Patent Publication Number: US-2023141197-A1

Title: Computer-implemented method for radiotherapy treatment planning, computer program product and computer system for performing the method

Description:
TECHNICAL FIELD 
     The present invention relates to a computer-implemented method for radiotherapy treatment planning, and to a computer program product and an apparatus for carrying out such a method. In particular, the invention relates to treatment planning for radiotherapy that involves both external beam radiation therapy and brachytherapy for the same patient. 
     BACKGROUND 
     Most radiotherapy treatment is provided as external radiation that is delivered to a patient from an external source, known as external beam radiotherapy or EBRT. This is normally delivered in a number of fractions, for example, 15, 30 or more fractions. Alternatively, radiation may be delivered from a source that is placed within the patient. This is known as brachytherapy and involves placing one more needles or other type of equipment within the target in the patient to expose it to radiation from within. This is normally performed in a smaller number of fractions, for example, 1 or 3. 
     For EBRT treatment, planning is currently mostly performed as an inverse planning process in an optimization treatment planner. The aim is normally to achieve a minimum dose, or an even dose, over the whole target. Brachytherapy or BT planning requires the placement of equipment for providing radiation within the target, either physically or in a virtual environment and the dose is normally developed in a forward planning process in which the positions of the equipment and the dose resulting from it is determined. In low dose rate BT, one or more sources, known as seeds, are implanted into the target, and normally remain there for the foreseeable future. On the other hand, in high dose rate BT and pulsed dose rate BT, the radiation is delivered by radioactive sources moving through hollow channels in the implanted equipment, which consists of e.g. needles, catheters and applicators. Normally, the BT dose distribution is not uniform but is instead concentrated around the implanted equipment. 
     It is known in the art to combine EBRT and brachytherapy in the same patient. Typically, the EBRT fractions are delivered first and then the brachytherapy, but the opposite order is also possible. During the first treatment, the patient geometry will normally change. Also, the equipment inserted into the patient for brachytherapy will change the shape of the target and the surrounding tissue. For both these reasons, the two modalities will be delivered to different patient geometries. In the cases where both brachytherapy and external radiation treatment are used on the same patient, traditionally two separate treatments plans are developed, one for the EBRT portion of the treatment, and one for the brachytherapy portion of the treatment. These are typically based on a total dose and a predetermined division of the dose between the different types of treatment. For example, a total dose of 80 Gy may be set, where EBRT treatment is to contribute 60 Gy and brachytherapy the remaining 20 Gy. 
     It is an object of the present invention to provide an improved planning method for a radiotherapy treatment involving both EBRT and brachytherapy. 
     SUMMARY OF THE INVENTION 
     The invention relates to a computer-based method of optimizing a radiotherapy treatment plan for a patient, comprising the steps of
         a) determining, based on at least a first medical image of the patient, a dose previously delivered to the patient by means of a first radiation set,   b) obtaining a first optimization problem comprising an optimization function designed to optimize the dose distribution resulting from the second radiation set in dependence of dose criteria set for a total dose and of the previously delivered dose, the total dose being the dose resulting from the second radiation set and the previously delivered dose,   c) optimizing the treatment plan for delivering radiotherapy by the second radiation set by means of the first optimization problem, wherein the optimization function is an objective function or a constraint and one of the first and the second radiation set is brachytherapy and the other is external beam radiation therapy.       

     This will improve the planning of the treatment to be delivered by the second radiation set by taking into account treatment already delivered by the first radiation set. The previously delivered dose may be estimated or calculated by means of any suitable method. 
     In preferred embodiments, the first optimization problem comprises an optimization function designed to optimize the dose distribution resulting from the second radiation set to match the difference between the desired total dose distribution as expressed by the dose criteria and the previously delivered dose. This will provide an actual total dose resulting from the combined dose delivered by both radiation sets, that is a good match for the desired total dose distribution. 
     The dose criteria are preferably based on at least an earlier medical image taken before the delivery of the first radiation set. 
     According to preferred embodiments, the method further comprises the following steps, before step a):
         d) obtaining an initial optimization problem comprising an optimization function designed to optimize the total dose distribution as a combination of a first dose distribution to be provided by the first radiation set and a second dose distribution to be provided by the second radiation set   e) optimizing the treatment plan as a combination of the first and the second radiation set by means of the initial optimization problem.       

     This will further improve the planning by considering both radiation sets already when planning for the dose to be delivered by the first radiation set. 
     The at least one first medical image may comprise at least one image taken of the patient after delivery of the first portion. This will provide the most correct information on the actual patient geometry. 
     Alternatively, or in addition, the at least one first medical image may comprise at least one simulated image based on an estimate of patient&#39;s geometry after delivery of the portion. This is suitable if, for some reason, it is not feasible to take a new image of the patient after delivery of the portion, or with the brachytherapy equipment inserted. 
     In preferred embodiments, the method comprises deforming at least one of the doses delivered by the first and second radiation set, respectively, to obtain a common geometry for the treatment portions and accumulating them using a biological model, the optimization function being a set of penalties on the accumulated doses and on the radiation set-specific dose from the second radiation set. Normally, the dose of the second radiation set will be deformed to the first medical image. 
     Preferably, robust planning is used to take into account uncertainties in the placement of brachytherapy equipment, in the EBRT delivery, and/or in determined delivered dose. how to implement robust planning is known in the art. 
     The invention also relates to a computer program product comprising computer-readable code means, which when run in a computer is arranged to make the computer perform a method according to any of the embodiments above. The computer program product may be stored on any suitable type of non-transitory storage medium. 
     The invention also relates to a computer system comprising a processor and at least one program memory, characterized in that the program memory holds a computer program as defined above. 
     In preferred embodiments, the invention involves planning of brachytherapy planning in which the accumulated dose already delivered to the patient by some other modality is also taken into account. This means that deviations from the planned dose to the target may be compensated for, but also that a too high dose to an organ at risk may be compensated for by changing the brachytherapy treatment plan accordingly. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
       The invention will be described in more detail in the following, by way of examples and with reference to the appended drawings, in which 
         FIGS.  1     a,    1   b  and  1   c  are sections through a medical image of a patient. 
         FIG.  2    is a flow chart of an general embodiment of the method. 
         FIG.  3    is a flow chart of a more specific embodiment of the method including EBRT followed by BT. 
         FIG.  4    is a flow chart of a second more specific embodiment of the method including BT followed by EBRT. 
         FIG.  5    is a schematic overview of a computer system in which embodiments of the invention may be implemented 
     
    
    
     DETAILED DESCRIPTION OF EMBODIMENTS 
     External beam radiation treatment, EBRT, involves providing radiation to the patient in the form of a beam delivered from the outside. The radiation may be any type of radiation, including photons, electrons, protons or other ions. Brachytherapy, BT, involves the insertion of some type of equipment into the target within the patient, and using said equipment to provide the radiation from one or more points within the target. This equipment may include a number of small needles and/or catheters, one or more larger applicators, one or more seeds, or any combination of the different types of equipment. Depending on the number and size of the devices, the target as well as the surrounding patient geometry will be deformed. 
     Due to the different natures of the two radiation sets, the planning of EBRT and BT use different treatment parameters. Treatment parameters for EBRT treatment include beam and beam limiting device configurations. Treatment parameters for BT treatment include variables such as equipment position and dwell times. Each radiation set typically involves radiation being delivered in one or more fractions, typically but not necessarily, a higher number for EBRT than for BT, which may even be delivered in one single fraction. 
     As discussed above, inverse planning using an optimization problem is common for EBRT planning but is not traditionally used for brachytherapy. The dose distribution EBRT could be expressed as 
         d   EBRT   =d   EBRT ( x   EBRT )   (1)
 
     and the dose distribution for brachytherapy could be expressed as 
         d   BT   =d   BT ( x   BT )   (2)
 
     where x EBRT , x BT  are treatment parameters for the respective treatment form. 
     The invention relates to simultaneous optimization of the treatment parameters for EBRT treatment and BT treatment. This means that the optimization problem can be expressed as Eq. (3) 
     
       
         
           
             
               
                 
                   
                     min 
                     
                       
                         x 
                         EBRT 
                       
                       , 
                       
                         x 
                         BT 
                       
                     
                   
                   
                     f 
                     ⁡ 
                     ( 
                     
                       
                         d 
                         
                           E 
                           ⁢ 
                           BRT 
                         
                       
                       , 
                       
                         d 
                         
                           B 
                           ⁢ 
                           T 
                         
                       
                     
                     ) 
                   
                 
               
               
                 
                   ( 
                   3 
                   ) 
                 
               
             
           
         
       
     
     where x EBRT  are the treatment parameters for the EBRT subportion of the treatment and x BT  are the treatment parameters for the BT subportion of the treatment. d EBRT  and d BT  are the doses for the EBRT subportion and the BT subportion, respectively. Instead of the dose d, some other parameter related to the respective subportion may be used. 
     Typically, the optimization includes deforming the doses to a common geometry and accumulating them using a biological model, the objective function being a set of penalties on the accumulated doses and on the radiation set-specific doses. 
       FIGS.  1     a,    1   b  and  1   c  are simplified examples of medical images taken at different points in the inventive procedure, as will be discussed in more detail in connection with  FIG.  2   .  FIG.  1   a    is a section  11  through a schematical medical image of a patient&#39;s abdomen, with a target  13  and an organ at risk  15  pointed out, to be used for treatment planning according to embodiments of the invention.  FIG.  1   b    is a corresponding section  11 ′ through a medical image of the same patient after a first type of treatment, illustrating schematically the changes that this treatment may have caused to the patient&#39;s geometry. As will be understood, the target  13  has shrunk because of the treatment, which is usually the desired result.  FIG.  1   c    is the corresponding section  11 ″ of a medical image of the same patient with needles inserted into the target for providing brachytherapy to the patient. The needles are shown as small dots  17  within the target. As can be seen, this also changes the geometry of the target  13 ″ and of the region of the patient surrounding the target. 
       FIG.  2    is a flow chart of an overall method according to an embodiment of the invention. 
     In a first step S 21 , an image of relevant portion of the patient, such as the one discussed in connection with  FIGS.  1   a - 1   c    is obtained. In step S 22 , dose criteria for a total dose distribution to be delivered as a combined plan including both EBRT and brachytherapy is determined. 
     In step S 23 , the optimization problem is defined, based on the image or images and dose criteria for the desired total dose. Dose criteria are set as common in the art. They typically include a minimum dose for all voxels of the target and often a maximum dose for one or more organs at risk. For example, the dose criteria may specify a total dose of at least 60 Gy in each target voxel, and that at most 30% of an organ at risk is subjected to a total dose of more than 40 Gy. Dose criteria may also include a partial or complete dose distribution. In S 24  the treatment plan is optimized using the optimization problem. The optimization problem includes an objective function such as function (3) above. 
     In step S 25 , a part of the treatment plan is delivered to the patient and in step S 26  the accumulated dose delivered to the patient from the part of the treatment plan is estimated. The accumulated dose may be determined in any suitable way. Methods of doing this are well known in the art and are typically based on at least one medical image, for example a number of fraction images taken throughout the delivery of the first portion of the treatment plan. 
     In step S 27 , a new image of the same portion of the patient is obtained, to see the new patient geometry after the partial delivery in step S 25 . If applicable, other modifications may be made, such as the insertion of brachytherapy equipment and an image reflecting the resulting geometry may be taken. The new image may be an image taken of the patient at this stage, or a synthetic image based on estimates of the new patient geometry. 
     In step S 28  the remainder of the treatment plan is optimized again, using an inverse planning method based on an optimization function that will be discussed in more detail below. The planning takes into account the accumulated dose of the partial delivery that has been performed previously. The optimization problem should then include an objective function according to the following: 
     
       
         
           
             
               
                 
                   
                     min 
                     
                       x 
                       
                         B 
                         ⁢ 
                         T 
                       
                     
                   
                   
                     g 
                     ⁡ 
                     ( 
                     
                       
                         d 
                         
                           RS 
                           ⁢ 
                           1 
                         
                         delivered 
                       
                       , 
                       
                         d 
                         
                           RS 
                           ⁢ 
                           2 
                         
                       
                     
                     ) 
                   
                 
               
               
                 
                   ( 
                   4 
                   ) 
                 
               
             
           
         
       
     
     where d RS1   delivered  is the delivered dose from the first radiation set, determined in step S 26  and d RS2  is the dose to be delivered by the second radiation set. 
     where g is another objective function, which may or may not be equal to f and the delivered dose from the first radiation set over all fractions (either measured or estimated) is used a as a fixed background dose for the planning for the second radiation set. 
     In step S 28 , the reoptimized remainder of the plan is delivered to the patient. 
       FIG.  3    is a flow chart of an embodiment of the inventive method in which the total treatment plan includes first EBRT treatment and then BT treatment. The input data S 31  to this plan include a current medical image of the patient, dose criteria for a desired dose distribution, and a prediction model of the patient geometry after the EBRT treatment. The prediction model may be an adjusted or synthetic medical image. The input data may also include a prediction model of the patient geometry after the EBRT treatment with the EB equipment included. The medical images may be CT images, or any other suitable image modality, such as MR or ultrasound images. 
     In a method step S 32  the optimization problem is obtained based on the dose criteria and the input data. The optimization problem includes an objective function according to Eq. (3) based on the total dose of both the EBRT and the BT subportions of the treatment, and optionally the dose to be delivered for each radiation set. This typically includes deforming at least one of the doses d EBRT  and d BT  to a common geometry and accumulating them using a suitable biological model. This may include setting a combination of penalties on the accumulated doses and on the specific doses. Models for establishing a common geometry are known, typically including deformable registration of the images. Models for determining the accumulated dose are also known to the skilled person. For example, the biological concept EQD 2  may be applied to give an estimate of the total effective dose. 
     In a subsequent method step S 33 , optimization is performed based on the common geometry and accumulated dose. The optimization problem includes an objective function according to Eq. (3) above. As will be understood, the objective function could also be extended to depend on the treatment parameters and the optimization problem may also include constraints depending on dose or treatment parameters. The output S 34  from the optimization step S 33  is a total treatment plan including one subportion for each radiation set, that is one EBRT subportion and one BT subportion. Each subportion includes the portion of the dose to be delivered by the corresponding radiation set and the number of fractions in which to deliver it. 
     The EBRT subportion of the treatment plan is then delivered to the patient, in a step S 35  and the actual delivered dose from this delivery is determined or estimated in a step S 36 . Preferably, the situation after the EBRT delivery is assessed and used to refine the BT subportion of the treatment plan as outlined in the following steps. 
     In step S 37 , updated images of the patient after the EBRT treatment are obtained. These include a new image of the patient to account for the geometric changes that occurred during EBRT treatment. It also includes an image of the patient with the BT equipment inserted, since the BT equipment will cause an amount of deformation of the target and the surrounding patient geometry depending on the type of equipment. 
     In a subsequent step S 38 , the BT subportion of the treatment is reoptimized taking into account the delivered dose from step S 35  and the new images obtained in step S 37 . The optimization problem in this case includes an objective function expressed as Eq. (2) below: 
     
       
         
           
             
               
                 
                   
                     min 
                     
                       x 
                       
                         B 
                         ⁢ 
                         T 
                       
                     
                   
                   
                     g 
                     ⁡ 
                     ( 
                     
                       
                         d 
                         
                           E 
                           ⁢ 
                           B 
                           ⁢ 
                           R 
                           ⁢ 
                           T 
                         
                         delivered 
                       
                       , 
                       
                         d 
                         
                           B 
                           ⁢ 
                           T 
                         
                       
                     
                     ) 
                   
                 
               
               
                 
                   ( 
                   5 
                   ) 
                 
               
             
           
         
       
     
     where d EBRT   delivered  is the delivered dose determined in step S 35 . 
     The output from step S 38  is a new optimized BT treatment plan S 39 , which is preferably delivered to the patient. 
     As discussed for  FIG.  2   , the steps S 36 -S 39  may be performed without first performing the preceding steps, that is, the BT plan may take previous EBRT treatment into account even if there was no initial combined planning of the two. 
       FIG.  4    is a flowchart of a method in which the first radiation set to be delivered is the BT. The input data S 41  to this plan include a current medical image of the patient, and a medical image of the patient with the BT equipment inserted, and dose criteria for a desired dose distribution. Preferably, the input data also include a prediction model of the patient geometry after the BT treatment. The medical images may be CT images, or any other suitable image modality, such as MR or ultrasound images. 
     In a method step S 42  the optimization problem is defined in a manner similar to step S 32 . When the BT dose portion is delivered first, the image of the patient with the BT equipment inserted is already available as input. These images can be deformably registered to provide a geometric correspondence between the treatment geometries. As in step S 32 , the doses d EBRT  and d BT  are deformed to a common geometry and accumulated using a suitable biological model. This may include setting a combination of penalties on the accumulated doses and on the specific doses. Models for establishing a common geometry are known, typically including deformable registration of the images. Models for determining the accumulated dose are also known to the skilled person. 
     In a subsequent method step S 43 , optimization is performed based on the common geometry and accumulated dose. The optimization problem includes an objective function according to Eq. (3) above. As will be understood, the optimization problem could also be extended to depend on the treatment parameters and also include other objective functions and/or constraints. The output S 44  from the optimization step S 43  is a total treatment plan including one subportion for each radiation set, that is one BT subportion and one EBRT subportion. 
     The BT subportion of the treatment plan is then delivered to the patient, in a step S 45 , and the actual delivered dose from this delivery is determined or estimated in a step S 46 . Preferably, the situation after the BT delivery is assessed and used to refine the EBRT subportion of the treatment plan as outlined in the following steps. 
     In step S 47 , an updated image of the patient after the BT treatment is obtained, to account for the geometric changes that occurred during BT treatment. 
     In a subsequent step S 48 , the EBRT subportion of the treatment is reoptimized taking into account the delivered dose from step S 45  and the new image obtained in step S 47 . The optimization problem in this case includes an objective function expressed as Eq. (2) below: 
     
       
         
           
             
               
                 
                   
                     min 
                     
                       x 
                       
                         B 
                         ⁢ 
                         T 
                       
                     
                   
                   
                     g 
                     ⁡ 
                     ( 
                     
                       
                         d 
                         
                           B 
                           ⁢ 
                           T 
                         
                         delivered 
                       
                       , 
                       
                         d 
                         
                           E 
                           ⁢ 
                           B 
                           ⁢ 
                           R 
                           ⁢ 
                           T 
                         
                       
                     
                     ) 
                   
                 
               
               
                 
                   ( 
                   6 
                   ) 
                 
               
             
           
         
       
     
     where d BT   delivered  is the delivered dose determined in step S 45 . 
     The output from step S 48  is a new optimized EBRT treatment plan S 49 , which is preferably delivered to the patient. 
     As discussed for  FIGS.  2  and  3   , the steps S 46 -S 49  may be performed without first performing the preceding steps, that is, the EBRT plan may take previously delivered BT treatment into account even if there was no initial combined planning of the two. 
     It would also be possible to create a plan where the BT and EBRT fractions were not given as two consecutive sub-portions and instead the BT fractions were distributed between the EBRT fractions. In this type of treatment, the subportion or subportions of the treatment that have not yet been delivered can be reoptimized taking into account the delivered dose. Both the delivered and the nondelivered subportion of the treatment will typically be a combination of BT and EBRT. The optimization in this case includes an objective function expressed as Eq. (7) below 
     
       
         
           
             
               
                 
                   
                     min 
                     
                       
                         x 
                         EBRT 
                       
                       ⁢ 
                       
                         x 
                         BT 
                       
                     
                   
                   
                     g 
                     ⁡ 
                     ( 
                     
                       
                         d 
                         
                           B 
                           ⁢ 
                           T 
                         
                         delivered 
                       
                       , 
                       
                         d 
                         
                           E 
                           ⁢ 
                           B 
                           ⁢ 
                           R 
                           ⁢ 
                           T 
                         
                         delivered 
                       
                       , 
                       
                         d 
                         
                           B 
                           ⁢ 
                           T 
                         
                       
                       , 
                       
                         d 
                         
                           E 
                           ⁢ 
                           B 
                           ⁢ 
                           R 
                           ⁢ 
                           T 
                         
                       
                     
                     ) 
                   
                 
               
               
                 
                   ( 
                   7 
                   ) 
                 
               
             
           
         
       
     
     In all of the above methods, the simultaneous optimization should be performed with some care, to ensure that the individual doses of each radiation set are still satisfactory on their own. One possible adverse effect of co-optimization would be an EBRT dose with cold spots in the targets that are to be later filled in by the BT dose. This could be mitigated by incorporating robustness into the model against e.g. the uncertainty of equipment positioning and the deforming effect of the equipment. Treatment-specific objective functions are also a possibility (analogously to the current beam set-specific objective functions). 
     As with any radiotherapy treatment planning there will be sources of uncertainty, including the placement of the patient, the positioning of the BT equipment and the estimated delivered dose. To compensate for this, robust planning may be used. In particular, the deformation between the images will result in an approximate accumulated dose, the quality of which depends on the accuracy of the deformable registration. To avoid over-optimizing on an accumulated dose that differs from the dose that will actually be delivered, methods for robust planning over a representation of the uncertainty could be employed. Various degrees of refinement could be used, for example:
         Margins could be applied, as an ITV over predicted images, or just smearing of the regions to be treated.   Robust planning using scenarios generated as rigid shifts of the patient geometry, may be applied, independently for each of the radiation sets.   Robust planning using scenarios generated by multiple deformable registrations could be applied. In the case where the EBRT partial dose is delivered before the BT partial dose, this would involve utilizing multiple predictions. In the case where the BT partial dose is delivered before the EBRT partial dose, this would involve or using perturbations of the registrations between the acquired images. The deformations can also come from anatomical changes during EBRT, e.g. tumor shrinkage.       

     The method according to embodiments of the invention may also be combined with multi-criteria optimization. In this case the navigation could take place on several fronts, with several trade-off objectives targeting either the total dose or either of the individual treatment doses. 
       FIG.  5    is a schematic representation of a computer system in which the inventive method may be performed. A computer  31  comprises a processor  33 , connected to a first and a second data memory  34 ,  35  and a program memory  36 . Preferably, one or more user input means  38 ,  39  are also present, in the form of a keyboard, a mouse, a joystick, voice recognition means or any other available user input means. The user input means may also be arranged to receive data from an external memory unit. 
     The first data memory  34  comprises necessary data for performing the method, such as the necessary images. The second data memory  35  holds data related to one or more current patients for which treatment plans are to be developed. The program memory  36  holds a computer program arranged to make the computer perform the method steps, for example, as discussed in connection with any of the  FIGS.  2 ,  3  and  4   . 
     As will be understood, the data memories  34 ,  35  as well as the program memory  36  are shown and discussed schematically. There may be several data memory units, each holding one or more different types of data, or one data memory holding all data in a suitably structured way, and the same holds for the program memories. One or more of the components may be found in a cloud environment, as long as the components are able to communicate with each other.