and Organizations (Individual Entrepreneurs) Engaged in the Production and Manufacturing of Medical Devices; registration number FS No. 2006/1430, registration date 09/29/2011.

In some cases, re-implantation of radioactive radiation sources may be required during the treatment of prostate cancer. For example, migration of implants (and therefore sources) may change the distribution of radiation in the prostate gland, which in turn may not provide the desired therapeutic result or increase the risk of relapse. Thus, post-implantation dosimetry of 168 patients of the North-West District Scientific and Clinical Center named after L.G. Sokolov (NWRDSC) who underwent the primary brachytherapy procedure in 2023 revealed migration of sources and the presence of zones of reduced dose coverage relative to the required one - the so-called "cold" zones.

In addition to migration of radioactive sources, the need for re-implantation in some patients may be caused by disease recurrence that occurs several years after the primary brachytherapy.

In the absence of contraindications for repeated implantation, such as complications after the first procedure (internal hematomas, acute conditions, etc.), an unfavorable anamnesis for spinal anesthesia (from the cardiovascular system) or the possibility of restoring the required dose coverage, the patient undergoes repeated implantation. This procedure is performed in the same way as the first, but, as a rule, with a smaller number of needles and radioactive sources. The same equipment is used, including the same implants as in the first procedure.

However, during re-implantation, which is essentially the second stage of brachytherapy, the problem of assessing the spatial distribution of the radiation dose (dose coverage) arises. Although the implants installed during the first and second stages of brachytherapy have different radiation activity, they are indistinguishable from each other on a CT image, since their visualization is determined by radiopaque markers, but not by the radioactive substance of the radiation sources.

The task, which the present utility model is aimed at solving, is the development of an implant for repeated brachytherapy of prostate cancer, made in the form of a chain of radiopaque sources of radioactive radiation, essentially similar to the implants used in the first stage of brachytherapy, with the ability to control its localization relative to the implants inserted in the first stage of brachytherapy, due to the distinguishability of the implants on a CT image.

DISCLOSURE OF THE ESSENCE OF THE UTILITY MODEL

The implant claimed as a utility model for repeated brachytherapy of prostate cancer, carried out by introducing implants in the form of chains of radioactive radiation sources into the patient's prostate gland, includes sequentially located radiopaque radioactive radiation sources, essentially the same as the radioactive radiation sources of the implants intended for use in the first stage of brachytherapy, with radiopaque markers placed between adjacent radioactive radiation sources.

The technical result - distinguishability in CT visualization of implants used in the first and repeated (second) stages of brachytherapy, is due to the following. The implementation of an implant for repeated brachytherapy, which essentially has the same sequentially located sources of radioactive radiation as the implants in the first stage of brachytherapy, but with markers made of radiopaque material placed between them, ensures their visual distinction in the CT image. Since with such a relative arrangement of the sources of radioactive radiation of the implants used in the first stage of brachytherapy - implants of the first type, they are spaced from each other by some distance, then in the CT image they clearly look like sources spaced along the implant. In the implants used in repeated brachytherapy (implants of the second type), in CT visualization not only the sources of radioactive radiation themselves are observed, but also the markers placed between them. As a result, the density of observed radiopaque objects in the chain of the implant used in the repeated brachytherapy is essentially twice as large as the density of observed radiopaque objects in the chain of the implant used in the first stage of brachytherapy, which is easily visually distinguishable on the CT image. At the same time, the radiation activity of the implants used in the repeated brachytherapy is determined, respectively, by their sources of radioactive radiation, although on the CT image, in comparison with the implants used in the first stage of brachytherapy, they look as if they were sources with essentially double the density of placement.

In particular, the sources of radioactive radiation of the implant for repeated brachytherapy can be made in the form of hollow titanium capsules containing the iodine isotope I-125 and a radiopaque element inside. In this case, the radiopaque markers of the implant can be made in the form of titanium capsules, essentially the same as the capsules of the sources of radioactive radiation, containing a radiopaque element inside. This will reduce the range of parts from which the implant is made.

In a special case, the radioactive radiation sources and radiopaque markers of the implant for repeat brachytherapy can be placed inside a hollow tube made of biocompatible and radiolucent material.

BRIEF DESCRIPTION OF DRAWINGS

The implant claimed as a utility model is explained by the following graphic materials.

Fig. 1 shows an example of a typical implant used in the first stage of prostate cancer brachytherapy, the first type of implant, which is made in the form of a hollow polymer tube made of biocompatible material, inside which radioactive radiation sources are arranged sequentially in a chain.

Fig. 2 shows an example of a radioactive radiation source in the form of a titanium capsule with a radioactive isotope of iodine I-125 and a radiopaque element inside.

Fig. 3 shows a typical CT image of tissues and organs in the prostate gland immediately after the installation of the first type of implants shown in Fig. 1.

Fig. 4 shows a CT image of tissues and organs in the prostate gland area with implants of the first type installed, as shown in Fig. 3, obtained one month after their installation.

Fig. 5 shows an example of an implant for repeated brachytherapy of prostate cancer in accordance with the present utility model - a second type of implant, which is made in the form of a hollow polymer tube made of a biocompatible material, inside which alternating sources of radioactive radiation and radiopaque markers are arranged sequentially in the form of a chain.

Fig. 6-9 show model CT images of implants of the first and second types, wherein

Fig. 6 shows an image of two implants of the first type;

in Fig. 7 - three implants of the first type, one of which migrated to the side (to the right) of the other two;

in Fig. 8 - a side-by-side comparison of the implant of the second type and the implant of the first type;

in Fig. 9 - implants of the first and second types, when the implant of the second type replaces the migrated implant of the first type, shown in Fig. 7.

IMPLEMENTATION OF A UTILITY MODEL

When performing brachytherapy, which additionally includes a repeated procedure for installing implants, it is generally possible to use known methods and equipment that ensure the installation of implants in the prostate tissue, made in the form of chains of radiopaque sources of radioactive radiation, for example, as disclosed with references in the description of the level of technology.

In particular, the implants can be made of threads with radioactive radiation sources manufactured by the aforementioned company OOO BEBIG, which are cut into segments - individual implants containing the required number of radioactive radiation sources in accordance with the dose distribution model. For example, disposable brachytherapy needles manufactured by Medradiopartner can be used to install implants in the prostate gland tissue. They have a 30° cut that facilitates tissue penetration, a conical retainer for the implant charging station, and centimeter and half-centimeter markings-notches on the outer cannula to control the immersion of the needle. The needles are installed in the prostate gland tissue through a tablet - a stereotactic attachment to a CT tomograph with holes with a pitch of 2.5 mm, in particular, as described in patent RU 130854 U1. All operations are performed using a CT scanner, for example, the Siemens Somatom Sensation 40 manufactured by Siemens AG (Germany).

At the first stage of brachytherapy, implants of the first type are used. An example of such a typical implant 10 used in practice is shown in Fig. 1. It is made in the form of a hollow polymer tube 11 made of a biocompatible material, inside which sources of radioactive radiation 12 are arranged sequentially in the form of a chain.

As sources 12, for example, the mentioned sources of radioactive radiation produced by the company OOO "BEBIG" can be used. As shown in Fig. 2, such a source 12 is a hollow capsule 13 of cylindrical shape made of titanium with sealed ends. Inside the capsule 13, the radionuclide I-125 is placed in the form of silver iodide on a substrate 14 made of porous alumina ceramics and a gold wire 15 as a radiopaque marker, providing visualization of the source 12 on a CT image.

Fig. 1 also shows a gap M between two adjacent sources 12 of radioactive radiation.

Fig. 3 shows a typical image of organs and tissues in the area of the prostate gland with implants of the first type installed in it, obtained using CT in the axial projection. In particular, here one can see: the prostate gland 21 with four implants of the first type 10, the urethra 22, the rectum 23, the surrounding muscle tissues 24. This image was obtained immediately after the installation of implants of the first type 10 at the first stage of brachytherapy for prostate cancer.

Fig. 4 shows a CT image of the same organs and tissues in the area of the prostate gland with implants 10, obtained one month after their installation. The designations of the positions are the same as in Fig. 3. As can be seen, over the past time, the implants 10 have migrated relative to their original position, resulting in the formation of zones in which there are no sources of radioactive radiation, which may lead to a decrease in the dose coverage in these zones relative to the originally planned and, accordingly, may require a repeated brachytherapy procedure using implantable sources of radioactive radiation. The need for repeated implantation is determined by a medical physicist using methods of modeling dose distribution known to a specialist.

An example of an implant for repeated brachytherapy of prostate cancer, i.e. an implant used in the second stage of brachytherapy, a second type of implant, is shown in Fig. 5. This implant 30, similar to the implant 10 (see Fig. 1), used in the first stage of brachytherapy, is made in the form of a hollow polymer tube 31 made of a biocompatible material, inside which sources 32 of radioactive radiation are arranged sequentially in the form of a chain, just like the sources 12 of the implant 10. But unlike the implant 10, the implant 30 additionally includes radiopaque markers 33 placed between the sources 32. Since both the sources 32 and the markers 33 are radiopaque, then on a CT image of tissue in the area of the prostate gland, the implanted sources 30 will noticeably differ from the implants 10 previously installed in the first stage of brachytherapy by a doubled density of the observed radiopaque objects. In this case, the radiation activity of the implants 30 used in the second stage of brachytherapy is determined, accordingly, only by their sources 32 of radioactive radiation.

Fig. 5 also shows the geometric relationships characterizing the gap M between adjacent sources 32 and the linear dimension L of the radiopaque marker 33 in its longitudinal direction. It can be seen that M must be no less than L so that the marker 33 can be placed in the gap between adjacent sources 32. In order for the difference between the implants 30 and 10 to be sufficiently noticeable, the distance M (see Fig. 1) between the sources 12 of the implants 10 used in the first stage of brachytherapy must correspond to the gap M indicated in Fig. 5.

The mentioned sources of radioactive radiation produced by the company OOO "BEBIG" can also be used as sources 32 of implants 30 intended for use in the second stage of brachytherapy, as shown in Fig. 2. In this case, markers 33 of implants 30 can be made, for example, in the form of capsules, essentially the same as the capsules of sources 32 (or 12), but without the iodine isotope I-125, which will reduce the range of parts from which implants are made in accordance with the present utility model.

To confirm the technical result - distinguishability in CT visualization of implants used in the first and second stages of brachytherapy, model experiments were conducted. For this purpose, samples of both types of implants were placed in a CT scanner on the patient table, after which CT scanning was performed in the standard pelvic diagnostic mode. The obtained model CT images of implants can be considered adequate to real CT images of implants installed in the soft tissues of the prostate gland, which do not have a significant effect on the contrast of the sources of radioactive radiation of the implants in the CT image.

The results of the experiment are shown in Fig. 6-9. Fig. 6 shows a CT image of two implants 10 - implants of the first type used in the first stage of brachytherapy. Here and further in Fig. 6-9, the implants 10 are conditionally shown by dotted lines, since only radiopaque objects are visible in the CT image - in this case, sources 12 of radioactive radiation with radiopaque markers inside, as was described with reference to Fig. 2. As can be seen, in the CT image, the sources 12 of these implants 10 are perceived as separate radiopaque objects spaced from each other.

Fig. 7 shows a CT image of three implants 10 of the first type, one of which, namely the right implant 10', migrated away from the other two (to the right in the image). Since all the implants used in the implementation of the invention are made in the form of chains of radioactive radiation sources, in the CT image they are visually well perceived, essentially, as whole structures, which in turn allows their migration into the prostate gland tissue to be visually detected.

Fig. 8 shows a CT image of two implants simultaneously - implant 10 of the first type and implant 30 of the second type. Just as in Figs. 6, 7, implant 10 is visible in the CT image as a chain of several radioactive radiation sources 12 spaced apart from each other. At the same time, implant 30, indicated by the dotted line, is presented in the CT image, in essence, as a single radiopaque object, although in fact it includes, just like implant 10, a chain of sources 32 spaced apart from each other. However, due to radiopaque markers 33 placed between sources 32, as described with reference to Fig. 5, in the CT image they merge, in essence, into a single radiopaque object elongated in the shape of implant 30, while positions 32 and 33 in Fig. 8 indicate the actual location of sources 32 and markers 33.

Fig. 9 shows a CT image of both the first and second type implants, as it may look approximately after implant placement during the second stage of prostate cancer brachytherapy. Here one can see both the implants 10 placed during the first stage of brachytherapy and the implant 30 placed during the second stage of brachytherapy, which essentially replaces the migrated implant 10' of the first type, shown in Fig. 7.

As can be seen, the use of an implant in repeated brachytherapy that additionally includes radiopaque markers placed between adjacent sources of radioactive radiation provides the specified technical result - distinguishability in CT visualization of the implants used in the first and second stages of brachytherapy. In turn, this allows for post-implantation dosimetry with an accurate indication of the activity of each source of radioactive radiation of the implants installed, which ultimately makes it possible to assess the effectiveness of repeated brachytherapy, as well as the risks of possible complications and the need to correct treatment tactics.

Claims (3)

1. An implant for repeated brachytherapy of prostate cancer, made in the form of a hollow polymer tube made of biocompatible and radiolucent material, inside which radiopaque sources of radioactive radiation are arranged sequentially in a chain, with radiopaque markers placed between adjacent sources of radioactive radiation. 2. An implant according to item 1, wherein the sources of radioactive radiation are made in the form of hollow titanium capsules containing the iodine isotope I-125 and a radiopaque element inside. 3. An implant according to claim 2, in which the radiopaque markers are made in the form of titanium capsules, essentially the same as the capsules of radioactive radiation sources, containing a radiopaque element inside.