Abstract:
A dose calculator for heavy-ion therapy systems uses a limited number of spread out Bragg peak models obtainable by a particular therapy system, the models which may be adjusted in energy (offset) and dose contribution (treatment time) to produce a unique composite dose having a complex dose profile with limited reduced time.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional application 60/990,121 filed Nov. 26, 2007 and hereby incorporated by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     The present invention relates to heavy-ion therapy systems for the treatment of cancer and the like, and in particular to a treatment planning tool for generating settings for particular dose profiles for heavy-ion beams. 
     External beam radiation therapy may treat a tumor within a patient by directing high-energy radiation in one or more beams toward the tumor. The radiation commonly may be photons, such as x-rays or electrons. 
     Standard electron beam and photon devices are often used to provide single energy beams during treatment. More complex dose patterns can be obtained, however, with combinations of beams of multiple radiation energy. U.S. Pat. No. 7,202,486 to Gentry et al. issued Apr. 10, 2007, entitled: Treatment Planning Tool For Multi-Energy Electron Beam Radiotherapy, assigned to the same assignee as the present invention and hereby incorporated by reference, describes a tool allowing a physician to combine multiple electron beam energies or combined electron/photon energies available on a standard, single beam radiotherapy system. The tool, which may operate on a stand-alone desktop computer, accepts a simple characterization of a desired beam depth dose profile and produces a treatment plan using multiple energies and that can be entered into a radiation therapy treatment planning system and implemented using successive exposures from the radiation therapy machine. The use of multiple energy beams allows for better dose conformance to a treatment zone. 
     Recent interest has developed in the use of protons or other heavy-ions for external beam therapy. Unlike electrons and x-rays, protons may be given sufficient energy to penetrate an arbitrary amount of tissue and then to stop within the tissue, eliminating exit dose through healthy tissue on the far side of a tumor. Further, the dose deposited by a proton beam is not uniform along the entrance path of the beam, but rises substantially at a “Bragg peak” near a point where a proton stops within the tissue. These two features allow improved concentration of dose within the tumor. 
     A mono-energetic beam of protons produces a narrow Bragg peak whose range (depth in the tissue) can be controlled by controlling the energy or acceleration of the protons. In theory, an arbitrary dose profile can be produced using a mono-energetic beam of protons by moving the beam in energy range and angle to dimensions to sequentially “paint” a treatment zone. By changing a dwell time of the proton beam at a particular location, an arbitrary dose profile may be produced. 
     Current proton therapy may alternatively use a “spread out Bragg peak” (SOBP) employing a poly-energetic proton beam having multiple Bragg peaks extending over a range of depths to produce a plateau of roughly constant dose. This approach accommodates poly-energetic proton sources and greatly simplifies the mechanics of treatment by allowing an entire tumor area, embraced by the plateau, to be treated simultaneously without complex movement of the beam. 
     Producing a spread out Bragg peak may be done, for example, by passing a mono-energetic or narrow poly-energetic beam of protons through a rotating wedge “propeller” that modulates the energy of the proton beam with constantly changing variable thickness of material or through a grid having varying thicknesses within the cross-section of the beam. The overall energy of the beam, and hence the center of the plateau may be adjusted in range or depth by using a bolus or movable wedge to center the spread out Bragg peak at the tumor. 
     Treatment planning using an SOBP beam simply requires adjusting the width of the plateau of the SOBP to cover the tumor and centering the range of the plateau on the tumor, and then applying the proton beam for a desired period of time to achieve a uniform tumor dose. 
     SUMMARY OF THE INVENTION 
     The present inventors have recognized that the approach of using an SOBP beam for treatment does not require a uniform dose to be applied to the area of the beam but that multiple successive applications of different SOBP beam profiles can be used to create more complex dose distributions. The present invention provides a tool for combining SOBP beams to realize more sophisticated treatments without the need for the complexity of equipment or planning required when using a mono-energetic beam. 
     Specifically then the present invention provides a treatment planning tool for use with a heavy-ion therapy machine producing a spread out Bragg peak (SOBP) beam where the treatment tool models one or more predefined SOBP dose profiles for a range of energies and treatment times, and mathematically combines the models of the SOBP dose profiles with different energies and/or treatment times to define a treatment profile that is not obtainable with one model at any given energy and treatment time. Identification of the models, the energies, and treatment times for implementation are output and used for sequential exposures on the heavy-ion therapy machine. 
     It is thus a feature of at least one embodiment of the invention to provide a middle ground between the alternatives of many exposures with mono-energetic proton beams and single exposures with flat profile SOBP beams. It is another feature of at least one embodiment of the invention to provide a system that may work effectively with a limited number of verified machine settings by providing models of those verified settings and combining those models. It is a further feature of at least one embodiment of the invention to provide an improved SOBP treatment protocol providing less abrupt distal treatment edges for better immunity to patient motion. 
     The models may employ the form: 
                 D   SOBP     ⁡     (   d   )       =       D   0       1   +       k   ⁡     (         d   a     -   d         d   b     -     d   a         )       p               
where:
     d a  is a distance along the beam of a proximal edge of an SOBP plateau;   d b  is a distance along the beam of a distal edge of an SOBP plateau; and   D 0  is a predefined normal dose value for a given treatment.   

     It is thus another feature of at least one embodiment of the invention to provide an analytic form for a spread out Bragg peak that may be applied to empirical measurements of machine performance (without knowledge of the underlying proton energy distributions) and that may be readily summed to produce a composite dose per the present invention. 
     In this model, k may be substantially 0.44 and p may be substantially 0.6. 
     It is thus a feature of at least one embodiment of the invention to provide a model suitable for protons in watery tissue. 
     The program may further output a graph of a depth-dose profile of combined sequential proton exposures and may also show a plot of a depth-dose profile of each constituent sequential proton exposure in isolation. 
     It is thus a feature of at least one embodiment of the invention to provide a simple display allowing verification by a physician and/or interactive adjustment of the constituent beams. 
     The program may further accept input from a user to select particular ones of the models, energy, and dose of the combined models. 
     It is thus a feature of at least one embodiment of the invention to allow manual combination of models and hence beams. 
     The program may accept a conformance limit defining a maximum variation in dose between the treatment profile of the composite beam and a desired dose over a depth range. 
     It is thus a feature of at least one embodiment of the invention to permit automatic construction of desired doses out of multiple models by providing a quantitative endpoint. 
     The models may be prepared by taking measurements on an ion-therapy machine at different settings and fitting them to mathematical functions or by entering pre-defined standardized data from the ion-therapy machine, i.e. “gold data”. Different models may be provided for each energy-spreading element of a heavy-ion therapy machine, for example. 
     Thus it is a feature of at least one embodiment of the invention to provide a system that may greatly simplify treatment planning by providing a range of dose profiles from a smaller number of relatively simple and well-characterized dose profiles. 
     These particular objects and advantages may apply to only some embodiments falling within the claims and thus do not define the scope of the invention. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a graph of dose vs. distance for a mono-energetic proton beam showing a resultant narrow Bragg peak that may be used to produce a complex dose profile to a tumor over many exposures; 
         FIG. 2  is a graph similar to that of  FIG. 1  for a weighted poly-energetic proton beam showing a spread out Bragg peak (SOBP) that may be used to deposit a uniform dose to a tumor with a single exposure; 
         FIG. 3  is a simplified cross-sectional representation of a standard heavy-ion therapy system using a propeller system to produce a spread out Bragg peak; 
         FIG. 4  is a figure similar to that of  FIG. 3  showing a dielectric wall accelerator based heavy-ion therapy system providing a spread out Bragg peak; 
         FIG. 5  is a block diagram of a standard desktop computer system suitable for implementing the present invention as a program; 
         FIG. 6  is a flow chart showing the steps of the execution of the program of  FIG. 5  implementing the present invention; 
         FIG. 7  is a graphical display on the computer of  FIG. 5  showing the combination of modeled SOBP models and manual controls to manipulate those models that may be implemented by the program of  FIG. 6  for production of a complex dose profile; and 
         FIG. 8  is a simplified perspective representation of treatment planning using the present invention along two beam axes. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Referring now to  FIG. 1 , a mono-energetic beam of protons provides a dose profile  10  indicating energy deposition by a mono-energetic beam of protons as a function of distance into normal tissue. For such a mono-energetic beam, the dose profile  10  will be a relatively sharp Bragg peak as is understood in art. By changing the energy of the mono-energetic beam, multiple such Bragg peaks  10 ′ may be produced at different distances or ranges in the tissue and, by controlling the flux of the beam or changing of the dwell time of the beams at each range, an arbitrary dose profile  12  may be created. 
     Increased treatment speed and simplicity of treatment planning and construction of the heavy-ion therapy machine may be provided by using a poly-energetic proton beam producing a spread out Bragg peak  14  having a plateau region  16  of substantially constant dose. The range of energies of protons within the beam may apply a substantially uniform dose profile  12  to a treatment area. 
     Referring now to  FIG. 3 , a heavy-ion therapy machine  20  for producing a spread out Bragg peak per  FIG. 2  may provide for a proton source  21  providing a proton beam  22  having a substantially uniform cross-section and area. Currently, such proton sources are particle accelerators such as synchrotron, cyclotron, or the like, but may include dielectric wall particle accelerators (DWPA) in the future. The proton beam  22  may pass through a range shifter  23 , for example, a movable wedge inserting a predetermined known thickness of material into the proton beam  22  to control its average energy E 0  and hence range, roughly according to the equation:
 
 R ( E )=α E   0   p   (1)
 
     where R is the range of the center of the Bragg peak and E 0  is the center energy of the poly-energetic beam. The value of p is approximately 1.8 for protons with energies between 10 and 200 Mev.             is approximately 1.9×10−3 for protons in water.
     The energy adjusted proton beam  22  may be received by a range spreader  24 , for example, a propeller of material rotating to rapidly vary a thickness of material inserted in the beam  22  thereby producing a varying energy of the beam  22  and, in turn, effectively spreading the length of the plateau of the SOBP as will be described. Range shifter  23  and range spreader  24  both vary the energy of the beam  22 ; however, range shifter  23  operates more slowly and may for example be maintained in a constant position determined by an operator during an exposure, while the range spreader  24  is in constant rotary motion during an exposure, sweeping through energy ranges at a much higher rate than the range shifter  23 . 
     The beam  22  may be received by a patient  19  to deposit energy in patient tissue according to a SOBP model  26 . Generally the SOBP model  26  will have a substantially constant plateau  27  defined with a width defined by a proximal edge at a depth da and a distal edge at a depth db and a height  28  determined by the total flux of protons during the exposure time. 
     The center of the plateau  27  will be determined by the range shifter  23  while the length of the plateau  27  will be determined by the range spreader  24 . Several different range spreaders  24  may be used to provide for different lengths of plateau  27  in the SOBP, for example, by replacing the propeller with one having different variations in material thickness or by changing the radius at which the beam  22  intersects the propeller for propellers whose thickness varies both circumferentially and radially. Other mechanisms may be used for range spreading, for example gratings having triangular grooves ruled in their surface to provide a statically variable width material. Spreading foils may be used to change the cross-sectional area of the beam  22  which will generally have a Gaussian profile. 
     Referring now to  FIG. 4 , in an alternative embodiment, the heavy-ion therapy machine  20 ′ may have a proton source  21  that is a dielectric wall particle accelerator (DWPA) such as is described in U.S. Patent Application 20070145916 to Caporaso et al. published Jun. 28, 2007 and entitled: “Sequentially Pulsed Traveling Wave Accelerator Producing Directly A Mono-Energetic Or Narrowly Poly-Energetic Proton Beam”. The DWPA may directly produce a mono-energetic or narrowly poly-energetic proton beam  22 . This beam  22  may be received by a range shifter  23  or range spreader  24  or these functions may be implemented electronically by control of the acceleration provided by the DWPA possibly with a filter/spreader  25  adjusting the weighting of a beam of energy swept protons. This embodiment may also be used to generate a SOBP model  26  with a substantially flat plateau  27  for ease of planning and treatment. The filter spreader may provide a weighting to different energies of protons to produce the flat plateau  27  of the SOBP model  26 . This SOBP model  26  may be desired even if a mono-energetic beam is possible either for simplicity of treatment planning or to simplify the validation of the beam strength as may be done easily for a limited number of settings. 
     Referring now to  FIG. 7 , the present invention allows SOBP models  26  to be combined to produce a more complex composite dose profile  30 , for example, having, in this example, greater dose (indicated by the height of the composite dose profile  30 ) at the center of a treatment region and a less abrupt distal edge to accommodate location error caused by patient motion or the like. The present invention aids in generating this complex composite dose profile  30  by permitting a summation of several SOBP models  26   a ,  26   b , and  26   c , each achievable with a different setting of the heavy-ion therapy machine  20 . Together, sequential exposures of the patient  19  with these settings will produce the complex composite dose profile  30 . 
     Referring now also to  FIG. 5 , the present invention is preferably implemented as a software tool to generate settings for a heavy-ion therapy machine  20  or  20 ′ that will produce a composite dose profile  30  matching a user-entered desired dose  80 . In the preferred embodiment, software  46  (including both a program and data structures) is executed on a standard desktop computer system  32  having a graphic display screen  36  that may display the representation of  FIG. 7  and a data entry device  38  such as a keyboard and trackball or mouse, and having a graphics tablet  39 , scanner, light pen, touch screen or other drawing input device for accepting hand-drawn inputs such as the desired dose  80 . The terminal  34  may communicate with a processor unit  40  including a processor  44  and memory  47 , the latter holding the software  46  including data files  56  and modeling program  50  reading the data files  56  and executing the method of the present invention. 
     The processor unit  40  may provide for a connection to an external device  55  to receive the data generated by the invention. The external device  55  may be as simple as a printer or may be control electronics for heavy-ion therapy machine  20  or  20 ′. The computer system  32  need not have direct electrical connection to the heavy-ion therapy machine  20  or  20 ′ of  FIGS. 3 and 4 , but the latter may instead receive data manually entered by an operator based on output from the present invention. 
     Referring now to  FIG. 6 , the method of the present invention starts with the collection of SOBP files  56  as indicated by process block  71 . As noted above, these SOBP files  56  hold normalized depth dose data for each SOBP model  26  taken along the central axis of the heavy-ion therapy machine  20  or  20 ′ for different settings. Generally for heavy-ion therapy machine  20 , a single SOBP model  26  will be obtained for each setting of the range spreaders  24  but one SOBP model  26  can be used and mathematically modified for different settings of the range shifter  23 . Alternatively, multiple profiles can be obtained for each particular setting of the range spreaders  24  and for various different settings of the range shifter  23 . For the heavy-ion therapy machine  20 ′, a single SOBP model  26  will be obtained for each filter/spreader  25  and possibly for different energy settings of the proton source  21 . Not all settings need to be modeled if a composite dose profile  30  can be adequately formed from a limited number of SOBP models  26 . 
     These SOBP models  26  can be expressed and stored as data points describing the curves shown in  FIG. 7  and thus serve as a numerical model for the behavior of the heavy-ion therapy machine  20  or  20 ′. Alternatively, if the SOBP models  26  have a substantially flat plateau  27 , the data may be approximated with an analytical model according to the following equation described in: “An Analytical Approximation Of Depth-Dose Distributions For Therapeutic Proton Beams” Bortfeld et al, Phys. Med. Biol. 41 (1996) 1331-1339: 
                       D   SOBP     ⁡     (   d   )       =       D   0       1   +       k   ⁡     (         d   a     -   d         d   b     -     d   a         )       p                 (   2   )               
where:
     d a  is a distance along the beam of a proximal edge of an SOBP plateau;   d b  is a distance along the beam of a distal edge of an SOBP plateau   D 0  is a predefined normal dose value for a given treatment;   k is substantially 0.44; and   p is substantially 0.6.   

     This equation provides a reasonably accurate description of a spread out Bragg peak to within plus or ±1.5% of D 0  so long as the quantity 
             (         d   a     -   d         d   b     -     d   a         )         
is less than 10.
 
     Using this analytical model, less data need be stored and the mathematical combination of different SOBP models  26  is greatly simplified. Another advantage of an analytic approach is that the SOBP models  26  may be easily extracted from actual measurements on a heavy-ion therapy machine  20  or  20 ′ by measuring distal and proximal edges of the profile of an actual beam together with the dose height  18 . 
     Generally the SOBP model  26  may be normalized to a standard dose value for a fixed period of time, for example, one second, allowing new SOBP models  26  to be created simply by multiplying the values of the SOBP model  26  by either number of seconds of exposure or the like. In addition each SOBP model  26  may be normalized to a standard center energy value E 0  so that SOBP models  26  shifted in range may be readily generated using equation (1). 
     The SOBP models  26  may be computed or measured for particular types of heavy-ion therapy machines  20  and  20 ′ and placed in different files  56  that may be selected among depending on the type of heavy-ion therapy machine  20 ,  20 ′ employed. Each SOBP model  26  may be identified to the particular settings (e.g. setting of range shifter  23 , range spreader  24  or filter/spreader  25 ) so as to be readily identifiable. In addition, the particular heavy-ion therapy machine  20 ,  20 ′ to which the modeled SOBP model  26  relates (e.g., manufacturer and model number) may be included in this identification of file  56  for use in facilities with multiple machines. 
     After the collection of the SOBP models  26   a - c , a proton treatment plan may be determined. As indicated by process block  72 , at the beginning of the treatment process, the user is prompted to enter a description of a desired dose  80 . Referring again also to  FIG. 5 , this description can be entered by drawing the desired dose  80  using the tablet  39  or other device, and this drawing is digitized for display on the screen  36 . At this time a dose conformance limit may be entered indicating how closely to this desired dose  80  the composite dose profile  30  should conform. 
     Referring now to  FIGS. 6 and 7 , at process block  74  all or selected SOBP models  26   a - c  may be displayed on the screen  36  at arbitrary energy and dose levels. The user may select the particular SOBP models  26  to use in forming the composite dose profile  30 . For this purpose, the screen may provide for user controls  75 , for example, a pair of controls  70 , for example virtual knobs, associated with each of the SOBP models  26   a - 26   c . These controls  70  allow adjustment of the energy E 0  (range) and treatment time to be assigned to each of the SOBP models  26   a - 26   c  in producing the composite dose profile  30 . Values for energy, treatment time and model identification are provided in corresponding text boxes  79  that change as the controls  70  are changed. A color-coding also may be used to associate controls  70  with particular curves of SOBP models  26   a - 26   c.    
     As the controls  70  are moved, a particular SOBP model  26  plateau  27  will move left and right (with energy) according to equation (1) widening and shrinking slightly. As the controls  70  are moved, the height of the plateau  27  will move up or down with respect to changes in treatment time for the particular associated SOBP model  26 . A plot of the changing SOBP model  26  may be generated from energy calculated points da and db and the normalized dose from equation (2) described above. 
     During this process, the selected SOBP models  26   a - 26   c  will be summed to produce a composite dose profile  30  which is plotted so that it can be conformed to the desired dose  80  also visible on the screen  36 . A quantitative conformance value  81 , for example integrating the error between the composite dose profile  30  and desired dose  80  may also be displayed. In this way, an individual may fit existing SOBP models  26   a - 26   c  representing achievable beams from the heavy-ion therapy machine  20  or  20 ′ to the desired dose  80 . 
     Alternatively, as indicated by process block  82  this matching may be automated through the use of a number of well-known algorithms, including for example a greedy algorithm starting with the SOBP model  26  having the largest plateau width  17  (greatest range spreading) that will fit within the dose profile  16 ′ which is adjusted in range and dose iteratively to fit appropriately with the desired dose  80 , then moving down the SOBP model  26  with respect to widths  17  to fit the difference between the desired dose  80  and the dose achieved so far. This approach may be rendered possible with normalized SOBP models  26  because of the great flexibility in shifting range and height of the normalized SOBP models  26 . In this process, the user may select the particular SOBPs models  26  to be used for the automated fitting process, and the number of different treatments (or SOBP models) that will be employed. 
     Multiple different combinations of SOBP models  26  may be generated and presented to the user for selection upon completion of the automatic fitting process. Each solution may indicate how closely it conforms to the entered dose profile  16 ′ with a display of a quantitative conformance value  81  (not shown). Each composite dose profile  30  may be a different color and presented with a corresponding number that maybe entered into the data entry device  38  to select that composite dose profile  30 . In the event that there is no solution within a pre-determined conformity limit, the user is informed of such and prompted to consider relaxing the conformity limit or to generate a different composite dose profile  30 . 
     If a solution is obtained either through block  74  or block  82  it is output at process block  86  for verification by the user. This verification process may include for example displaying the statistics indicating the conformity of desired dose  80  to composite dose profile  30  as well as the data provided by text box  79 . 
     As indicated by process block  88 , the data describing the particular SOBP models  26  and their energy and treatment times may then be entered as settings on a heavy-ion therapy machine  20  or  20 ′ and used to select range shifting per range shifter  23 , and energy spreading per range spreader  24  or filter/spreader  25 , or this information may be provided directly to the heavy-ion therapy machine  20  or  20 ′ for automatic implementation. 
     Referring now to  FIG. 8 , in an alternative embodiment the present invention may be incorporated into a treatment planning system  90  providing dose planning for treatments made along multiple axes  94   a  and  94   b . The treatment planning system  90  may also be executable on the processor unit  40  and may use the calculated total composite dose profiles  30   a  and  30   b  (along the different axes  90   a  and  90   b  to compute a dose applied to a particular region  92 ). In this case, the composite dose profile  30  will also include a cross-sectional profile  96  being generally a Gaussian distribution determined by the collimation of a proton beams. This information may be used to develop a two or three-dimensional dose profile  100  indicating the combination of dose deposited along with two different axes  94   a  and  94   b . Additional axes may also be incorporated into a complex treatment planning system  90 . 
     It will be understood that the present invention does not require the use of SOBP models  26  with flat plateaus  27  but may use beams modeled to have, for example, a declining plateau for better summation properties. In addition, the present invention may be used to provide modeling of electrons or photons in addition to the SOBP models for hybrid treatments. 
     It should be understood that the invention is not limited in its application to the details of construction and arrangements of the components set forth herein. The invention is capable of other embodiments and of being practiced or carried out in various ways. Variations and modifications of the foregoing are within the scope of the present invention. It also being understood that the invention disclosed and defined herein extends to all alternative combinations of two or more of the individual features mentioned or evident from the text and/or drawings. All of these different combinations constitute various alternative aspects of the present invention. The embodiments described herein explain the best modes known for practicing the invention and will enable others skilled in the art to utilize the invention.