Methods for creating radiation therapy plans, computer program products, and computer systems, as well as radiation therapy delivery systems.

Abstract

A radiation therapy treatment planning method for achieving a FLASH radiation therapy treatment plan involves optimizing the plan using an optimization problem specifically designed to maximize the fraction of radiation delivered under FLASH conditions to organs at risk and minimize damage to the organs at risk.

Description

【Technical Field】 【0001】 The present invention relates to radiotherapy treatment planning, and more specifically, to a radiotherapy treatment planning method for creating a treatment plan involving irradiation under FLASH conditions, a computer program and a computer system for executing such a plan, and a radiotherapy delivery system for delivering such a treatment to a patient. 【Background Art】 【0002】 When performing a radiotherapy treatment on a target, there is always a dose delivered to healthy tissues or risk organs outside the target, and thus there is always a risk that healthy organs or tissues will be damaged by radiation. One new treatment method that is thought to cause less unnecessary damage is FLASH therapy, which involves treatment at a much higher dose rate than conventional treatments, for example at 70 Gy / s. In the literature on FLASH, various lower limits of dose rate have been proposed, such as at least 40 Gy / s or 50 Gy / s. For example, if a dose of 20 Gy is delivered at a dose rate of 70 Gy / s, the total dose will be delivered in 0.29 s. In contrast, conventional radiotherapy treatments are delivered at a much lower dose rate, and a typical dose rate for conventional radiotherapy treatments is fractions of a Gy per minute. It has been found that the damage caused to healthy tissues by a specific dose in FLASH therapy is lower than that of conventional therapies, while the effect on the target, i.e., the tumor tissue response, remains the same, but the mechanism underlying this is not yet fully understood. In FLASH therapy, the radiation dose for the entire treatment session can be delivered as one single ultra-high dose in less than 一秒 (should be "one second"), as one broad beam, or as several pencil beams delivered as spots at short time intervals at a high dose rate and with the beam moving left and right to scan the target horizontally. 【0003】 It should be noted that there seems to be a typo in the original text where "一秒" appears in the English translation part of the example sentence in item

[12] . It should probably be "one second". The above translation has made the correction according to the correct meaning.Vozenin et al.: The advantage of FLASH radiotherapy confirmed in mini pig and cat-cancer patients, HAL Id: hal-01812514, https: / / hal-univ-rennesl.archives-ouvertes.fr / hal-01812514v2 confirmed that the difference in effectiveness between normal tissue and tumors after FLASH treatment, previously shown in mice, could also be observed in pigs and cats. 【0004】 Under FLASH conditions, the dose delivered to a risk organ causes less damage by a factor of approximately 30%. Therefore, the equivalent harmful dose to a risk organ is higher than the physical dose, which in this example is 1 / 0.7 times the physical dose. 【0005】 Concurrent European Patent Application No. 20163840.0 discloses a method for planning a FLASH treatment configured to compensate for the fact that, due to the nature of dose delivery, a portion of the radiation dose is delivered to each voxel at a lower non-FLASH dose rate when delivering a FLASH treatment to a patient. The method includes defining a desired dose distribution, including a targeted 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 taking the targeted dose prescription into consideration. [Overview of the Initiative] 【0006】 The object of the present invention is to provide a FLASH treatment that further improves the FLASH effect of pencil beam scanning therapy. 【0007】 The present invention relates to a computer-based method for creating a radiotherapy treatment plan for a patient, wherein the plan involves a flash treatment, which is delivered as at least a first beam such that a portion of the irradiation is delivered as a flash irradiation, and the method includes defining a desired dose distribution including a target dose prescription, and optimizing the plan using an optimization problem designed to include the delivery of spots in a pattern designed to deliver clusters of adjacent spots in succession. The pattern includes both the location of the spots and the order in which the spots are irradiated. 【0008】 This invention is based on the insight that the time structure of dose delivery is crucial for achieving the effect of FLASH therapy, and that voxels receive the dose delivered to adjacent spots. If these spots are delivered at very short time intervals, the FLASH effect is enhanced. Conventional pencil beam scanning is performed row by row. In this method, by the time adjacent spots in the lower line are delivered, the synergy between spots is reduced or eliminated. By grouping spots within a target sub-region so that the pencil beam continuously delivers doses to clusters of spots within the same sub-region, the FLASH effect can be maintained by the amount irradiated by spots within the same cluster. 【0009】 In other words, downstream of a spot cluster voxel, dose delivery is concentrated over a shorter period, and the flash effect within such voxels is enhanced. This does not affect the quality of the plan at all, as the same spot and weight are delivered. 【0010】 Clusters may be configured to be of the same shape and size, or clusters may be allowed to differ in at least one of their shapes and sizes. While a hexagonal shape for clusters is often advantageous, any shape or set of shapes may be specified to cover the target in the most favorable way. 【0011】 In some embodiments, the optimization problem includes a penalty function configured to penalize spot delivery commands that result in a low flash effect. This means that the optimization problem includes a function designed to continuously prioritize irradiation from adjacent spots, since the flash effect within each voxel is amplified by radiation delivered to the voxel from several spots within a sufficiently short time interval. 【0012】 In a preferred embodiment using proton radiation, the optimization problem is defined as optimizing with respect to the relative biological effect (RBE). RBE is a measure of the damage caused by a particular dose compared to a baseline dose, and it differs depending on the type of radiation, being different for flash and non-flash radiation. For photons under non-flash conditions, the RBE is 1. In non-flash proton therapy, current clinical practice uses a coefficient of 1.1, meaning that 70 Gy delivered as non-flash proton radiation is equivalent to 77 Gy 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-flashy portion of the plan. As is understood, the total dose is the sum of the flash and non-flashy portions, so these are just two different ways of expressing the same objective. 【0014】 As in the aforementioned concurrent patent applications, the optimization problem may, in some cases, be as follows: • Spot size • Spot shape • Spot placement • Spot weight • Beam configuration relating to energy, number of beams, and / or beam direction By optimizing or selecting one or more of these, the system can be designed to maximize the FLASH portion or minimize the non-FLASH portion. 【0015】 As an alternative or addition, the optimization problem may be defined as maximizing the FLASH portion or minimizing the non-FLASH portion by optimizing or selecting the scanning order of the spots. 【0016】 It is possible to optimize a design in which both beams have at least a first beam and a second beam, both containing flash portions. These can be delivered by a rotating 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. 【0017】 It is also possible to optimize a plan that includes at least a first beam and a second beam, wherein the first beam includes a FLASH portion and the second beam includes only conventional non-FLASH irradiation. In this case, the optimization problem is preferably configured to minimize the total effective dose from both the FLASH and conventional treatment portions of the first and second beams in at least one organ at risk. 【0018】 The present invention also relates to a computer program product comprising computer-readable code that, when run on a processor in a computer, causes the processor to execute a method according to any one of the embodiments described above. The computer program product may include a non-temporary storage means having code stored therein. The present 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. 【0019】 The present invention also relates to a system for delivering a radiation treatment to a patient, comprising a radiation source. The radiation source may be arranged, for example, within a gantry in any suitable manner or may be realized by a fixed beam line, and the radiation source is configured to provide radiation at a dose rate high enough to provide a FLASH treatment to the patient. The system further comprises a computer for controlling the system, and the computer comprises a processor and a memory containing a treatment plan obtained by the embodiments of the method described above. 【Brief Description of the Drawings】 【0020】 The present invention will be described in more detail below by way of example and with reference to the accompanying drawings. [Figure 1] Illustrate, as an example, the time structure of dose delivery by pencil beam scanning. [Figure 2] Illustrate the order of spot delivery in conventional pencil beam scanning. [Figure 3a-3b] Illustrate different methods of splitting spots into clusters for FLASH treatment according to embodiments of the present invention. [Figure 4] It is a flowchart of a method according to an embodiment of the present invention. [Figure 5a-5b] Illustrate, as examples, the effects of delivering spots with lines and clusters respectively. [Figure 6] It is an overview of a system 80 for radiation treatment and / or treatment planning. 【Mode for Carrying Out the Invention】 【0021】 FLASH treatment can be delivered by pencil beam scanning, i.e., as several beams that are delivered at a high dose rate and at short time intervals. Short in this context is to be interpreted as much shorter than the normal time required to rotate the gantry from one beam angle to another, which is usually about 30 seconds. High dose rate in this context is assumed to be above 40 Gy / s, but can be considerably higher. This means that the delivery time of a certain dose in FLASH treatment is much lower than in conventional treatments. For example, in conventional treatments, a dose of 2 Gy can be delivered as continuous radiation over a period of about 1 minute, while a FLASH dose of 2 Gy will be delivered in fractions of a second, in 1 / 20 seconds when the dose rate is 40 Gy / s. FLASH treatment means that the effective dose to the target is close to the physical dose, but the effective dose to the surrounding healthy tissue can be lower by a factor that can be 30%. Such treatment is advantageous in terms of reducing damage to healthy tissue. The time frame of FLASH dose delivery should be somewhere in the order of milliseconds to seconds. 【0022】 The treatment plan is here discussed assuming that it is based on one energy layer per beam, and that the spots within the energy layer are placed in a hexagonal pattern and delivered row by row as shown in Figure 2. 【0023】 Figure 1 illustrates, as an example, the temporal structure for FLASH irradiation of a single voxel in a patient, for example, a voxel in an organ at risk, as the dose rate per unit of time (cGy / s). The irradiation is delivered as a pencil beam scan, which means that as the central axis of the pencil beam passes through the voxel at a certain distance, part of the delivery irradiates the voxel only partially, while the other part hits near the center of the voxel. The part that hits only partially the voxel will result in a lower dose rate, and therefore a lower dose, typically a non-FLASH level, while the part that hits near the center of the voxel will have a higher dose rate to the voxel, and therefore a higher dose, which constitutes the FLASH component. In the example shown in Figure 1, the non-FLASH component is initially present at 0.1 s, followed by two higher peaks at 0.18–0.2 s, with dose rates high enough to constitute a FLASH irradiation, instantaneously reaching approximately 7000 Gy / s in this example, and finally, a lower non-FLASH component is present around 0.22 s. As can be understood, there may be more or fewer FLASH and non-FLASH components, but in practice, at least one of each will always be present. A similar temporal structure for conventional non-FLASH dose delivery would be, for example, a substantially continuous irradiation over a longer period, e.g., 2 Gy per minute. 【0024】 In general cases, the total effective dose (TED) to organs at risk is given by the following equation: TED = x*D(Non-FLASH) + y*D(FLASH) In the equation, 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 coefficients that model the RBE for each component. This means that x and y represent the total effective dose from those components relative to the physical doses of the non-FLASH and FLASH components, respectively. Typical values ​​for y are 0 and 7. For photons, x=1, and for charged particles, x is slightly higher than 1, for example, 1.1 for protons. 【0025】 Accordingly, according to the present invention, a FLASH treatment procedure is planned by optimizing an optimization problem designed to deliver a desired dose to a target at a high dose rate, as discussed above, for a short period, typically less than 1 s, while maintaining the total effective dose rate to surrounding tissues at an acceptable level for healthy tissue, including any organ at risk. This is done in part by taking advantage of the fact that, for each actual dose component, the total effective dose from the FLASH component is lower than the total effective dose from the non-FLASH component. The dose may be delivered as one beam or as several beams. To achieve this, the optimization problem includes an objective function designed to select a spot order that maximizes the FLASH component in at least one organ at risk. As understood, this can also be formulated to minimize the non-FLASH component in at least one organ at risk. Finally, the optimization problem may include a penalty function configured to penalize spot delivery commands that result in a low FLASH effect. As described above, each voxel is affected by several adjacent spots. When these spots are approaching in time, the concentrated radiation from some spots can lead to a FLASH effect. As is common in the art, this objective can be achieved in various ways, including optimizing one or more of the following: • Spot scanning order, and / or • Spot placement, and / or • Spot weight, and / or • Beam configuration in terms of energy, direction, and / or number of beams • Spot shape 【0026】 Figure 2 illustrates a conventional pencil beam scanning pattern. Target 21 is covered by spots 23 by delivering spots along the columns, as indicated by arrow 25, horizontally from left to right along the first column, then from right to left along the second column immediately below the first column, then from left to right along the third column, and so on. Each voxel is typically affected by spots from several columns, e.g., five columns. In FLASH therapy, as described above, the dose rate is much higher than in conventional therapy, e.g., 100 Gy / s or higher. Delivery of one row can typically take 5-50 ms. As can be understood, at any given spot, the time until an adjacent spot in the next row is delivered can be up to twice that time, meaning that for most spots, spots more than one row away, in particular, have too long a time interval to achieve or enhance the FLASH effect. 【0027】 Figures 3a and 3b illustrate different methods for dividing spots into clusters in FLASH therapy according to embodiments of the present invention. In Figure 3a, the region 31 containing the target is divided into a honeycomb pattern comprising several hexagons 32. Spots 33 are delivered sequentially within each hexagon to ensure that each voxel receives a dose from each spot that delivers a dose to this voxel in the shortest possible time. Within each hexagon, spots may be delivered in any preferred pattern, for example, in a helical pattern starting from the center of the hexagon and moving outward or in the opposite direction. Each hexagon may be divided into smaller sub-parts, each sub-part comprising a matrix of 4, 9, or 16 adjacent spots, or any other preferred number, that are delivered sequentially. 【0028】 In another example, as shown in Figure 3b, the target 35 is divided into sections 36 like a pie by a line crossing approximately the center of the target, and spots 33 are delivered sequentially within each section so that each voxel receives a dose from each spot that brings a dose to this voxel in the shortest possible time. Within each section 36, spots may be delivered row by row, or in any preferred pattern including smaller groups of adjacent spots, for example 4 or 9, or any preferred number, forming a matrix. 【0029】 As can be understood, any suitable shape can be used, determined by factors such as the overall shape of the target. Also, the parts do not need to be the same size and / or shape, but can be freely selected to fit the target in the best possible way. The flash effect is reduced in voxels that fall at cluster boundaries. This can be mitigated by having the optimizer attempt to compensate for such spots as much as possible while eliminating them. Alternatively, such boundary spots may be retained, but may be forced to have a weight lower than, for example, 30%, in order to smooth out the corrected dose of the flash effect. 【0030】 The regions defining each cluster of spots can be pre-tuned within the system by patterns commonly found to provide good synergistic effects between spots. Alternatively, the regions can be individually defined for each patient or target to conform to the specific shape and structure of the target. In either case, the patterns are input into the optimization problem as constraints. 【0031】 It would also be possible to handle the partitioning into clusters and / or spot delivery commands during the optimization process. This can be achieved by an optimization problem modeled as a “traveling salesman” problem with a cost function based on a delivery command modeled FLASH effect. 【0032】 Figure 4 is a schematic flowchart of a method for optimizing a pencil beam treatment plan according to an embodiment of the present invention. In the first step S21, the desired dose distribution for a specific patient is defined. In the second step S22, the optimization problem is defined. In the third step S23, dose optimization is performed based on the optimization problem. 【0033】 The optimization problem is preferably designed to output only the plan for FLASH treatment. FLASH treatment can be delivered with one or more beams from the same or different angles. As shown above, the optimization problem includes one or more optimization functions designed to group spots into clusters. 【0034】 As discussed above, the optimization problem is preferably designed to maximize the flash effect while taking into consideration the target dose formulation. According to the present invention, the flash effect is enhanced by delivering spots that approach each other within a sufficiently short time interval to achieve the accumulated flash dose. Regarding proton irradiation, this means that the optimization problem can be designed to also consider the relative biological effect (RBE) of the dose, which in FLASH therapy is a function of both the dose rate and time structure of the radiation, as well as other factors such as tissue type and type of irradiation. Other factors may also be considered. The timeframe of dose delivery should be somewhere on the order of milliseconds to seconds. 【0035】 The goal of treatment plan optimization is to achieve the desired dose at the target while minimizing the total effective dose at at least one organ at risk, where the total effective dose is the sum of the FLASH dose component adjusted with the FLASH effect coefficient and the conventional treatment component of the treatment. One way to implement this would be to use different types of scorers in the dose engine. For example, in a Monte Carlo dose engine, this would involve scoring one or more of the following: - For example, time tracking of energy accumulation per voxel, broken down into time bins of approximately milliseconds. - The concept of dirty dose. In this context, "dirty" can refer to the non-FLASH dose in a risk organ. 【0036】 Monte Carlo simulations follow different particle paths, including particle direction and energy, particle type, and the physical effects of the particles. Those skilled in the art will be able to implement this in other types of dose engines. 【0037】 Figures 5a and 5b illustrate the effects of spot delivery in lines and clusters, respectively. In Figures 5a and 5b, the dose to the voxel is shown as a function of time, as in Figure 1. In Figure 5a, the spots are delivered with the beam conventionally used in pencil beam scanning. As can be seen, some of the spots affecting the voxel are delivered at time intervals of up to approximately 50 ms, which is too long for the effective spots to accumulate to achieve FLASH treatment. In particular, the first spot is just before 0.04 s, two spots are between approximately 0.06 s and 0.07 s, and the fourth spot is at approximately 0.09 s. The relatively long time intervals are caused by spots belonging to different lines or columns in the conventional pattern shown in Figure 2. In Figure 5b, the spot delivery command is modified so that the first and fourth spots are delivered at times closer to the second and third spots, and so that the doses of all four spots accumulate and enhance the FLASH effect. 【0038】 Figure 6 is an overview of a system 80 for radiotherapy and / or treatment planning. As can be understood, such a system may be designed in any preferred mode, and the design shown in Figure 4 is merely an example. The patient 81 is positioned on a treatment couch 83. The system comprises an imaging / treatment unit having a radiation source 85 mounted on a gantry 87 for emitting radiation toward the patient positioned on the couch 83. Typically, the couch 83 and the gantry 87 are movable in several dimensions relative to each other to deliver radiation to the patient 81 as flexibly and precisely as possible. These parts and their functions are well known to those skilled in the art. The main difference between the system used in connection with the present invention and conventional radiotherapy delivery systems is that the system according to the present invention is adapted to deliver much higher dose rates than those made according to conventional radiotherapy. Preferred magnitudes of dose rates are discussed above. 【0039】 Several passive devices typically exist for shaping the beam in the lateral and depth directions, but these will not be discussed in further detail here. The means are configured to provide a beam grid, for example, in the form of a grid block, or a means for providing a pencil beam. The system also includes a computer 91 which may be used for planning and / or controlling radiotherapy procedures. As understood, the computer 91 may be a separate unit not connected to the imaging / treatment unit. 【0040】 The computer 91 comprises a processor 93, data memory 94, and program memory 95. Preferably, there is also one or more user input means 98, 99 in the form of a keyboard, mouse, joystick, voice recognition means, or any other available user input means. The user input means may also be configured to receive data from an external memory unit. 【0041】 The data memory 94 contains clinical data and / or other information used to obtain a treatment plan or related to the plan itself. Typically, the data memory 94 contains one or more patient images used to create a treatment plan according to an embodiment of the present invention. The program memory 95 holds at least one computer program configured to cause the processor to manage the delivery system according to the optimized treatment plan. 【0042】 To ensure understanding, data memory 94 and program memory 95 are illustrated and discussed only schematically. There may be several data memory units, each holding one or more different types of data, or one data memory, each holding all data in a suitably structured manner, and the same applies to program memory. One or more memories may also be stored on other computers. Both programs and data can be found in one or more memories within the computer system or in other units accessible from the computer system.

Claims

[Claim 1] A computer-based method for creating a radiotherapy treatment plan for a patient, wherein the radiotherapy treatment plan involves a flash treatment delivered as at least a first beam such that a portion of the irradiation is delivered as flash irradiation, the method comprising: a computer defining a desired dose distribution including a target dose prescription, and the computer optimizing the radiotherapy treatment plan using an optimization problem designed to include spot delivery in a pattern designed to deliver a plurality of clusters of adjacent spots in succession, wherein the optimization problem includes a penalty function configured to penalize spot delivery commands that give a low flash effect in at least one organ at risk, and the adjacent spots approach each other in time as a result of the optimization problem. [Claim 2] The method according to claim 1, wherein the plurality of clusters are defined to have the same shape and size. [Claim 3] The method according to claim 1, wherein the plurality of clusters are defined to differ in at least one of their shape and size. [Claim 4] The method according to any one of claims 1 to 3, wherein at least one cluster is specified to have a hexagonal shape. [Claim 5] The optimization problem is defined as optimizing the dose with respect to relative biological effects (RBE). The method according to any one of claims 1 to 4. [Claim 6] The aforementioned optimization problem, - The weight of the spot, and / or Beam configuration in terms of energy, number of beams, and / or beam direction. The method according to any one of claims 1 to 5, wherein the FLASH effect is further enhanced by optimizing or selecting at least one of the following. [Claim 7] The method according to any one of claims 1 to 6, wherein the optimization problem is defined to maximize the FLASH component or minimize the non-FLASH portion by optimizing or selecting the scanning order of the spots. [Claim 8] The method according to any one of claims 1 to 7, wherein the radiotherapy treatment plan includes at least a first beam and a second beam, each delivered as a FLASH irradiation. [Claim 9] The method according to claim 1, wherein the radiotherapy treatment plan comprises a first beam including a FLASH treatment portion and a second beam including only a conventional treatment with a lower dose rate of delivered radiation than the FLASH treatment, and the optimization problem is configured to minimize the total effective dose from both the FLASH treatment portion and the conventional treatment portion of the first beam and the second beam in at least one organ at risk. [Claim 10] A computer program product comprising computer-readable code that, when executed on a processor in a computer, causes the processor to perform the method according to any one of claims 1 to 9. [Claim 11] A computer system (31) comprising a processor (33), at least one data memory (34, 35), and a program memory (36), wherein the program memory comprises the computer program product described in claim 10. [Claim 12] A system (80) for delivering a radiotherapy procedure to a patient, including a radiation source (85) in a gantry (87), wherein the radiation source is configured to provide radiation at a radiation rate sufficiently high to provide the patient with a FLASH procedure, and the system further includes a computer (91) for controlling the system, the computer including a processor and a memory containing a procedure plan obtained by the method of any one of claims 1 to 9. [Claim 13] The method according to any one of claims 1 to 9, further comprising reducing the reduction of the FLASH effect in voxels at the boundaries of the cluster.