Abstract:
An apparatus and method for treatment of lesions or imperfections in or near exposed anatomic surfaces using low-level ionizing radiation includes a substantially transparent applicator to administer radiation from an energy source to a surface area with the lesion. The applicator is positioned over the lesion to be treated, a treatment plan is created to achieve the desired therapeutic effect to the lesion, and execution of the treatment plan is executed by the energy source. Verification of the treatment to plan and safety methods are disclosed.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    This invention relates to the field of radiation therapy by means of ionizing radiation energy applied to tumors or other imperfections in skin or near-skin tissues, or in or near other exposed anatomical surfaces. 
         [0002]    For many years, a variety of skin or near skin medical conditions have been treated by application of superficial voltage (50-150 kV) or orthovoltage (150-500 kV) x-ray therapy. These methods have drawn criticism because their penetration depth often puts deeper tissues at risk. As a result, external electron-beam radiation has come into greater use because its characteristic penetration can more easily be controlled. Such radiotherapy often follows surgery to excise a tumor or other defect. Often, the radiation apparatus used for electron beam treatment purposes is large, unwieldy, and incapable of being directed to the lesion with precision. Because it is designed to deliver high-energy radiation, the patient usually must be extensively shielded except for the area of the tumor, and radiation safety may require such apparatus only be operated from within a shielded room or “bunker”, from which all personnel other than the patient must be excluded during active treatment. This creates a situation which can be highly intimidating or claustrophobic for the patient. Because of the capital investment required for such an installation, this sort of treatment is often unavailable in small clinic or office situations. Reduction in capital expenditure requirements and intimidation factors would be great improvements over current external beam practice. 
         [0003]    Furthermore, the available radiation output levels from such equipment may greatly exceed those required for the intended treatment, and output patterns are generally fixed. These output characteristics usually necessitate that the tumor be covered with radiation absorbing material such that the radiation intensity incident on the skin is more appropriate for the desired treatment. In addition, any necessary collimation of the radiation pattern to accommodate the patient&#39;s treatment requirements would be accomplished by conventional methods known to those of skill in the art. 
         [0004]    In use, the machine is positioned properly over the patient to assure protection of adjacent normal tissues, with the collimated beam passing through secondary shielding which is directed at the subject tumor site. The patient must not move once alignment is determined, otherwise the treatment is not delivered to the desired area. When all is ready, the therapist leaves the room, and treatment is initiated. Because of the number of parameters in play to produce a satisfactory treatment and the complexity of the treatment setup, the potential for error and therefore imprecision in dosage delivery is significant. Clearly, smaller apparatus specifically designed for treatment of lesions and not requiring such extensive setup, treatment expense or safety precautions would be preferred to the apparatus and methods described above. 
         [0005]    Contact applicators, usually including tungsten shielding, have been developed which utilize isotope (usually iridium) radiation sources (See Nucletron, Columbia, Md. 21046.) These applicators are difficult to position accurately over the lesion or imperfection to be treated, and as with high energy x-ray treatment, the characteristic penetration depth of iridium may well compromise underlying tissue. Use of isotopes like iridium in this manner will also require that treatment be carried out within a bunker as described above. 
         [0006]    It is an object of this invention to provide methods for identifying the region to be treated on the patient, planning the radiation therapy quantitatively to be administered within that region, and executing the therapy conveniently, and in a timely manner. A further object of this invention is to provide a method of treatment of surface lesions and imperfections utilizing x-rays having controlled, minimal depth of penetration and which eliminate many of the safety concerns common to prior art methods as described above. A further object is to provide a convenient applicator which can be positioned over the lesion or imperfection to be treated under direct visualization, assuring proper treatment of diseased tissues, but sparing adjacent tissues. Still further, it is an object of this invention to provide a record of the therapy delivered, and to verify that the treatment was to plan. 
       SUMMARY OF THE INVENTION 
       [0007]    Specifically, this invention encompasses methods for treatment of skin or near-skin lesions or imperfections and is directed to the use of small ionizing radiation sources, preferably miniature x-ray sources comprising elements such as those described in U.S. Pat. Nos. 6,319,188, 7,127,033 and/or 7,158,612, all of which facilitate such radiation therapy in small clinical settings and are herein incorporated in their entirety by reference. The preferred x-ray energy level is in the range of up to about 50 kV, with preferred treatment depths between the tissue surface and 5 mm depth. Such x-ray sources can be modulated with regard to penetration depth by varying x-ray tube voltage, and to incident dose intensity by varying tube current, although in practice, it may be preferable to adjust exposure time rather than varying tube current to achieve a prescribed absorbed dose. These sources can in general be switched on and off as needed. The principles underlying such tubes may be found in  Atoms, Radiation and Radiation Protection,    
         [0008]    Second Edition, by James E. Turner, printed by John Wiley &amp; Sons, 1995, incorporated herein in its entirety by reference. 
         [0009]    The preferred embodiment of this invention further comprises an applicator incorporating provision for positioning the radiation beam over the region to be treated under direct visualization. The applicator comprises a base, preferably of stainless steel, and optionally a thin polymeric cover on the working side of the base, having a generally planar distal face substantially in contact with the skin. In the center of the base is a window of a size and shape to expose the lesion to the radiation emitted from within the applicator. The window size and shape may be chosen by the therapist to suit the therapeutic needs of the patient, via interchangeable bases. Except for the window, the base is substantially radio-opaque. We have found a thickness of stainless steel adjacent the window on the order of 2 mm adequate to provide sufficient attenuation in a typical therapeutic situation. More highly attenuating materials, for example tantalum, would permit thinner sections having the same levels of attenuation. 
         [0010]    Proximal of the base of the preferred embodiment is an optically transparent housing preferably of leaded acrylic polymer (Nelco, Woburn, Mass.), or equivalent, through which the therapist may view the window overlying the lesion to achieve the alignment desired for therapy delivery. The attenuation of the leaded acrylic is preferably about 1/24 that of solid lead for equivalent thickness. The thickness of the acrylic housing therefore needs to be on the order of about 6 mm to sufficiently attenuate the back-scattered radiation. In positioning the applicator the therapist&#39;s view may be distorted, but it is still easy to observe and assure that the window circumscribes the desired treatment area. In an alternative embodiment without direct visualization, the housing may be of stainless steel or other materials as is further discussed below. In other respects, the embodiments are similar. In all embodiments described herein, it is preferable that elements in contact with or near the patient be capable of convenient sterilization, or be one-time-use components. 
         [0011]    The base and housing generally share a common axis which is substantially transverse to the area of skin to be treated. Proximal of the housing is a cup-shaped filter of a low Z material, for example aluminum (or other materials in accordance with the isodose shaping discussion below), and proximal of that, a tubular source guide leading to other treatment system elements including a source power supply and controller. The source guide contains the source on the end of its cable and any utilities or support functions necessary to operate the x-ray tube, such as the coolant and cooling apparatus necessary to cool the x-ray source tube. See U.S. Pat. No. 7,127,033. 
         [0012]    The aluminum filter may be contoured so as to shape the isodose patterns (imaginary surfaces of constant dose intensity), for example to flatten them, at the window where the radiation is incident on the skin, as well as distal of the applicator within the patient&#39;s body at or about the prescribed treatment depth. Further, the filter serves to strip off any low energy portions of the x-ray tube spectrum, hardening the beam in a conventional manner. The low energy elements of the unhardened spectrum are generally absorbed by the skin or other tissue which the beam initially encounters. With a hardened beam lacking these low energy components, the dose absorbed by the skin is reduced which may have cosmetic advantages or may even prevent substantial tissue inflammation. 
         [0013]    In instances where the prescription is specified as a skin dose, alternate filter materials, for example silver or molybdenum, can also be designed to shape the x-ray intensity patterns as described above. We have found that filters of these materials essentially do not harden the beam and leave the energy spectrum substantially unaltered. That means a similar beam shaped by a silver or molybdenum filter is more quickly absorbed at the skin with less energy absorbed at depth. Such attenuators are discussed in more detail in co-pending U.S. patent application Ser. No. 12/072,620, and that application is incorporated herein in its entirety by reference. 
         [0014]    When assembled and positioned properly over the lesion to be treated, the applicator may be held in position manually, clamped with respect to the operating table upon which the patient is lying, clamped with respect to the patient and his/her lesion, or otherwise supported. 
         [0015]    In an alternate embodiment, the base and/or window element may be eliminated, and the leaded acrylic housing may be in direct contact with the skin surrounding the lesion. 
         [0016]    In a further preferred embodiment, the applicator is similar to either of the descriptions above, but without optically transparent elements and therefore without provision for direct visualization. The applicator can optionally include targeting or reference marks which can be aligned with marks or features on the patient near the lesion to be treated. 
         [0017]    In a still further embodiment, the applicator can be used in conjunction with a flexible shield (see U.S. patent application publication No. 2007/0075277, for example, incorporated herein in its entirety by reference) having a window of the desired shape which is positioned on the patient to expose the lesion to be treated, and to protect adjacent tissue. The applicator is then placed over the window and held in position as described above. 
         [0018]    In all embodiments described above, the shape of the treatment window can be custom shaped to suit a given patient or lesion, or may be a member of a standard set of window shapes supplied as a kit. In the case of the flexible shield which can for example be of tungsten-loaded silicone rubber, a variety of silk-screened window patterns may optionally be printed on the sheet as supplied, such that the therapist can cut out a window in the shield to suit the case at hand. 
         [0019]    Furthermore, a beam shaping filter can be used in conjunction with the applicator embodiments described above to harden or not harden the transmitted x-ray beam, and/or to shape the isodose patterns to suit the prescription for the case at hand. The applicator can also be instrumented to control the progression of the therapy, including in real time, or to create a record of the therapy delivered for inclusion in the patient&#39;s records. These and other objects, features and advantages of the invention will be apparent from the attached drawings and description of preferred embodiments which follow. 
     
    
     
       DESCRIPTION OF THE DRAWINGS 
         [0020]      FIG. 1  depicts an applicator of a preferred embodiment of the invention in longitudinal (elevational) cross section. 
           [0021]      FIG. 2  depicts an applicator similar to that of  FIG. 1  instrumented with a radiation sensor that can be in communication with a central controller, and with a radio-chromic film used to create a record of the treatment delivered. 
           [0022]      FIG. 3  shows an alternate embodiment to that of  FIG. 1 . 
           [0023]      FIGS. 4   a, b,  and  c  show schematically various filters used to shape the x-ray beam emitted when used in conjunction with embodiments of the invention. 
           [0024]      FIGS. 5   a  and  b  show various silk-screened window patterns that can be placed on the surface of a flexible shield used in conjunction with applicators and/or methods of the invention. 
       
    
    
     DESCRIPTION OF PREFERRED EMBODIMENTS 
       [0025]      FIG. 1  shows a preferred applicator  100  of the invention comprising a base  102  which may be of stainless steel fastened on its proximal side to the distal end of a lead-loaded acrylic housing  104 , such as by screws  106 . Distal of the base is a preferably detachable window element  108 , preferably also of stainless steel and secured to the circular base  102  by screw threads  110  (the window element/base combination can be referred to as a “base” or “base end”, although the two preferably are separable components). The window  112  limits the projection of the x-ray beam incident on the patient&#39;s skin to the shape of the window. Although the circular (cylindrical) base with screw threads is preferred, other shapes can be used, with other securing means. 
         [0026]    Note also, the removable (and optionally interchangeable) window element  108  could be secured directly to the housing  104  if desired, by threads, machine screws, snap-on or otherwise. 
         [0027]    An optional x-ray-transparent, thin polymeric cover  114  is snapped onto the distal face of the window element  108 . This cover provides a level of cleanliness, and can be used to retain a radio-chromic film (not shown) as is discussed below. In use, the window element  108  (or cover  114 , if present) is in contact with the patient&#39;s skin and positioned such that the lesion to be treated is exposed in the window  112 . When in contact with the skin as described, the base and window element control both the shape and size of the incident beam onto the patient&#39;s skin, and substantially attenuate the beam elsewhere. 
         [0028]    Proximal of the acrylic housing  104  is a flanged sleeve  116 , the flange of which is used to secure the flanged sleeve to the acrylic housing  104  by screws  118 . Internally at its proximal end, the flanged sleeve  116  is fastened by screw threads  120  to an adapter  122 . The adapter serves several purposes. At its proximal end, the adapter  122  is permanently secured to the distal end of a source guide  124  as shown, by brazing, welding or silver soldering. Other conventional fastening methods, including by non-permanent screw-threads could also be used. The source guide could be non-metal. 
         [0029]    The adapter  122  extends distally through the lumen of the flanged sleeve  116  to external threads  126  used to mount a cup-shaped radiation filter  128  which has an internally threaded ring or rim  129 . Details of the radiation filter are discussed in greater detail below. If desired to protect the acrylic housing from undue radiation exposure, the distal end of the flanged sleeve  116  may be extended or configured relative to the filter in order to form an aperture limiting the spread of radiation within the housing such that radiation directly incident on the internal surface of the housing is reduced or eliminated. 
         [0030]    Note that the assembly shown and described constitutes one preferred way of connecting the source guide  124  to the housing  104  and base  102 ; other types of assemblies can be employed, preferably providing for a filter  128 , most preferably an interchangeable filter. 
         [0031]    Through the source guide  124 , a source catheter  130  is advanced until it abuts the inner side of the face of the radiation filter  128 . Within the source catheter are the source  132  mounted on its cable  134 , and any necessary x-ray tube utilities or apparatus necessary to support its proper functioning. 
         [0032]    In use, the therapist selects the window (from a plurality of sizes and/or shapes) appropriate to the case at hand and determines the prescription to be delivered. A series of different window elements  108  can be provided. If treatment merely consists of an x-ray intensity level and treatment time, the necessary parameters are input to the system for delivery of the prescription. If the prescription is more complicated, the necessary settings for treatment delivery may be preset or noted in a convenient manner for manual control. Preferably, the treatment plan may be entered into an automated controller (not shown) as part of a treatment system such that once initiated, the prescribed treatment is delivered automatically. 
         [0033]    Next, the elements of the applicator and source are assembled, and made ready for treatment delivery. The assembled apparatus is positioned over the skin area to be treated. By viewing the skin area through the housing (at least a portion of which is substantially optically transparent in a preferred embodiment), the operator correctly locates the applicator over the lesion to be treated. The applicator is then clamped in place, or alternatively, held in position manually, and treatment is initiated. At the conclusion of treatment, the x-ray emissions are switched off, and the apparatus is removed from the patient. 
         [0034]      FIG. 2  shows the applicator of  FIG. 1 , further comprising a radiation sensor  136 , which may be of the MOSFET type, mounted in the x-ray beam adjacent to the window of the window element  108 . Conventional wiring  138  is routed through passages in the applicator apparatus for connecting the sensor to treatment system elements (not shown). Depending on the treatment system design, the sensor can be used to control through feedback x-ray tube output following the treatment plan, to create a record of treatment delivered, or to provide a safety cut-off if radiation should exceed the levels permitted by the prescription. Use of radiation sensors in this manner is disclosed in greater detail in U.S. Pat. No. 7,322,929, which is incorporated herein by reference in its entirety. 
         [0035]      FIG. 2  further depicts a radio chromic film element  140  held in position between window element  108  and the polymeric cover  114 . Such film (preferably GAF chromic type EBT film, International Specialty Products, Inc., Wayne, N.J.) is responsive to incident radiation, and after exposure can be used as a record of the treatment delivered for inclusion in the patient&#39;s medical record. In order to provide film orientation with respect to the lesion being treated, match marks or keying features relative to known apparatus orientation can be provided to uniquely record treatment delivered. Such orienting techniques are familiar to those skilled in the art. 
         [0036]      FIG. 2  also shows a liner  139  inside an alternate, opaque housing. These elements are discussed in detail in connection with the description of  FIG. 5   a  below. 
         [0037]      FIG. 3  shows an alternate applicator apparatus embodiment  150  in which the housing  152  is in direct contact with the patient&#39;s skin  151 . In other respects, the flanged sleeve  116 , adapter  122 , and filter  128  are substantially the same as described with reference to  FIG. 1 . In this case the base end of the applicator is the skin-contacting end  153  of the housing  152 . As shown, the housing limits the x-ray beam incident on the skin to a small area rather than larger as shown in  FIG. 1 . In principle, however, window size and housing shape are independent of other features provided in either of the embodiments. Preferably, the housing  152  is transparent to visible light as in the embodiment of  FIG. 1 , and again, the window  154  is positioned over the skin lesion under direct visualization (with angled viewing through the housing  152 ). 
         [0038]      FIGS. 4   a, b  and  c  show variations in filter designs, and in general, the differences in isodose shapes which result.  FIG. 4   a  depicts a filter  160  having a flat, uniformly thick face  162  which attenuates uniformly. That is, the beam intensity is reduced, but its isodose surfaces  164  are substantially the same as those emanating from the unfiltered source.  FIG. 4   b  shows a similar filter  166  having a face  168  which is thicker in the middle than at its edges, and having the effect of flattening the shape of the isodose surfaces  170 . Flattening the isodose surfaces at the skin or treatment depth is a common objective in radiotherapy. It is clear that the degree of flattening is correlated with the filter face  168  contour, and that simple experimentation can be used to flatten or otherwise shape the isodose surfaces of sources having various emission characteristics. We have also found that stepped variations in filter face surfaces which approximate similar but continuously shaped faces produce substantially the same isodose surfaces. Such a stepped face is shown in  FIG. 4   c  where the filter  172  has a stepped face  174 . The isodose surfaces produced are very similar to those surfaces  170  of  FIG. 4   b.    
         [0039]    As described in the summary above, and in the aforementioned co-pending application Ser. No. 12/072,620, most low Z filter materials, such as aluminum for example, serve to conventionally harden the x-ray beam, that is they strip off low-energy portions of the emitted spectrum, which tightens the energy spectrum of what is transmitted through the filter. Since energy equates to penetration depth, such filters can be tuned to target a narrow penetration depth, thereby reducing the dose absorbed at the skin. As described in the referenced application, we have found that a few filter materials, notably silver and molybdenum, have little effect on the energy distribution of the transmitted beam, and can be effectively used where a skin dose is required, and to reduce the dose absorbed at depth. The beam shaping principles are the same with either sort of materials, but the ranges over which they are most useful to the therapist differ. 
         [0040]      FIG. 5   a  shows in plan view, a flexible shield  180  of tungsten-loaded silicone rubber, or as might otherwise be described in co-pending U.S. patent application No. 2007/0075277. Silk-screened on the surface is an exemplary pattern of radial lines  182  emanating from a center position which can be used for orienting the shield, and concentric, circular pattern of lines  184  which can be used by the therapist as a guide for cutting windows responsive to the patient&#39;s prescription and needs. When so prepared, the shield can be used to form a treatment window rather than using the window element  108  described above. Such use may eliminate the need for direct visualization through the applicator housing  104  or housing  152  during placement since the shield and window can be placed and secured over the lesion first, followed by positioning of the applicator using the silk screened lines on the shield for guidance. The outer silk-screened circle  185  may be sized to correspond with the outside diameter of the window element  108  of the applicator  100 , or of the polymer cover  114  if present (see  FIG. 1 ), and used to position the applicator. 
         [0041]    Without the need for visualization, the preferred applicator embodiment would be as shown in  FIG. 1 , except the housing may now be metallic, for example, stainless steel as described earlier. Further, it may be advantageous if the housing inner surface is of a low Z material like aluminum, since the portion of the x-ray beam incident on the housing inner surface will be at a small angle, Compton scatter may be expected and such scattered radiation will generally be directed at the edges of the window. Such scattered energy will therefore have an effect similar to a flattening filter, perhaps even eliminating the need for such a filter. A housing inner liner  139  is shown in  FIG. 2  and can be a machined part, for example, positioned within the housing at assembly, or alternatively, such a low Z layer can be added onto the housing by a conventional vapor deposition process. 
         [0042]    A flexible shield  180  ( FIG. 5   a ) can also be used in conjunction with the applicator embodiments of  FIGS. 1 and 3 , and since the shield contributes importantly to the overall attenuation, including shielding the tissue outside the applicator itself, the thickness (hence attenuation value) of the applicator elements can likely be reduced making the shield/applicator combination more ergonomically attractive. 
         [0043]      FIG. 5   b  depicts a flexible shield  186  similar to that of  FIG. 5   a,  but having an exemplary silk-screened pattern of concentric oval (racetrack shaped) lines  188  to facilitate cutting oval masks. Other patterns may also be used if the level of need justifies the differentiation. Again, as with the circle  185  of  FIG. 5   a,  the outer silk-screened circle  189  may be sized to assist in positioning the applicator with respect to the oval window formed in the shield  186 . 
         [0044]    Several different combinations of features have been incorporated in the different embodiments described above. In principle, these may be included in different combinations, or the elements arranged in different configurations relative to one another but such that the functions of each are still effective. 
         [0045]    The above described preferred embodiments are intended to illustrate the principles of the invention, but not to limit its scope. Other embodiments and variations to these preferred embodiments will be apparent to those skilled in the art and may be made without departing from the spirit and scope of the invention as defined in the following claims.