111111
`
`1111111111111111111111111111111111111111111111111111111111111111111111111111
`US 20090024225Al
`
`(19) United States
`c12) Patent Application Publication
`Stubbs
`
`(10) Pub. No.: US 2009/0024225 Al
`Jan. 22, 2009
`(43) Pub. Date:
`
`(54)
`
`IMPLANT FOR TARGETING THERAPEUTIC
`PROCEDURE
`
`(76)
`
`Inventor:
`
`James B. Stubbs, Palo Alto, CA
`(US)
`
`Publication Classification
`
`(51)
`
`Int. Cl.
`A61F 2102
`A61B 19100
`
`(2006.01)
`(2006.01)
`
`Correspondence Address:
`NUTTER MCCLENNEN & FISH LLP
`WORLD TRADE CENTER WEST, 155 SEA(cid:173)
`PORT BOULEVARD
`BOSTON, MA 02210-2604 (US)
`
`(21) Appl. No.:
`
`12/173,881
`
`(22) Filed:
`
`Jul. 16, 2008
`
`Related U.S. Application Data
`
`(60) Provisional application No. 60/949,963, filed on Jul.
`16, 2007.
`
`(52) U.S. Cl. ...................................... 623/23.72; 128/898
`
`(57)
`
`ABSTRACT
`
`An implantable device has a body that is substantially rigid
`and has a predetermined shape. The body is further bioab(cid:173)
`sorbable and has a density less than or equal to about 1.03
`glee. When the device is implanted in a resected cavity in soft
`tissue, it causes the cavity to conform to the predetermined
`shape. The implantable device is further imageable due to its
`density being less than that of soft tissue such that the bound(cid:173)
`aries of the tissue corresponding to the predetermined shape
`can be determined.
`
`122
`
`110
`
`100
`
`122
`102
`
`Focal Exhibit 1011 Page 1
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`Patent Application Publication
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`Jan. 22, 2009 Sheet 1 of 4
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`US 2009/0024225 Al
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`10 - - - -
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`FIGURE I
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`Electron beams
`
`FIGURE2
`(Prior Art)
`
`Focal Exhibit 1011 Page 2
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`

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`Patent Application Publication
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`Jan. 22, 2009 Sheet 2 of 4
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`US 2009/0024225 Al
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`- -10
`
`12
`
`14
`
`FIGURE3
`
`FIGURE4
`(Prior Art)
`
`102
`
`100
`
`Focal Exhibit 1011 Page 3
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`

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`Patent Application Publication
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`Jan. 22, 2009 Sheet 3 of 4
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`US 2009/0024225 Al
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`FIGURES
`
`FIGURE6
`
`Focal Exhibit 1011 Page 4
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`

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`Patent Application Publication
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`Jan. 22, 2009 Sheet 4 of 4
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`US 2009/0024225 Al
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`FIGURE 7
`
`Focal Exhibit 1011 Page 5
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`

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`US 2009/0024225 Al
`
`Jan. 22, 2009
`
`1
`
`IMPLANT FOR TARGETING THERAPEUTIC
`PROCEDURE
`
`RELATED APPLICATIONS
`
`[0001] This application claims priority to U.S. Provisional
`Patent Application No. 60/949,963, entitled "Implant for Tar(cid:173)
`geting Therapeutic Procedure," filed on Jul. 16, 2007, which
`application is incorporated herein by reference in its entirety.
`
`BACKGROUND
`
`[0002] Two trends have become significant in driving the
`delivery of medical treatments: 1) treatments, be they drugs,
`energy or surgery, are moving towards local and focal deliv(cid:173)
`ery, and 2) treatments are being tailored and optimized for
`each patient based on their specific anatomy, physiology and
`disease features. These directions both are designed to mini(cid:173)
`mize the likelihood of adverse effects from the therapies as
`well provide a more patient-specific treatment, which in
`theory should improve disease cure or control rates.
`[0003] These trends were started in surgery where large,
`open surgical procedures have been and continue to be
`replaced by minimally-invasive procedures and endoscopic
`procedures. Drug therapies are moving to more local delivery,
`directly to the treatment site (e.g., drug eluting stents and
`Gliadel wafers for brain tumors). Until recently, the desire to
`do the same in radiation therapy has been hampered by inad(cid:173)
`equate technology for focused delivery. However, significant
`progress in local radiation delivery has been accomplished in
`the brachytherapy subspecialty of radiation oncology, most
`notably in prostate and breast cancer patients. Breast brachy(cid:173)
`therapy, whereby the radiation source is inserted temporarily
`into an implanted catheter inside the breast has had great
`success in popularizing both accelerated and smaller volume
`treatments. These trends have been less successful at improv(cid:173)
`ing the delivery of external beam radiation.
`[0004] External beam radiation therapy (EBRT) is one of
`the most common adjuvant therapies for cancer patients in the
`U.S., with chemotherapy being the other one. EBRT is deliv(cid:173)
`ered to cancer patients as either the first line of therapy (for
`non-resected cancers) or as a means of maximizing local
`control of the cancer following surgical removal of the tumor.
`In EBRT, one or more beams of high energy x-rays are aimed
`at the part of the body needing radiotherapy. A linear accel(cid:173)
`erator (often called a linac) produces the beams and has a
`collimator that helps to shape the beams as they exit the linac.
`It is very common for a tumor to be treated using two or more
`beams, each of which is delivered from different directions
`around the tumor, and that all intersect at the tumor site. In this
`manner, the tissue surrounding the target can be exposed to
`lower radiation doses than the sum of the treatment beams
`yields at the tumor target. The tumor target volume is delin(cid:173)
`eated by the radiation oncologist using CT scans of the
`patient. The tumor target volume and radiation dose prescrip(cid:173)
`tion parameters are entered into a treatment planning com(cid:173)
`puter. Treatment planning software (TPS) then produces a
`plan showing how many beams are needed to achieve the
`radiation oncologist's prescription dose, as well as the size
`and shape of each beam.
`[0005] The complete course of EBRT is divided (called
`fractionation) into numerous small, discrete treatments called
`fractions. A typical prescribed dose of 60 Gray (Gy) is frac(cid:173)
`tionated into 30 daily treatments of 2 Gy per day. During a
`fraction, the treatment beam may be "on" for -1 minute.
`
`Thus, the full radiotherapy treatment takes about 6 weeks (5
`fractions per week) to complete.
`[0006] Historically, EBRT has been practiced exactly as
`has chemotherapy, namely, the radiation doses delivered to
`the patient are limited only by the tolerance of normal tissues
`surrounding the site to be treated. Hence, often, the radiation
`therapy is continued until side-effects become intolerable for
`the patient. Effectively, radiation therapy has been a "radiate
`until the patient can't take it anymore" type of treatment. The
`target volume, in which it is desired to deliver essentially
`100% of the prescribed radiation dose, has historically been
`defined as the tumor (the gross tumor volume, or GTV) plus
`a surrounding volume of tissue that is like to harbor micro(cid:173)
`scopic tumor cell foci (the clinical target volume, or CTV).
`Another margin of surrounding normal tissue is added to the
`CTV to account for errors in positioning of the patient for
`therapy and movement of the tumor site both during a fraction
`and between fractions. Chest and upper abdomen radiation
`therapy (e.g., lung cancer and pancreatic cancer) are two
`examples where large margins are needed to make sure the
`changes in tissue position during respiration do not result in
`the target leaving the beam during some portion of the frac(cid:173)
`tion.
`In the last few years, the treatment planning soft(cid:173)
`[0007]
`ware and linear accelerator technology have dramatically
`improved in their ability shape the radiation therapy beams to
`better avoid nearby sensitive structures. The latest treatment
`planning software allows the radiation oncologist and medi(cid:173)
`cal physicist to define the volume of tissue to be treated using
`CT scans and provide therapy constraints (e.g., minimum
`radiation dose inside the target volume, maximum radiation
`dose to structures nearby target volume) and have the soft(cid:173)
`ware compute the beam angles and shapes in a process called
`inverse treatment planning. Improved beam shaping is
`achieved using a technique called Intensity Modulated Radia(cid:173)
`tion Therapy (IMRT). Another feature of the newer linacs is a
`type of radiographic (and/or ultrasonic) imaging that is used
`to better position the patient and his/her tumor for more
`accurate targeting of the treatment beams. This latter method
`is called Image Guided Radiation Therapy, or IGRT.
`[0008] Both IMRT and IGRT techniques use numerous,
`smaller and better focused beams that intersect at the target
`volume. IGRT differs from IMRT in at least one important
`aspect-imaging prior to each fraction is used to reduce posi(cid:173)
`tioning errors and make sure the treatment beam is properly
`targeted. Typically, IGRT uses bony anatomy (e.g., pelvic
`bones for prostate patients) for radiographic targeting and
`soft tissue interfaces (prostatic capsule and bladder wall) for
`ultrasound targeting. Rarely, implanted radio-opaque mark(cid:173)
`ers (e.g., Visi-Coil) have been used to facilitate targeting for
`IGRT. Radio-opaque markers are very common for delineat(cid:173)
`ing the target for post-lumpectomy radiation therapy treat(cid:173)
`ment planning, however these markers have not been used for
`targeting each fraction or each beam of every fraction as is
`done in IGRT.
`[0009]
`IMRT uses a special type of collimator, a multi-leaf
`collimator (MLC) that changes the shape of the beam during
`each fraction to modulate or "sculpt" the radiation dose to
`more closely fit the actual target volume shape in three dimen(cid:173)
`sions. Linacs with MLCs can control the size and shape of the
`beam to within a few millimeters accuracy.
`[0010]
`IGRT is a relatively new option on linacs. New
`linacs are being sold today that have on-board imaging capa(cid:173)
`bility via mega-voltage (MY) or kilo-voltage (KV) x-rays/
`
`Focal Exhibit 1011 Page 6
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`

`

`US 2009/0024225 Al
`
`Jan. 22, 2009
`
`2
`
`fluoroscopy. The on-board imaging capability can also be
`retrofitted to existing linacs. On-board imaging is a technical
`capability that has been introduced into the newest linac
`product lines by all the major linac manufacturers (Varian
`Medical Systems, Elekta, Tomotherapy, Accuray and
`Siemens). While the technology made by these companies
`provides the possibility of performing better targeting for
`external beam radiation therapy, the targets (e.g., bony
`anatomy) is inadequate for accurate targeting.
`[0011] As described above, targeting the external beam
`radiation therapy accurately requires one to point out the
`target using fiducial markers having different radiographic
`properties than that of surrounding tissue (e.g., bone, and soft
`tissue). To date, this has been accomplished using radio(cid:173)
`opaque markers (e.g., permanently implanted foreign bod(cid:173)
`ies). Alternatively, Patrick and Stubbs described a device and
`method for shaping and targeting EBRT using a temporarily
`implanted balloon catheter (published United States patent
`application US 2005/0101860 A1). This device and method
`required implantation of a foreign body whose removal
`necessitated a second surgical procedure. Removal of this
`foreign body would leave a volumetric defect in the patient's
`breast.
`[0012] Hence, the need exists for a better device and
`method for positioning the target volume and providing a
`visual target for the external beam treatments, without intro(cid:173)
`duction of foreign bodies requiring surgical removal at a later
`date and without leaving behind a surgical defect that
`adversely affects cosmetic results.
`
`SUMMARY
`
`[0013] The present invention includes methods, as well as
`devices and systems, for the delivery of therapeutic rays to
`regions of tissue within a patient, or for improving the accu(cid:173)
`racy and precision of such methods, devices and systems. In
`a first aspect, the invention includes a method for treating a
`proliferative tissue disease in a patient. The method includes
`excising diseased tissue from the patient and thereby creating
`a tissue cavity. A bioabsorbable implant is then placed within
`the tissue cavity. The implant can have a predetermined shape
`and include a means for visualizing the implant. The location
`of the implant within the patient is then determined and tissue
`surrounding the tissue cavity is treated with therapeutic rays.
`[0014]
`In a further aspect of the invention, a method for
`targeting and delivering therapeutic rays to a patient's soft
`tissue is provided. This method includes imaging an
`implanted device within soft tissue in the patient where the
`implanted device is substantially rigid, has a predetermined
`shape, and has a density that is lower than the density of the
`patient's soft tissue. A region of target tissue surrounding the
`implanted device is then determined, a radiation dose from a
`source external to the patient is targeted to the target tissue,
`and the targeted radiation dose is delivered.
`[0015]
`In a still further aspect of the invention, a system for
`targeting therapeutic rays to target tissue surrounding a tumor
`resection cavity is provided. The system includes an implant(cid:173)
`able device having a body that is substantially rigid and has a
`predetermined shape. The body is further bioabsorbable and
`has a density less than or equal to about 1.03 glee. When the
`device is implanted in a resected cavity in soft tissue, it causes
`the cavity to conform to the predetermined shape. The
`implantable device is further imageable due to its density
`
`being less than that of soft tissue such that the boundaries of
`the tissue corresponding to the predetermined shape can be
`determined.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`[0016] The invention will be more fully understood from
`the following detailed description taken in conjunction with
`the accompanying drawings:
`[0017] FIG.1 illustrates an implantable device of the inven(cid:173)
`tion;
`[0018] FIG. 2 illustrates the targeting and delivery of thera(cid:173)
`peutic rays as it is known in the prior art;
`[0019] FIG. 3 provides a cross-sectional view of the device
`of FIG. 1, with a multi-layered version on the left and a
`single-layered version on the right;
`[0020] FIG. 4 illustrates a resected tumor cavity in soft
`tissue as is known in the prior art;
`[0021] FIG. 5 illustrates the delivery of therapeutic rays
`according to the invention;
`[0022] FIG. 6 shows a radiograph with an implanted shap(cid:173)
`ing target device and a treatment margin is shown around the
`implanted device; and
`[0023] FIG. 7 shows image guided radiotherapy beams
`intersecting at the implanted device plus margin.
`
`DETAILED DESCRIPTION
`
`[0024] The invention described herein use implantable
`devices that can allow for more accurate targeting of external
`beam radiation to the region of tissue that is to be treated. The
`devices provide a reproducibly-shaped 3-dimensional target
`that is used to focus the radiation therapy treatment beams
`directly onto the targeted tissue-for example, the tissue sur(cid:173)
`rounding a resected tumor cavity. The device can be formed of
`an absorbable material that is implanted at the time of tumor
`resection and requires no second procedure to remove (it
`dissolves in situ leaving no foreign material in the patient's
`body).
`In one embodiment, the invention includes a bioab(cid:173)
`[0025]
`sorbable surgical implant 10 (illustrated in FIG. 1 in a spheri(cid:173)
`cal configuration) with at least one integral radiographic (or
`ultrasonic) visualization (targeting) property. The device can
`have sizes ranging from 5 mm in diameter to 5 em in diameter
`(other sizes are possible depending upon the application).
`Preferably, the implant 10 has a predetermined shape that can
`facilitate easy and simple treatment beam profiles, such as
`spheres, ellipsoids, parallelepipeds (e.g., rectangular boxes).
`In this way, the implant can be visualized, and its contours
`(and thus the contours of the target tissue to be treated(cid:173)
`typically marginal regions surrounding an excised tumor)
`readily determinable. Treatment can then be applied to the
`target tissue. The size and shape of the implant can be varied
`to correspond to the most common resection cavity sizes and
`shapes. The implant may be in its predetermined shape before
`implant or assume that shape upon mechanical manipulation
`or implantation (e.g., it may be evacuated such that upon
`contact with air or fluids it absorbs the air or fluids and returns
`to its intended shape).
`[0026] The implant 10 can have one or more of the follow(cid:173)
`ing key features:
`1) Integrated targeting feature (altered material composition
`allowing radiographic or ultrasonic localization);
`2) Multiple sizes of implant, each having a relatively fixed
`shape upon implantation;
`
`Focal Exhibit 1011 Page 7
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`

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`US 2009/0024225 Al
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`Jan. 22, 2009
`
`3
`
`3) Bioabsorption over a specified or desired time period;
`4) Sufficient volume to replace resected tissue preventing
`poor cosmetic outcomes by eliminating volume defects due
`to tissue loss (breast models); and
`5) The device/implant can be inserted at the time of surgical
`resection of the tumor or as a minimally invasive procedure at
`some time period following surgery.
`It is important that the implanted targeting device 10
`[0027]
`be visible on radiographic films (MV and/or KV x-rays) and
`ultrasound equipment. FIG. 2 illustrates how this is impor(cid:173)
`tant. On the left, two electron beams are properly targeted
`onto a lumpectomy cavity and its margin. On the right a single
`electron beam, using only the skin scar as its target, misses
`much of the cavity and its margin. The figure on the left is the
`result of being able to see the target for every fraction and
`adjust the beam to make certain the target is hit. The figure on
`the right is the result of using movable or deformable ana(cid:173)
`tomicallandmarks for the target.
`[0028] While a number of methods, devices, and materials
`are known to provide radiographic marking, in a preferred
`embodiment, the implant 10 can have "negative contrast" (a
`density less than that of soft tissue), which provides radio(cid:173)
`graphic and ultrasonic contrast to facilitate visualization on
`these imaging modalities. Ultrasound visualization may also
`be accomplished when the material of the device has different
`echogenic properties as to those of tissue surrounding it.
`Other properties may be beneficial for these and other imag(cid:173)
`ing modalities. With the requisite physical properties that
`allow on-board imaging systems to "see" the target provides
`the means to reposition the patient and alter the treatment
`beams to insure optimal targeting. This targeting can be used
`for every fraction delivered to the patient.
`[0029] Preferably, the implant 10 is completely bioabsorb(cid:173)
`able, though other configurations with at least portions of the
`implant being non-resorbable may be desirable. One example
`is the incorporation of one or more wireless transponders that
`provide wireless signals that can be interpreted as to the 3-D
`location (in the Linac's frame of reference) of the transpon(cid:173)
`ders. Calypso Medical's Beacon Transponder™ is an
`implantable transponder that provides localization data for
`targeting purposes (it is not, however, an image guided local(cid:173)
`ization device). There are numerous ways to alter bioabsorb(cid:173)
`able materials to achieve the desired imaging capability. One
`way is to incorporate air or gas pockets or bubbles into the
`resorbable material.
`[0030] Various materials that could be used to construct
`such an implant include known biosorbable materials such as
`polyglycolic acid (Dexon, Davis & Geck); polyglactin mate(cid:173)
`rial (Vicryl, Ethicon); poliglecaprone (Monocryl, Ethicon);
`and synthetic absorbable lactomer 9-1 (Polysorb, United
`States Surgical Corporation). Other materials include mold(cid:173)
`able bisorbable materials such as PLLA and PLLA/PGA
`blends. Other foamable materials that can be utilized in the
`present invention include, without limitation, proteins such as
`collagen, fibronectin, laminin and fibrin, most preferably col(cid:173)
`lagen, and high molecular weight polysaccharides, such as
`heparan sulphate, chondroitin sulphate, hylauronic acid and
`dermatan sulphate. Mixtures of any of the aforementioned
`materials also can be used, as required. The materials can be
`modified, by cross-linking for example, to control degrada(cid:173)
`tion rates over varying lengths of time, after which they are
`substantially or completely resorbed.
`[0031] Collagen is a preferred material. Examples of col(cid:173)
`lagen materials and methods for making them can be found,
`
`for example, in U.S. Pat. No. 5,019,087 to Nichols; U.S. Pat.
`No. 3,157,524 to Artandi; and U.S. Pat. No. 3,520,402 to
`Nichols eta!., each of which is hereby incorporated by refer(cid:173)
`ence for its teachings of collagen materials and methods of
`manufacture.
`[0032]
`In one preferred embodiment, the device has mul(cid:173)
`tiple layers ofbioabsorbable materials. For example, the core
`of the largely spherical device is filled with collagen (in one of
`its many physical forms) and is surrounded by a layer of other,
`stiffer or more resilient bioabsorbable materials such as Vic(cid:173)
`ryl. The Vicryl material can laid down as a sheet ofVicryl or
`as a winding ofVicryl thread. Alternatively, the outer layer
`may be a continuous shell or a discontinuous (e. g. geodesic)
`structure made of molded PLLA or PLLA/PGA blend. This
`layer of tougher material produces the resiliency of the device
`to maintain a specific shape (e.g., a sphere) and the internal
`bioabsorbable material (e.g., collagen) serves as a filler. The
`outer material may govern the overall rate of resorption and
`may include a semi-permeable membrane or as a temporarily
`impermeable membrane.
`[0033]
`In one embodiment, the density of the implant 10
`should be less than 1.04 gram/cc. It may be substantially
`lower ( <0.80 gram/cc ), slightly lower (0.95-1.03 gram/cc) or
`intermediately lower (0.80-0.95 gram/cc) than the density of
`soft tissue. There may be utility in an implant with density
`higher than that of soft tissue as that type material can be
`easily seen on KV x-rays. The density should not be signifi(cid:173)
`cantly larger as too much attenuation of the radiation beams
`may result in dose perturbations that current treatment plan(cid:173)
`ning systems cannot compensate for. Thus higher densities
`should not exceed about 1.3 gram/cc. For these higher con(cid:173)
`trast embodiments, the higher contrast material does not need
`to be uniformly spread throughout the device. Rather, a por(cid:173)
`tion of the outer aspect of the device may be high density
`(contrast) with the inner aspect being of lower density. For
`example, in a spherical embodiment, the outermost few mil(cid:173)
`limeters of material may be impregnated with x-ray media
`(e.g., barium sulfate, Iohexol™, Onmipaque™ or other bio(cid:173)
`compatible high density matter), while inside this shell, the
`device would be made of any bioabsorbable material oflower
`density.
`[0034] The material for implant 10 should be rigid enough
`to provide a fixed and predetermined shape in situ. A fixed and
`predetermined shape can be a significant advantage in that it
`provides a standard shape for targeting. In deformable tissues
`(i.e., breast and perhaps lung), having the implant remodel the
`surrounding surgical margins into a specific shape (i.e., a
`sphere) allows the clinical target volume and planning target
`volumes (i.e., the target for radiotherapy) to also take this
`shape. For resected breast cancer cases, the resection cavity
`has irregular shape, the shape can change day to day and even
`during different portions of the respiratory cycle, and the
`cavity can grow or shrink over the time period during which
`radiation therapy is to be delivered. Having the target volume
`in the same shape every day of therapy increases the prob(cid:173)
`ability of always hitting the target and reduces the chance of
`a "geographic miss". A simple shape such as a sphere is one
`of the easiest shapes for linacs to sculpt to, using either the
`multi-leaf collimator or compensator. Thus, shaping the treat(cid:173)
`ment filed is substantially easier, and quicker to plan and
`execute. The desired shapes are ones in which the external
`surface(s) is( are) convex rather than concave.
`[0035] The sizes of the implant are most preferably in the
`2-4 em diameter range (diameter of the major axis). Other
`
`Focal Exhibit 1011 Page 8
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`US 2009/0024225 Al
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`Jan. 22, 2009
`
`4
`
`sizes may be preferable, depending on the patient's anatomy
`and anatomical location of the target. For breast, the diameter
`range of 2-4 em is preferred.
`[0036] The implant should take a rather stiff configuration
`in vivo. This will allow the implant to better conform the
`surrounding tissue to its shape. It is also a benefit to have some
`rigidity (though not rock hard) in that the shape will remain
`the same for each radiation therapy treatment. It is not nec(cid:173)
`essary, and is in fact less desirable, for the implant to be
`completely rigid until resorbed. The desirable property is one
`that is deformable (to improve comfort for the patient) but
`rebounds to its desired shape upon release from stress or
`tension. For example, the breast implant may deform to a
`compressed shape (think of a beach ball being pressed
`between two hands) when the patient is wearing a bra or is
`prone, but returns to spherical shape when the bra is removed
`and the patient is supine. As used herein, the term "substan(cid:173)
`tially rigid" refers to the preferred situation in which the
`implant reproducibly provides the desired predetermined
`shape to the tissue surrounding a tumor resection cavity while
`allowing some compliance for the purpose of providing
`implantation through a smaller incision and/or to provide
`increased comfort for the patient.
`[0037] The most desirable rate of resorption for bioabsorb(cid:173)
`able implants will depend on the specific application and
`anatomic location. In all cases, it is desired that the implant
`maintain its size, shape and imaging capacity until radiation
`therapy is complete. Those experienced in radiation therapy
`will realize this spans a wide range of time intervals. For
`patients who will move swiftly to radiation therapy, and
`receive a hypofractionated radiation therapy, the resorption
`can start as early as 3 weeks post implant. For others, the
`radiation therapy may not start for 12-18 weeks post surgi(cid:173)
`cally and may last 7 weeks, thus requiring an implant that
`remains fully functional for as long as 6 months.
`[0038] The rate of resorption can be controlled by the
`manufacturing techniques used to produce the bioabsorbable
`material. Alternatively, the inner material may be a substance
`that resorbs fairly quickly when in contact with bodily fluids
`or tissue, but surrounded by a more slowly resorbing outer
`shell or matrix that dissolves more slowly (thus governing the
`rate of the implants absorption). Various configurations and
`materials are also described in U.S. Pat. No. 6,638,308 to
`Corbitt Jr. et a!, which is hereby incorporated by reference.
`The rate ofbioabsorption may also be dictated by the rate at
`which tissue in-growth may occur (which fills the surgical
`defect as the implant resorbs).
`[0039] Regardless of the rate of resorption, having the
`implant largely bioabsorb means there is no second surgery to
`remove foreign material from the patient. The controlled
`absorption allows the implant to remain in place until radio(cid:173)
`therapy is complete, and in the case of breast radiotherapy, to
`replace the resected tissue until the body's healing response
`replaces it with fibrous tissue.
`[0040] The implant can be ideally inserted upon comple(cid:173)
`tion of the tumor resection, but prior to closing of the surgical
`wounds. If done in this fashion, one excellent embodiment of
`the invention is a preformed bioabsorbable implant having
`the desired size and shape, without need for the surgeon to
`alter it in any fashion prior to implant. Alternatively, the
`implant may be adjustable in terms of size or shape by the
`surgeon using surgical instruments readily available in most
`operating rooms (e.g., scissors), or by a special tool supplied
`
`with the implant (e.g., hemi-spherical cutting tool that rounds
`the edges of the implant as it is resized.
`[0041] As illustrated in FIG. 3, the implant 10 can be a
`single layer as illustrated on the right, or the implant 10 can be
`a multi-component system as illustrated on the left. For the
`multi-component system, a portion (e.g., the outer shell12) of
`the implant is inserted into the resection cavity and the inner
`bioabsorbable materials 14 infused or injected into the shell,
`causing it to attain its desired size and shape. One or both of
`these steps can be performed prior to closing the surgical
`wounds (open implantation) or both can be performed after
`closing (immediately post-surgically or after some time has
`passed following the surgery) using minimally invasive meth(cid:173)
`ods (e.g., laparoscopically or under ultrasound guidance). If
`these steps (or one step) are performed post-surgically, the
`implant or components of the implant can be inserted into the
`cavity using a variety of techniques. The preferred method
`involves using a trocar or cannula to access the cavity and
`provide a conduit for subsequent insertion of the implant or
`implant components.
`[0042] There are a variety of methods of interest to achieve
`a fully filled implant. The implant shell can be filled remotely
`using a syringe filled with the inner material. The syringe
`contents are injected into the implant shell via a long needle or
`cannula attached to the syringe and piercing the surface of the
`shell. Instead of a needle, a long flexible tube may be used.
`Also, a metering can system can be used. In this embodiment,
`a metering can contains a specific, excess volume of the inner
`absorbable material. A dial or meter adjustment can be made
`on the can that will allow the user to dispense a specified
`volume of inner material without having to further monitor
`the amount dispensed or how full the implant has become.
`[0043] A method according to the invention for treating
`these and other malignancies begins by surgical resection of
`a tumor site to remove at least a portion of the cancerous
`tumor and create a resection cavity as illustrated in FIG. 4. As
`illustrated, an entry site or incision 102 is created in patient
`100 in order to remove tissue and create an irregularly shaped
`cavity 104.
`[0044] Following tumor resection, as further illustrated in
`FIG. 5, an implant of the invention 10 is placed into the tumor
`resection cavity 104. This can occur prior to closing the
`surgical site 102 such that the surgeon intra-operatively
`places the device, or alternatively device 10 can be inserted
`once the patient has sufficiently recovered from the surgery.
`In the later case, a new incision for introduction of device 10
`can be created. In either case, the surface of device 10, which
`is preferably sized and configured to reproducibly position
`tissue surrounding the resection cavity 102 in a predeter(cid:173)
`mined geometry, is placed within the resected tissue cavity.
`[0045] Following insertion of the implant 10, such as by an
`open method or using a mini-open or minimally invasive
`procedure, the implant occupies the tissue cavity 102 and
`supports the surrounding target tissue 112 until such time as
`it resorbs or biodegrades. Where the implant 10 is sponge-like
`or porous, after initial implantation the patient's own fluids,
`fibroblast, and stem cells, such as adipocytes, vascular stem
`cells, and others, can permeate the implant. In the case of a
`small implant, such permeation would occur naturally, sub(cid:173)
`sequent to implantation. In the case of a larger implant, pro(cid:173)
`viding the implant at least partially filled with fluids prior to
`implantation may be indicated.
`[0046] With device 10 in place, it supports the target tissue
`112 surrounding the tissue cavity and reduce tissue shifting.
`
`Focal Exhibit 1011 Page 9
`
`

`

`US 2009/0024225 Al
`
`Jan. 22, 2009
`
`5
`
`In addition, the surface of device 10 can position the target
`tissue 112 in a predetermined geometry. For example, a
`spherical implant 10 as illustrated can position the target
`tissue 112 surrounding the tissue cavity 104 in a generally
`spherical shape. With the target tissue 112 positioned, a
`defined surface is provided so that radiation can more accu(cid:173)
`rately be delivered to the previously irregular tissue cavity
`walls. In addition, device 10 helps reduce error in the treat(cid:173)
`ment procedure introduced by tissue movement. The posi(cid:173)
`tioning and stabilization