WO2019198478A1 - 照射計画装置、照射計画方法、および荷電粒子照射システム - Google Patents

照射計画装置、照射計画方法、および荷電粒子照射システム Download PDF

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WO2019198478A1
WO2019198478A1 PCT/JP2019/012590 JP2019012590W WO2019198478A1 WO 2019198478 A1 WO2019198478 A1 WO 2019198478A1 JP 2019012590 W JP2019012590 W JP 2019012590W WO 2019198478 A1 WO2019198478 A1 WO 2019198478A1
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irradiation
specific energy
dose
average specific
domain
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Japanese (ja)
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拓 稲庭
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National Institutes For Quantum Science and Technology
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National Institutes For Quantum Science and Technology
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/103—Treatment planning systems
    • A61N5/1031—Treatment planning systems using a specific method of dose optimization
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1077—Beam delivery systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/103—Treatment planning systems
    • A61N5/1031—Treatment planning systems using a specific method of dose optimization
    • A61N2005/1034—Monte Carlo type methods; particle tracking
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N2005/1085—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy characterised by the type of particles applied to the patient
    • A61N2005/1087—Ions; Protons

Definitions

  • the present invention relates to, for example, an irradiation planning apparatus, an irradiation planning method, and a charged particle irradiation system that determine irradiation parameters of a charged particle irradiation system that irradiates a target by accelerating charged particles generated by an ion source with an accelerator.
  • SMK model a probabilistic microdosimetric kinetic model (see Non-Patent Documents 1 and 2) has been proposed as a method for estimating RBE of a heavy particle radiotherapy field (mixed field).
  • This SMK model is known to reproduce experimental values well, including high doses and high LET radiation.
  • this model is a method for estimating the cell killing effect (biological effect) of the radiation from the specific energy given to the domain and cell nucleus by the radiation.
  • it is necessary to calculate the distribution of specific energy (specific energy spectrum) given to the domain and cell nucleus by the heavy particle beam at each position in the irradiation field. For this reason, in the treatment plan of the scanning irradiation method which requires a successive approximation repetition calculation, calculation time is too long and it was difficult to apply this model in the field of actual treatment.
  • an object of the present invention is to provide an irradiation planning apparatus, an irradiation planning method, and a charged particle irradiation system that can accurately predict RBE of a mixed field in a short time and determine irradiation parameters. .
  • the present invention is an irradiation planning apparatus that includes a storage unit that stores data and a calculation unit that performs calculation, and that generates irradiation parameters when a charged particle is irradiated as a pencil beam.
  • the storage unit includes: Domain dose average specific energy, which is a dose average specific energy, cell nucleus dose average specific energy, which is a dose average specific energy of a cell nucleus including a large number of the domains, and domain saturation dose average specific energy, which is a saturation dose average specific energy of the domain
  • the calculation means is configured to store the biological effect at the position of interest from the domain dose average specific energy, the cell nucleus dose average ratio energy, and the domain saturation dose average ratio energy given from the pencil beam to the position of interest. And predicting the irradiation parameters based on the biological effect. Determining the irradiation planning device, characterized in that it is a charged particle irradiation system using irradiation planning method, and the same.
  • an irradiation planning apparatus capable of accurately determining RBE of a mixed field in a short time and determining irradiation parameters.
  • the system block diagram of a charged particle irradiation system Explanatory drawing explaining the measured cell viability and the estimated cell viability.
  • Z - d, D, Z - * d, D, Z - n illustration of a graph showing the dose average specific energy per event D.
  • the present inventor uses carbon beams or heavier particles, or combines light particles with carbon beams or heavier particles in order to increase the dose of radiation in one treatment and shorten the treatment period.
  • we conducted intensive research we conducted intensive research. And invented an arithmetic expression that can be calculated at a calculation speed that can be used at the actual treatment site with higher accuracy than the calculation used in the case of the conventional carbon beam, and an irradiation planning device using this arithmetic expression, Invented a particle beam irradiation system for irradiating a particle beam using irradiation parameters determined by this irradiation planning apparatus.
  • the specific energy which is the absorbed dose by each domain, becomes a random variable that varies depending on the domain throughout the cell population. Ionizing radiation is presumed to cause two types of damage in the domain, lethal and sublethal damage.
  • a lethal injury is lethal to the domain that contains the injury.
  • Sublethal damage is non-lethal at generation and can combine with other sublethal damage that occurs in the domain to become lethal, spontaneously turn into lethal damage, or spontaneously heal .
  • Domain death causes inactivation of cells containing the domain.
  • the generation number of each damage is proportional to the saturation specific energy z ′ d of the domain given by [Equation 1].
  • z 0 is a saturation parameter that represents a decrease in the number of complex DNA damage per dose in the high LET region (Hada and Georgakilas 2008 * 1). * 1: Hada M and Georgakilas AG 2008 Formation of clustered DNA damage after high-LET irradiation: a review J. Radial. Res.
  • the survival rate s d of the domain subjected to z d is determined as the probability that there is no lethal damage in the domain, and its natural logarithm is calculated by [Equation 2].
  • a and B are parameters independent of the energy imparted by radiation.
  • the natural logarithm of the survival rate S n of cells undergoing specific energy z n of the cell nucleus can be represented by [Equation 3].
  • f d (z d , z n ) is the probability density of the specific energy z d of the domain in the cell nucleus that receives the specific energy z n of the cell nucleus.
  • f n (z n , D) is the probability density of z n in the cell population irradiated with the macroscopic dose D, and has the following relationships of [Equation 5] and [Equation 6].
  • Non-Patent Document 1 a calculation model for calculating f d (z d , z n ) and f n (z n , D) under a given irradiation condition was developed, and [Equation 3] and [Equation 4]. was solved numerically.
  • Non-Patent Document 1 further assumes that the saturation effect caused by multiple irradiation events on the domain is negligibly small, and f d, 1 ( The convolution integral of z d ) was omitted. Then, lnS n can be simplified as [Equation 8].
  • Non-Patent Document 1 estimates the cell viability using the SMK model, and the dose range in which they are used in most charged particle beam therapy (for example, if the therapeutic carbon ion beam is D equal to 10 Gy) It was found that when [Equation 3] and [Equation 4] are solved directly for absorbed doses less than that, they are almost the same.
  • the stored f n, 1 (z n ) is then used to update f n (z n , D) at each position in the field at each iteration of the successive approximation operation. Therefore, at least in computers commonly used in commercial treatment planning systems, adaptation of the SMK model to a scanning charged particle beam treatment treatment plan is difficult both in terms of time and storage area.
  • the inventors have devised a new model as ⁇ modified SMK model> described below, and solved the problem. I planned.
  • ⁇ Modified SMK model> In charged particle therapy, the domain specific energy z d is generally composed of a number of low energy application events, and rare events that induce saturation of complex DNA damage. In other words, events where z d > z o are rare.
  • Equation 8 can be transformed into [Equation 14] by [Equation 15] and [Equation 16].
  • InS can be transformed into [Equation 23] using [Equation 19] to [Equation 21], or can be transformed into [Equation 24] in the form of cell survival rate.
  • ⁇ Determination of parameters of modified SMK model> parameters necessary for estimating the cell survival rate are ⁇ 0 in [Equation 15], ⁇ 0 in [Equation 16], saturation parameter z 0 in [Equation 1], and the radius of the domain, respectively.
  • r d and cell nucleus radius R n .
  • r d is Z - is used to derive a * d
  • D R n is Z - - d
  • D and Z n are used to derive D.
  • the radius R n can be measured directly with an optical microscope.
  • R n is, as a 16 result of measuring the R n of human cell lines, in the range of 6.7 .mu.m ⁇ 9.5 .mu.m, it has been reported that the average is 8.1 ⁇ m in (Suzuki et al 2000 ⁇ 2).
  • Suzuki M Kase Y, Yamaguchi H, Kanai T and Ando K 2000 Relative biological effectiveness for cell-killing effect on various human cell lines irradiated with heavy-ion medical accelerator in chiba (HIMAC) carbon-ion beams Int. J Radiat. Oneal. Biol. Phys. 48 241-250
  • the cell viability is the dose average specific energy Z ⁇ d, D and Z ⁇ * d, D per event given to the domain and the dose average specific energy Z ⁇ n per event given to the cell nucleus. , D from [Equation 24].
  • the specific energy is derived by a known calculation procedure (Inaniwa et al 2010 * 3). * 3: Inaniwa T, Furukawa T, Kase Y, Matsufuji N, Toshito T, Matsumoto Y, Furusawa Y and Noda K 2010 Treatment planning for a scanned carbon ion beam with a modified microdosimetric kinetic model. Phys. Med. Biol. 55 6721 -37
  • the sensitive volume of the domain and cell nucleus is assumed as a cylinder of water with radii r d and R n and lengths 2r d and 2R n respectively.
  • Incident ions traverse around the sensitive volume with a uniform probability and their paths are always parallel to the cylinder axis.
  • the radial dose distribution around the orbit of ions is described by the Kiefer-Chatterjee amorphous ion track structure model (Chatterjee and Schaefer 1976 * 4, Kiefer and Straten 1986 * 5, Kase et al 2006 * 6). * 4: Chatterjee A and Schaefer H J 1976 Microdosimetric structure of heavy ion tracks in tissue Radial. Environ. Biophys.
  • SMK parameters other than R n are changed stepwise, and the parameter values that minimize the total square deviation of log 10 S calculated in [Equation 25] are determined as their optimum values.
  • S i, exp , S i, cal are measured and indicate the survival rate estimated under the i-th irradiation condition, and the number n of survival rate data used in the regression for each cell line is approximately 300. Met.
  • MK model parameters were determined separately to reproduce the same in vitro experimental data of HSG and V79 cells.
  • the measured cell survival data for the 3 He, 12 C and 20 Ne ion beams were used directly in this embodiment rather than the 10% survival dose obtained from the data. Otherwise, the procedure of Inaniwa et al 2010 * 3 was followed.
  • ⁇ x and ⁇ x are the linear and quadratic coefficients of the LQ model of the reference radiation.
  • the natural logarithm of the survival rate in the therapeutic irradiation field (mixed field) of the therapeutic charged particle beam at the position x, lnS (D), is expressed by [Equation 27].
  • Z ⁇ d, D, mix and Z ⁇ * d, D, mix are the dose average specific energy and saturation dose average specific energy per event absorbed in the domain
  • Z ⁇ n, D, mix are The average energy of the dose per event absorbed by the cell nucleus of the mixed field.
  • the absorbed dose D at x is expressed by [Equation 28].
  • d j is a dose given by the scanning pencil beam of the j-th spot (j-th beamlet) with respect to x
  • w j is the number of incident ions of the j-th beamlet.
  • the specific energy at x in the mixing field is described as follows: Where Z ⁇ d, D, j and Z ⁇ * d, D, j are the dose average specific energy and saturation dose average specific energy for each event of the domain given by the j th beamlet for x, Z ⁇ d, D, j are dose average specific energies for each nuclear event by the j-th beamlet with respect to x.
  • the number of particles w for all beamlets must be determined by successive approximation iterations to achieve the desired biological dose distribution for the patient.
  • the analysis solution of the biological dose gradient with respect to the number of particles w j (see [Expression 36] described later) is used in a successive approximation iterative calculation algorithm, for example, a quasi-Newton method. Details of this will be described later in the supplementary explanation.
  • the distributions of d, Z - d, D , Z- * d, D and Z - n, D of the pencil beam in water are determined in advance, and are registered in the treatment planning software as pencil beam data.
  • the data is applied to patient dose calculation by density scaling using the stopping power ratio of body tissue to water, and the amount of the jth beamlet of each treatment plan, d j , Z ⁇ d, D, j , Z ⁇ * d, D, j and Z ⁇ n, D, j are calculated.
  • (Z - n, D) k is the dose average specific energy per event of the cell nucleus in the x by k-th track.
  • e k, (Z - d, D) k, (Z - * d, D) k, and (Z - n, D) the value of k, Carlo beam transport of the ion beam which imitates an illumination system for each facility It can be determined using simulation.
  • three ion species having initial energy E 0 having an underwater range of 2 mm steps ranging from 10 mm to 300 mm, ie, 146 energies, are 2D symmetric gauss with a standard distribution of 2 mm. It was generated just upstream of the scanning magnet to be distributed. The generated ions pass through a scanning irradiation system and enter a 200 ⁇ 200 ⁇ 400 mm 3 water phantom.
  • voxels Dividing the phantom volume into 1.0 ⁇ 1.0 ⁇ 0.5 mm 3 units (called “voxels”) and varying amounts of simulated ions, ie, ions defined by mass number Ap and atomic number Zp The species, voxel position, ion kinetic energy T, and spatial distribution of energy e applied to the voxel were recorded.
  • the dose distribution d of the pencil beam was simply derived by [Equation 32] from the recorded distribution of e.
  • the distributions of Z ⁇ d, D , Z ⁇ + d, D , and Z ⁇ n, D for the beams of [Equation 33], [Equation 34], and [Equation 35] from the recording amounts of Z p , T, and e, respectively to efficiently derive, of Z p 1-10 monoenergetic ion Z - tabulated n, the D as a function of their kinetic energy T - d, D, Z - * d, D, and Z .
  • the cross-beam dose distribution of the beam was represented as a superposition of three Gaussian distributions, and different specific energies were assigned to the three Gaussian components to represent the radial change in specific energy across the beam cross section.
  • Z ⁇ d, D , Z ⁇ * d, D and Z ⁇ n, D of primary ions, heavy fragments with atomic number Z p ⁇ 3, and light fragments with Z p ⁇ 2 are assigned first, second and third Gaussian components, respectively.
  • the primary ion Z - d, D, Z - * d, D, Z - n, D is assigned to the first component, the third Gaussian components thereof and the second other fragments (Inaniwa et al 2017 * 10).
  • the effects of large angle scattered particles on the dose and specific energy distribution can be taken into account in treatment planning using the pencil beam algorithm.
  • the irradiation parameters can be determined by calculating in a significantly shorter time than the conventional method and the accuracy is high. Therefore, after the following supplementary explanation, an embodiment of an irradiation planning apparatus and a particle beam irradiation system using the irradiation planning apparatus will be described.
  • FIG. 1 is a system configuration diagram showing a system configuration of the particle beam irradiation system 1.
  • the particle beam irradiation system 1 includes an accelerator 4 that accelerates and emits a charged particle beam 3 emitted from an ion source 2, a beam transport system 5 that transports the charged particle beam 3 emitted from the accelerator 4, and the beam.
  • An irradiation device (scanning irradiation device) 6 that irradiates a target portion 8 (for example, a tumor portion) that is an irradiation target of a patient 7 with a charged particle beam 3 that has passed through a transport system 5, and a control device 10 that controls the particle beam irradiation system 1.
  • a target portion 8 for example, a tumor portion
  • control device 10 that controls the particle beam irradiation system 1.
  • an irradiation planning device 20 as a computer for determining the irradiation parameters of the particle beam irradiation system 1.
  • carbon and helium are used as the nuclides (ion species) of the charged particle beam 3 irradiated from the ion source 2, but the present invention is not limited to this, and neon, oxygen, protons, etc.
  • the present invention can be applied to a particle beam irradiation system 1 that irradiates various charged particle beams (ion species).
  • the particle beam irradiation system 1 uses a spot scanning method, but may be another scanning irradiation method such as a raster scanning method.
  • the accelerator 4 adjusts the intensity of the charged particle beam 3.
  • the irradiation device 6 includes a scanning magnet (not shown) that deflects the charged particle beam 3 in the XY directions that form a plane perpendicular to the beam traveling direction (Z direction), and a dose monitor that monitors the position of the charged particle beam 3. (Not shown) and a range shifter (not shown) that adjusts the stop position of the charged particle beam 3 in the Z direction, and scans the charged particle beam 3 along the scan trajectory with respect to the target unit 8.
  • the control device 10 corrects the intensity of the charged particle beam 3 from the accelerator 4, the position correction of the charged particle beam 3 in the beam transport system 5, scanning by a scanning magnet (not shown) of the irradiation device 6, and a range shifter (not shown).
  • the beam stop position etc. are controlled by (omitted).
  • the irradiation planning device 20 includes an input device 21 composed of a keyboard and a mouse, a display device 22 composed of a liquid crystal display or a CRT display, a control device 23 composed of a CPU, ROM and RAM, a CD-ROM and a DVD.
  • a medium processing device 24 composed of a disk drive or the like that reads / writes data from / to a storage medium 29 such as a ROM, and a storage device 25 (storage means) composed of a hard disk or the like.
  • the control device 23 reads the irradiation plan program 39 stored in the storage device 25, and performs a region setting processing unit 31, a prescription data input processing unit 32, a calculation unit 33 (calculation means), an output processing unit 34, and a three-dimensional CT. It functions as the value data acquisition unit 36.
  • the storage unit 25 stores pencil beam source data 41 preset for each radionuclide (for each ion species).
  • the pencil beam source data 41 includes the depth dose distribution d in water, which is obtained in advance as information in the beam axis direction of the pencil beam, and the dose average specific energy (Z ⁇ d, D , Z ⁇ n, D ) of the domain and the cell nucleus. , And the saturation dose average specific energy (Z ⁇ * d, D ) of the domain.
  • each functional unit operates as follows according to the irradiation planning program 39.
  • the 3D CT value data acquisition unit 36 acquires 3D CT value data of an irradiation target (patient) from a separate CT apparatus.
  • the region setting processing unit 31 displays the three-dimensional CT value data as an image on the display device 22 and accepts the region designation (designation of the target unit 8) input by the plan creator through the input device 21.
  • the prescription data input processing unit 32 displays a prescription input screen on the display device 22 and receives prescription data input by the plan creator through the input device 21.
  • This prescription data includes the irradiation position of the particle beam at each coordinate of the three-dimensional CT value data, the survival rate (or equivalent clinical dose) desired at the irradiation position, the irradiation direction of the beam, the type of particle beam (nuclide) ).
  • Various settings such as minimizing the influence on the periphery of the irradiation position are also input as prescription data.
  • the calculation unit 33 receives the prescription data and the pencil beam source data 41, and creates an irradiation parameter and a dose distribution based on these data. That is, the type and amount (particles) of the particle beam to be irradiated from the particle beam irradiation system 1 in order to perform irradiation at which the irradiation target at the irradiation position of the prescription data (for example, a tumor such as a cancer cell) becomes the survival rate of the prescription data (Number) is calculated back using the pencil beam source data 41, and the irradiation parameters of the particle beam irradiated from the particle beam irradiation system 1 are calculated. This calculation will be described later.
  • the output processing unit 34 outputs the calculated irradiation parameters and dose distribution to the display device 22 for display. Further, the output processing unit 34 transmits the irradiation parameter and the dose distribution to the control device 10 that controls the particle beam irradiation system 1.
  • the pencil beam source data 41 is determined by [Expression 32], [Expression 33], [Expression 34], and [Expression 35] described above from the spatial distribution of e, Zp, and T acquired by Monte Carlo simulation. However, in order to simplify [Equation 33], [Equation 34], and [Equation 35], table data is created for each nuclide and stored in the storage device 25.
  • parameters necessary for estimating the cell survival rate S (D) using [Equation 24] are ⁇ 0 in [Equation 15], ⁇ 0 in [Equation 16], and [Equation 1], respectively.
  • Saturation parameter z 0 , domain radius r d , and cell radius R n are ⁇ 0 , ⁇ 0 , saturation parameter z 0 , and domain radius r d .
  • ⁇ 0, ⁇ 0, z 0, r d is a parameter determined by the cell type.
  • the respective cell survival rates when the nuclide is irradiated a plurality of times with different energies are measured. 24] is optimized by an appropriate optimization method such as the least-squares method so that the deviation of the calculation value calculated using [24] is minimized for all nuclides (multiple nuclides) and all energies (plural different energies).
  • ⁇ 0 , ⁇ 0 , saturation parameter z 0 , and domain radius r d are derived.
  • FIG. 2 is an explanatory diagram of a graph obtained by approximating the measured value and the calculated value by the modified SMK model in this way.
  • the vertical axis represents the survival rate and the horizontal It is a graph which makes an axis
  • FIG. 2 (A) and 2 (B) show measured values (black dots in the figure) and calculated values (solid lines in the figure) for helium ions as nuclides for a certain cell type.
  • FIG. ) And FIG. 2D show measured values (black dots in the figure) and calculated values (figure in FIG. 2) for a certain cell type (the same cell type as FIG. 2A and FIG. 2B) as a nuclide. The solid line inside).
  • the calculated values (survival rates) obtained in [Equation 24] for a certain cell type are all types of radiation having different LETs in all types of nuclides used in the particle beam irradiation system 1.
  • a set of ( ⁇ 0, ⁇ 0, z0, rd) that best reproduces the measured value (survival rate) when irradiated with different doses is determined.
  • FIG. 2 shows examples of measured and estimated cell viability for HSG and V79 cells exposed to 3 He and 12 C ion beams over a wide range of doses and LETs, respectively.
  • the dotted lines in FIGS. 2 (A) to 2 (D) show the case of calculation using the conventional MK model.
  • the difference appears to be small in the drawing, for example, a significant difference appears when carbon ions are irradiated at 333 keV / ⁇ m, neon ions are irradiated at 654 keV / ⁇ m, or the like.
  • the measured values are measured multiple times (4 times or more, preferably 5 times or more, and preferably about 6 times) with different doses in the range where the survival rate is larger than 0 and smaller than 1. It is shown.
  • the dose for obtaining a measurement value for each nuclear type is a survival rate of 0.1 or more (preferably 0.3 or more) at the dose with the highest survival rate, and a survival rate at the dose with the lowest survival rate. Is made 0.05 or less (preferably 0.03 or less) so that it does not deviate all to one end within the range of the both ends.
  • LET Although two types of LET are shown in FIG. 2, it is preferable to determine a set ( ⁇ 0, ⁇ 0, z0, rd) in which measured values and calculated values are best reproduced in a wider range of LETs. .
  • [Table 1] shows examples of fixed parameters in the modified SMK model determined to reproduce the measured cell viability of HSG and V79 cells.
  • the parameters of the conventional MK model are also displayed here.
  • R n same parameter values between the modified SMK model and MK models are determined.
  • the mean square deviation obtained by [Equation 25] per data point for each cell line and model is also shown in Table 1.
  • ⁇ 0 , ⁇ 0 , r d , R n , z 0 determined as the modified SMK model parameters (fixed parameters) are stored in the storage unit 25 as a part of the pencil beam source data 41.
  • X2 / n in the table indicates the fitting accuracy and is not included in the fixed parameters.
  • alpha 0, by utilizing the fact that ⁇ 0, z 0, r d is definite for each cell type, Z - d, D, Z - * d, D, and Z - n, for each and D, A graph is calculated by calculating how much energy is given with respect to the kinetic energy of the particles (or the speed at which the particles are irradiated), and this graph is used as table data.
  • FIG. 3 is an explanatory diagram for explaining the graph.
  • FIG. 3A is a graph of Z ⁇ d, D for each nuclide
  • FIG. 3B is a graph of Z ⁇ * d, D for each nuclide.
  • 3 (C) is each type of Z - shows a n, graph D.
  • the relationship between the energy given from the speed and pencil beam pencil beams are graphed, whether and how nuclide is irradiated at any rate how much energy is applied by using the Z -
  • Each of d, D , Z- * d, D , and Z - n, D is registered as table data.
  • the table data may be in a table format or an equation that can be calculated each time using a calculation formula.
  • FIGS. 4A to 4D are obtained.
  • FIGS. 4A to 4D is shown as a function of depth for two types of energy pencil beams. 4A to 4D, the horizontal axis indicates the depth, the vertical axis indicates the dose average specific energy, the dotted line indicates the first beam, and the solid line indicates the second beam.
  • FIG. 5 shows dose average specific energy at a certain depth (L) for the first beam d 1 and the second beam d 2 described above. That is, the doses d 1 (L) and d 2 (L) of each beam at the depth L in the integrated dose distribution d (see FIG. 5 (A)), and the dose averages at the depth L in Z ⁇ d and D the specific energy Z - d, D1 (L) , Z - ( see FIG. 5 (B)) d, D2 (L), Z - n, energy each dose the average ratio of a depth L in the D Z - n, D1 ( L), Z - reference n, D2 (L) (Fig. 5 (C)), and Z - * d, energy each dose the average ratio of a depth L in the D Z - * d, D1 ( L), Z - * D, D2 (L) (see FIG. 5D).
  • FIG. 6 shows a graph in which the vertical axis indicates the dose and the horizontal axis indicates the depth, and the first beam and the second beam are superimposed. From this FIG. 6, the following [Equation 43] can be obtained.
  • Z is given to the target position L by a plurality of pencil beams - d, D, Z - * d, D, and Z - n, of the mixing field by each dose weighted average of D Z - d, D, Z -* Calculate d, D and Z - n, D.
  • This mixing field Z - d, D, Z - * d, D, and Z - n, with a D biological effects of mixing field by the above-described [Expression 24] (survival rate) and RBE (biological Effect ratio).
  • Z - d, D, Z - * d, D, and Z - n since D is the physical quantity measurable, Z at each position of the mixing field - d, D, Z - * d, D , and Z - n, by measuring the D, it can be predicted by using the theory of SMK model RBE (relative biological effectiveness) at that location from the measured values.
  • the operator inputs the beam survival rate at which position and the desired survival rate.
  • the operator is configured to input the corresponding clinical dose, and the input clinical dose is replaced with or converted to the survival rate and used for the calculation.
  • the operator also inputs the direction of the beam and the type (plurality) of nuclides to be used.
  • the calculation unit 33 uses the above [Equation 24] and the fixed parameters ( ⁇ 0 , ⁇ 0 , z 0 , r d ) of the nuclide to be irradiated, and how much the survival rate when the nuclide is irradiated to the position. Calculate what will be.
  • the calculation unit 33 repeats this calculation while changing the beam dose and nuclide, and calculates which nuclide is irradiated to which position at which dose with respect to the input prescription data. Then, an optimum irradiation parameter is determined by combining a plurality of designated nuclides.
  • the conventional appropriate method is used as the method for determining the optimum irradiation parameter by repeating the calculation in this way.
  • the irradiation planning device 20 transmits the irradiation parameters determined in this way to the control device 10, and the control device 10 performs irradiation of the charged particle beam by the particle beam irradiation system 1 using the irradiation parameters.
  • the RBE of the mixed field can be determined from a measurable physical quantity, and the biological effect of the mixed field can be predicted without performing a cell irradiation experiment.
  • RBE of a mixing field can be estimated accurately in a short time, and an irradiation parameter can be determined.
  • biological effects and biological dose calculations, irradiation plans, and treatment plans for heavy LET / dose heavy ion beam treatment fields are planned in a short time without incurring an increase in calculation time. can do.
  • the biological effect of the heavy ion radiotherapy field can be confirmed from the measured values based on the theory of the SMK model.
  • the specific energy obtained by correcting the excessive killing effect at each depth as shown in FIG. 7B.
  • the saturation dose average specific energy at the depth is obtained from the spectrum, and is registered in the storage unit 25 as the beam axis direction component of the pencil beam source data 41 together with the integrated dose distribution as shown in FIG. it can.
  • the particle beam irradiation system 1 using the irradiation planning apparatus 20 can predict biological effects in a high LET / dose radiation field with high accuracy, it uses not only carbon but also high LET radiation such as oxygen and neon. Short-term irradiation with a large dose can be realized and the treatment period can be shortened.
  • pencil beams with heavy particles carbon, oxygen, neon, etc.
  • light beams helium, protons, etc.
  • the calculation time and the memory usage area can be greatly reduced. Accordingly, it is possible to realize an irradiation plan by successive approximation and repetitive calculation within a time that can be used in an actual field.
  • the present invention is not limited to the configuration of the above-described embodiment, and many embodiments can be obtained.
  • the present invention can be used in a charged particle irradiation system that irradiates a particle beam with an accelerator, and in particular, can be used in a scanning particle irradiation system such as a spot scanning method and a raster scanning method. .

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