Patent Publication Number: US-2023158334-A1

Title: A method of generating a radiotherapy treatment plan for a patient, a computer program product and a computer system

Description:
TECHNICAL FIELD 
     The present invention relates to a method of producing a radiotherapy treatment plan and a method of training a machine learning system, and to a computer program product and a computer system 
     BACKGROUND 
     Treatment planning is an important part of preparing for radiotherapy treatment and to an increasing degree involves the use of machine-learning. In such cases it consists of two main stages: dose prediction for producing a desired dose distribution and dose mimicking for producing a deliverable and physically feasible treatment plan based on the desired dose. These two stages are performed completely independently of each other. 
     Dose prediction may be machine learning based and produces a desired spatial dose distribution adapted to the patient geometry, according to a model that has been learned from a dataset of delivered doses. Dose mimicking uses the desired dose distribution as input to an optimization process. This stage is typically computationally heavy and time-consuming. The optimization problem is designed to take into account optimality criteria including the machine constraints of the delivery system and the physicality of the radiation delivery process and typically some other optimality criteria to determine a treatment plan that will result in an optimal deliverable dose to the patient. 
     US patent publication No. 2019/192880 and EP publication 3 628 372 disclose machine learning based dose prediction methods in which the machine learning systems have been trained using training sets comprising image data and a desired result, being trained to minimize the difference between the output based on image data and the known desired result. 
     The resulting dose from the optimization usually deviates from the predicted dose distribution because of various optimality factors tailored to what is physically and technically possible, which are applied at the dose mimicking stage. If the resulting deliverable dose is not useful, it may be difficult to determine whether the error occurred in the dose prediction stage or the dose mimicking stage. 
     SUMMARY OF THE INVENTION 
     It is an object of the invention to enable faster and more reliable treatment planning using a machine learning system. 
     The invention relates to a computer-based method of generating a radiotherapy treatment plan for a patient, said plan comprising providing radiation to a patient from a radiation source, the method comprising the steps of
         dose prediction by using a machine learning system to generate a predicted dose distribution or a set of irradiation parameters that can be used to generate a dose prediction for the patient dependent on patient geometry, based on a medical image and structure data comprising at least one delineated structure of the patient;   dose mimicking by using the predicted dose distribution and/or set of irradiation parameters to generate a deliverable treatment plan, wherein   the dose prediction step involves using a machine learning system that has been trained to consider at least one optimality criterion related to physical or technical restrictions that will affect the delivery of the treatment plan.       

     The invention also relates to a method of training such a machine learning system training a machine learning system for use in radiotherapy treatment planning, comprising the steps of
         providing a set of input data related to a medical image of a patient, structure date comprising at least one delineated structure of the patient, and a desired dose distribution dependent on patient geometry, determined on the basis of the medical image, to a machine learning system,   comparing the output from the machine learning system to the desired dose distribution and feeding the result of the comparison to the machine learning system,   wherein the set of input data further comprises at least one optimality criterion related to physical or technical restrictions that will affect the delivery of the treatment plan, and the training comprises training the machine learning system to consider the at least one optimality criterion related to physical or technical restrictions that will affect the delivery of the treatment.       

     According to the invention at least one of the factors that are normally taken into account in the dose mimicking step is introduced in the dose prediction step. This is in contrast to prior art methods in which the dose prediction step is based only on patient geometry, whereas the physical and technical restrictions associated with the delivery process are not considered until the dose mimicking step. By considering at least some of these restrictions already in the dose prediction step, the planning method will return a predicted dose that is closer to a dose that can actually be delivered to the patient to produce the desired result, or a set of irradiation parameters that may be used to determine such a predicted dose. Preferably, the set of irradiation parameters comprises sufficient information to determine the predicted dose. As a result, the dose mimicking step can be made faster while also returning a dose that better matches the predicted dose. 
     In preferred embodiments, the machine learning system comprises a non-trainable layer based on a dose function for the patient and is arranged to output a fluence distribution for each beam, spot positions and weights for each beam and energy or a set of brachy seed positions and dwell times, depending on the type of radiotherapy, and/or a dose distribution. 
     In a preferred embodiment, the machine learning system is a neural network that has been designed to consider at least one technical constraint of a delivery system to be used when delivering the treatment as the optimality criterion. 
     The training of the machine-learning model preferably comprises refining an optimization process, wherein the optimization procedure is based on an optimization problem comprising an optimization function related to the at least one optimality criterion. 
     The method of the invention also reduces the number of factors that may cause the deliverable dose to deviate from the predicted dose distribution by ensuring that some of the factors that influence dose mimicking are also considered in the dose prediction step, thereby enabling easier evaluation of machine learning models. Also, the learning process can be constrained since only the space of physically feasible solutions has to be searched, which makes it possible to produce good generalizations based on fewer patients than with conventional systems. 
     In preferred embodiments, the at least one optimality criterion includes parameters related to the physicality of the delivery process, including the interaction of the patient&#39;s geometry and the properties of the radiation source and the output from the dose prediction step, is expressed as a dose distribution or a set of irradiation parameters, or both. This means that the properties of the radiation source, including the type of radiation, and the effect of the radiation on the patient&#39;s body, is considered in the dose prediction step. The at least one optimality criterion may instead, or in addition to this, include one or more of the technical constraints of the system used for delivering the radiotherapy, such as the machine constraints of a delivery system. This means that the predicted dose will be closer to something that can actually be delivered by the delivery system. In preferred embodiments, optimality criterion or criteria are included in the optimization problem in the form of at least one constraint related to the optimality criteria. 
     The method is applicable to conventional radiation therapy planning using external beams and also to brachytherapy. It may be used for photon-based treatment plans and for particle-based treatment plans including plans using protons, neutrons or charged ions such as carbon or helium ions. 
     In a first preferred embodiment, the factor that is taken into account in the dose mimicking step is the physicality of the delivery process, which will affect factors such as path loss. This is done by considering the mapping function from irradiation parameters to dose distribution, which for photon radiation therapy may be described by a dose matrix. 
     This embodiment takes into account that the process generating the dose is either a set of beams producing photons or ionized particles, or, in the case of brachytherapy, a source of radioactive material inside the body. Therefore, the dose will be distributed according to the laws of physics that govern the spreading of radiation into matter. This is to a great extent dependent on the properties of the parts of the patient&#39;s body affecting the radiation. As is well known, the irradiation is affected differently by passing through, water, air, bone, fat or other types of tissue. 
     In a second preferred embodiment, the factor that is taken into account in the dose mimicking step is the deliverability of the dose. This is done by considering the properties of the delivery system. In this way it can be ensured that the predicted dose is one that is deliverable with respect to the machine constraints. 
     Both factors, the geometry and the deliverability, may be considered together. Preferably, they are considered again in the dose mimicking step in the conventional way to ensure the best possible plan. This will be faster than in prior art systems because the deliverable dose that forms input data to dose mimicking is created taking the physicality and/or the machine constraints into account. 
     The invention also relates to a computer program product comprising computer readable code means which, when run in a computer, will cause the computer to perform the method of generating a radiotherapy treatment plan as discussed above. The invention also relates to a computer program product comprising computer readable code means which, when run in a computer, will cause the computer to perform the method of training a machine-learning model as discussed above. The computer program products may be stored on any type of suitable carrier, for example, a non-transitory carrier. The invention also relates to a computer system comprising a processor, a program memory and a data memory, wherein the program memory comprises one or both such computer program product. 
    
    
     
       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. 
         FIG.  1    is an overview of a procedure of dose prediction and dose mimicking. 
         FIG.  2    illustrates the structure of a U-Net neural network adapted for use in an embodiment of the invention. 
         FIG.  3    is a flow chart of a method according to an embodiment of the invention. 
         FIG.  4    is a schematic drawing of a computer system which may be used according to the invention. 
     
    
    
     DETAILED DESCRIPTION OF EMBODIMENTS 
       FIG.  1    is an overview of a prior art method of dose prediction and dose mimicking. Input data to the procedure include at least one of a medical image S 11  and structure data S 12 . The medical image S 11  is a medical image of a portion of a patient, such as a CT image or an MR image. Structure data include delineated structures of the patients, of one or more regions of interest (ROI). These input data are used in a dose prediction step S 13  that is performed in a machine learning system to generate a predicted dose which is a spatial dose adapted to the patient&#39;s geometry. The output from the dose prediction step S 13  is a predicted dose S 14 , or a set of irradiation parameters that may be used in a subsequent step (not shown) to generate a predicted dose. The predicted dose S 14  is used as input data to a dose mimicking step S 15 , which generates a deliverable treatment plan S 16  for the patient. As is common in the art, the dose mimicking step is designed to ensure that the treatment plan comes as close as possible to producing the desired dose distribution, taking into account the actual physiological and technical conditions. This means that the dose mimicking step is typically designed to enforce the following criteria:
         the dose distribution resulting from the interaction of the irradiation with the patient tissue, taking the geometry and anatomy of the patient into account,   the physicality of the radiation source,   the deliverability of the plan with respect to the machine constraints of the delivery system that is to be used,   the optimality criteria with respect to the predicted dose,   other optimality criteria such as radiobiological effect (RBE)       

     The radiation source may be any known radiation source used for radiotherapy, including a device for providing an external beam to the patient or a radiation source introduced into the patient&#39;s body for brachytherapy. The radiation provided may be photon or ion based. 
     According to the invention at least one of the factors that are normally taken into account in the dose mimicking step S 15  is introduced in the dose prediction step S 13  to increase that chance that the predicted dose is close to an actually deliverable dose. 
     In a first preferred embodiment, the invention involves considering physical descriptors in the dose prediction stage, together with the physicality of the source of radiation. That is, the combined properties of the source of radiation and how it interacts with the patient tissue. The physical descriptors are given by the dose function 
         d = f ( x ) 
     where x is the set of treatment parameters, d is the resulting dose distribution in the patient, and f is the mapping function from treatment parameters to dose. The physical descriptors of the patient may come from any suitable source, typically from a medical image of the patient taken at an earlier point in time or in connection with the treatment planning. The medical image may be, for example, a planning image acquired for the initial treatment planning, or a fraction image taken before the delivery of a fraction, or a combination of two or more such images. 
     As a first possible implementation, an approximation of the dose mapping function f(x) could be introduced as a non-trainable layer in the machine learning system. For this embodiment, the machine learning system is preferably a neural network, which in the case of photon radiotherapy planning is arranged to output a desired fluence instead of the desired dose, as is done conventionally. In this case, accordingly, the output S 14  from the dose prediction step, would be a desired fluence map instead of a predicted dose distribution. The dose mimicking step could in this case be adapted to work either on the dose distribution or on the fluence map, or on both. 
     A second possible implementation of the first embodiment would be to introduce a metric related to the difference between the output of the dose function and the dose, that is, |f(x)−d| as a penalty term part of the loss function for the machine learning system. The metric may, for example, be the absolute value of the difference, but any suitable metric may be used. For this second option, any optimization-based machine learning system could be used. Alternatively, a method based on a combination of machine learning and constraint satisfaction programming could be used. In this case d=f(x) would be imposed as a hard constraint in the machine learning system during training, so that the constraint would be an intrinsic part of the trained model. 
     In a second preferred embodiment, the invention involves considering machine constraints of the delivery system in the dose prediction stage. The machine constraints involve such factors as how much and how fast components of the delivery system, such as gantry and collimator leaves, can move. The machine constraints could be added to the optimization problem of any optimization-based machine learning system as an objective function or, preferably, as a constraint, to be treated analogously to the physics constraints discussed above. 
     The first and second preferred embodiments can be implemented independently of each other but can also be used together, to ensure that the predicted dose takes into account both the physicality of the patient and the technical constraints of the delivery system. 
       FIG.  2    illustrates a simplified architecture of a neural network known as a U-Net, adapted for use according to embodiments of the invention. The basic function of a U-Net is known to the skilled person and will only be discussed in general terms. As is common in the art, the U-Net comprises a number of layers;  FIG.  2    shows a model with four layers. As will be known to the skilled person, the U-Net has a contracting path  21 , the leftmost leg of the U and an expanding path  23 , the rightmost leg of the U shape shown in  FIG.  2   . The contracting path consists of repeated application of convolutions  211 ,  213 ,  215 , each followed by a rectified linear unit (ReLU) and a max pooling operation, as will be known to the skilled person. During the contraction, the spatial information is reduced while feature information is increased. The fourth layer is the fully contracted layer  220 . The expansive pathway  23  combines the feature and spatial information through a sequence of up-convolutions  231 ,  233 ,  235  and concatenations with high-resolution features from the contracting path. The uppermost layer  235  of the expanding path includes a concatenation function and a convolution function as is common in the art, and the output of this according to embodiments of the invention will be a predicted dose  236 . The predicted dose is input to a non-trainable layer  237  arranged to calculate irradiation parameters  239  based on the predicted dose. The irradiation parameters may be used to control dose delivery. 
     As explained above, input data to the machine learning model will include a medical image and structure data related to the patient. 
       FIG.  3    is a flow chart of a method of training the machine learning system according to embodiments of the invention. The training preferably comprises refining an optimization process, wherein the optimization procedure is based on an optimization problem comprising an optimization function related to at least one optimality criterion. In a first step S 31 , a set of input data is provided to a machine-learning system that is to be trained. The set of input data is related to a medical image of a patient, a structure data set, and a desired dose distribution dependent on patient geometry, determined on the basis of the medical image. According to embodiments of the invention, the set of input data also comprises at least one optimality criterion related to physical or technical restrictions that will affect the delivery of the treatment plan. 
     In step S 32 , the machine learning system produces an output based on the input data. In step S 33 , the output from step S 32  is compared to a desired dose distribution already available and in step S 34  the result of the comparison is fed to the machine-learning system as feedback. 
     The at least one optimality criterion may be related to the combined effect of the properties of the radiation source and the geometry of the patient. Alternatively, or in addition, the at least one optimality criterion may be related to the technical constraints of a delivery system to be used when delivering the treatment. Preferably, as shown in  FIG.  2   , the machine learning system includes a non-trainable layer based on a dose function for the patient and the machine learning system is arranged to output a predicted dose distribution or a set of irradiation parameters that can be used to generate a dose prediction for the patient to be used as input data to the dose mimicking stage. 
       FIG.  4    is a schematic representation of a computer system in which the inventive method may be performed. A computer  31  comprises a processor  33 , a data memory  34  and a program memory  35 . Preferably, a user input means  37 ,  38  is 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. It should be understood that  FIG.  4    is only provided to illustrate different components that may be used to implement the method according to the invention and that the actual computer architecture can vary. One or more of the components, or the whole system, may be implemented in a cloud environment. 
     The data memory  34  typically comprises the necessary input data and the output data from the dose prediction step, as well as the treatment plan. The treatment plan may be generated in the computer  31 , or received from another storage means in any way known in the art. As will be understood, the data memory  34  is only shown schematically. There may be several data memory units, each holding one or more different types of data, for example, one data memory for the input data, one for the dose distribution or irradiation parameters, etc. 
     The program memory  35  holds a machine learning system as discussed above and a dose mimicking program. As will be understood, the data memory  34  and/or program memory  35  are not necessarily part of the same computer as the processor  33 , and may be located in any computer that is reachable from the processor, such as in a cloud environment.