JP5521225B2 - Irradiation plan creation device and irradiation plan creation program - Google Patents

Description

The present invention scans a pencil beam while modulating the intensity by multi-port irradiation and superimposes each spot to form a dose distribution so that a dose prescription inputted in advance for a target irradiation target is formed. create plan (decision) to that irradiation morphism planning apparatus and a radiation planning program.

  In heavy ion radiotherapy, heavy particles generated from an ion source are accelerated by an accelerator, and the resulting heavy particle beam is narrowed down to about 9 mm with a half-value width and scanned with an irradiation target such as a tumor. There is a scanning irradiation method that irradiates while performing.

In the scanning irradiation method, when a heavy particle beam is irradiated, the pencil beam is irradiated from a plurality of different directions (generally 2 to 4) for the purpose of increasing dose concentration on the same tumor. Multi-gate irradiation is performed.
When performing multi-gate irradiation, there are single gate optimization and multi-gate optimization as methods for optimizing the dose distribution to the irradiation target.

  As shown in FIGS. 26 (a) to (d), the single gate optimization refers to the irradiation target (tumor) from a plurality of different directions (in the illustration of FIG. 26, from the left shown in (a), When irradiating heavy particle beams (from the front shown in b) and from the three directions from the right shown in (c)), it is planned that each irradiation field has a uniform dose distribution. The combined dose distribution obtained by superimposing the irradiation fields ((d) in the figure) means that a dose prescription input in advance to the irradiation target is realized.

Here, the dose prescription refers to the target dose for the irradiated region and the dose limitation for the non-irradiated region. The dose prescription is set by an irradiation planner such as a doctor or medical physicist.
Further, in this specification, a direction parallel to the traveling direction of the pencil beam irradiated to form each irradiation field is referred to as a z direction, and one direction parallel to a plane perpendicular to the z direction is referred to as a z direction. The x direction is referred to as a y direction that is parallel to the vertical plane and perpendicular to the x direction. In FIG. 26, the x direction and the z direction are drawn as directions parallel to the paper surface, so the y direction is drawn as a direction perpendicular to the paper surface.

  On the other hand, as shown in FIGS. 27 (a) to (d), multi-gate optimization is from a plurality of different directions with respect to the irradiation target (tumor) (from the left shown in (a) in the illustration of FIG. 27). When irradiating a heavy particle beam (from three directions from the front shown in (b) and from the right shown in (c)) to form an irradiation field in each direction, the single gate optimization described above is performed. Instead of planning every single field to have a uniform dose distribution, the first condition is to give the tumor a necessary and sufficient dose, damage to the organ at risk (OAR) A plurality of irradiation fields whose intensity is modulated under the second condition of suppressing the dose limit (allowable value) or less are planned, and a combined dose distribution ((d) in the figure) is obtained by superimposing all the irradiation fields. To realize a dose prescription input in advance for a subject.

  As can be seen by comparing FIG. 26 and FIG. 27, in the single gate optimization of FIG. 26, a uniform dose distribution is formed from each gate for a substantially U-shaped tumor, whereas in FIG. In multi-gate optimization, the dose distribution of each gate for a substantially U-shaped tumor is non-uniform, and there is a dose gradient as shown by the isodose line.

  As multi-gate irradiation methods applying multi-gate optimization, intensity-modulated particle irradiation (IMIT), intensity-modulated proton irradiation (IMPT), intensity-modulated irradiation Method (IMRT: Intensity-Modulated Radiation Therapy), superposition irradiation (patch irradiation) method to the maximum irradiation field, and the like.

  According to these multi-port irradiation methods, even when there is an OAR in the vicinity of a tumor such as a brain tumor, it is possible to concentrate the dose on the tumor while avoiding it, and compared with the multi-port irradiation method applying single gate optimization Thus, there is an advantage that the dose given to the OAR can be suppressed to about one third, for example.

  However, the final dose distribution in the multi-port irradiation method with multi-gate optimization depends on how multiple fields are superimposed, compared to the multi-port irradiation method with single-gate optimization. Irradiation range error due to organ movement or deformation, irradiation range error due to pencil beam range calculation error, etc. (Because these errors are errors related to beam stop position (range), If there is an error in the setup of the irradiated object and / or the setup of the irradiated object, the dose distribution may be deteriorated and the dose density may be increased. Therefore, at present, it is the only one in the world that is being conducted at the Paul Scherrer Institute in Switzerland.

  When performing carbon beam scanning irradiation such as IMIT, although it varies depending on the volume of the irradiation target, for example, a spot exceeding 10,000 is irradiated by scanning a pencil beam according to the dose distribution for each irradiation field determined in the irradiation plan. Need to be stacked. In this specification, the spot means a position where irradiation with a pencil beam is scheduled before irradiation with the pencil beam, and irradiation with the pencil beam is performed after irradiation with the pencil beam. Refers to the position.

  Therefore, when performing the carbon beam scanning irradiation, it is necessary to determine the weights (spot weights) of the pencil beams of a plurality of irradiation fields to be overlapped so as to satisfy the set dose prescription.

  Usually, dose limits are set for Planning Target Volume (PTV) and OAR, and spot weights have non-negative limits, so the dose optimization problem is an incomplete inverse problem . Therefore, the dose optimization problem in the irradiation plan cannot be solved analytically, but is solved by applying the successive approximation method. 'Incomplete' implies that there may be multiple solutions that meet the dose limit (condition). In fact, for example, there are innumerable combinations of weights (ratio of dose) for each spot in each irradiation field for uniformly giving a dose to the PTV. On the contrary, this means that there are solutions that satisfy the dose restriction, and that even if there are range errors and / or setup errors, it is less likely to cause a deterioration in dose distribution.

  Plans that create solutions that are unlikely to cause dose distribution deterioration are called 'Robust Plans', and to date, multiple approaches have been proposed for this robust plan and its development is intensifying worldwide. doing.

  For example, Non-Patent Document 1 describes that an evaluation index value is obtained in order to obtain a robust plan, and an equation therefor (for example, Equation (4) on page 151 of Non-Patent Document 1).

A conventional irradiation plan employing the approach described in Non-Patent Document 1 is performed as follows.
First, as shown in FIG. 28, the irradiation planner performs irradiation site (that is, PTV) and non-irradiation site (for example, OAR), the number of irradiation gates, and irradiation based on an image obtained by CT imaging of the irradiation target in advance. The direction, the target dose for the above-mentioned irradiation site and the dose limit (ie, dose prescription) for the above-mentioned non-irradiation site are determined, and these pieces of information are input from the input means of the irradiation plan creation device.

The irradiation plan creation apparatus determines the irradiation position of the pencil beam with respect to the irradiation target (target) based on the input information.
Next, the dose distribution of the pencil beam for each spot is determined (that is, a pencil beam dose kernel is created), and then the initial value of the weight of the pencil beam is determined so as to be the created dose distribution.

  Thereafter, in order to obtain a robust plan based on the approach described in Non-Patent Document 1, a possible error, for example, a range error and / or a setup error, is assumed, and the evaluation index value update count m The initial value is set (m = 1) and the initial value n of the number of times of updating the weight of the pencil beam is set (n = 1), and an evaluation index value e assuming a possible error is derived. The evaluation index value e is derived under a first condition that a necessary and sufficient dose is given to the target dose with respect to the irradiated portion, and below the dose limit for the non-irradiated portion. It is derived from the second condition of suppressing.

Next, the evaluation index value E is updated (E = Σf), and it is determined whether or not the number m of updates exceeds a predetermined number M (m> M). If m> M is not satisfied (in the case of No) ) Updates m = m + 1 and the update count m, assumes the next error, and again derives an evaluation index value e assuming a possible error.
On the other hand, when m> M (in the case of Yes), the updated evaluation index value E is greater than or equal to a preset specified value (threshold) C, and the number n of times to update the weight of the pencil beam is preset. If it is less than or equal to the set value N (No in E <C or n> N), the weight of the pencil beam is updated with n = n + 1, and the evaluation index value e assuming again a possible error is derived.

When m> M (in the case of Yes) and the updated evaluation index value E is lower than a preset specified value (threshold value) C, or the number n of times of updating the weight of the pencil beam is predetermined. When the number is larger than the set value N (Yes in E <C or n> N), the updated weight is output as the irradiation parameter.
Then, based on the output irradiation parameters (weights), carbon beam scanning irradiation by IMIT is performed.

Jan Unkelbach, Thomas Bortfeld, Benjamin C. Martin, Martin Soukup, “Reducing the sensitivity of IMPT treatment plans to setup errors and range uncertainties via probabilistic treatment planning”, Med. Phys. 36 (1), January 2009, p.149- 163

  However, in the irradiation plan having pencil beams (spots) exceeding 10,000 as described above, when calculation for obtaining a robust plan is performed by the method proposed in Non-Patent Document 1, several days (for example, 2-3 days) ), Which requires a long calculation time that cannot be put into practical use. Therefore, apart from those at the research level, there is no example in which a technique for obtaining a robust plan is applied to a commercially available irradiation plan creation device.

The present invention has been made in view of the above problems, to provide a relatively create robust plan (decision) can Ru irradiation morphism planning apparatus that, and irradiation planning program shorter than the conventional time Is an issue.

This invention which solved the above-mentioned subject is as the following (1)-( 4 ) .

(1) The present invention scans a pencil beam while modulating the intensity by multi-port irradiation, and superimposes the spots for each spot, and includes an irradiation part that irradiates radiation and a non-irradiation part that should not be irradiated. In creating an irradiation plan for forming a dose distribution so as to be a pre-input dose prescription for the target, with respect to the input pencil beam weight, with respect to the pre-input irradiation site, A first condition that a necessary and sufficient dose is given with respect to a pre-input target dose; a second condition that the pre-input non-irradiated part is suppressed to a dose input limit or less; Is an irradiation plan creation device that performs an iterative approximate iterative calculation to derive an evaluation index value and creates the irradiation plan based on the evaluation index value. A third successive iteration operation means for performing an approximate repetition calculation further suppresses a gradient of the dose distribution given to the irradiation object from a previously input irradiation direction in addition to the first condition and the second condition. The evaluation index value is derived using a condition.

( 2 ) The present invention is the irradiation plan creation device according to the above ( 1 ), wherein the successive approximation iterative calculation means is further provided in advance in addition to the first condition, the second condition, and the third condition. When an error occurs within a set range, it is preferable to derive the evaluation index value using a fourth condition that a spot that increases the dose given to the non-irradiated part is not used.

( 3 ) The present invention scans a pencil beam while modulating the intensity by multi-port irradiation and superimposes each spot, and includes an irradiation part that irradiates radiation and a non-irradiation part that should not be irradiated with radiation. In creating an irradiation plan for forming a dose distribution so that a pre-input dose prescription is obtained for a target, a computer is input to the pre-input irradiation site for the input pencil beam weight. Thus, a first condition that a necessary and sufficient dose is given with respect to a target dose that is input in advance, and a second condition that the non-irradiated portion that is input in advance is kept below a dose limit that is input in advance. And calculating the irradiation plan based on the evaluation index value by deriving the evaluation index value. An irradiation plan creation program that functions as a return calculation means, wherein the successive approximation repetition calculation means is given to the irradiation object from a pre-input irradiation direction in addition to the first condition and the second condition. The derivation of the evaluation index value is executed using a third condition that suppresses the gradient of the dose distribution.

( 4 ) The present invention is the irradiation plan creation program according to the above ( 3 ), wherein the successive approximation iterative calculation means is further provided in advance in addition to the first condition, the second condition and the third condition. When an error occurs within a set range, it is preferable to execute the derivation of the evaluation index value using a fourth condition that a spot that increases the dose given to the non-irradiated part is not used.

Planning device morphism engaged Ru light of the present invention, and by either of the irradiation planning program can create a relatively robust plan in a shorter time than the conventional (decision).

It is a flowchart which shows the content of the irradiation plan preparation method which concerns on this invention. It is a flowchart which shows the content of evaluation index value derivation | leading-out step S5 of FIG. The spread of the pencil beam in the horizontal direction (x direction) σ _x (z _i ; z _j ) is the water depth Z _i and the range shifter thickness (0 mm (circle mark), 30 mm (square mark), 60 mm (triangle mark) ) Is parameterized as a function. The horizontal axis is the depth of water [mm], and the vertical axis is the spread σ _x [mm] of the pencil beam in the horizontal direction (x direction). Parallel plate ionization chamber the dose distribution of the pencil beam: with measured in (PPIC circles) is a diagram as a function of depth Z _i of water. In addition, the small graph in FIG. 4 expands the part of the depth of water 200-230 mm. The horizontal axis is the water depth [mm], and the vertical axis is the relative dose. It is a Gaussian distribution diagram showing the spread of the dose response d _{i, j} of the pencil beam in the lateral direction. The horizontal axis is the position [mm] in the horizontal direction (x direction) of the pencil beam, and the vertical axis is the relative dose value at the position in the horizontal direction (x direction) of the pencil beam. In the figure, the broken line represents the range shifter thickness of 3 mm (σ = 3 mm), the solid line represents the range shifter thickness of 4 mm (σ = 4 mm), and the alternate long and short dash line represents the range shifter thickness of 5 mm (σ = 5 mm). It is a partial differential distribution map of the Gaussian distribution showing the breadth of the dose response d _{i, j} of the pencil beam in the lateral direction. The horizontal axis is the position [mm] in the horizontal direction (x direction) of the pencil beam, and the vertical axis is the relative dose partial differential value at the position in the horizontal direction (x direction) of the pencil beam. In the figure, the broken line represents the range shifter thickness of 3 mm (σ = 3 mm), the solid line represents the range shifter thickness of 4 mm (σ = 4 mm), and the alternate long and short dash line represents the range shifter thickness of 5 mm (σ = 5 mm). It is the figure which expressed the spread (standard deviation of Gaussian distribution) of the pencil beam of the horizontal direction as a function of the depth and the thickness of the range shifter. The horizontal axis is the depth [mmWEL] (z direction), and the vertical axis is the spread [mm] of the pencil beam in the horizontal direction (x direction). In the figure, the broken line represents the range shifter thickness of 0 mm (RSF = 0 mm), the solid line represents the range shifter thickness of 30 mm (RSF = 30 mm), and the alternate long and short dash line represents the range shifter thickness of 60 mm (σ = 60 mm). It is the figure which represented the partial differentiation of the breadth of the pencil beam of the horizontal direction (standard deviation of Gaussian distribution) as a function of the depth and the thickness of the range shifter. The horizontal axis is the depth [mmWEL] (z direction), and the vertical axis is the partial differential value [mm] of the spread of the pencil beam in the horizontal direction (x direction). In the figure, the broken line represents the range shifter thickness of 0 mm (RSF = 0 mm), the solid line represents the range shifter thickness of 30 mm (RSF = 30 mm), and the alternate long and short dash line represents the range shifter thickness of 60 mm (σ = 60 mm). It is a figure which shows the depth and integrated dose distribution regarding a 350 MeV / u carbon beam. The horizontal axis is the depth [mmWEL] (z direction), and the vertical axis is the integrated dose value at each depth of the pencil beam. It is a figure which shows the depth and differential dose distribution regarding a 350 MeV / u carbon beam. The horizontal axis is the depth [mmWEL] (z direction), and the vertical axis is the integrated dose differential value at each depth of the pencil beam. (A) And (b) is a figure which shows an example of the result produced by the irradiation plan preparation method to which the one aspect | mode of evaluation index value derivation | leading-out step S5 was applied, respectively. (A) And (b) is a figure which shows an example of the result produced by the conventional irradiation plan creation method with an isodose line, respectively. Using RTOG benchmark phantom horseshoe CTV surrounds a cylindrical OAR, there FIG shows a procedure of calculating schematically risk measures P _j ^R and risk indicators P _j ^S of the j-th pencil beam emitted (A) is a diagram showing the shape of an RTOG benchmark phantom composed of CTV and OAR, (b) is a diagram showing how an FTV is generated from CTV, and (c) and (c ′) Are diagrams showing ROAR and SOAR, respectively, (d) and (d ′) are diagrams showing a state where penumbras are added in the horizontal direction of ROAR and SOAR, respectively, and (e) and (e ′) ) Is a diagram showing how the Bragg peaks of each pencil beam are arranged in the FTV as indicated by the small hollow circles in the figure. (A) And (b) is a figure which shows an example of the result produced by the irradiation plan to which the other aspect of evaluation index value derivation | leading-out step S5 was applied, respectively by an isodose line. (A) And (b) is a figure which shows an example of the result produced by the conventional irradiation plan which is not robust with an isodose line, respectively. It is a block diagram which shows the structure of the irradiation plan preparation apparatus which concerns on this invention. It is a figure which shows the shape of a RTOG benchmark phantom. It is a figure which shows the shape of the RTOG benchmark phantom containing the expanded area | region. It is a figure which shows the clinical dose distribution planned by the conventional irradiation plan preparation method (comparative example 1). It is a figure showing the dose volume histogram of PTV and OAR corresponding to FIG. 16A. The horizontal axis is the dose [%], and the vertical axis is the volume [%]. The solid line is the dose for PTV and the dashed line is the dose for OAR. It is the figure which displayed the dose distribution given by the individual beam from a 225 degree direction by the conventional irradiation plan preparation method (comparative example 1) with the isodose line. It is the figure which displayed the dose distribution given by the individual beam from 135 degrees direction by the conventional irradiation plan preparation method (comparative example 1) with the isodose line. It is a figure which shows the clinical dose distribution planned by the robust irradiation plan preparation method (Example 1). FIG. 17B is a diagram showing a dose volume histogram of PTV and OAR corresponding to FIG. 17A. The horizontal axis is the dose [%], and the vertical axis is the volume [%]. The solid line is the dose for PTV and the dashed line is the dose for OAR. It is the figure which displayed the dose distribution given by the individual beam from a 225 degree direction by the robust irradiation plan preparation method (Example 1) with the isodose line. It is the figure which displayed the dose distribution given by the individual beam from 135 degrees by the robust irradiation plan preparation method (Example 1) by the isodose line. It is a figure which shows an example of the irradiation plan (comparative example 2) which does not use a dose gradient suppression term, Comprising: It is the figure which displayed the dose distribution in the setup position as planned in color. It is a figure which shows an example of the irradiation plan (comparative example 2) which does not use a dose gradient suppression term, Comprising: It is the figure which displayed the dose distribution in the setup position as planned by the isodose line. It is a figure which shows an example of the irradiation plan (comparative example 2) which does not use a dose gradient suppression term, Comprising: A separate beam (BEAM1) in the isocenter of x = 208.9, y = 192.9, z = 55.0 It is the figure which displayed the dose distribution given by (5) by the isodose line. It is a figure which shows an example of the irradiation plan (comparative example 2) which does not use a dose gradient suppression term, Comprising: A separate beam (BEAM2) in the isocenter of x = 208.9, y = 192.9, z = 180.0 It is the figure which displayed the dose distribution given by (5) by the isodose line. It is a figure which shows an example of the irradiation plan (comparative example 2) which does not use a dose gradient suppression term, Comprising: The figure which displayed the dose distribution which arises when the distance between Beam1 and Beam2 shortens by 4 mm due to the setup error in color It is. It is a figure which shows an example of the irradiation plan (comparative example 2) which does not use a dose gradient suppression term, Comprising: The dose distribution which arises when the distance between Beam1 and Beam2 shortens by 4 mm due to a setup error is displayed with an isodose line FIG. It is a figure which shows an example of the irradiation plan which does not use a dose gradient suppression term (comparative example 2), Comprising: The figure which displayed the dose distribution produced when the distance between Beam1 and Beam2 is 4 mm away due to the setup error in color It is. It is a figure which shows an example of the irradiation plan (comparative example 2) which does not use a dose gradient suppression term, Comprising: The dose distribution produced when the distance between Beam1 and Beam2 is 4 mm away by the setup error is displayed with an isodose line FIG. It is a figure which shows the dose volume histogram of PTV by the conventional irradiation plan (comparative example 2). The horizontal axis is the dose [GyE], and the vertical axis is the volume [%]. The solid line is the ideal dose, the broken line is the dose when the distance between Beam1 and Beam2 is reduced by 4 mm, and the alternate long and short dash line is the dose when the distance between Beam1 and Beam2 is 4 mm apart. It is a figure which shows an example of the irradiation plan (Example 2) using a dose gradient suppression term, Comprising: It is the figure which carried out color wash display of the dose distribution in the setup position as planned. It is a figure which shows an example of the irradiation plan (Example 2) using a dose gradient suppression term, Comprising: It is the figure which displayed the dose distribution in the setup position as planned by the isodose line. It is a figure which shows an example of the irradiation plan (Example 2) using a dose gradient suppression term, Comprising: An individual beam (BEAM1) in the isocenter of x = 208.9, y = 192.9, and z = 55.0 It is the figure which displayed the dose distribution given by (5) by the isodose line. It is a figure which shows an example of the irradiation plan (Example 2) using a dose gradient suppression term, Comprising: A separate beam (BEAM2) in the isocenter of x = 208.9, y = 192.9, z = 180.0 It is the figure which displayed the dose distribution given by (5) by the isodose line. FIG. 5 is a diagram showing an example of an irradiation plan (Example 2) using a dose gradient suppression term, and a color distribution showing a dose distribution generated when the distance between Beam1 and Beam2 is reduced by 4 mm due to a setup error. It is. It is a figure which shows an example of the irradiation plan (Example 2) using a dose gradient suppression term, Comprising: The dose distribution produced when the distance between Beam1 and Beam2 shortens by 4 mm due to the setup error is displayed with an isodose line FIG. FIG. 10 is a diagram showing an example of an irradiation plan (Example 2) using a dose gradient suppression term, and a color distribution showing a dose distribution generated when the distance between Beam1 and Beam2 is 4 mm away due to a setup error. It is. It is a figure which shows an example of the irradiation plan (Example 2) using a dose gradient suppression term, Comprising: The dose distribution produced when the distance between Beam1 and Beam2 is 4 mm away by the setup error is displayed with an isodose line FIG. It is a figure which shows the dose volume histogram of PTV by a robust irradiation plan (Example 2). The horizontal axis is the dose [GyE], and the vertical axis is the volume [%]. The solid line is the ideal dose, the broken line is the dose when the distance between Beam1 and Beam2 is reduced by 4 mm, and the alternate long and short dash line is the dose when the distance between Beam1 and Beam2 is 4 mm apart. It is a figure explaining the RTOG benchmark phantom like shape used in the 3rd example. Plan No. 1 (top), plan no. 2 (middle), plan no. It is each dose distribution figure of the beam in 0 degree (left column), 45 degrees (center column), and synthetic dose distribution (right column) in 3 (lower stage). What is drawn in a substantially U shape in (a) to (i) is CTV, and what is drawn in a round shape at the center of (a) to (i) is OAR. The dose distribution DVH recalculated to have 11 different effective densities in the CTV and the OAR. 1 is a DVH having a dose distribution of 1. 2 is a DVH of the dose distribution of FIG. 3 is a DVH of a dose distribution of 3. The thick solid lines in (a) to (c) are DVHs when all pencil beams are irradiated and an irradiation field is formed as assumed in the optimization. Plan No. 1 (top), plan no. 4 (middle), plan no. It is each dose distribution figure of the beam in 0 degrees (left column) and 45 degrees (middle column) and synthetic dose distribution (right column) in 5 (lower stage). What is drawn in a substantially U shape in (a) to (i) is CTV, and what is drawn in a round shape at the center in (a) to (i) is OAR. It is DVH of the dose distribution recalculated for 729 possible combinations of the combined dose distribution in the CTV and the OAR. 1 is a DVH having a dose distribution of 1. 2 is a DVH of the dose distribution of FIG. 3 is a DVH of a dose distribution of 3. The thick solid lines in (a) to (c) are DVHs when all pencil beams are irradiated and an irradiation field is formed as assumed in the optimization. The dose contributions from each of the 0 ° and 45 ° beams, (a) and (d) are the plan numbers. 3 is a diagram showing the dose contribution created in FIG. 6 is a diagram showing the dose contribution created in FIG. FIG. 7 is a diagram showing the dose contribution created in FIG. It is a figure which shows an example of the result of the conventional irradiation plan in the irradiation method irradiated so that a uniform dose may be given to the whole tumor from several different directions, (a) is left with respect to irradiation object The irradiation field irradiated with heavy particle beams from the side is shown, (b) shows the irradiation field irradiated with heavy particle beams from the front to the irradiation target, and (c) shows the irradiation field irradiated from the right with respect to the irradiation target. The irradiation field which irradiated the particle beam is shown, (d) is a synthetic | combination figure which shows the synthetic dose distribution which overlap | superposed (a)-(c). It is a figure which shows an example of the result of the conventional irradiation plan in the irradiation method which gives a dose partially from several different directions, and damages the whole tumor uniformly as a whole, and (a) is irradiation The irradiation field irradiated with heavy particle beams from the left side of the object is shown, (b) shows the irradiation field irradiated with heavy particle beams from the front of the irradiation object, and (c) shows the irradiation field with respect to the irradiation object. The irradiation field irradiated with heavy particle beams from the right side is shown, and (d) is a composite diagram showing a combined dose distribution in which (a) to (c) are superimposed. It is a flowchart which shows an example of the conventional irradiation plan.

  Hereinafter, an embodiment of an irradiation plan creation method, an irradiation plan creation device, and an irradiation plan creation program according to the present invention will be described in detail with reference to the drawings as appropriate.

[Irradiation plan creation method]
First, an irradiation plan creation method according to an embodiment of the present invention will be described.
An irradiation plan creation method according to an embodiment of the present invention performs irradiation with a radiation site such as a tumor that is irradiated with radiation by scanning a pencil beam while modulating the intensity by multi-port irradiation and overlapping each spot. An irradiation plan for forming a dose distribution is created (determined) so as to obtain a dose prescription input in advance for an irradiation target including a non-irradiated part such as OAR that should not be.

  As shown in FIG. 1, the irradiation plan is created (determined) generally by an information input step S1, a pencil beam irradiation position determination step S2, a pencil beam dose distribution generation step S3, a weight input step S4, and an evaluation index value derivation step S5. The output step S6 is performed.

  The derivation of the evaluation index value by the above-described successive approximation iteration calculation is performed in the evaluation index value derivation step S5, and an irradiation plan is created by comparing the derived evaluation index value with a preset threshold value. Details of the evaluation index value deriving step S5 will be described later.

(Information input step S1)
The information input step S1 is a step for inputting information necessary for obtaining an irradiation plan.
Information necessary to create an irradiation plan includes, for example, irradiation sites and non-irradiation sites, the number of irradiation gates and the irradiation direction, the target dose for the irradiation sites described above and the dose limitation for the non-irradiation sites described above (that is, Dose prescription).

Information necessary to create such an irradiation plan is input by the irradiation planner.
An irradiation planner can irradiate a pencil beam based on medical findings based on a CT image obtained by imaging a target irradiation target in advance (irradiation site), or a site that should not be irradiated with a pencil beam (non-irradiation). (Irradiation site) is identified, the number of irradiation gates and the irradiation direction that seems to be effective for the identified irradiation site are determined, and the target dose for the irradiation site and the dose limit for the non-irradiation site are determined. Input to the irradiation plan creation device (electronic computer).

  The irradiation site is generally set as PTV, and for example, a region including a site where a tumor or the like is formed and a site where the tumor may be infiltrated is set. Further, the non-irradiated part is set as OAR, and for example, an important organ such as a brain or an optic nerve is set. The target dose for the irradiated part and the dose limit for the non-irradiated part are appropriately set by the irradiation planner.

(Pencil beam irradiation position determination step S2)
In the pencil beam irradiation position determination step S2, the irradiation position of the pencil beam with respect to the irradiation target is determined based on the irradiation site and non-irradiation site, the number of irradiation gates, and the irradiation direction input in advance.

(Pencil beam dose distribution creation step S3)
In a pencil beam dose distribution creation step S3 to be performed next, a dose distribution of a pencil beam to be superimposed at the pencil beam irradiation position determined in the pencil beam irradiation position determination step S2 is created. That is, this step creates a pencil beam dose distribution kernel.
The above-described contents in the pencil beam irradiation position determining step S2 and the pencil beam dose distribution creating step S3 can be performed by using a known treatment plan calculation engine for heavy particle beam scanning irradiation.

  In this pencil beam dose distribution creation step S3, a pencil beam dose distribution kernel is created, a partial differential filter related to the dose distribution in the z direction, which is the direction of travel of the pencil beam, and a plane perpendicular to the z direction. Create partial differential filters for x- and y-direction dose distributions. That is, a kernel relating to a dose gradient (dose gradient kernel) in the axial direction of the pencil beam and the lateral direction perpendicular to the axial direction is created.

If the dose gradient kernel created in pencil beam dose distribution creation step S3 is used in evaluation index value derivation step S5, which will be described later, a calculation loop for dose superposition integration that is repeatedly performed in evaluation index value derivation step S5 will be described later. The gradient of the dose distribution given from each gate to the target (irradiation target) can be derived, and the evaluation index value in the evaluation index value deriving step S5 can be efficiently derived. The use of the calculation loop repeatedly performed in the evaluation index value derivation step S5 does not add a new calculation loop, so that a significant calculation time is required for deriving the gradient of the dose distribution given to the irradiation target from each gate. It means that no extension occurs.
The creation of the dose gradient kernel will be described in detail later.

(Weight input step S4)
In a weight input step S4 to be performed next, the weight of the pencil beam is input. The initial value of the weight is arbitrarily set on the basis of the target dose for the irradiated region and the dose limit for the non-irradiated region previously input in the information input step S1. As will be described in detail later, in order to obtain a better solution, the weight of the pencil beam is updated to a new value until the evaluation index value derived in the evaluation index value deriving step S5 described later satisfies a specific condition. Repeated.

(Evaluation index value deriving step S5)
The next evaluation index value deriving step S5 will be described after the description of the output step S6.

(Output step S6)
In the output step S6, the weight of the pencil beam determined or updated in the evaluation index value deriving step S5 is output as an irradiation parameter.

(One aspect of evaluation index value deriving step S5)
As one aspect of the evaluation index value deriving step S5 mentioned above, the pencil beam dose distribution kernel created in the pencil beam dose distribution creating step S3 is preferably used for the weight of the pencil beam inputted in the weight input step S4. In addition to the following first and second conditions, the dose gradient kernel created in step 1 is used, and in addition to the following first condition and second condition, the successive approximation is repeated using the following third condition. Performing an evaluation index value and comparing the evaluation index value with a preset threshold value to create an irradiation plan.

First condition: With respect to the weight of the input pencil beam, a necessary and sufficient dose is given to the pre-input target dose with respect to the pre-input irradiation site.
Second condition: For a non-irradiated portion input in advance, it is possible to suppress the dose to a dose input that has been input in advance.
Third condition: An evaluation index value can be derived by suppressing a gradient of a dose distribution given to an irradiation object from an irradiation direction input in advance.

That is, in one aspect of the evaluation index value deriving step S5, the evaluation index value is derived so as to suppress the dose gradient, thereby creating a more robust irradiation plan.
A mathematical expression that embodies one aspect of the evaluation index value deriving step S5 will be described later.

  In the evaluation index value deriving step S5 according to the above-described one aspect, as shown in FIG. 2, the derived evaluation index value E is lower than a preset threshold C, or is set in the evaluation index value deriving step S5. When the management value n exceeds the preset limit value N (Yes in determination step S51), the derivation of the evaluation index value E is terminated, and the input pencil beam weight is output as an irradiation parameter. Therefore, the process proceeds to the above-described output step S6.

Here, examples of the management value n include the number of repetitions of the calculation in the evaluation index value deriving step S5 and the time required for the calculation.
Examples of the limit value N include the number of times set in advance as the upper limit value of the number of repetitions of calculation, the time set in advance as the upper limit of calculation time, and the like.
The threshold value C and the limit value N can be arbitrarily set by the irradiation planner.

  On the other hand, when the derived evaluation index value E is not less than the preset threshold C and the management value n set in the evaluation index value deriving step S5 is not more than the preset limit value N (No in the determination step S51) ), The management value n is updated in the weight update step S52 (n = n + 1), the weight of the pencil beam is updated, the process returns to the weight input step S4, and the evaluation index value derivation step S5 is performed again. The updating of the weight of the pencil beam may be performed based on the following formula (7).

(Regarding a mathematical expression embodying one aspect of the evaluation index value deriving step S5)
The evaluation index value E derived in the evaluation index value deriving step S5 can be obtained by Expression (1). Note that the objective function f (w) in Expression (1) corresponds to the evaluation index value E.

In Equation (1), w _l is the beam weight of each irradiation field l, and w is the sum of the beam weights w _l of each irradiation field l.
T indicates an irradiation site that is a target, and O indicates a non-irradiation site such as OAR. H ′ [] is expressed as H ′ [r] = rH [r], and is 1 when the calculated value of the expression r shown between “[” and “]” is greater than zero. Sometimes it is a heavy side step function defined as zero.
Q _T ^o is the overdose specified in the irradiated portion is the target penalty factor for (overdose) (impact factor), D _i (w _l) is a total dose from all radiation field l at position i D _T ^max is the maximum dose irradiated to the target irradiation site.
Q _T ^u is the penalty coefficient for underdose specified in the irradiated portion is the target (underdose), D _T ^min is the minimum dose delivered to the irradiation site is the target.
Q _O ^o is a penalty coefficient for overdose at a non-irradiated site such as OAR, and D _O ^max is a maximum dose allowed for a non-irradiated site such as OAR.
N _field is the number of incident irradiation fields, and D _{i, l} (w _l ) is a dose irradiated from the irradiation field 1 to the position i with the beam weight w ₁ . z is the z direction, x is the x direction, and y is the y direction. Q _x , Q _y , and Q _z are penalty coefficients for the dose gradient in each direction. Such a penalty coefficient is set in proportion to the prediction error in that direction.
These symbols mean the same contents in the following mathematical expressions.
Of course, D _i (w _l ) and D _{i, l} (w _l ) satisfy the relationship of equation (2).

  The first term of Equation (1) corresponds to the first condition, and describes the dose limit (target dose) to PTV. The second term corresponds to the second condition, and describes the dose limitation to OAR. The third term corresponds to the third condition, and describes the dose gradient limitation within the PTV in the irradiation field unit.

The dose distribution D _i (w _l ) is expressed by the superposition of pencil beams and can be expressed by Expression (3).

In Expression (3), N _spot is the total number of spots to be irradiated, and the spot in each irradiation field l satisfies the relationship of Expression (4). Note that j indicates the jth beam irradiated.

  And if Formula (3) is expanded using Formula (2) and Formula (4), it will become Formula (5).

  And if Formula (1) is expanded using Formula (2)-(5), it will become Formula (6).

According to Equation (6), the dose gradient suppression term (third term) in each irradiation field 1 is expressed in the form of a superimposed integral of partial differentials of the dose response d _{i, j} of the pencil beam.
That is, it can be understood that the calculation can be performed in the same calculation loop as the overlap integral of the dose distribution calculation used in the evaluation index value deriving step S5.

  Here, the problem of dose optimization in the scanning irradiation method is that of a beam that realizes a three-dimensional spot intensity distribution (dose distribution) that minimizes the objective function f (w) given by Equation (6). This results in finding the weight w under non-negative conditions.

As a method for deriving the minimum value of the objective function f (w), a successive approximation method is generally used. In order to obtain an optimum dose distribution by the successive approximation method, the next approximate value w ^{k + 1} is ^obtained from the k-th approximate value w ^k by equation (7). In Expression (7), h and μ represent the direction vector of the correction vector and its length (size), respectively.

In order to efficiently obtain the beam weight w that gives the minimum value to the objective function f (w), how to obtain h and μ is the key.
The calculation algorithm for the direction vector h includes the most steepest descent method, the conjugate gradient method, the Newton method, the modified Newton method, and the pseudo Newton method ( quasi-Newton method).
In any algorithm for obtaining the direction vector h by the successive approximation method in dose optimization, it is necessary to obtain (at least) the gradient of the objective function f (w). In the case of the present invention, the slope of the objective function f (w) can be obtained by Expression (8).

According to the equation (8), as in the equation (6), the dose gradient suppression term (third term) only shows a partial integration of partial differentiation of the dose response d _{i, j} of the pencil beam.
Therefore, it can be understood that the calculation can be performed in the same calculation loop as the overlap integral of the dose distribution calculation in the pencil beam dose distribution creation step S3.

The dose response d _{i, j} of each pencil beam is factored as shown in Equation (9) in the z direction of the pencil beam giving an integrated dose distribution, and in the x and y directions perpendicular to the z direction. be able to.

Here, d _x (x _i ; x _j , σ _x (z _i ; z _j )) and d _y (y _i ; y _j , σ _y (z _i ; z _j )) in the formula (9) are standards. These can be expressed as equations (10) and (11), respectively.

In the equations (10) and (11), σ _x (z _i ; z _j ) and σ _y (z _i ; z _j ) representing the spread in the x direction and the y direction are functions of the range shifter thickness and depth. And is incorporated as dose source data (see FIG. 3). The dose convolution of in the computer, in advance which was memory table as a function of spread sigma, may be stored in the storage means as a Gaussian filter, which is derived in accordance with the spot position in the CT image sigma _x ( Z _i ; z _j ), σ _y (z _i ; z _j ) can be referred to as an index so that it can be processed appropriately.

  On the other hand, the z-direction component representing the integrated dose distribution may be stored in the storage means as radiation source data (see FIG. 4), for example, by complementing the measured value in the parallel plate ionization chamber.

Taking these into consideration, partial differentials of the dose response d _{i, j} of the pencil beam appearing in the equation (6) with respect to the x direction and the y direction are as shown in the equations (12) and (13).

は、ガウス分布の偏微分である。
従って、例えば、図５Ａに示すガウス分布は、図５Ｂに示すような関数形状のガウス偏微分分布となる。Here, it appears in Equation (12) and Equation (13)

Is the partial derivative of the Gaussian distribution.
Therefore, for example, the Gaussian distribution shown in FIG. 5A becomes a Gaussian partial differential distribution having a function shape as shown in FIG. 5B.

は、線量重畳積分での着目方向についてのガウスフィルターを図５Ｂに示したようなガウス分布の偏微分フィルターに置き換えるのみでよいことになる。In other words, the partial integration of the partial differential in the x and y directions of the pencil beam appearing in equations (6) and (8).

Therefore, it is only necessary to replace the Gaussian filter in the direction of interest in the dose superposition integral with a partial differential filter having a Gaussian distribution as shown in FIG. 5B.

  Therefore, in the calculation code for the irradiation plan, a Gaussian partial differential filter and a Gaussian filter as well as a Gaussian filter may be stored in a memory table as a function of the spread σ. This Gaussian partial differential filter becomes a dose gradient filter (dose gradient kernel).

  On the other hand, the partial differentiation of the pencil beam in the z direction can be obtained by equation (14).

For the first term and the second term of the equation (14), as shown in FIG. 3, the spreads σ _x (z _i ; z _j ), σ _y (z _i ; z _j ) in the x direction and the y direction are , Parameterized as a function of depth and range shifter, and incorporated into a treatment planning calculation engine (eg, IDOSE) for heavy particle beam scanning irradiation using a successive approximation method.

である。
この関数形を概観すれば、図６Ａのような拡がりに対して、図６Ｂのようになる。
重粒子線スキャニング照射用治療計画計算エンジンには、線源データとしてｘ方向およびｙ方向への拡がりσ_x(ｚ_i；ｚ_j)、σ_y(ｚ_i；ｚ_j)が、深さとレンジシフターの関数としてパラメータ化されている。Therefore, the function that appears for the first time in the equation (14) is the partial differential in the depth direction of the expansion in the x and y directions.

It is.
If this function form is overviewed, it will become like FIG. 6B with respect to the expansion like FIG. 6A.
In the treatment plan calculation engine for heavy particle beam scanning irradiation, the spreads σ _x (z _i ; z _j ), σ _y (z _i ; z _j ) in the x direction and the y direction as the source data are set as depth and range shifters. It is parameterized as a function of.

は、式（１５）、式（１６）として容易に計算することができる。Therefore, these partial derivatives

Can be easily calculated as equations (15) and (16).

を割り当てることによって偏微分フィルター（線量勾配カーネル）を作成することができる。These are the same as σ _x (z _i ; z _j ), σ _y (z _i ; z _j ) when creating a pencil beam dose distribution kernel for each pencil beam.

Can be used to create a partial differential filter (dose gradient kernel).

が現れる。Next, looking at the third term of the equation (14), the partial differentiation of the integrated dose d _z (z _i ; z _j ) in the z direction.

Appears.

を割り振れば偏微分フィルター（線量勾配カーネル）を作成することができる。This has a functional form as shown in FIG. 7B with respect to the integrated dose d _z (z _i ; z _j ) as shown in FIG. 7A.
As with the spread in the x and y directions, normal dose calculation and dose optimization can be performed.
In dose optimization, since the integrated dose d _z (z _i ; z _j ) is registered as source data in the treatment plan calculation engine for heavy particle beam scanning irradiation, a pencil beam dose distribution kernel is set for each pencil beam. Partial differentiation according to equation (17) when creating

Can be used to create a partial differential filter (dose gradient kernel).

  As described above, according to one aspect of the evaluation index value deriving step S5, it is possible to obtain a better evaluation index value E by including the calculation loop by the successive approximation method for updating the weight of the pencil beam and the equation (1). (Weight of the pencil beam that realizes the minimum objective function f (w)) can be derived. As a result, a relatively robust plan in which the dose gradient of the pencil beam to be superimposed is suppressed can be obtained in a short time without causing an increase in calculation time.

  Also, by using the pencil beam dose distribution kernel created in the pencil beam dose distribution creation step S3 and its partial differential kernel, the dose overlap integral and partial derivative overlap integral are performed in the same calculation loop, so that it is relatively robust and efficient. Simple plans can be derived.

  FIGS. 8A and 8B show an example of a result created by an irradiation plan creation method to which one aspect of the evaluation index value deriving step S5 is applied, with isodose lines, and FIGS. 9A and 9B. An example of a result created by a conventional irradiation plan creation method that is not robust is shown by an isodose line.

  In FIGS. 8A and 8B, since the dose gradient suppression term (third term) is used, the dose gradient of the portion where the two irradiation fields overlap is suppressed. For this reason, even if a range error or setup error occurs, it is not easily affected and is resistant to these errors.

  On the other hand, in FIGS. 9A and 9B, since the dose gradient suppression term (third term) is not used, a large dose gradient appears at the portion where the two irradiation fields overlap. Therefore, if an error in the range or an error in the setup occurs, it is easily affected, and is vulnerable to these errors.

(Other aspects of evaluation index value deriving step S5)
Then, in another aspect of the evaluation index value deriving step S5, in addition to the first condition, the second condition, and the third condition described above, the successive approximation calculation is further performed using the following fourth condition, and the evaluation index is calculated. A value E is derived, and the evaluation index value E is compared with a preset threshold C to create an irradiation plan.

  Fourth condition: When an error occurs within a preset range, a spot that increases the dose given to the non-irradiated part is not used. The error includes at least one of a range error and a setup error, as will be described later.

  In other words, in another aspect of the evaluation index value deriving step S5, the evaluation index value E is derived so as to suppress the dose gradient and not to use the spot where the dose given to the non-irradiated part is increased. Create an irradiation plan.

(Regarding a mathematical expression embodying another aspect of the evaluation index value deriving step S5)
Next, another aspect of the evaluation index value deriving step S5 will be described.
The magnitude of the error is anisotropic and is specific to the relevant field. As described above, these errors are decomposed into a component parallel to the z direction and a component perpendicular to the z direction.

Uncertainty that leads to range error (hereinafter referred to as “range uncertainty”) is often a component parallel to the z direction.
There are multiple factors in range uncertainty, such as CT artifacts, patient weight gain or weight loss, conversion from Hounsfield units (HU) to stopping power. The range uncertainty is proportional to the water equivalent depth, and in extreme cases the range uncertainty (δR) may be ± 5.0%.

  As for uncertainty due to setup errors (hereinafter referred to as “setup uncertainty”), since the irradiation target can move equally in each direction, it is necessary to consider isotropic uncertainty. Isotropic setup errors are assumed to be independent of setup errors for each field direction, components parallel to the z direction and components perpendicular to the z direction (ie both x and y directions). Component).

A shift parallel to the z-direction causes an increase or decrease in the air gap in the front of the patient, but the result is minimal variation in the dose distribution. Thus, regarding setup uncertainty, it is sufficient to consider a shift perpendicular to each treatment beam.
The x-direction setup uncertainty ΔS _x and the y-direction setup uncertainty ΔS _y are described in Ruts HP and Lomax AJ, “Donut-shaped high dose configuration for proton beam radiation therapy”, Strahlenther. ., 2005, 181, p.49-53, an error of ± 3.0 mm is assumed for each.

As described above, the main objectives of intensity-modulated heavy ion radiotherapy are (i) giving a necessary and sufficient dose in CTV (Clinical Target Volume), and (ii) undesirable to OAR ( Unintentional) to prevent irradiation and limit damage below the dose limit. A robust irradiation plan creation method achieves both objectives simultaneously by combining algorithms for each objective.
For the purpose of (i), Inaniwa T, Kanematsu N, Furukawa T and Noda K, “Robust dual-field optimization of scanned ion beams against range and setup uncertainties”, Phys. Med. Biol., (2010) submitted. The described method can be used.
The target algorithm (ii) will be described below.

  Usually, only a few pencil beams are at risk of irradiating adjacent OARs with high doses in an irradiation plan. In IMIT and IMPT, the dose contribution of such a risky pencil beam can be reduced and compensated by a pencil beam irradiated at a different incident angle.

Therefore, it may be possible to penalize a pencil beam that is at risk of irradiating the OAR with a high dose in optimizing the dose distribution. This is implemented by Equation (18).
This expression (18) is an expression that embodies another aspect of the evaluation index value deriving step S5, and is given to the non-irradiated part when an error occurs in the expression (1) within a preset range. The fourth condition that a spot with a high dose is not used is added as a fourth term. In equation (18), a risk index P _j , which is a quantitative measure characterizing the risk of the j-th pencil beam, is introduced in dose optimization.

In Equation (18), N _l is the number of pencil beams in the irradiation field l, w _j is the weight of the j-th pencil beam, w _k is the weight of the k-th pencil beam, and Q _pb ^R and Q _pb ^S are penalty coefficients for adjusting the importance of the added term, P _j ^R is a risk index of the range of the j-th pencil beam range, and P _j ^S Is a risk measure of the uncertainty of the jth pencil beam setup. Other symbols are according to the example of the formula (1).

In Expression (18), by setting Q _pb ^R = Q _pb ^S = 0, it is possible to obtain an irradiation plan that considers only the range error. Q _x = Q _y = Q _z = Q _pb ^R = Q _By setting _pb ^S = 0, it is possible to obtain a conventional irradiation plan that does not consider the range error and the setup error.

The risk of using a pencil beam increases with the probability that the pencil beam will deliver a high dose to the OAR. Therefore, in order to quantify the risk of one pencil beam irradiated at the j-th, two risk indices, P _j ^R and P _j ^S , are introduced as shown in Expression (18).

Here, calculation of the risk index P _j ^R and the risk index P _j ^S will be described with reference to FIG.
FIG. 10 schematically shows a procedure for calculating the risk index P _j ^R and the risk index P _j ^S by using an RTOG benchmark phantom in which a horseshoe-shaped CTV surrounds a cylindrical OAR. Note that FIG. 10 is based on the premise that the pencil beam is irradiated at an angle of 0 °, as indicated by the thick arrow in FIG. That is, the thick arrow is the z direction, and the direction perpendicular to the z direction on the paper surface of FIG. 10 is the x direction.

  As a first step in the calculation of the two risk indicators, as shown in FIG. 10 (b), to deal with the low dose irradiation of the peripheral area of the CTV due to the range error and the setup error, The volume is expanded to a volume surrounding the CTV and the surrounding area, and an FTV (Field-specific Target Volume) is generated.

  Here, ΔR shown in FIG. 10B is a range error, and is calculated as ΔR = R × δR from the water equivalent depth R of the CTV boundary and the estimated range uncertainty δR. it can.

As a second step in deriving the risk index P _j ^R of the range uncertainty, a “significant organ (ROAR) unique to the corresponding radiation field at risk for the range uncertainty” is generated. Here, as shown in FIG. 10C, ROAR is OAR itself. Therefore, the risk factor F = 1.0 is applied to the entire ROAR.

As a third step, as shown in FIG. 10D, in calculating the risk index P _j ^R, a penumbra is added to the ROAR in consideration of the lateral width of the pencil beam to be scanned.
The penumbra risk factor F is determined by the following equation (19) as a function of the distance l from the ROAR boundary.

In equation (19), σ is the lateral width of the pencil beam at the Bragg peak. σ can be set to 5 mm, for example, but can be arbitrarily set according to the lateral width of the pencil beam.
In Expression (19), when the distance l is a negative value, it means the inside of the ROAR, and when the distance l is a positive value, it means the outside of the ROAR.

Next, the position of each Bragg peak is determined throughout the FTV.
First, in order to calculate the risk index P _j ^R , the range error ΔR _j is calculated as ΔR _j = R _j × δR based on the water equivalent depth R _j for each Bragg peak position.
Further, since there is a range error ΔR, the risk index P _j ^R is defined as a normalized dose irradiated to the OAR as shown in Expression (20) for the j-th pencil beam.

In equation (20), d _j (z) is the plane integral of the dose of the j-th pencil beam normalized for the range from z = 0 to 1.0, and F (z) is the ROAR and its This is a risk coefficient applied to the penumbra, and z _max is the maximum depth of the calculation region along the z direction. Further, the normalization constant 2ΔR _j is a length that F (z) that is not zero can take in the z direction, and D _j (z) is an enlarged Bragg peak calculated by Expression (21).

In equation (21), d (z, r) is a plane integral dose of a pencil beam having a range r, and d _j (z) is equal to d (z, R _j ). Further, in equation (21), it is assumed that the range errors are equal and are in the range of R _j −ΔR _j ≦ r ≦ R _j + ΔR _j .

As a second step in the calculation of the risk parameter P _j ^S for the uncertainty of setup, a “significant organ (SOAR) unique to the corresponding irradiation field at risk for the uncertainty of setup” is generated.
Since there is a setup error ΔS, the risk index P _j ^S is defined as the normalized dose irradiated to the OAR for the j-th pencil beam, similar to the definition of the risk index P _j ^R.

Therefore, for example, as shown in FIG. 10C ′, the SOAR is defined as a region in which the OAR is expanded in the horizontal direction (x direction) by the setup error ΔS.
Further, in calculating the risk index P _j ^S , a penumbra is added to the SOAR as shown in FIG. 10 (d ′) in consideration of the lateral width of the pencil beam to be scanned.
The procedure for applying the risk factor F ′ to the SOAR and its penumbra may be the same as the procedure for ROAR and its penumbra. Therefore, the risk index P _j ^S for the uncertainty of setup can be calculated as in Expression (22).

In equation (22), F ′ (z) is the risk factor applied to the SOAR and its penumbra due to setup uncertainty, and V _OAR is the volume of the OAR. In addition, the denominator of the expression (22) is the average code of the SOAR assuming that the SOAR is a sphere of the volume V _OAR corresponding to the non-zero length in the z direction that F ′ (z) can take. This is a normalization constant representing the length.

  As described above, according to another aspect of the evaluation index value deriving step S5, by providing an equation (18) using a calculation loop by a successive approximation method for updating the weight of a pencil beam and a risk index, It is possible to derive a better evaluation index value (the weight of the beam that realizes the minimum objective function f (w)). As a result, it is possible to obtain a more robust plan in a short time without increasing the calculation time, while suppressing the dose gradient of the pencil beam to be superimposed and not using the spot that increases the dose given to the non-irradiated part. be able to.

  FIGS. 11A and 11B show an example of a result created by an irradiation plan to which another aspect of the evaluation index value derivation step S5 is applied, and FIGS. 12A and 12B show conventional techniques that are not robust. An example of the result created by the irradiation plan is shown.

  In (a) and (b) of FIG. 11, in addition to the dose gradient suppression term (third term), a spot that increases the dose given to the non-irradiated part when an error occurs within a preset range is used. The term (No. 4) is used. Therefore, the dose gradient in the part where the two irradiation fields overlap is suppressed, and the dose distribution immediately before the OAR is suppressed to a low dose. As a result, even if range errors and setup errors occur, they are not easily affected and are resistant to these errors.

  On the other hand, in FIGS. 12A and 12B, since the dose gradient suppression term (third term) is not used, the dose gradient of the portion where the two irradiation fields overlap is large. In addition, since the fourth term is not used, the dose distribution immediately before the OAR is a high dose as seen from the incident direction of the beam. Therefore, if an error in the range or an error in the setup occurs, it is easily affected, and is vulnerable to these errors.

[Irradiation plan creation device]
Next, an irradiation plan creation apparatus according to the present invention will be described.
The irradiation plan creation device according to the present invention includes an irradiation site where radiation is irradiated and a non-irradiation region where radiation should not be irradiated by scanning a pencil beam while modulating intensity by multi-port irradiation and overlapping each spot. An irradiation plan is generated for forming a dose distribution so as to obtain a dose prescription input in advance for the irradiation target.

  Since the irradiation plan creation apparatus according to the present invention causes the computer to function as described above, when calculating the evaluation index value, the sequential calculation based on the first condition to the third condition or the first condition to the fourth condition already described. Perform approximate iteration.

  As an embodiment of the irradiation plan creation apparatus 1 of the present invention, as shown in FIG. 13, a pencil beam irradiation position determination means 2, a pencil beam dose distribution creation means 3, a weight input means 4, and an evaluation index value derivation. Means 5 and output means 6 are included.

  Each of these means is executed by a CPU (Central Processing Unit) executing an irradiation plan creation program according to the present invention, which will be described later, stored in a storage device such as a hard disk drive (not shown) in a computer. This is achieved by realizing the contents of each step described in (1).

  That is, each means of the irradiation plan creation apparatus 1 corresponds to each step of the above-described irradiation plan creation method. That is, the pencil beam irradiation position determination means 2 and the pencil beam irradiation position determination step S2 correspond, the pencil beam dose distribution generation means 3 and the pencil beam dose distribution generation step S3 correspond, and the weight input means 4 and the weight input step. S4 corresponds, evaluation index value deriving means 5 and evaluation index value deriving step S5 correspond, determination means 51 and determination step S51 correspond, weight update means 52 and weight update step S52 correspond, The output means 6 corresponds to the output step S6. Therefore, the detailed description here about the contents of each means is omitted.

  The irradiation plan creation device 1 includes various devices included in a normal computer, such as a RAM, a ROM, and a hard disk drive (all not shown), and also includes display means for performing various displays, and irradiation plans. Information input means (not shown) such as a keyboard, a mouse, an input port for inputting a CT image, and the like for inputting information necessary for obtaining the information are provided.

[Irradiation plan creation program]
The irradiation plan creation program according to the present invention is a non-irradiation in which a computer is scanned with a pencil beam while modulating the intensity by multi-port irradiation, is overlapped for each spot, and is irradiated with radiation and should not be irradiated with radiation. The irradiation target including the region is caused to function so as to create an irradiation plan for forming a dose distribution so that a dose prescription inputted in advance is obtained.

  In order to cause the computer to function as described above, the irradiation plan creation program according to the present invention sequentially calculates the evaluation index value based on the first condition to the third condition or the first condition to the fourth condition already described. Perform approximate iteration.

  As an embodiment of the irradiation plan creation program of the present invention, a computer is provided with a pencil beam irradiation position determination step, a pencil beam dose distribution creation step, a weight input step, an evaluation index value derivation step, a determination step, a weight update step, and an output step. Is executed.

  These steps are sequentially performed in the pencil beam irradiation position determination step S2, the pencil beam dose distribution generation step S3, the weight input step S4, the evaluation index value derivation step S5, the determination step S51, and the weight described in the irradiation plan generation method according to the present invention. This corresponds to the update step S52 and the output step S6. Therefore, the detailed description here is omitted.

  An irradiation plan creation program according to the present invention is recorded on a computer-readable recording medium (not shown) such as a CD-ROM or a flexible disk, and the irradiation plan creation program is recorded from the recording medium by a recording medium driving device (not shown). May be read out, installed in a storage means (not shown), and executed.

  In addition, when a computer (client) that functions as an irradiation plan creation apparatus includes communication means such as a communication network, the irradiation plan creation program according to the present invention is connected to another computer (server) connected via the communication network. Downloading and executing an irradiation plan creation program stored in the computer via a communication network or executing an irradiation plan creation program according to the present invention stored in a server so as to obtain a relatively robust plan It may be. In this case, the result of numerical analysis may be stored in storage means (not shown) provided in the server.

  In order to show the usefulness of the irradiation plan creation method, the irradiation plan creation device, and the irradiation plan creation program according to the present invention, the following examination was performed.

[First embodiment]
In the first embodiment, for an RTOG (Radiation Therapy Oncology Group) benchmark phantom (see FIG. 14) used in an IMRT benchmark test, a 135 °, 225 ° coplanar IMIT irradiation is applied by a conventional method (ie, non-robust irradiation). (Plan) (Comparative Example 1), pencil beam irradiation position determination step S2, creation of the dose distribution of the pencil beam, and the direction of travel of the pencil beam and the direction perpendicular to the travel direction (that is, the travel direction of the pencil beam) Pencil beam dose distribution creation step S3 for creating a partial differential filter for a dose distribution in one direction on a plane perpendicular to the one direction and a direction perpendicular to the one direction), weight input step S4, and evaluation Irradiation plan of the present invention including index value deriving step S5 and output step S6 Comparing the irradiation plan according to the forming method (Example 1).
As a premise for planning, a setup error margin of 4 mm was provided around the horseshoe-shaped PTV in all the x, y, and z directions (see FIG. 15).

In FIG. 16, the result planned by the conventional irradiation plan preparation method (comparative example 1) using only the 1st condition and the 2nd condition is shown.
FIG. 16A is a diagram showing a composite clinical dose distribution according to a conventional irradiation plan, and FIG. 16B shows a dose volume histogram (DVH) of PTV and OAR corresponding to FIG. 16A.
16C and 16D are diagrams showing dose distributions given from 225 ° and 135 ° directions by isodose lines, respectively. As shown in FIGS. 16C and 16D, the 90%, 80%, and 70% lines are very close to each other, and a large dose gradient appears at the portion where the two irradiation fields overlap. Therefore, it can be seen that it is not resistant to range errors or setup errors.

On the other hand, FIG. 17 shows the result planned by the irradiation plan creation method (Example 1) of the present invention using the third condition in addition to the first condition and the second condition according to the expression (1).
FIG. 17A is a diagram showing a combined clinical dose distribution planned by the irradiation plan creation method (robust irradiation plan creation method (Example 1)) of the present invention, and FIG. 17B shows the PTV and OAR corresponding to FIG. 17A. DHV. As shown in FIG. 17B, it can be seen that when the irradiation plan creation method of the present invention is used for planning, there is no deterioration in dose distribution, that is, there is no dose non-uniformity at PTV and no increase in dose application to OAR.
17C and 17D show dose distributions given from 225 ° and 135 ° directions. As shown in FIGS. 17C and 17D, when the irradiation plan creation method of the present invention is used for planning, the dose gradient is suppressed even in the portion where the two irradiation fields overlap, and it can be seen that it is resistant to range errors and setup errors.

When an attempt was made to create an irradiation plan using a Dell Precision 690 workstation equipped with 3.0 GB of RAM, Example 1 using the first condition to the third condition required 2 minutes and 30 seconds. On the other hand, in Comparative Example 1 using only the first condition and the second condition, it took 2 minutes with a computer having the same specifications. Thus, according to the irradiation plan creation method of the present invention, compared with the irradiation plan by the conventional method that is currently generally performed (irradiation plan that is not robust), without significantly extending the calculation time, We were able to get a relatively robust plan.
Moreover, as already stated, in order to obtain a robust plan by the approach described in Non-Patent Document 1, it takes several days (for example, 2-3 days), according to the irradiation plan creation method of the present invention, A relatively robust plan could be created (determined) in just a few minutes.

[Second Example]
In the second embodiment, as an example of patch irradiation in the maximum irradiation field, for the uterine cancer to be irradiated, two vertical pre-irradiations (that is, from the front and the side with respect to the uterine cancer to be irradiated) Irradiation plan for pre-irradiation) was performed.

  18A and 18B, only the first condition and the second condition (not using the dose gradient suppression term (third condition)) are used. The irradiation plan for patch irradiation created by the conventional irradiation plan creation method (Comparative Example 2) ) Shows the combined dose distribution. In addition, FIGS. 18C and 18D show the dose distribution of each pencil beam (Beam1, Beam2) that is the basis of the combined dose distribution. Both distributions had dense isodose lines and a steep dose gradient.

  Next, FIGS. 18E and 18F show dose distributions generated when the distance between Beam1 and Beam2 is reduced by 4 mm due to setup errors. Thus, when the interval between the beams from each irradiation direction was reduced, remarkable overdose was observed at two locations, and a high dose of 115% or more was given to the region. This region corresponds to a position where a steep dose gradient appears in FIGS. 18C and 18D.

Further, FIGS. 18G and 18H show dose distributions generated when the distance between Beam1 and Beam2 is 4 mm apart due to setup errors. As described above, when the distance between the beams from the respective irradiation directions is increased, an underdose of 90% or more occurs in the same region.
The DVH corresponding to each dose distribution is shown in FIG. 18I.

  On the other hand, the pencil beam irradiation position determination step S2 and the creation of the pencil beam dose distribution, as well as the pencil beam dose for creating the partial differential filter for the direction of travel of the pencil beam and the dose distribution in the direction perpendicular to the direction of travel. Irradiation of the present invention includes a distribution creation step S3, a weight input step S4, an evaluation index value deriving step S5 using the equation (1), and an output step S6 (that is, including the first condition to the third condition). FIG. 19A and FIG. 19B show the combined dose distribution in the patch irradiation plan (Example 2) to which the plan creation method is applied. In addition, FIGS. 19C and 19D show the dose distributions of the beams (Beam1, Beam2) from the respective irradiation directions that are the basis of the combined dose distribution. In both distributions, the isodose lines were almost evenly spaced and a gradual dose gradient occurred.

  Next, FIGS. 19E and 19F show dose distributions generated when the distance between Beam1 and Beam2 is reduced by 4 mm due to an error in setup. Thus, when the beam interval from each irradiation direction is reduced, an overdose of about 105% is recognized, but the overdose is smaller than that of the conventional method.

In addition, FIGS. 19G and 19H show dose distributions generated when the distance between Beam1 and Beam2 is 4 mm away due to setup errors. As described above, when the distance between the beams from each irradiation direction is increased, an under dose of about 95% occurs in the same region, but the degree of the under dose is smaller than that in the conventional method.
The DVH corresponding to each dose distribution is shown in FIG. 19I.

When an attempt was made to create an irradiation plan using a Dell Precision 690 workstation equipped with 3.0 GB of RAM, Example 2 using the first to third conditions required 2 minutes and 30 seconds. On the other hand, in Comparative Example 2, it took 2 minutes with a computer having the same specifications. As described above, according to the irradiation plan creation method of the present invention, it is relatively possible to extend the calculation time as compared with the irradiation plan (non-robust irradiation plan) according to the conventional method that is currently generally performed. I was able to get a robust plan.
Moreover, as already stated, in order to obtain a robust plan by the approach described in Non-Patent Document 1, it takes several days (for example, 2-3 days), according to the irradiation plan creation method of the present invention, A relatively robust plan could be created (determined) in just a few minutes.

[Third embodiment]
In the third embodiment, for the RTOG benchmark phantom-like shape shown in FIG. 20, when an error occurs within a preset range, a spot that increases the dose given to the non-irradiated part is not used. We examined the effectiveness of the robust optimization method using the term (fourth term).

  The RTOG benchmark phantom-like shape shown in FIG. 20 is provided with a cylindrical OAR having a diameter of 30 mm and a height of 40 mm at the center of a cylindrical body having a diameter of 232 mm and a height of 80 mm that is regarded as a patient. The OAR is surrounded by a horseshoe CTV having an inner diameter of 36 mm, an outer diameter of 80 mm, and a height of 40 mm.

This RTOG benchmark phantom-like shape was assumed to be uniform and equivalent to water. The size of the voxel is Δx = Δy = Δz = 2.0 mm.
Then, as shown by broken lines in FIG. 20, three beams irradiated at 315 °, 0 °, and 45 ° were examined. That is, each irradiation field is formed by a beam incident from these angles.

  Inaniwa T, Furukawa T, Sato S, Tomitani T, Kobayashi M, Minohara S, Noda K and Kanai T, “Development of treatment planning for scanning irradiation at HIMAC”, Nucl. Instrum. Methods. Phys. Res. B, 266 ( 2008), p.2194-2198, the pencil beam algorithm was used for dose calculation. In the third embodiment, an IMPT using a 146 MeV proton beam was assumed. The maximum depth of the Bragg peak of a 146 MeV proton beam is 150 mm in water.

  In the third embodiment, the range of the beam was shifted using a range shifter installed 600 mm upstream from the isocenter. Further, the width of the pencil beam in the third embodiment is assumed to be 4.0 mm at the incident position of the cylindrical body that is assumed to be a patient in the absence of the range shifter, and the spread of the beam due to the insertion of the range shifter is calculated as a dose. Sometimes considered. For each irradiation field, a Bragg peak is formed on a square grid regularly arranged at intervals of 3 mm in the beam traveling direction (z direction) and the lateral direction (x direction and y direction) on the plane perpendicular to the beam traveling direction. Was arranged.

Under the above-mentioned conditions, seven different irradiation plans (plan Nos. 1 to 7) are prepared, and optimization parameters D _T ^max , D _T ^min , D _O ^max , Q _T ^o , Q _T ^u and Q _{O are used.} ^o was fixed at 3.0 Gy, 3.0 Gy, 1.0 Gy, 1.0, 2.0 and 2.0, respectively.
Plan No. Table 1 shows an outline of other optimization parameters in 1-7. In this study, the penalty coefficients Q _x , Q _y , Q _z , Q _pb ^R and Q _pb ^S were provisionally set to the values shown in Table 1.

Q _x , Q _y , Q _z , Q _pb ^R, and Q _pb ^S shown in Table 1 are parameters related to the matters described in the formula (1) and the formula (18). δR is a parameter set as the range uncertainty, ΔS _x is a parameter set as the x direction setup uncertainty, and ΔS _y is the y direction setup uncertainty. The parameter to be set. T is the calculation time required for creating each plan, and N _pb is the total number of spots used for creating each plan.

The results and examination of the third example are as follows.
[1] Range Uncertainty As mentioned above, the main purpose of intensity-modulated heavy ion radiotherapy is to maintain a dose range within (i) CTV (Clinical Target Volume). (Ii) to prevent unwanted (unintentional) irradiation of the OAR.

In order to examine the sensitivity to the range uncertainty in the robust irradiation plan creation method using the fourth term (that is, the sensitivity to influence), the plan No. 1-3 were compared.
Plan No. 1 is a conventional irradiation plan that does not take uncertainty into consideration at all.
Plan No. 2 is an irradiation plan for dealing with uncertainty in the range considering only (ii).
And plan no. 3 is an irradiation plan that deals with range uncertainty considering (i) and (ii).

21 (a) to 21 (c) are plan Nos. 1 shows the dose distribution created (determined).
Figures 21 (a) and (b) show the dose contribution of each beam at 0 ° and 45 °. The dose contribution from the 315 ° beam is a mirror image of the 45 ° beam dose because the phantom is symmetrical, but is not shown in FIG.
FIG. 21 (c) shows plan no. 1 shows the combined dose distribution with the dose contributions from all three fields planned in 1 superimposed.

As shown in FIG. In No. 1, when no range error occurs, a very uniform dose distribution with respect to CTV and good maintenance of OAR can be realized.
This gives a high weight to the Bragg peak located just before the OAR in the optimization, giving a significantly non-uniform dose distribution by the individual beams. That is, the plan No. In 1, the high dose is given immediately before the OAR, and a steep dose gradient is formed between the OAR and the CTV, thereby maintaining the OAR well.

However, since there is actually range uncertainty (error), plan no. The features expected at 1 may be reduced.
Therefore, in order to analyze the uncertainty of the range, plan no. 1 was recalculated with geometric perturbations. The perturbation refers to adding a slight disturbance to the main movement and an additional term for that purpose.

  The recalculation was performed by deliberately shifting the range by 1% from -5% to + 5%, including the planned density. A dose volume histogram (DVH) corresponding to these 11 recalculated dose distributions is shown in FIG.

The sensitivity of the conventional IMPT plan (plan No. 1) to range uncertainty was clearly observed in FIG. 22 (a). Specifically, significant overdose for OAR was observed along with significant underdose for CTV.
Plan No. In the case of 1, the 95% dose (D95) in the CTV is 54.8% (1.64 Gy) and the maximum dose delivered to the OAR is 103.2% (3.10 Gy) in the worst case. ).

Next, FIGS. 21D to 21F show the plan Nos. 2 shows the dose distribution created (determined).
Figures 21 (d) and 3 (e) show the dose contribution from each of the 0 ° and 45 ° beams. In addition, plan No. As in the case of 1, the dose contribution from the 315 ° beam is not shown.
FIG. 21 (f) shows plan no. 2 shows the combined dose distribution overlaid with the dose contributions from all three fields planned in 2.

Plan No. 2 penalized a pencil beam with a high risk index P _j ^R for range uncertainty. For this reason, a pencil beam having a Bragg peak arranged immediately before OAR is preferably avoided in dose optimization.

  This plan No. 2, in order to preserve the OAR, the dose attenuation of the side of the pencil beam arranged next to the OAR is used instead of the dose attenuation of the end of the pencil beam arranged to stop immediately before the OAR. . In addition, the plan No. In No. 2, by generating FTV, the high dose region is slightly expanded in the z direction to compensate for the underdose in the peripheral region of the CTV due to range uncertainty.

Plan No. These features in 2 can avoid both OAR overdose when the range is expanded and CTV underdose when the range is reduced. However, the dose distribution of each beam remains non-uniform in the z direction.
Therefore, plan no. For plan 2, the plan no. The dose distribution was recalculated with the same perturbation as in 1. FIG. 22 (b) shows DVH related to these dose distributions.

As shown in FIG. 22 (b), the sensitivity of the irradiation plan to the range uncertainty is the plan no. 2 is considerably reduced, but due to the non-uniform dose distribution of each beam, the CTV DVH is no longer known as plan no. Compared with the case where the dose distribution was formed as planned in 2, it was slightly deteriorated.
Plan No. In the case of 2, the CTV D95 was 90.5% (2.72 Gy) and the maximum dose delivered to the OAR was 74.3% (2.23 Gy) in the worst case.

Next, FIG. 3 shows the dose distribution created (determined).
Figures 21 (g) and (h) show the dose contribution from each of the 0 ° and 45 ° beams. In addition, plan No. As in the case of 1, the dose contribution from the 315 ° beam is not shown.
FIG. 21 (i) shows plan no. 3 shows the combined dose distribution with the dose contributions from all three fields planned in 3.

Plan No. The irradiation plan of No. 3 is qualitatively shown in FIG. Same as 2. In other words, both plans use dose attenuation on the side of the pencil beam placed next to the OAR instead of the dose attenuation at the end of the pencil beam placed to stop just before the OAR to preserve the OAR. doing.
In addition, plan No. In No. 3, since the dose gradient suppression term is effective, the high dose region is slightly enlarged in the z direction of each beam, and a wide and uniform dose distribution is formed in the z direction.

  Plan No. For plan 3, plan no. The dose distribution was recalculated with the same perturbation as 1 and 2. FIG. 22 (c) shows DVH relating to these dose distributions.

As shown in FIG. 22 (c), the sensitivity of the irradiation plan to the uncertainty of the range is the plan no. 3 significantly reduced.
In addition, the plan No. In contrast to 2, a uniform dose distribution was formed in the CTV even in the presence of range uncertainty.
Plan No. In case 3, the D95 in the CTV was 93.8% (2.81 Gy), and the maximum dose irradiated to the OAR was 67.2% (2.02 Gy) in the worst case.

[2] About Uncertainty of Setup In order to examine the sensitivity to the uncertainty of setup in the robust irradiation plan creation method using the fourth term, the plan no. 1, 4, 5 were compared.
Plan No. 1 is a conventional irradiation plan that does not take uncertainty into consideration as described above.
Plan No. 4 is an irradiation plan for dealing with the uncertainties of the setup in consideration of only the above (ii).
Plan No. Reference numeral 5 denotes an irradiation plan that deals with the uncertainties of the setup in consideration of the above (i) and (ii).

23 (a) to 23 (c) are similar to the plan No. 5 in the same manner as FIGS. 1 shows the dose distribution created (determined).
For analysis of setup uncertainty, plan no. 1 was recalculated with geometric perturbations.
It should be noted that setup uncertainty can occur in the dose distribution of each of the three fields. Therefore, the calculation was performed by intentionally moving ± 3 mm in both the x and y directions.
That is, if the set-up position as planned is included in this, nine dose distributions are obtained for each irradiation field. Therefore, since there are 9 ³ = 729 possible combinations of the combined dose distribution for each irradiation field, these were recalculated. FIG. 24A shows DVH of 729 dose distributions.

  Since the dose attenuation on the side of the pencil beam is not as steep as the end dose attenuation, the sensitivity of the conventional irradiation plan to set-up uncertainty is not as critical as the sensitivity to range uncertainty. However, the setup error is still the plan no. 1 may lead to degradation of the dose distribution.

  As shown in FIG. In case 1, the D95 in the CTV was 85.2% (2.56 Gy) and the maximum dose delivered to the OAR reached 69.0% (2.07 Gy) in the worst case.

Next, FIG. 4 shows the dose distribution created (determined).
Figures 23 (d) and (e) show the dose contribution from each of the 0 ° and 45 ° beams. For the same reason as before, illustration of the dose contribution from the 315 ° beam is omitted.
FIG. 23 (f) shows plan No. Figure 4 shows the combined dose distribution with the dose contributions from all three fields planned in 4.

  In order to deal with the underdose in the peripheral region of the CTV due to setup error in FTV, the high dose region was expanded transversely.

Plan No. 4 penalized a pencil beam with a high risk index P _j ^S for set-up uncertainty. Therefore, a pencil beam placed close to the side of the OAR is penalized by dose optimization.

  Therefore, the plan No. 4, the dose attenuation at the end of the Bragg peak is preferably used to generate a dose gradient between CTV and OAR. However, the dose distribution provided by each beam is non-uniform across, as shown in FIGS. 23 (d) and (e).

  Therefore, there are 729 combinations with possible setup errors. The dose distribution of 4 was recalculated. The DVH of these dose distributions is shown in FIG.

Because of set-up errors, pencil beams that are at risk of delivering high doses to the OAR are penalized in dose optimization. Therefore, the maximum dose irradiated to the OAR could be suppressed to 53.6% (1.61 Gy) even in the worst case.
However, the D95 in the CTV was reduced to 83.9% (2.52 Gy) due to the non-uniform dose distribution provided by each beam.

Next, FIG. 5 shows the dose distribution created (determined).
FIGS. 23 (g) and (h) show the dose contribution from each 0 ° and 45 ° beam. For the same reason as described above, the dose contribution from the 315 ° beam is not shown.
FIG. 23 (i) shows plan no. 5 shows the combined dose distribution obtained by superimposing all three irradiation fields planned in 5.

  In the irradiation plan shown in FIG. 23 (i), the dose attenuation at the end of the Bragg peak is preferably used to generate a dose gradient between the CTV and the OAR, and is close to the side of the OAR in the optimization. A low weight is applied to the pencil beam placed in

  Plan No. These features of No. 5 are planned No. This is the same as the feature 4. However, plan no. In contrast to 4, the dose distribution given by each beam was uniform across, as shown in FIGS. 23 (g) and (h).

As before, plan no. 5 was recalculated for 729 possible combinations of setup errors. The DVH of these dose distributions is shown in FIG. As shown in FIG. 24 (c), the sensitivity of the dose plan to the setup uncertainty is the plan no. Even 5 was reduced.
As shown in FIG. In the case of 5, the D95 in the CTV was 90.1% (2.70 Gy), and the maximum dose irradiated to the OAR was 55.5% (1.67 Gy) in the worst case.

[3] Uncertainty of range and setup As described in [1] above, when considering the range uncertainty in the irradiation plan, the dose attenuation on the side of the pencil beam is between CTV and OAR. It was preferably used to generate a dose gradient. In addition, the dose distribution in each irradiation field was flattened in the z direction.
However, as described in [2] above, the dose attenuation at the end of the Bragg peak is preferably used to generate a dose gradient between CTV and OAR when taking into account setup uncertainty in dose planning. The dose distribution in each field was flattened across.

  These characteristics are exactly contradictory. Therefore, if both range and set-up uncertainties are considered simultaneously in the dose plan, a compromise between these two conflicting objectives will be found.

To examine this point, plan no. 3, plan no. 6, plan no. 7 irradiation plans were compared.
In these plans, the range uncertainty optimization parameters Q _z , Q _pb ^R and δR were set to 1 × 10 ² , 1 × 10 ⁴ and 5%, respectively.
The setup uncertainty penalty factors Q _x , Q _y and Q _pb ^S were set as shown in Table 1. That is, each of the plan Nos. 3 is 0, 0, 0, and the plan No. 6 was 8.0, 8.0, 5 × 10 ³ , and Plan 7 was 32, 32, 2 × 10 ⁴ .
The dose contribution from each 0 ° and 45 ° beam in these plans is shown in FIG.

  Plan No. 3 avoids assigning a high weight to the Bragg peak arranged immediately before the OAR. Therefore, as shown in FIGS. 25A and 25D, the dose distribution of the pencil beam arranged beside the OAR is increased, and valleys are formed.

  Plan No. 6 and plan no. 7 increases the penalty factor for setup uncertainty. Therefore, as shown in FIGS. 25B and 25E and FIGS. 25C and 25F, the valleys are filled with the flat shape of the lateral dose.

  The results of these simulations are based on Pflugfelder D, Wilkens JJ and Oelfke U, “Worst case, which applied the worst case optimization algorithm to optimize the dose distribution for a horseshoe-shaped target volume that simulated the periphery of the spinal cord. Optimization: a method to account for uncertainties in the optimization of intensity modulated proton therapy ”, Phys. Med. Biol. 53 (2008), p.1689-1700.

[4] Calculation time Plan No. using Dell Precision 690 workstation with 3.0 GB of RAM. The calculation times of the seven irradiation plans 1 to 7 are as shown in T of Table 1.

As shown in Table 1, plan No. which is a conventional irradiation plan. The calculation of 1 took 4 minutes.
On the other hand, the plan No. considering only the uncertainty of the range. The calculation of 3 took 9 minutes. In addition, the plan no. The calculation of 5 took 8 minutes.
And plan No. which considered uncertainty of both range and setup at the same time. 6 and plan no. The calculation of 7 took 11 minutes.

Table 1 also shows the total number of pencil beams N _pb irradiated in each irradiation plan.
Plan No. Calculation time and plan No. The ratio of calculation time required in 1 is about the same as the ratio of N _pb in these plans. This relationship is related to plan no. 4 and plan no. Also seen between 1.

  These facts mean that the calculation time required for the term penalizing a pencil beam with a high risk index, ie the last fourth term of equation (18), is almost negligible.

  On the other hand, the calculation time is the plan no. Compared to the plan no. 3 becomes longer and the plan no. Plan No. 4 5 is longer because the dose gradient suppression term (third term) is introduced into the objective function.

  As described above, in the third embodiment, the irradiation plan creation method according to the present invention is applied to an RTOG benchmark phantom-like shape that is assumed to be equivalent and uniform to water. As a result, it was possible to obtain a robust irradiation plan in which the sensitivity of the irradiation plan was reduced with respect to the range error and the setup error.

[Conclusion]
As explained in the first to third embodiments, the conventional irradiation plan is very sensitive and sensitive to the range error and the setup error.
However, in the irradiation plan creation method according to the present invention, the third condition (third term) for suppressing the gradient of the dose distribution given to the irradiation object from the irradiation direction inputted in advance, or the third condition (third term) In addition to the above, if an error occurs within a preset range, iterative approximate calculation using the fourth condition (fourth term) that does not use a spot that increases the dose given to the non-irradiated part By creating (determining) the irradiation plan, it was possible to significantly reduce the effects of range errors and setup errors.

  For example, when a range error occurs, the 95% dose in the CTV in the conventional irradiation plan was 54.8%, but increased to 93.8% in the method of the present invention. On the other hand, in the conventional irradiation plan, the maximum dose irradiated to the OAR was 103.2% in the worst case, but was reduced to 67.2% in the method of the present invention.

  On the other hand, if setup errors occur, the 95% dose in CTV in the conventional irradiation plan was 85.2%, but increased to 90.1% in the method of the present invention. On the other hand, in the conventional irradiation plan, the maximum dose irradiated to the OAR was 69.0% in the worst case, but was reduced to 55.5% in the method of the present invention.

  The irradiation plan creation method, apparatus, and program according to the present invention can obtain a robust irradiation plan that is hardly affected by the range error and the setup error in a short time.

S1 Information input step S2 Pencil beam irradiation position determination step S3 Pencil beam dose distribution creation step S4 Weight input step S5 Evaluation index value derivation step S51 Determination step S52 Weight update step S6 Output step 1 Irradiation plan creation device 2 Pencil beam irradiation position determination means 3 Pencil beam dose distribution creation means 4 Weight input means 5 Evaluation index value derivation means 51 Determination means 52 Weight update means 6 Output means

Claims (4)

A pencil beam is scanned while modulating the intensity by multi-port irradiation and superimposed for each spot, and input in advance for irradiation targets that include irradiation sites that should be irradiated with radiation and non-irradiated sites that should not be irradiated. In creating an irradiation plan to form a dose distribution so that the prescribed dose prescription is obtained,
With respect to the weight of the input pencil beam, a first condition that a necessary and sufficient dose is given to a pre-input target dose with respect to the irradiation portion input in advance,
For the non-irradiated part input in advance, the second condition of suppressing below the dose limit input in advance,
It is an irradiation plan creation device for deriving an evaluation index value by performing successive approximation iteration calculation including, and creating the irradiation plan based on the evaluation index value,
In addition to the first condition and the second condition, the successive approximation iterative computing means for performing the successive approximation iterative calculation further includes:
The irradiation plan creation apparatus, wherein the evaluation index value is derived using a third condition of suppressing a gradient of the dose distribution given to the irradiation target from an irradiation direction input in advance. An irradiation plan creation device according to claim 1 ,
In addition to the first condition, the second condition, and the third condition, the successive approximation iterative calculation means further includes:
An irradiation plan characterized in that, when an error occurs within a preset range, the evaluation index value is derived using a fourth condition that a spot that increases the dose given to the non-irradiated part is not used. Creation device. A pencil beam is scanned while modulating the intensity by multi-port irradiation and superimposed for each spot, and input in advance for irradiation targets that include irradiation sites that should be irradiated with radiation and non-irradiated sites that should not be irradiated. In creating an irradiation plan to form a dose distribution so that the prescribed dose prescription is obtained,
Computer
With respect to the weight of the input pencil beam, a first condition that a necessary and sufficient dose is given to a pre-input target dose with respect to the irradiation portion input in advance,
For the non-irradiated part input in advance, the second condition of suppressing below the dose limit input in advance,
Is an irradiation plan creation program that functions as a successive approximation iteration calculation means for deriving an evaluation index value by executing a successive approximation iteration calculation including, and creating the irradiation plan based on the evaluation index value,
In addition to the first condition and the second condition, the successive approximation iterative calculation means further includes:
An irradiation plan creation program, wherein the derivation of the evaluation index value is executed using a third condition of suppressing a gradient of the dose distribution given to the irradiation object from an irradiation direction input in advance. An irradiation plan creation program according to claim 3 ,
In addition to the first condition, the second condition, and the third condition, the successive approximation iterative calculation means further includes:
When the error occurs within a preset range, the evaluation index value is derived using the fourth condition that a spot that increases the dose given to the non-irradiation site is not used. Planning program.

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