MXPA06005061A - Tissue positioning systems and methods for use with radiation therapy - Google Patents

Abstract

A system for treating tissue surrounding a resected cavity that is subject to a proliferative tissue disorder is provided. The system includes a tissue fixation device including a catheter body member having a proximal end, a distal end, an inner lumen, and an expandable surface element disposed proximate to the distal end of the body member, the expandable surface element sized and configured to reproducibly position tissue surrounding a resected tissue cavity in a predetermined geometry upon expansion. After expansion of the expandable surface element within a resected tissue cavity, an external radiation device positioned outside the resected cavity delivers a dose of radiation to the tissue surrounding the expandable surface element.

Description

Published: For two-letter codes and other abbreviations, refer to the "Guid- - without intemational search report and to be republished anee Notes on Codes and Abbreviations" appearing at the begin- ning receipt oftliat report no ofeach regular issue of the PCT Gazette.

SYSTEMS AND METHODS OF TISSUE POSITIONING FOR USE IN RADIATION THERAPY Field of the Invention The present invention relates generally to systems and methods for use in the treatment of tissue proliferative disorders and more particularly, to systems and methods for the treatment of said disorders in the chest, by placing the tissue and applying radiation. Background of the Invention Malignant tumors are often treated by surgical resection of the tumor to remove as much of the tumor as possible. However, the infiltration of the tumor cells into the normal tissue surrounding the tumor may limit the therapeutic value of the surgical operation, because the infiltration may be difficult or impossible to treat surgically. Radiation therapy may be used to supplement the surgical operation targeting the margin of the residual tumor after the operation, with the goal of reducing its size or stabilizing it. Radiation therapy can be administered through one of several methods or a combination of methods, including permanent or temporary interstitial brachytherapy and external beam radiation. Brachytherapy refers to radiation therapy administered by a radioactive material confined to the space inserted within the body at or near a tumor or other site of tissue proliferative disorders. For example, brachytherapy is carried out by implanting the radiation sources directly into the tissue to be treated. Brachytherapy is the most appropriate in cases where 1) the new growth of the malignant tumor occurs locally, within 2 or 3 cm of the original limit of the site of the primary tumor; 2) radiation therapy is a proven treatment to control the growth of the malignant tumor and 3) there is a response relationship to the radiation dose for the malignant tumor, but the dose that can be safely administered with radiation therapy conventional external is limited by the tolerance of normal tissue. In brachytherapy, the dose of radiation is highest in close proximity to the radiotherapeutic source, providing a high dose to the tumor while it diffuses into the normal tissue surrounding it. Interstitial brachytherapy is useful for the treatment of malignant tumors of the brain and chest, among others. U.S. Patent No. 5,429,582, issued to Williams, entitled "Treatment of Tumors", describes a brachytherapy method and apparatus for the treatment of tissue surrounding a tumor surgically excised with radioactive emissions to kill any cancer cells that may be present in the tumor. tissue surrounding the excised tumor. In order to implement the radioactive emissions, Williams provides a catheter that has a balloon that can be inflated at its distant end and that defines a container that can be stretched. After the surgical removal of a thyroid, the surgeon inserts the balloon catheter into the surgically created bag that is left after tumor removal. Then the balloon is inflated by injecting a liquid having one or more uclid radions into the vessel which can be stretched by a lumen in the catheter. Although brachytherapy procedures have successfully treated cancerous tissue, alternative treatments of radiation are sometimes preferred, including radiation therapies, which are administered from an external source to the patient. For example, External Ray Radiation Therapy involves directing a "beam" of radiation from the outside to the patient's body., focused on the target tissue inside the patient's body. The procedure does not cause pain and is often compared to the experience of having an x-ray. As with any radiation therapy, the goal is to administer a prescribed dose of radiation to target tissue while minimizing damage to healthy tissue. The most recent advances in radiation therapy, such as Three-dimensional Shape Radiation Therapy (3DCRT) and Modulated Intensity Radiation Therapy (IMRT) have increased the accuracy of external radiation therapy with the formation and direction of the sophisticated therapeutic radiation rays. In addition, imaging techniques allow delineating a volume of the more complex planning objective ("PTV", PTV refers to the mass of tissue which includes both the malignant tumor residue and a margin of healthy tissue surrounding it ). These imaging procedures use modalities of transversal image elaboration that include a computed tomography (CT), the elaboration of magnetic resonance image (MRI), the positron emission tomography (PET), computed tomography of emission of simple photons (SPECT) and elaboration of the portal image to visualize the target tissue. The treatment planning software combines the anatomical details of the imaging procedures and a PTV highlighted by the doctor, to optimize the number, shape and size of the radiotherapy beams used to treat the patient. The goal of the treatment plan is to administer a radiation dose of conformation to the PTV and minimize the radiation delivered to the adjacent normal tissue outside the PTV. During use, the 3DCRT provides radiation beams that have a shape that "takes shape" from the volume of a target tissue and with the ability to visualize and accommodate radiation therapy beams, doctors can maximize the coverage of the target tissue and minimize the exposure of normal tissue. I M RT in a similar way takes the shape of the radiation rays to the size, shape and location of the target tissue using hundreds of thousands of small modulated radiation rays, striking the target tissue with varying intensities. The multitude of rays treats the target tissue and minimizes damage to healthy tissues. Still, even the most advanced procedures require that the patient and the target tissue be placed in a correct way and in some cases un mobilized. Unfortunately, the regular surface of a cavity created by tissue resection can make it difficult for imaging techniques to determine the exact location of the target tissue and even with the opportunity to completely map the target area, the unsupported tissue. which surrounds the expanded cavity may change during the procedure or between imaging and treatment, particularly where the treatment regimen comprises radiation doses delivered within several days or weeks. As a result, there is still a need for additional methods for administering radiation from an external radiation source to the tissue adjacent to the tissue cavity excised with a desired accuracy and without overexposure of surrounding tissue. SUMMARY OF THE INVENTION The present invention provides methods, systems and apparatus for the treatment of a proliferative tissue disease by placing the tissue surrounding the cavity of the expanded tissue and applying the external radiation. The method first includes surgical resection or at least a portion of the proliferative tissue and thus creates a resection cavity. A tissue fixing apparatus having an expandable surface is then provided, the expandable surface being dimensioned and configured to reproducibly place the tissue surrounding the resection cavity in a predetermined geometry at the time of surface expansion. expandable in an expanded position. Then, the expandable surface is placed within the resection cavity and the expandable surface is expanded to place the tissue surrounding the resection cavity in the previously determined geometry. Finally, an external radiation treatment is applied to the tissue surrounding the resection cavity.

In another aspect of the present invention, the excised cavity and the expanded tissue attachment apparatus positioned therein can be visualized in three dimensions. The invention may also preferably include the application of at least one external beam radiation treatment, a radiation therapy treatment taking the three-dimensional shape and a intensity modulation radiation therapy treatment. The method may further include repeating the steps of the treatment several times during the treatment regimen. In one embodiment, the expandable surface of the tissue fastening apparatus includes a solid, stretchable surface defining a closed, stretchable chamber and in a further embodiment, the tissue fastening apparatus is a balloon catheter. Still in a further embodiment, a second balloon can be placed with the first balloon. The balloons can be expanded with a variety of media including a non-radioactive substance. In other aspects of the present invention, a treatment material is used to expand the balloon. The treatment material may include a drug such as a chemotherapy drug, which is administered through the wall of the balloon to surrounding tissue. In an alternative embodiment, the expandable surface is created by an expandable box. In another aspect of the present invention, fiducial markers may be placed in the tissue fixation apparatus to determine the spatial location of the apparatus and the surrounding PTV. For example, by determining the spatial position of the markers in relation to the origin of a coordinate system of the treatment room (for example, in relation to the isocenter of the treatment beam or the ray source), the location of the apparatus and the PTV can be compared with their desired locations. If there is any change in the PTV or in the location of the device, adjustments may be made to the placement of the patient's body, the device and / or the direction and / or shape of the planned radiation beams before the fraction is initiated. of radiation. Fiducial markers and their detection systems can be radio-opaque markers that have radiographically processed images or transponders that signal their position to a receiving system. Another embodiment of the present invention includes a system for treating a tissue surrounding an excised excipient that is subject to a tissue proliferative disorder. The system includes a tissue fixation device having a catheter body element with a proximal end, a distal end, an inner lumen and an expandable surface element positioned near the distal end of the body member, being dimensioned and configured The expandable surface element is fixed for reproducible placement in the tissue surrounding a tissue cavity excised in a previously determined geometry at the time of expansion. An external radiation apparatus is placed outside the expanded cavity, so that the external radiation apparatus can administer a dose of radiation to the tissue surrounding the expandable surface element. With the tissue fixing apparatus positioned within the tissue cavity excised and expanded to the position of the tissue surrounding it, the accuracy of the radiation from the external radiation apparatus is greatly improved. In still another embodiment, the present invention includes an apparatus for the treatment of a tissue proliferative disorder after a liumpectomy procedure. The apparatus includes an elongated body element having a proximal open end and defining a proximal port, a distal end and an interior lumen extending from the open proximal end, the elongate body member being sized to administer a Expandable surface element within an excised cavity created by a lipectomy procedure. A spatial volume is defined by the expandable surface element placed near the far end of the body element, the expandable surface element being dimensioned and configured to reproducibly place the tissue surrounding a tissue cavity excised in a previously determined geometry at the time of expansion. The expandable surface element is of a size to fill a tissue cavity created in a breast during a liumenpectomy procedure to position the surrounding tissue and to allow an external radiation source to accurately deliver a radiation dose. BRIEF DESCRIPTION OF THE DRAWINGS The present invention will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings: Figure 1 illustrates a system of the present invention that includes an external radiation source and an apparatus for placing the tissue; Figure 2 illustrates one embodiment of the tissue positioning apparatus which can be used in the system illustrated in Figure 1; Figure 3 illustrates another embodiment of the tissue positioning apparatus which can be used with the system illustrated in Figure 1; Figure 3A illustrates a cross-sectional view of the apparatus illustrated in Figure 3; Figure 4 illustrates another embodiment of the tissue positioning apparatus which can be used with the system illustrated in Figure 1; Figure 5A illustrates another embodiment of the tissue positioning apparatus which can be used with the system illustrated in Figure 1; Figure 5B illustrates the apparatus of Figure 5A in an expanded position; Figure 6A illustrates another embodiment of the tissue placement apparatus which can be used with the system illustrated in Figure 1; Figure 6B illustrates the apparatus of Figure 6A in an expanded position; Figure 7 illustrates another embodiment of the tissue placement apparatus which can be used with the system illustrated in Figure 1; Figure 8 illustrates another embodiment of the tissue placement apparatus which can be used with the system illustrated in Figure 1. Detailed Description of the Invention The present invention provides systems and methods for the treatment of tissue proliferative disorders, such as tumors. malignant breast, by surgically operating at least a portion of the proliferative tissue to create a resection cavity, followed by external radiation therapy of the residual tumor margin. To improve the accuracy of the radiation treatment, a tissue fixing apparatus is provided for positioning and / or stabilizing the tissue surrounding the excised cavity. External radiation therapies depend on accurate imaging and / or delivery techniques to the target and any movement of target tissue may introduce an error. Patient positioning is often critical, and large measures are taken to place and mobilize patients, including, for example, marking the patient's skin using foam coatings on the body. Still with the patient immobilized, the change of the target tissue still presents a problem, including for example, tissue change as a result of the patient's breathing and inconsistencies in the placement of the patient's body between the radiotherapy fractions. The cavities of the tissue present an even greater difficulty, because the tissue surrounding the cavity is often soft, irregular tissue which lacks the support generally provided by the adjacent tissue. Therefore, it is difficult to present in an image the regular surface of the wall of the cavity, including the residual margin of the tumor. The unpredictable change of the tissue surrounding the cavity, possibly caused by a slight movement of the patient, can further complicate the procedure and result in an unacceptable movement of the target tissue. For example, where the target tissue changes position after visualization, but before the radiation treatment, the change in tissue can result in radiation beams that find mainly healthy tissues. As a result, the margin of your residual mor can be substantially untreated, while healthy tissue can be damaged by the treatment. The present invention provides these problems of the prior art by providing a tissue positioning apparatus, which can be inserted into the excised and expanded cavity at the position of the tissue surrounding it in a predetermined geometry. The methods of the present invention also facilitate the image processing of the tissue by placing the tissue against a defined surface. Figure 1 illustrates an embodiment of the present invention that includes a system for the treatment of tissue surrounding an excised cavity that is subjected to a tissue proliferative disorder. The system includes a tissue fixation device 1 0 which includes a catheter body element 12 which has a proximal end 14, a distal end 1 6, an interior lumen 1 8 (not shown) and an expandable surface element 20. The element of its expandable surface 20 is preferably positioned near the distal end 1 6 of the catheter body element 12 and is Dimensioned and configured to reproducibly place the tissue surrounding the cavity of the tissue excised in a previously determined geometry at the time of expansion. The system also includes an external radiation apparatus 22 positioned outside the excised cavity, so that the external radiation apparatus 22 can deliver a radiation dose to the tissue surrounding the expandable surface element 20. The external radiation apparatus 22 can any external radiation source known in the art or to be developed subsequently, however, in the preferred embodiments of the present invention, precisely sources sent to the target are used, such as those used in the 3DCRT and the IMRT. As shown in Figure 1, the tissue fixing apparatus 10 can be placed within a cavity of the excised tissue 24, in this example within the patient's chest after a liumpectomy and expanded to place the surrounding tissue, of so that the radiation beam dose 26 of the external radiation source 22 is administered accurately. Figures 2 through 8 illustrate exemplary embodiments of the tissue positioning apparatus 10, which may function with the system of the present invention. Fig. 2 shows a basic design of a fabric laying apparatus 10 including an elongate body element 12 having an inner lumen 18 extending from a proximal port 28 to an inflation port 30. The inflation port 30 is formed through the side wall of the body member 12 and intersected with the inner lumen 1 8. Fixed to the tubular body 1 2, close to a distal end 1 6 thereof, is a spatial volume 32, which is defined by an expandable surface 20. The interior of the volume 32 is in fluid communication with the proximal port 28. The expandable surface 20 of the apparatus 1 0 can be defined by a balloon that can be inflated. It should be understood that the term "balloon" is intended to include apparatus that can be stretched which may be, but need not be, constructed of an elastic material. The balloon of the present invention may include a variety of balloons or other stretchable devices designed for use with surgical catheters. The balloon can be expanded by injecting an inflation material through the body 12 and into the balloon and preferably, the inflation material comprises liquids or gases that are not radioactive. Alternatively, the inflating material is a treatment material, such as a radioactive treatment material wherein the balloon will also be used to provide an interstitial brachytherapy treatment, as provided in US Pat. Nos. 5,61 1 , 923 and 5, 931, 774 granted to Williams et al. , both of which are incorporated by reference to the present description.

In one embodiment, the balloon is constructed of a solid material that is substantially impermeable to the active components of the treatment fluids with which it can be filled and is also impermeable to body fluids, for example, in the blood, cerebrospinal fluid and Similar. A waterproof balloon is useful in conjunction with a radioactive treatment fluid to prevent radioactive material from escaping from the treatment apparatus and contaminating the surgical field or tissue of the patient. In another embodiment, the balloon is permeable to the treatment fluid and allows a treatment fluid to pass out of the apparatus 10 and into the lumen of the body or cavity. A permeable balloon is useful when the treatment fluid is a drug, such as, for example, a chemotherapeutic agent which must make contact with the tissue to be effective. U.S. Patent Nos. 5,611,923 and 5,931,774 issued to Williams et al., Describe exemplary permeable balloons and treatment substances. Semi-permeable balloons may also find use in the method of the present invention. For example, a semipermeable material that has the ability to prevent the passage of a radioactive material through the wall of the balloon can be used to contain a treatment fluid, wherein certain components of the fluid can pass through the membrane while that the radioactive components of the treatment fluid are retained inside the balloon. Although the balloon and the body element 12 may coincide in a variety of ways, in some embodiments, the balloon coincides with the body member 12 at substantially a single point, or only one side of, the body of the balloon. Such adhesion allows the balloon (ie, a spherical balloon) to maintain a substantially constant (e.g., spherical) shape by a range of volume up to inflation. That is, the balloon is not restricted in the form by multiple addition points to the body member, as is generally the case with, for example, Foley catheter balloons. In other modalities, the ball is attached to the body element in multiple points on the body of the ball, although it allows the ball to maintain a constant shape over a range of inflation sizes. For example, a balloon attached to an element of the body at both points distant and close to the body of the balloon may not be restricted at the time of inflation, wherein the body member includes the expansion element (eg, a latching element). slidable) that allows the body element to adjust in length as the balloon expands or contracts. A balloon which maintains a substantially constant shape over the range of inflation volumes allows a surgeon to select a balloon with less concern about the size of the cavity. The body member 12 of the apparatus 10 provides means for positioning its expandable surface 20 within the excised tissue cavity and provides a path for the administration of the inflation material (if used). Although the elements of the example body illustrated in the figures have a tubular construction, one skilled in the art will appreciate that the body member 12 can have a variety of shapes and sizes. Body elements suitable for use in the present invention may include catheters which are known in the art. Although the body member 12 can be constructed from a variety of materials, in one embodiment the material of the body member is silicone, preferably a silicone which is at least partially radio-opaque, thereby facilitating the x-ray location of the body member 12 after the insertion of the apparatus 1 0. The body member 1 2 may also include conventional adapters for addition to a receptacle of treatment and the balloon., as well as apparatuses, for example, right angle devices, so that the body element 1 2 breaks the shape of the contours of the patient's body. The position of the apparatus 1 0 in a patient's body can also be determined using fiducial markers 60. By placing the markers on the apparatus (for example, on the element of its expandable surface 20 or a body element 12), a user can determine the spatial position of the apparatus and the objective tissue that surrounds it. The spatial data can be used to correct errors in the location of the target tissue by adjusting the location of the patient's body in the treatment mattress or by altering the shape and direction of the radiotherapy rays. The fiducial markers are explained in more detail later. The apparatus 10 may include a variety of alternative embodiments designed to facilitate tissue placement. For example, an apparatus 10 may include multiple spatial volumes, as well as a variety of shapes adapted to take the shape of the excised cavity. In addition, the expandable surface can be placed on or coupled with a tubular body member 12 in different ways to facilitate placement of the expandable surface within the tissue cavity. The expandable surface thereof can also be adapted to allow the administration of a treatment material to the tissue surrounding the cavity. The present invention also contemplates the use of multiple balloons, for example, a double walled structure as shown in FIGS. 3 and 4. Such a balloon may, for example, comprise an im permeable inner wall and a permeable outer wall. In this embodiment, the inner balloon can be filled with, for example, radioactive treatment fluid, while the outer balloon (i.e., the shape between the inner and outer balloon walls) is filled with a chemotherapeutic treatment liquid. This modality allows multiple modalities of therapy (for example, chemotherapy, brachytherapy and external radiation) to be administered with only one device. In this double-walled balloon modality the two balloons can be inflated with two treatment liquids at the same time or at different times during therapy. Inflation of an inner balloon can provide pressure on an outside balloon, which can cause the outer balloon to expand and can force or push the fluid into the space between the inner and outer walls of the balloon through the outer porous membrane of a ball. Higher-order balloons, that is to say, triple-walled balloons, can also be used in the apparatuses of the present invention. Figure 3 illustrates an embodiment of apparatus 1 0 with a second spatial volume 34 surrounding the interior spatial volume 32 and defined by a second expandable surface 36. The second spatial volume is in fluid communication with a second inflation port 38 and a second proximal port 40. The body 12 also includes a second inner panel 42 extending from the proximal port 40 to the inflation port 38. Figure 3A illustrates an interior lumen 18 and a second interior lumen 42. As shown in Figure 4, the expandable surface may include a variety of shapes. For example, a generally spherical cavity can be filled and made to take the form of a substantially spherical expandable surface although it may be preferable to use an elongated expandable surface to place the tissue surrounding an elongated body cavity. Figure 4 illustrates an exemplary elongated expandable surface. In some cases, it may be desired to use an expandable surface which has a different shape than the cavity removed, so that when it is expanded, the expandable surface applies an increased relative pressure to part of the wall of the cavity., that is, it applies pressure to a problem area. One skilled in the art will appreciate that the inner and outer expandable surfaces 20, 36 may define a variety of shapes depending on the shape of the original excised cavity and the desired shape of the cavity after taking the shape of the expandable surface including, by way of non-limiting example, a cube, a parallelepiped, a cylinder, a tetrahedron, a prism, an irregular shape or a combination thereof. In Figures 5A and 5B, another embodiment of the apparatus 10 is illustrated in its expanded and unexpanded form. The apparatus 10 includes an elongate flexible tubular body 12 having at least one inner lumen 18 extending the length thereof from a proximal end and a distal end. The openings in the side wall of the body member 12 define one or more inflation ports 30 that provide fluid communication between the inner lumen 14 and a spatial volume 32. The expandable surface 20 may be adhered to a tubular body member 12, connecting the proximal and distant ends 44, 46 of the expandable surface 22 to the tubular body 12. As shown in Figure 4B, injection of an inflation material at the proximal end of the catheter body 12 forces the inflation material to flow through the inner lumen 18 outside the inflation ports 30, and that it fills the spatial volume 32 with the expandable surface 20, thereby inflating the expandable surface 20. In FIG. 6A, a further embodiment of the apparatus 10 is illustrated. , which has an expandable surface 20 which resides within the inner lumen 18 of the tubular body 12. In this embodiment, the inner lumen 18 extends along the length of the body 12 and the expandable surface 20 is fixed adhered to the distal end 16 of the body 12. As the inflation material is injected through the inner lumen 18, the expandable surface 20 expands outwardly from the tubular body 12 as illustrated in the figure 6B. This apparatus can be particularly advantageous for placing fabrics surrounding a spherical tissue cavity because the expandable surface can maintain a substantially spherical shape in a range of volumes. In addition, the embodiment of Figures 6A, 6B may be desirable when the body member 12 of the apparatus 10 is placed close to the body cavity before expanding it. The expandable surface 20 can be defined by a variety of structures, including a box 48, as illustrated in Figure 7. Similar to other embodiments, the apparatus 10 includes a body member 12 and an expandable surface 20, but the surface expandable 20 is defined by a box 48, positioned near the distal end of body member 12. Preferably, box 48 is formed of a shape memory metal, such as nitinol, or a suitable plastic, such as a polyethylene box expandable During use the box can be formed in the desired shape to take the form of the particular excised cavity, contracted for administration to the target site in vivo, and then expanded to cause the tissue surrounding the surgically excised region to take the appropriate shape . Figure 8 illustrates a perspective view of a preferred embodiment of the apparatus 1 0 that includes a body member 12 and an expandable surface 20. The apparatus includes outer and outer expandable surfaces (not shown) 20, 36 which they are adhered to the element of the body 12, near the distant end. The body member 12 includes a first and second interior lumens and a control handle 50 at the proximal end to place the apparatus within a body cavity. The proximal ports 28, 40 provide the inputs for the nflation materials and / or treatment materials. In some embodiments, the apparatuses of the invention are provided in a preassembled form, that is to say, the components are assembled in advance to a surgical insertion procedure. However, in certain embodiments, the apparatuses of the present invention are configured to allow the modular assembly of components, for example, by a surgeon. For example, in this way, the treatment liquid receptacle can be provided with an element adapted for connection to any of a plurality of catheters. The connection element may be, for example, any element known in the art to effect the connection between components such as catheters, injection ports and the like. Illustrative connectors include luer adapters and the like. In this embodiment, a variety of catheters and balloons can be provided, each of which is adapted for easy connection to a treatment liquid receptacle. The surgeon may then select an appropriate shape and size of the expandable surface (e.g., the balloon) for the treatment of a particular proliferative disorder, without the need to provide several receptacles of treatment fluids. The catheter and the balloon can be selected according to the results of the pre-operative tests (for example, x-rays, MRI and the like), or the selection can be made based on observation, during a surgical procedure of the cavity. target (for example, a surgical cavity is the result of the excision of a tumor). When the surgeon selects an appropriate balloon (e.g., a balloon having the proper size and shape for placement in a body cavity), then the catheter and balloon can be adhered to the previously selected treatment fluid container and the Treatment apparatus can be assembled in this way. A method of the present invention can be used to treat a variety of tissue proliferative disorders, including malignant breast and brain tumors. Many breast cancer patients are candidates for breast conservation surgery, also known as lupectomy, a procedure that is usually performed on smaller tumors at the early stage. Breast conservation surgery can be followed by radiation therapy to reduce the chance of recurrence near the original tumor site. By providing a strong direct dose to the affected area, it can destroy remaining cancer cells and help prevent such recurrences. Surgery and radiation therapy are also standard treatments for malignant disorders which develop in other areas of the body, such as brain tumors. The goal of surgery is to remove as much of the tumor as possible without damaging the vital tissue of the brain. The ability to eliminate the entire malignant tumor is limited by its tendency to infiltrate adjacent to normal tissue. Partial removal reduces the amount of the tumor that is going to be treated by radiation therapy and under some circumstances, helps relieve symptoms by reducing pressure on the brain. A method according to the present invention for treating these and other malignant disorders begins with surgical resection of a tumor site to remove at least a portion of the cancerous tumor and create a resection cavity. After resection of the tumor, the apparatus 10 is placed inside the tumor resection cavity. This may occur before closing the surgical site, so that the surgeon places the device intra-operatively, or alternatively the apparatus 10 may be inserted once the patient has recovered sufficiently from the surgery. In the latter case, a new incision may be created for the introduction of the apparatus 10. In any case, the expandable surface 20 which is preferably dimensioned and configured to reproducibly place it in the tissue surrounding the resection cavity in a geometry previously determined, then it is expanded into the cavity of the excised tissue. Where the expandable surface 20 is defined by a balloon, the balloon can be expanded by administering an inflation material through the inner lumen 18 within the balloon to expand the balloon. The expandable surface 20 can be selected so that, at the time of expansion, the expandable surface 20 compresses the tissue which is being treated, or the tissue surrounding it. Therefore, where the expandable surface 20 is a balloon, it can be selected to have the desired size and the amount of material injected can be adjusted to inflate the balloon to the desired size. When inflated the expandable surface 20 preferably fills a volume of at least about 4 cm 3, and still more preferably has the ability to fill a volume of at least about 35 cm 3. The preferable inflation volumes are in a range of 35 cm3 to 150 cm3. In general, when the balloon is deflated, it must have a small profile, that is, a small size to allow easy placement within and removal of the patient's body and to minimize the size of a surgical incision necessary to place and remove the balloon. at the desired site of action. With the expanded apparatus 10, it supports the tissue surrounding the tissue cavity and reduces tissue exchange. In addition, the expandable surface 20 can place the tissue in a previously determined geometry. For example, a spherical expandable surface can place the tissue surrounding the tissue cavity in a generally spherical shape. With the placed tissue, a defined surface is provided so that the radiation can be more accurately delivered to the walls of the previously irregular tissue cavity. In addition, the apparatus 10 helps to reduce errors in the treatment procedure introduced by the movement of the tissue. The positioning and stabilization provided by the apparatus 10 significantly improves the effectiveness of the radiation therapy by facilitating the dosing of radiation and improving its accuracy. The result is a treatment method which concentrates the radiation in the target tissue and helps preserve the healthy tissue that surrounds it.

Before administering the radiation, but after expanding the expandable surface, the apparatus 10 and the surrounding tissue may be preferably visualized with an image processing apparatus, including by way of non-limitative example, lightning. -x, M RI, CT scan, PET, SPECT and combinations thereof. These imaging apparatuses provide a photograph of the apparatus 10 and the tissue surrounding it to assist in the planning of external radiation therapy. To assist with visualization, apparatus 1 0 can be constructed of materials which have an expandable surface 20 which is highlighted during the image processing process, for example, the expandable surface can be constructed of a radio-opaque material. Alternatively, radiation transparent materials may be used, so that the image processing of the tissue is not blocked by the expandable surface. In any mode, the expandable surface can be inflated with a diagnostic image processing agent, including a radioactive radiation absorbing material, such as an air, water or contrast material. In the case of external radiation therapies, such as 3 DCRT and I M RT, the image processing procedure provides a map of the residual margin of the tissue and helps to focus the tissue for radioiodination. The radiation rays are then adapted to deliver a very precise dose of radiation to the target tissue. With the placement of the apparatus 1 0, in the tissue surrounding the resection cavity, there is less danger of a change in target tissue (within the body) and therefore, the loss of planned radiation to the PTV and the damage unnecessary to healthy tissue. Some treatment regimens require repeated dosages of radiation over a period of days or weeks, and the apparatus may be used in those cases for repeated placement in the tissue surrounding the excised tissue cavity. For example, after administering the radiation from the external source, the expandable surface is collapsed. Although the apparatus 10 can be removed after the collapse step, preferably the apparatus is left inside the tissue cavity between the radiation treatments. When the subsequent radiation treatment is to be administered, the expandable surface can be expanded and the adjacent tissue can be repositioned for another step of image processing and / or radiation dose. These steps may be repeated as necessary during the course of a treatment regimen. Alternatively, the apparatus is left within the tissue cavity and is maintained in a generally constant volume of expansion / inflation during the entire course of the radiation therapy.

Another embodiment of the present invention incorporates fiducial markers that provide real-time wireless information about the spatial position of the apparatus in relation to the origin of a coordinate system of the treatment room (i.e., the isocenter of the control apparatus). radiation supply or location of the source of radiation rays). The spatial position data can be used to correct errors in the location of the target volume. For example, by adjusting the position of the patient's body on the treatment mattress and / or altering the shape and direction of the radiotherapy rays to correct the position of the altered PTV. Preferably, the real-time wireless feedback allows correction of positioning errors before administering any fraction of radiation. Fiducial markers can also provide users with more and more accurate PTV placement, thus allowing for greater repair of normal tissue and smaller normal tissue margins within the PTV. Preferably, fiducial markers and their detection systems are radio-opaque markers that have radiographically processed images (eg, fluoroscopically), and transponders that signal their positions to a receptor system. A fiducial marker example is the Beacon Transponder, made by Calypso Medical Tech nologies of Seattle, Washi ngton. The placement of the fiducial markers 60 in the apparatus 10 provides an advantage over other placements of said markers (eg, placement within a tumor). For example, by placing a fiducial marker on an expandable surface element 20, the position of the expandable surface thereof can be determined accurately and the amount of expansion can be adjusted. In addition, a marker placed on the outside of the apparatus 10 may be used to delineate the surrounding objective tissue (a.k.a. the PTV). As an additional benefit of having the marker placed on the apparatus, the separate insertion step for the marker is not required. Also, when the device is used, the marker will also be used, thus ensuring that foreign objects are not permanently left inside the patient at the conclusion of the treatment. In addition to external radiation, other treatments may complement the method of the present invention. In another embodiment, a brachytherapy treatment is combined with external radiation therapy in the present invention by administering a source of radiation through the body member 12 within the expandable surface 20, so that the resection cavity is irradiated from the inside. The brachytherapy procedures are described in US Patent No. 6,413,204 issued to Winkler et al., Commonly assigned and incorporated herein by reference. Other treatments may include the supply of treatment material to the tissue surrounding the resection cavity, for example, a chemotherapy drug or a radiation enhancement material. In one embodiment, the treatment material can be administered through the wall of the expandable surface which is constructed of a permeable hydrophilic polymer as described in US Patent No. 6,200,257 issued to Winkler, commonly assigned and incorporated herein. description as reference. Alternatively, the treatment material can be coupled to the expandable surface, so that after insertion of the apparatus 10, the expandable surface 20 delivers the treatment material to the surrounding tissue. The treatment material can diffuse from the expandable surface 20 to the tissue and / or the treatment material can be administered as the expandable surface presses against the walls of the excised cavity and makes contact with the tissue. Still in a further embodiment, the treatment material can be placed only in part of the expandable surface. Regardless of the method of administration, the treatment materials may include, by way of non-limiting example, a chemotherapeutic agent, an anti-neoplastic agent, an anti-angiogenesis agent, an immuno-regulator, a hormonal agent, an immunotherapeutic agent, an antibiotic, a radio-sensitization agent and combinations thereof. One skilled in the art will appreciate additional features and advantages of the present invention based on the described modalities. Accordingly, the present invention will not be limited to what has been particularly shown and described, except as indicated in the appended claims. All publications and references cited herein are expressly incorporated herein by reference in their entirety.

Claims (42)

1. CLAIMS 1. A method for the treatment of tissue proliferative disorders, which comprises: (a) the surgical removal of at least a portion of the proliferative tissue thereby creating a resection cavity; (b) providing a tissue fixing apparatus having an expandable surface dimensioned and configured to reproducibly position the tissue surrounding the resection cavity in a predetermined geometry at the time of expansion of the expandable surface in an expanded position; (c) positioning the tissue fixing apparatus so that the expandable surface is within the resection cavity; (d) expanding the expandable surface to the placement of the tissue surrounding the resection cavity in a previously determined geometry; and (e) applying an external radiation treatment to the tissue surrounding the resection cavity. The method as described in claim 1, characterized in that the expandable surface of the tissue fastening apparatus includes a solid, stretchable surface defining a closed chamber that can be stretched. 3. The method as described in claim 2, characterized in that the tissue fixation device is a balloon catheter. 4. The method as described in claim 3, characterized in that the second balloon is placed inside the first balloon. The method as described in claim 2, characterized in that the means used to expand the balloon consists of a non-radioactive substance. 6. The method as described in claim 2, characterized in that a treatment material is placed on the outer surface of the solid surface that can be stretched. The method as described in claim 6, characterized in that the treatment material is placed only part of the outer surface of the solid surface that can be stretched. The method as described in claim 2, characterized in that the solid surface that can be stretched is transparent to radiation. The method as described in claim 1, characterized in that a fiducial marker is placed in the tissue fixing apparatus. The method as described in claim 9, characterized in that the fiducial marker is radio opaque and image processing which is provided radiographically. The method as described in claim 9, characterized in that the fiducial marker is a signal transponder whose signals are read and interpreted by a receiver. The method as described in claim 2, characterized in that the fiducial marker is placed on a solid surface that can be stretched. The method as described in claim 1, characterized in that the expandable surface is defined by an expandable hydrophilic polymer membrane having a previously determined permeability. The method as described in claim 13, characterized in that a treatment material is diffused through the expandable hydrophilic polymer membrane after the positioning step of the tissue fixing apparatus. 15. The method as described in claim 1, characterized in that the expandable surface is created by an expandable box. 16. The method as described in claim 15, characterized in that the expandable box comprises a shape memory material. The method as described in claim 1, characterized in that the expansion step expands the expandable surface so that it substantially fills the volume of the excised cavity and presses against the walls of the excised cavity. 18. The method as described in claim 1, characterized in that the surgical resection step is performed during a liumenpectomy procedure. 19. The method as described in claim 1, characterized in that before the step of applying the external radiation treatment, the excised cavity and the tissue fixing apparatus placed within the cavity removed in three dimensions are visualized. The method as described in claim 1, characterized in that the external radiation treatment is a treatment of external radiation. The method as described in claim 1, characterized in that the external radiation treatment is a three-dimensional conformation radiation therapy treatment. 22. The method as described in claim 1, characterized in that the external radiation treatment is a therapy of intensity modulation radiation therapy. 23. The method as described in claim 1, characterized in that the expandable surface is maintained in an inflated condition for the duration of the radiation therapy. 24. The method as described in claim 1, characterized in that the expandable surface is collapsed after applying the first radiation fraction of external radiation treatment. 25. The method as described in claim 24, characterized in that the expandable surface is expanded at a second time to place the tissue surrounding the resection cavity. 26. The method as described in claim 25, characterized in that a second external radiation treatment fraction is applied after the expandable surface is expanded a second time. 27. The method as described in claim 1, which further comprises: removing the tissue attachment apparatus from the surgical resection cavity; inserting the tissue fixing apparatus having an expandable surface into the resection cavity; and expanding the expandable surface to place the tissue surrounding the resection cavity in a previously determined geometry. 28. A system for treating tissue surrounding an excised cavity that is subject to a tissue proliferative disorder, which comprises: a tissue fixation device that includes a catheter body element having a proximal end, a distal end, an inner lumen and an expandable surface element positioned near the distal end of the body member, the expandable surface element being dimensioned and configured to reproducibly position the tissue surrounding the cavity. of tissue excised in a previously determined geometry at the time of expansion; and an external radiation apparatus positioned outside the excised cavity so that the external radiation apparatus can deliver a dose of radiation to the tissue surrounding the expandable surface element, wherein the tissue fixation apparatus can be placed inside the cavity of tissue extirpated and expanded to place the tissue surrounding it so that it is delivered in a manner of a radiation beam from the external radiation apparatus. 29. The system as described in claim 28, characterized in that the element of its expandable surface is a solid surface that can be stretched and the spatial volume is a closed chamber that can be stretched and the element of Expandable surface is a wall transparent to radiation. 30. The system as described in claim 29, characterized in that the means used to expand the element of its expandable surface consists of a gas that is not radioactive. 31 The system as described in claim 28, characterized in that the expandable surface is created by an expandable box. 32. The system as described in claim 31, characterized in that the expandable box comprises a shape memory material. 33. The system as described in claim 28, characterized in that the resection cavity is created during a lipectomy procedure. 34. The system as described in claim 28, characterized in that the external radiation source is an external beam radiation apparatus. 35. The system as described in claim 28, characterized in that the external radiation source is a radiation therapy apparatus of three-dimensional conformation. 36. The system as described in claim 28, characterized in that the external radiation source is an intensity modulation radiation therapy apparatus. 37. The system as described in claim 28, characterized in that the fiducial marker is placed in the tissue fixing apparatus. 38. An apparatus for the treatment of a proliferative tissue disorder after the lumpectomy procedure, which comprises: an elongate body element having an open proximal end defining a proximal port, a distal end and an inner lumen extending from the open proximal end, the elongated body element being sized to administer an expandable surface element within a resection cavity created by a lumpectomy procedure; a spatial volume defined by an expandable surface element positioned near the distal end of the body member, the expandable surface element being dimensioned and configured to reproducibly place the tissue surrounding a tissue cavity excised in a previously determined geometry at the time of the expansion; wherein the expandable surface element is of a size to fill the tissue cavity created in a breast during a lupectomy procedure so as to position the tissue surrounding it and allow an external radiation source to accurately deliver a radiation dose. 39. The apparatus as described in claim 38, characterized in that the fiducial marker is placed in the tissue fixing apparatus. 40. The apparatus as described in claim 39, characterized in that the fiducial marker is radio opaque and image processing is radiographically provided. 41 The apparatus as described in claim 39, characterized in that the fiducial marker is a signal transponder whose signals are read and interpreted by a receiver. 42. The apparatus as described in claim 38, characterized in that the fiducial marker is placed on the element of its expandable surface. RESU MEN A system is provided for treating tissue surrounding an excised cavity that is subject to a tissue proliferative disorder. The system includes a tissue fixation device that includes a catheter body member having a proximal end, a distal end, an interior lumen, and an expandable surface element positioned near the distal end of the body member, the expandable element of the body. The surface has the dimensions and is configured to reproductively place a tissue surrounding the tissue cavity removed in a predetermined geometry after expansion. After expansion of the expandable surface element, an external radiation device positioned outside the excised cavity delivers a dose of radiation to the tissue surrounding the expandable surface.