Patent Application
`
`Attorney Docket No.: 14.029011 PR
`
`TARGET TISSUE LOCATOR FOR IMAGE GUIDED RADIOTHERAPY
`
`FIELD OF THE INVENTION
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`[01] A method for treating tissue surrounding a cavity that is subject to a proliferative tissue
`
`disorder is provided. The method includes a tissue fixation device to position the tissue
`
`surrounding a resection cavity in a predetermined geometry. The tissue fixation device
`
`contains a negative contrast agent for localizing target tissue by visualizing the negative
`
`contrast agent in three dimensions. Methods of delineating target tissue from non-target
`
`tissue using differences in radiographic properties of a device are also presented.
`
`A BACKGROUND OF THE INVENTION
`
`[02]
`
`The invention relates generally to systems and methods for use in treating proliferative
`
`tissue disorders, and more particularly to systems and methods for the treatment of such
`
`disorders in the breast by positioning tissue and applying radiation.
`
`[03] Malignant tumors are often treated by surgical resection of the tumor to remove as much
`
`of the tumor as possible. Infiltration of the tumor cells into normal tissue surrounding the
`
`tumor, however, can limit the therapeutic value of surgical resection because the
`
`infiltration can be difficult or impossible to treat surgically. Radiation therapy can be
`
`used to supplement surgical resection by targeting the residual tumor margin after
`
`resection, with the goal of reducing its size or stabilizing it. Radiation therapy can be
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`administered through one of several methods, or a combination of methods, including
`
`permanent or temporary interstitial brachytherapy, and external-beam radiation.
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`1
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`Focal Exhibit 1014 Page 1
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`

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`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`· [04] Brachytherapy refers to radiation therapy delivered by a spatially confined radioactive
`
`material inserted into the body at or near a tumor or other proliferative tissue disease site.
`
`For example, brachytherapy is performed by implanting radiation sources directly into
`
`the tissue to be treated. Brachytherapy is most appropriate where 1) malignant tumor
`
`regrowth occurs locally, within 2 or 3 em of the original boundary of the primary tumor
`
`site; 2) radiation therapy is a proven treatment for controlling the growth of the malignant
`
`tumor; and 3) there is a radiation dose-response relationship for the malignant tumor, but
`
`the dose that can be given safely with conventional external beam radiotherapy is limited
`
`by the tolerance of normal tissue. In brachytherapy, radiation doses are highest in close
`
`proximity to the radiotherapeutic source, providing a high tumor dose while sparing
`
`surrounding normal tissue. Interstitial brachytherapy is useful for treating malignant brain
`
`and breast tumors, among others.
`
`[OS] Williams U.S. Pat. No. 5,429,582, entitled "Tumor Treatment," describes a
`
`Brachytherapy method and apparatus for treating tissue surrounding a surgically excised
`
`tumor with radioactive emissions to kill any cancer cells that may be present in the tissue
`
`surrounding the excised tumor. In order to implement the radioactive emissions, Williams
`
`provides a catheter having an inflatable balloon at its distal end that defines a distensible
`
`reservoir. Following surgical removal of a tumor, the surgeon introduces the balloon
`
`catheter into the surgically created pocket left following removal of the tumor. The
`
`balloon is then inflated by injecting a fluid having one or more radionuclides into the
`
`distensible reservoir via a lumen in the catheter.
`
`[06] While brachytherapy procedures have successfully treated cancerous tissue, alternative
`
`radiation treatments are sometimes preferable, including radiation therapies which are
`
`2
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`Focal Exhibit 1014 Page 2
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`

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`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`delivered from a source external to the patient. For example, External Beam Radiation
`
`Therapy involves directing a "beam" of radiation from outside the patient's body, focused
`
`on the target tissue within a patient's body. The procedure is painless and often compared
`
`to the experience of having an x-ray.
`
`[07] As with any radiation therapy, the goal is to deliver a prescribed dose of radiation to the
`
`target tissue while minimizing damage to healthy tissue. More recent advances in
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`radiation therapy such as Three-Dimensional Conformal Radiation Therapy (3DCRT)
`
`and Intensity Modulated Radiation Therapy (IMRT) have increased the precision of
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`external radiation therapy with sophisticated shaping and directing of therapeutic
`
`radiation beams. In addition, imaging techniques allow delineation of a more complex
`
`planning target volume ("PTV", PTV refers to the mass of tissue which includes both the
`
`residual malignancy as well as a margin of surrounding healthy tissue). These imaging
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`procedures use cross-sectional imaging modalities including computed tomography (CT),
`
`magnetic resonance imaging (MRI), positron emission tomography (PET), single photon
`
`emission computed tomography (SPECT) and portal imaging to visualize target tissue.
`
`Treatment planning software combines the anatomical details from the imaging
`
`procedures and a PTV outlined by the physician, to optimize the number, size and shape
`
`of the radiotherapy beams used to treat the patient. The goal of the treatment plan is to
`
`deliver a conformal radiation dose to the PTV and minimize the radiation delivered to
`
`adjacent normal tissue outside the PTV.
`
`[08]
`
`In use, 3DCRT provides radiation beams shaped to "conform" to a target tissue volume,
`
`and with the ability to visualize and to arrange the radiation therapy beams, physicians
`
`can maximize coverage of the target tissue and minimize exposure to normal tissue.
`
`3
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`Focal Exhibit 1014 Page 3
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`

`
`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`IMRT similarly conforms radiation beams to the size, shape and location of the target
`
`tissue by using hundreds to thousands of small, modulated radiation beams, striking the
`
`target tissue with varying intensities. The multitude of beams treats the target tissue and
`
`minimizes damage to healthy tissue. Yet, even the most advanced procedures require the
`
`patient and the target tissue to be properly positioned, and in some cases immobilized.
`
`Unfortunately, the irregular surface of a cavity created by the resection of tissue can
`
`make it difficult for the 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 surrounding the resected cavity may shift during the procedure or between imaging
`
`and treatment, particularly where the treatment regimen involves radiation doses
`
`provided over the course of several days or weeks.
`
`[09] As a result, there is still a need for additional methods for delivering radiation from an
`
`external radiation source to tissue adjacent to a resected tissue cavity with a desired
`
`accuracy and without over-exposure of surrounding tissue. External beam radiation
`
`therapy involves directing or focusing a "beam" of radiation from the outside of a
`
`patient's body to an area of target tissue within the patient's body. The procedure is a
`
`non-invasive and relatively painless medical procedure which is used to treat abnormal or
`
`cancerous tissue in a patient. External radiation therapies rely on precise imaging and/or
`
`targeting techniques to locate tissues of interest for treatment. Patient positioning is often
`
`critical to the success of radiation therapy and great measures are often taken to ensure
`
`that patients are correctly positioned and immobilized. Even with the patient
`
`immobilized, internal movement of a patient's tissues as well as incorrect positioning of a
`
`'
`patient's body can result in the damaging of normal healthy tissue by the radiation.
`
`4
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`Focal Exhibit 1014 Page 4
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`

`
`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`[10] Radiographic imaging systems are commonly used in conjunction with external beam
`
`radiation systems (e.g., linear accelerators) to identify and target tissues. Targeting an
`
`external beam of radiation to a specific volume of interest requires a means of delineating
`
`the target tissues (e.g., a tumor), which have certain radiographic properties, from the
`
`surrounding non-target tissues (e.g., bone, soft tissue) which have different radiographic
`
`properties. There are different methods of delineating target tissue from non-target tissue
`
`using these differences in radiographic properties of the tissues. One such method is the
`
`insertion of radiographic markers around the targets volume's surface (or filing a cavity
`
`within the target) which further delineates the different radiographic properties of the
`
`tissues. The inserted markers are more radio-opaque than either the target tissue or the
`
`non-target tissue which allows the precise focusing of the external beam radiation to the
`
`target tissue. An example of such a method and markers can be found in copending,
`
`commonly assigned US patent application No. 2005/0101860, filed November 7, 2003,
`
`titled "Tissue Positioning Systems and Methods for Use with Radiation Therapy" which
`
`is incorporated by reference herein.
`
`SUMMARY OF THE INVENTION
`
`[11] The present invention provides methods, systems and devices for treating a proliferative
`
`tissue disorder by positioning tissue surrounding a resected tissue cavity and applying
`
`external radiation. The method includes first surgically resecting at least a portion of
`
`proliferative tissue and thereby creating a resection cavity. A tissue fixation device
`
`having an expandable surface is then provided, the expandable surface being sized and
`
`configured to reproducibly position tissue surrounding the resection cavity in a
`
`predetermined geometry upon expansion of the expandable surface into an expanded
`
`5
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`Focal Exhibit 1014 Page 5
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`

`
`Patent Application
`
`Attorney Docket No.: 14.029011 PR
`
`position. Next, the expandable surface is positioned within the resection cavity and the
`
`expandable surface is expanded to position the tissue surrounding the resection cavity in
`
`the predetermined geometry. Finally, an external radiation treatment is applied to the
`
`tissue surrounding the resection cavity.
`
`[12]
`
`In another aspect of the invention, the resected cavity and the expanded tissue fixation
`
`device positioned therein can be visualized in three dimensions. The invention can also
`
`preferably include applying at least one of an external beam radiation treatment, a three(cid:173)
`
`dimensional conformational radiation therapy treatment, and an intensity modulation
`
`radiation therapy treatment. The method may further include repeating the treatment steps
`
`several times during a treatment regimen.
`
`[13]
`
`In one embodiment, the expandable surface of the tissue fixation device includes a solid
`
`distensible surface defining a closed distensible chamber, an·d in a further embodiment
`
`the tissue fixation device is a balloon catheter. In yet a further embodiment, a second
`
`balloon can be positioned with in the first balloon. The balloons can be expanded with a
`
`variety of mediums including a non-radioactive substance. In other aspects of the
`
`invention, a treatment material is used to expand the balloon. The treatment material can
`
`include a drug such as a chemotherapy drug which is delivered through the wall of the
`
`balloon to the surrounding tissue.
`
`[14]
`
`In another aspect of the present invention, fiducial markers can be positioned on the
`
`tissue fixation device to determine the spatial location of the device and the surrounding
`
`PTV. For example, by determining the spatial position of the markers relative to the
`
`origin of a coordinate system of the treatment room (e.g., relative to the treatment beam
`
`6
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`Focal Exhibit 1014 Page 6
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`

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`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`isocenter or beam source), the location of the device and the PTV can be compared to
`
`their desired locations. If there are any changes in the PTV or in the location of the
`
`device, adjustments can be made to the position of the patient's body, the device, and/or
`
`the direction and/or shape of the planned radiation beams prior to initiation of the
`
`radiation fraction. The fiducial markers and their detection systems can be radio-opaque
`
`markers that are imaged radiographically or transponders that signal their position to a
`
`receiver system.
`
`[15] Another embodiment of the present invention includes a system for treating tissue
`
`surrounding a resected cavity that is subject to a proliferative tissue disorder. The system
`
`includes a tissue fixation device having a catheter body member with 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 being sized and
`
`configured to reproducibly position tissue surrounding a resected tissue cavity in a
`
`predetermined geometry upon expansion. An external radiation device is positioned
`
`outside the resected cavity such that the external radiation device can deliver a dose of
`
`radiation to the tissue surrounding the expandable surface element. With the tissue
`
`fixation device positioned within the resected tissue cavity and expanded to position the
`
`surrounding tissue, the accuracy of radiation from the external radiation device is greatly
`
`improved.
`
`[16]
`
`In yet a further embodiment, the invention includes a device for treating a proliferative
`
`tissue disorder after a lumpectomy procedure. The device including an elongate body
`
`member having an open proximal end defining a proximal port, a distal end and an inner
`
`lumen extending from the open proximal end, the elongate body member being sized for
`
`7
`
`Focal Exhibit 1014 Page 7
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`

`
`Patent Application
`
`Attorney Docket No.: 14.029011 PR
`
`delivering an expandable surface element into a resection cavity created by a lumpectomy
`
`procedure. A spatial volume is defined by 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. The expandable surface element is size to fill a
`
`tissue cavity created in a breast during a lumpectomy procedure so as to position the
`
`surrounding tissue and allow an external radiation source to accurately deliver a dose of
`
`radiation. This invention generally relates to a method and device for the improved
`
`targeting of tissues during external beam radiation therapy (EBRT). Improved targeting
`
`of tissues during EBRT would allow for reduced volumes of tissue surrounding the target
`
`site that receives a therapeutic dose of radiation. Lower doses of radiation to non-target
`
`tissues would lower complications due to tissue toxicities as well as allowing for a
`
`reduction in the fractionation scheme.
`
`[17] The device of the present invention is comprised of a catheter with a proximal and distal
`
`end, connected to an expandable reservoir on the distal end such as a balloon.
`
`[18]
`
`In another aspect of the present invention, a device does not use a balloon catheter to
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`target tissue. The device may be comprised of a catheter or introduction device for the
`
`placement of biocompatible materials, (foam, plastic, etc.) to occupy a resected tissue or
`
`natural cavity. The biocompatible material may or may not contain contrast medium.
`
`The placement device serves as a guide for a suitably protected radiation source which is
`
`able to increase the radiation delivered to the target tissue from within the body. The
`
`placement device may also be used to guide other tools including those for treatment such
`
`8
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`Focal Exhibit 1014 Page 8
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`

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`Patent Application
`
`Attorney Docket No.: 14.029011 PR
`
`as tools for the application of energy (e.g., heat, microwave, RF, etc.) to resect portions of
`
`tissue from the surrounding area.
`
`[19]
`
`In yet another aspect of the present invention, the biocompatible materials are
`
`bioabsorbable. Once the biocompatible materials are placed within the resected tissue or
`
`cavity, the material may remain within the patient's body for a period sufficient to
`
`complete the course of therapeutic treatment. Once the course of therapeutic treatment
`
`has been completed, the biocompatible material will be absorbed into the patient's body
`
`thus removing the requirement of additional invasive surgery or an additional visit to a
`
`doctor's office to undergo a procedure to remove a medical device.
`
`DETAILED DESCRIPTION OF THE INVENTION
`
`[20]
`
`The present invention provides systems and methods for treating proliferative tissue
`
`disorders, such as malignant tumors of the breast, by surgically resecting at least a portion
`
`of the proliferative tissue to create a resection cavity, followed by external radiation
`
`therapy of residual tumor margin. To improve the accuracy of the radiation treatment, a
`
`tissue fixation device is provided to position and/or stabilize the tissue surrounding the
`
`resected cavity.
`
`[21]
`
`External radiation therapies rely on precise imaging and/or targeting techniques, and any
`
`movement of the target tissue can introduce error. Patient positioning is often critical and
`
`great measures are taken to position and immobilize patients, including for example,
`
`marking the patient's skin and using foam body casts. Yet even with the patient
`
`immobilized, shifting of the target tissue still presents a proble!ll, including for example,
`
`9
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`Focal Exhibit 1014 Page 9
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`

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`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`shifting of tissue as a result of the patient breathing and inconsistencies in the positioning
`
`of the patient's body between radiotherapy fractions.
`
`[22]
`
`Tissue cavities present an even greater difficulty because the tissue surrounding the
`
`cavity is often soft, irregular tissue which lacks the support usually provided by adjacent
`
`tissue. The irregular surface of the cavity wall, including the residual tumor margin, is
`
`therefore difficult to image. Unpredictable shifting of the tissue surrounding the cavity,
`
`possibly caused by slight patient movement, can further complicate the procedure and
`
`result in unacceptable movement of the target tissue. For example, where the target tissue
`
`changes position after visualization, but before radiation treatment, the shifting tissue
`
`may result in radiation beams encountering primarily healthy tissue. As a result, the
`
`residual tumor margin may be substantially untreated, while healthy tissue may be
`
`damaged by the treatment. The present invention overcomes these prior art problems by
`
`providing a tissue positioning device which can be inserted into the resected cavity and
`
`expanded to position the surrounding tissue in a predetermined geometry. The methods of
`
`the present invention also facilitate tissue imaging by positioning tissue against a defined
`
`surface.
`
`[23] The methods of the present invention also provide for systems and methods for the
`
`treatment of early stage breast cancers. For example, a breast cancer is removed
`
`surgically by resecting a lesion to create a resection cavity. After resection, the margin of
`
`the cavity is exposed to external beam radiation therapy. In order to improve the
`
`accuracy of the radiation treatment, a tissue fixation device is provided to position and/or
`
`stabilize the tissue surrounding the resected cavity. The method of the present invention
`
`provides for a means for directing or targeting the radiation beams using radiographic
`
`10
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`Focal Exhibit 1014 Page 10
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`

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`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`imaging of the device or other fiducial markers with real-time feedback for direction of
`
`the radiation beams.
`
`[24]
`
`The method of the present invention is based upon features of a balloon brachytherapy
`
`catheter (e.g., MammoSite System, Cytyc Corporation, Marlborough MA) as provided in
`
`U.S. Patent Nos. 5,611,923 and 5,931,774, to Williams et al. and U.S. Patent Nos.
`
`6,200,257 and 6,413,204, and 6,482,142 to Winkler et al. all of which are incorporated by
`
`reference herein. Features of a balloon brachytherapy catheter which serves to bring
`
`radiation of the lumpectomy cavity margins can be applied in the method of the present
`
`invention for external beam radiation sources. Specifically, the implantation and
`
`inflation of a balloon catheter within a lumpectomy cavity provides for internal target
`
`fixation; external target fixation; and target localization.
`
`[25]
`
`The use of a balloon brachytherapy catheter allows for the fixation of an internal target.
`
`The inflation of a balloon brachytherapy catheter in a resected lumpectomy cavity
`
`configures the target volume reproducibly in a shaped geometry (i.e., a spherical).
`
`Having a regular and reproducible target volume allows for easier and more efficient
`
`radiation beam shaping to conform the radiation therapy to the target tissue, thus
`
`minimizing the radiation delivered to the adjacent healthy tissue. A more focused
`
`radiation beam also allows for reducing the size of the normal tissue margins typically
`
`added to the planning target volume (PTV).
`
`[26] The use of a balloon brachytherapy catheter also allows for the fixation of an external
`
`target. A portion of an implanted brachytherapy device will extend percutaneously
`
`through the skin. This external portion of the device can be coupled to a rigid fixture
`
`11
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`Focal Exhibit 1014 Page 11
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`

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`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`providing a means for holding the target volume (i.e., the tissue surrounding the balloon)
`
`fixed relative to the 3-dimensional space of the treatment facilities (e.g., a radiation
`
`treatment couch). Thus, while the target volume is held in a constant position in regard to
`
`an external fixture, other patient tissue (e.g., breast tissue) remains slightly mobile
`
`relative to the same external fixture or even relative to the patient's body (e.g., chest
`
`wall). The fixation of the target tissue by an external means allows for better targeting of
`
`the radiation beams which again allows for reducing the size of the normal tissue margins
`
`typically added to the planning target volume. Also, the fixation of target tissue to an
`
`external fixture reduces the movement of target tissue due to movement of the patient.
`
`For instance, even the slightest movement of a patient can have a deleterious effect on
`
`locating and targeting tissues. In particular, the target motion of lumpectomy cavities due
`
`to a patient's respiration can affect beam efficiencies. Thus, the fixation of target tissue
`
`can reduce or eliminate the movement of target tissue by involuntary patient movements.
`
`[27]
`
`The use of a balloon brachytherapy catheter also allows for target localization. A
`
`brachytherapy balloon inflated with air or other contrast material provides a radiographic
`
`method for real time aiming of the planned radiation beams. The location of the inflated
`
`device can be otherwise ascertained via a number of other fiducial marking systems that
`
`can telegraph their location within the treatment room (specifically relative to the linear
`
`accelerator's isocenter). An example of this capability is target localization via the
`
`Beacon® Electromagnetic Transponder (Calypso Medical Seattle, WA). Thus, radiation
`
`beams can be shaped on the fly to account for target location changes or can provide a
`
`means to tum the beam on and off as the target moves in space and intersects the beams.
`
`12
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`Focal Exhibit 1014 Page 12
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`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`[28] The present invention including a system for treating tissue surrounding a resected cavity
`
`that is subject to a proliferative tissue disorder. The system includes a tissue fixation
`
`device which includes a catheter body member having a proximal end, a distal end, an
`
`inner lumen and an expandable surface element. Expandable surface element is
`
`preferably disposed proximate to distal end of catheter body member and is sized and
`
`configured to reproducibly position tissue surrounding a resected tissue cavity in a
`
`predetermined geometry upon expansion. The system also includes an external radiation
`
`device positioned outside the resected cavity such that external radiation device can
`
`deliver a dose of radiation to the tissue surrounding expandable surface element. External
`
`radiation device can b,e any external radiation source known in the art or later developed,
`
`however, in preferred embodiments of the invention, precisely targeted sources such as
`
`those used in 3DCRT and IMRT are employed. The tissue fixation device can be
`
`positioned within a resected tissue cavity, for example within a patient's breast following
`
`a lumpectomy, and expanded to position the surrounding tissue such that the dose of
`
`radiation beams from external radiation device is accurately delivered.
`
`[29]
`
`The expandable surface of the device can be defined by an inflatable balloon. It will be
`
`understood that the term "balloon" is intended to include distensible devices which can
`
`be, but need not be, constructed of an elastic material. The balloon of the present
`
`invention may include the variety of balloons or other distensible devices designed for
`
`use with surgical catheters. The balloon can be expanded by injecting an inflation
`
`material through body and into the balloon, and preferably, the inflation material
`
`comprises non-radioactive liquids or gases.
`
`13
`
`Focal Exhibit 1014 Page 13
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`

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`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`[30]
`
`In one embodiment, the balloon is constructed of a solid material that is substantially
`
`impermeable to active components of a treatment fluid with which it can be filled, and is
`
`also impermeable to body fluids, e.g., blood, cerebrospinal fluid, and the like. An
`
`impermeable baBoon is useful in conjunction with a treatment fluid, to prevent the
`
`material from escaping the treatment device and contaminating the surgical field or
`
`tissues of the patient.
`
`[31]
`
`In another embodiment, the balloon is permeable to a treatment fluid, and permits a
`
`treatment fluid to pass out of device and into a body lumen or cavity. A permeable
`.,
`balloon is useful whep the treatment fluid is a drug such as for example, a
`
`I
`
`chemotherapeutic agent which must contact tissue to be effective. U.S. Pat. Nos.
`
`5,611,923 and 5,931,774 to Williams et al. disclose exemplary permeable balloons and
`
`treatment substances. Semi-permeable balloons can also find use in the method of the
`
`present invention. For example, a semi-permeable material that is capable of preventing
`
`the passage of a material through the balloon wall can be used to contain a treatment
`
`fluid, where certain fluid components can pass through the membrane while the
`
`components of the treatment fluid are retained within the balloon. Examples of which
`
`can be found in co-pending, commonly assigned US patent application No. 2005-
`
`0107653.
`
`[32]
`
`In another embodiment, materials may be impregnated or incorporated into the
`
`expandable surface of the implantable device. For example, the expandable surface may
`
`be made of metal, be coated with a metal, or may contain metal in a matrix which is
`
`integrated into the expandable surface of the device. When the expandable surface is
`
`deployed in a patient's body, the metal in the expandable surface provides contrast
`
`14
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`Focal Exhibit 1014 Page 14
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`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`between soft tissue and the surface of the device and thus imaging capability of the
`
`device becomes integral to the device (i.e., no longer needs a contrast agent). Examples
`
`of metals which may be incorporated into the expandable surface include any high Z
`
`material such as gold, silver, tungsten, etc., or stretchable metallized fabric mesh which is
`
`preferably knitted from a nylon and spandex knit plated with gold or other conductive
`
`material.
`
`[33] Although the balloon and body member can mate in a variety of ways, in some
`
`embodiments, the balloon is mated to body member at substantially a single point on, or a
`
`single side of, the balloon body. Such attachment permits the balloon (e.g., a spherical
`
`balloon) to maintain a substantially constant (e.g., spherical) shape over a range of
`
`inflation volumes. That is, the balloon is not constrained in shape by multiple attachment
`
`points to the body member, as is commonly the case with, e.g., balloons for Foley ·
`
`catheters. In other embodiments, the balloon is attached to the body member at multiple
`
`points on the balloon body, while allowing the balloon to maintain a constant shape over
`
`a range of inflation sizes. For example, a balloon attached to a·body member at both
`
`distal and proximal points on the balloon body can be unconstrained upon inflation where
`
`the body member includes an expansion element (e.g., a slidable engagement element)
`
`that permits the body member to adjust in length as the balloon expands or contracts. A
`
`balloon which maintains a substantially constant shape over a range of inflation volumes
`
`permits a surgeon to select a balloon with less concern over the size of the cavity.
`
`[34] The body member of device provides a means for positioning expandable surface within
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`the resected tissue cavity and provides a path for delivering inflation material (if used).
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`Although the exemplary body members have a tubular construction, one of skill in the art
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`15
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`Focal Exhibit 1014 Page 15
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`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`will appreciate that body members can have a variety of shapes and sizes. Body
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`members suitable for use in the invention can include catheters which are known in the
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`art. Although body members can be constructed of a variety of materials, in one
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`embodiment the body member material is silicone, preferably a silicone that is at least
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`partially radio-opaque, thus facilitating x-ray location of body member after insertion of
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`device. The body members can also include conventional adapters for attachment to a
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`treatment fluid receptacle and the balloon, as well as devices, e.g., right-angle devices,
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`for conforming body members to contours of the patient's body.
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`[35] The position of the device with in a patient's body can also be.determined using fiducial
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`markers. By positioning the markers on the device (for example on expandable surface
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`member or on body member), a user can determine the spatial position of the device and
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`the surrounding target tissue. The spatial data can be used to correct errors in target tissue
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`location by adjusting the patient's body location on the treatment couch or by altering the
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`radiotherapy beams' shape and direction. Fiducial markers are discussed in more detail
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`below.
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`[36] The device of the present invention can also include a variety of alternative embodiments
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`designed to facilitate tissue positioning. For example, the device can include multiple
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`spatial volumes, as well as, a variety of shapes adapted to conform and shape the resected
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`cavity. In addition, the expandable surface can be positioned on and mated with tubular
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`body member in various ways to facilitate placement of the expandable surface within a
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`tissue cavity. The expandable surface can also be adapted to allow delivery of a treatment
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`material to the tissue surrounding the cavity.
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`16
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`1 ••• ,
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`Focal Exhibit 1014 Page 16
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`Patent Application
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`Attorney Docket No.: 14.029011 PR
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`[37] The invention also contemplates the use of multiple balloons, e.g., a double-walled
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`structure. Such a balloon can comprise, for example, an impermeable inner wall and a
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`permeable outer wall. In this embodiment, the inner balloon can be filled with, e.g., a
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`radioactive treatment fluid, while the outer balloon (i.e., the space between the inner and
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`outer balloon walls) is filled with a chemotherapeutic treatment fluid. This embodiment
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`allows multiple modes of therapy (e.g., chemotherapy, brachytherapy and external
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`radiation) to be administered with a single device. In this double-walled balloon
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`embodiment the two balloons can be inflated with two treatment fluids at the same time
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`or at different times during therapy. Inflation of an inner balloon can provide pressure on
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`an outer balloon, wh