Method, computer program product and computer system for radiation therapy planning and radiation therapy delivery system

Abstract

The invention relates to a method, a computer program product and a computer system for radiotherapy planning and a radiotherapy delivery system. A radiation therapy treatment planning method for implementing a FLASH radiation therapy treatment plan, the method involving the use of an optimization problem to optimize the plan, the optimization problem aimed at maximizing the portion of the radiation that will be delivered under FLASH conditions, in particular to a hazardous organ, to minimize damage to the hazardous organ.

Description

[0001] This application is a divisional application of the application which entered the Chinese national phase on July 28, 2022, with PCT application number PCT / EP2021 / 056609, international application date March 16, 2021, Chinese application number 202180011568.1, and invention name “Methods, computer program products and computer systems for radiotherapy planning, and radiotherapy delivery systems”. Technical Field

[0002] The present invention relates to radiation therapy planning, and in particular to methods for generating radiation therapy treatment plans involving radiation under FLASH conditions, computer programs and computer systems for executing such plans, and radiation therapy delivery systems for delivering such treatment to a patient. Background Art

[0003] Radiotherapy treatment always involves delivering doses to healthy tissues outside the target area or to dangerous organs, so there is always a risk that healthy organs or tissues are damaged by radiation. An emerging treatment method that seems to involve less adverse damage is FLASH therapy, which involves treatment at a much higher dose rate than conventional therapy, such as 70Gy / s. In the literature related to FLASH, various lower limits of dose rates are suggested, such as at least 40Gy / s or 50Gy / s. For example, if a dose of 20Gy is to be delivered at a dose rate of 70Gy / s, the entire dose will be delivered within 0.29s. In contrast, conventional radiotherapy treatment is delivered at a much lower dose rate, and the typical dose rate of conventional radiotherapy treatment is several Gy per minute. It has been found that with FLASH therapy, the damage caused to healthy tissues by a specific dose is lower than that of conventional therapy, while the effect on the target area, i.e., the tumor tissue response, remains unchanged, although the mechanism behind it is not yet fully understood.

[0004] Vozenin et al.: Advantages of FLASH radiotherapy in small pigs and cats with cancer, HALID: hal-01812514, https: / / hal-univ-rennes1.archives-ouvertes.fr / hal-01812514v2 confirmed the differential effects between normal tissue and tumors treated with FLASH, which had been previously demonstrated in mice and can also be seen in pigs and cats.

[0005] The dose delivered to the risk organs under FLASH conditions may cause less damage by a factor of about 30%. Therefore, the equivalent harmful dose to the risk organs is higher than the physical dose, in this case 1 / 0.7 times the physical dose.

[0006] Published U.S. Patent Application No. 2019 / 0022411 also relates to FLASH therapy, which is said to reduce side effects at the same dose. Dose rates of 40 Gy / s or higher are mentioned, up to over 500 Gy / s, allowing dose fractions to be delivered in a fraction of a second. Radiation can be delivered via multiple beams from different angles. The problem of overlapping beams near the target is discussed, resulting in higher doses than required in the overlapped areas. The planning method focuses on minimizing the overlap between beams outside the target by taking into account the geometry of the patient and target as well as the beam angles. Summary of the invention

[0007] It is an object of the present invention to provide a FLASH therapy that exploits the positive effects of this therapy modality in the best possible way by reducing damage to healthy tissue while maintaining the response in the target area.

[0008] The present invention relates to a computer-based method for creating a radiotherapy treatment plan for a patient, the plan involving FLASH therapy provided as at least a first beam so that a portion of the radiation will be delivered as FLASH radiation, the method comprising defining a desired dose distribution including a target dose prescription, and optimizing the plan using an optimization problem designed to minimize the dose to at least one organ at risk while maximizing the FLASH portion of the dose to at least one organ at risk while adhering to the target dose prescription.

[0009] As will be explained below, when FLASH therapy is delivered to a patient, due to the nature of dose delivery, a portion of the radiation dose will be delivered to each voxel at a lower non-FLASH dose rate. The total effective dose (TED) is defined as the sum of the FLASH portion and the non-FLASH portion of the equally effective dose. As mentioned above, FLASH doses involve much higher dose rates than conventional therapy, for example, 40Gy / s or 50Gy / s or even up to 500Gy / s or more. This means that a typical dose can be delivered to a patient much faster than with conventional therapy. Since radiation delivered under FLASH conditions is less damaging to tissue than conventional non-FLASH radiation for the same dose, the present invention aims to maximize the portion of radiation delivered under FLASH conditions to at least one organ at risk. Assuming that the dose remains unchanged, this will minimize damage to the organ at risk. At the same time, the optimization must also ensure that the target volume receives the prescribed dose.

[0010] A key factor in dose planning is how to achieve a desired dose distribution in the patient that best matches the required dose distribution. Dose distribution-based optimization generally achieves a more optimal dose distribution than only considering patient geometry and beam geometry to avoid overlap between beams. Therefore, the method according to the present invention will produce a better treatment plan than the methods known in the prior art.

[0011] As will be discussed below, both the dose rate and the temporal structure of dose delivery are important in achieving the effectiveness of FLASH therapy.

[0012] In a preferred embodiment using proton radiation, the optimization problem is defined as optimizing for a relative biological effectiveness, RBE, dose. RBE is a measure of the harm caused by a specific dose relative to a reference dose, and is different for different types of radiation, and for FLASH and non-FLASH. For photons under non-FLASH conditions, the RBE is 1. For non-FLASH proton therapy, current clinical practice for us is a factor of 1.1, meaning that 70Gy delivered as non-FLASH proton radiation corresponds to 77Gy delivered as non-FLASH photon radiation.

[0013] In some embodiments, the optimization problem includes an objective function designed to maximize the FLASH portion of the plan. Alternatively, the optimization problem includes an objective function designed to minimize the non-FLASH portion of the plan. As will be appreciated, these are just two different ways of expressing the same goal, since the total dose will be the sum of the FLASH portion and the non-FLASH portion.

[0014] The optimization problem can, as the case may be, be designed to maximize the FLASH portion or minimize the non-FLASH portion by optimizing or selecting one or more of the following:

[0015] Spot size

[0016] Spot shape

[0017] Spot arrangement

[0018] Spot weight

[0019] Beam arrangement with respect to energy, number of beams and / or direction of beams

[0020] Alternatively or additionally, the optimization problem may be defined as maximizing the FLASH portion or minimizing the non-FLASH portion by optimizing or selecting the order in which the spots are scanned.

[0021] A plan with at least a first beam and a second beam, both of which include a FLASH portion, can be optimized. These can be delivered by a rotatable gantry or by two radiation sources positioned at an angle to each other. In the latter case, the two beams can be delivered with a very short interval between them to enhance the FLASH effect.

[0022] It is also possible to optimize a plan comprising at least a first beam and a second beam, wherein the first beam comprises a FLASH portion and the second beam comprises only conventional non-FLASH radiation. In this case, the optimization problem is preferably arranged to minimize the total effective dose from both the FLASH therapy portion and the conventional therapy portion of the first beam and the second beam in at least one organ at risk.

[0023] The invention also relates to a computer program product comprising a computer readable code, which, when executed in a processor of a computer, causes the processor to perform a method according to any of the above embodiments. The computer program product may comprise a non-transitory storage device having a code stored thereon. The invention also relates to a computer system comprising a processor, at least one data memory and a program memory, wherein the program memory comprises such a computer program product.

[0024] The present invention also relates to a system for delivering radiotherapy treatment to a patient, the system comprising a radiation source. The radiation source may be arranged in any suitable manner, such as in a gantry or by a fixed beamline, wherein the radiation source is arranged to provide radiation at a sufficiently high dose rate to provide FLASH treatment to the patient, the system further comprising a computer for controlling the system, the computer comprising a processor and a memory, the memory comprising a treatment plan obtained by an embodiment of the above method. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The present invention will be described in more detail below by way of examples and with reference to the accompanying drawings.

[0026] Figure 1 is a flow chart of a method according to the present invention.

[0027] Figure 2 The temporal structure of dose delivery is exemplified by pencil beam scanning.

[0028] Figure 3 A computer system which may be used for dose planning according to the invention is schematically shown.

[0029] Figure 4 A delivery system useful for dose delivery according to the present invention is shown. DETAILED DESCRIPTION

[0030] In FLASH therapy, the radiation dose of the entire treatment process can be delivered as one ultra-high dose in less than a second, or as multiple beams with high dose rates and delivered with short time intervals between them. In this case, short should be understood as much shorter than the normal time required to rotate the gantry from one beam angle to another, which is usually about 30 seconds. In this case, the high dose rate is assumed to be above 40Gy / s, but it may be much higher. This means that the delivery time of a specific dose using FLASH therapy will be much lower than conventional therapy. For example, in conventional therapy, a dose of 2Gy can be delivered as continuous radiation in about a minute, while a FLASH dose of 2Gy will be delivered in a fraction of a second, and if the dose rate is 40Gy / s, it will be delivered in 1 / 20 of a second. Since FLASH therapy means that the effective dose to the target area is close to the physical dose, while the effective dose to the surrounding healthy tissue is reduced by about 30%, the advantage of this therapy is that it reduces the damage to healthy tissue. The time range of FLASH dose delivery should be on the order of magnitude between milliseconds and seconds.

[0031] Figure 1 An example of the temporal structure of FLASH radiation for an individual voxel in a patient (e.g., a voxel within an organ at risk) is shown as a dose rate per time unit (cGy / s). The radiation is delivered in the form of a pencil beam scan, which means that part of the delivery will only partially hit the voxel, while other parts will hit closer to the center of the voxel. Those radiations that only partially hit the voxel will result in a lower dose rate and therefore a lower dose to the voxel, typically a non-FLASH level, while those radiations that hit closer to the center of the voxel will have a higher effective dose rate to the voxel, and therefore provide a higher dose, which will constitute the FLASH component. Figure 1 In the example shown, there is first a non-flash component of 0.1 s, followed by two higher peaks with sufficiently high dose rates to constitute FLASH radiation, in this example between 0.18 s and 0.2 s, reaching about 7000 Gy / s instantaneously, and finally a lower non-FLASH component of about 0.22 s. As will be appreciated, there may be more or fewer FLASH and non-FLASH components, but in practice there will always be at least one of each. A similar temporal structure for conventional non-FLASH dose delivery would be a substantially straight line at, for example, 2 Gy over a longer period of time, for example, within a minute.

[0032] In general, the total effective dose TED to dangerous organs can be expressed by the following formula:

[0033] TED = x*D(non-FLASH) + y*D(FLASH)

[0034] Where D(non-FLASH) is the physical non-FLASH dose component to the voxel and D(FLASH) is the physical FLASH dose component. x and y are factors that model the RBE of the individual components. This means that x and y represent the total effective dose of the non-FLASH component and the FLASH component, respectively, relative to the physical dose of that component. A typical value for y is 0.7. For photons, x = 1, and for charged particles, x is slightly higher than 1, e.g., for protons, x is 1.1.

[0035] Therefore, according to the present invention, a FLASH therapy treatment is planned by means of an optimization problem designed to provide a desired dose to the target volume at a high dose rate as described above in a short time (usually less than 1 s) while maintaining the total effective dose of the surrounding tissue at an acceptable level for healthy tissue (including any organs at risk). This is done in part by exploiting the fact that the total effective dose from the FLASH component is lower than the total effective dose from the non-FLASH component relative to the corresponding actual dose component. The dose can be delivered as one beam or multiple beams. To achieve this, the optimization problem includes an objective function designed to maximize the FLASH component in at least one organ at risk. As will be appreciated, this can also be expressed as minimizing the non-FLASH component in at least one organ at risk. As is common in the art, this goal can be achieved in different ways, including optimizing one or more of the following:

[0036] Spot scanning sequence, and / or

[0037] Spot arrangement and / or

[0038] Spot weight and / or

[0039] Beam arrangement with respect to beam energy, beam direction and / or number of beams

[0040] Spot shape

[0041] Figure 2 is a schematic flow chart of a method according to the present invention. In a first step S21, a desired dose distribution is defined for a specific patient. In a second step S22, an optimization problem is defined. In a third step S13, a dose optimization is performed based on the optimization problem.

[0042] In a first embodiment, the optimization problem is designed to output a plan for FLASH therapy only. FLASH therapy can be delivered in one beam or multiple beams from the same or different angles. In a second embodiment, the optimization problem is designed to output a plan that combines at least one beam involving FLASH therapy and at least one beam at a conventional non-FLASH dose rate.

[0043] In particular, the optimization should result in treatment plans that include a FLASH component in areas with organs at risk. By replacing conventional therapy with FLASH treatment in these areas, damage to tissue in these areas can be reduced. This is particularly important in areas where the dose is so high that damage to one or more organs at risk is likely. The risk is particularly high near the target volume, where beams aimed at the target volume from different angles may overlap.

[0044] As discussed above, the optimization problem is preferably designed so that the FLASH effect is maximized while adhering to the target dose prescription. For proton radiation, this means that the optimization problem can be designed to also consider the relative biological effectiveness (RBE) of the dose, which for FLASH therapy is a function of both the dose rate and the temporal structure of the radiation, as well as other factors such as tissue type and radiation type. Other factors can also be considered. The time frame for dose delivery should be on the order of milliseconds to seconds.

[0045] The goal of treatment plan optimization is to achieve the desired dose in the target volume while minimizing the total effective dose in at least one organ at risk, where the total effective dose is the sum of the FLASH dose component adjusted for the FLASH effector and the conventional therapy component of the treatment. One way to achieve this is to use different types of scorers in the dose engine. For example, in a Monte Carlo dose engine, this would involve scoring the following:

[0046] - The voxel-wise energy deposition time trace is decomposed into time segments of, for example, approximately milliseconds.

[0047] - The concept of visceral dose, where visceral may mean non-FLASH dose in organs at risk.

[0048] The Monte Carlo simulation follows the paths of the different particles, including the direction and energy of the particles, the type of particles and the physical effects of the particles. Those skilled in the art will be able to implement this in other types of dosing engines.

[0049] Figure 3 3 is a schematic diagram of a computer system that can perform the method of the present invention. The computer 31 comprises a processor 33, first and second data memories 34, 35 and a program memory 36. Preferably, there are also one or more user input devices 38, 39 in the form of a keyboard, a mouse, a joystick, a voice recognition device or any other available user input device. The user input device 38, 39 can also be arranged to receive data from an external memory unit.

[0050] The first data memory 34 comprises the necessary data for performing the method, typically comprising the desired dose distribution and segmented patient images. The second data memory 35 holds other data, such as RBE information. The first program memory holds a computer program arranged to cause a computer to perform the method steps according to some embodiments of the invention.

[0051] As will be appreciated, the data memories 34, 35 and program memory 36 are schematically shown and discussed. 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 manner, as well as the program memory. Both the program and the data may be found in one or more memories within the computer system or in another unit accessible from the computer system.

[0052] Figure 4 8 is an overview of a system 80 for radiation therapy treatment and / or treatment planning. As will be appreciated, such a system may be designed in any suitable manner and Figure 4 The designs shown in are merely examples. Patient 81 is positioned on a treatment couch 83. The system includes an imaging / treatment unit having a radiation source 85 mounted in a gantry 87 for emitting radiation to the patient positioned on the couch 83. Typically, the couch 83 and the gantry 87 can be moved relative to each other in several dimensions to provide radiation to the patient 81 as flexibly and correctly as possible. These parts and their functions are well known to those skilled in the art. The main difference between the system used in the context of the present invention and a conventional radiotherapy delivery system is that the system according to the present invention is suitable for delivering a much higher dose rate than that performed according to conventional radiotherapy. The appropriate size of the dose rate is discussed above.

[0053] There are typically a number of passive devices for shaping the beam laterally and in depth, which will not be discussed in further detail here. Means are arranged for providing a beam grid, for example in the form of grid blocks, or means for providing a pencil beam. The system further comprises a computer 91 which may be used for radiotherapy treatment planning and / or for controlling the radiotherapy treatment. As will be appreciated, the computer 91 may be a separate unit not connected to the imaging / treatment unit.

[0054] The computer 91 comprises a processor 93, a data memory 94 and a program memory 95. Preferably, there are also one or more user input devices 98, 99 in the form of a keyboard, a mouse, a joystick, a voice recognition device or any other available user input means. The user input device may also be arranged to receive data from an external memory unit.

[0055] The data storage 94 includes clinical data and / or other information used to obtain the treatment plan or related to the plan itself. Typically, the data storage 94 includes one or more patient images to be used in the treatment planning according to an embodiment of the present invention. The program storage 95 stores at least one computer program arranged to cause the processor to control the delivery system according to the optimized treatment plan.

[0056] As will be appreciated, the data memory 94 and program memory 95 are shown and discussed schematically only. There may be several data memory units, each storing one or more different types of data, or one data memory storing all data in a suitably structured manner, as well as the program memory. One or more memories may also be stored on other computers. The computer may also be arranged to perform the optimization.

Claims

1. A computer system (31), comprising a program memory (36), characterized in that: The program memory comprises a computer program product arranged to execute a computer-based method for creating a radiotherapy treatment plan for a patient (81), the plan involving FLASH therapy provided as at least a first beam so that a portion of the radiation will be delivered as FLASH radiation having a dose rate higher than 40 Gy / s, the method comprising defining a desired dose distribution including a target dose prescription, characterized in that the plan is optimized using an optimization problem designed to maximize the FLASH portion to at least one organ at risk while complying with the target dose prescription, wherein the optimization problem is designed to take into account the FLASH effect as a function of both the dose rate and the temporal structure of the radiation.

2. The computer system according to claim 1, wherein: The optimization problem includes an objective function designed to maximize the FLASH portion of the plan.

3. The computer system according to claim 1 or 2, wherein: The optimization problem includes an objective function designed to minimize the non-FLASH portion of the plan.

4. The computer system according to claim 3, wherein: The optimization problem is defined as maximizing the FLASH portion or minimizing the non-FLASH portion by optimizing or selecting spot size, spot shape and / or spot arrangement.

5. The computer system according to claim 3, wherein: The optimization problem is defined as maximizing the FLASH portion or minimizing the non-FLASH portion by optimizing or selecting at least one of the following: spot weight and / or beam arrangement with respect to energy, number of beams and / or direction of beams.

6. The computer system according to claim 3, wherein: The optimization problem is defined as maximizing the FLASH component or minimizing the non-FLASH component by optimizing or selecting the order in which the spots are scanned.

7. The computer system according to claim 1 or 2, wherein: The plan includes at least a first beam and a second beam, each beam being delivered as FLASH radiation.

8. The computer system according to claim 1, wherein: The plan involves a first beam including a FLASH therapy portion and a second beam including only conventional therapy, the optimization problem being arranged to minimize a total effective dose from both the FLASH therapy portion and the conventional therapy portion of the first beam and the second beam in at least one organ at risk.

9. A non-transitory storage device having stored thereon computer readable code which, when executed in a processor (33) in a computer (36), causes the processor to perform the computer-based method steps of any one of claims 1 to 8.

10. A system (80) for delivering radiation therapy treatment to a patient, the system comprising a radiation source (85) in a gantry (87), wherein the radiation source is arranged to provide radiation at a sufficiently high dose rate to provide FLASH treatment to the patient, the system further comprising a computer (91) for controlling the system, the computer comprising a processor, characterized in that The computer comprises a memory comprising a treatment plan obtained by a computer-based method according to any one of claims 1-8.

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