CN112618970B - Device and medium for boron neutron capture treatment biological dose calculation method - Google Patents
Device and medium for boron neutron capture treatment biological dose calculation method Download PDFInfo
- Publication number
- CN112618970B CN112618970B CN202110011840.8A CN202110011840A CN112618970B CN 112618970 B CN112618970 B CN 112618970B CN 202110011840 A CN202110011840 A CN 202110011840A CN 112618970 B CN112618970 B CN 112618970B
- Authority
- CN
- China
- Prior art keywords
- model
- dose
- tumor
- distribution
- boron
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- 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
- A61N5/1048—Monitoring, verifying, controlling systems and methods
- A61N5/1071—Monitoring, verifying, controlling systems and methods for verifying the dose delivered by the treatment plan
-
- 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
- A61N5/1048—Monitoring, verifying, controlling systems and methods
- A61N5/1075—Monitoring, verifying, controlling systems and methods for testing, calibrating, or quality assurance of the radiation treatment apparatus
-
- 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
- A61N2005/109—Neutrons
Abstract
The invention relates to a Boron Neutron Capture Therapy (BNCT) biological dose calculation method. The method of the invention is based on the neutron autoradiography technology to realize the accurate measurement of the tumor cell size and the boron concentration distribution of the tumor/normal tissue blood vessels; according to different boron drug distribution characteristics, neutron energy spectrums and tissue material characteristics, the corresponding relation between boron distribution and neutron energy and the Relative Biological Effect (RBE) or Compound Biological Effect (CBE) of each ray component of the BNCT is constructed through Monte Carlo simulation and a micro-dosimetry biological model; constructing an individualized radiation simulation human body model of a patient based on medical image data so as to obtain three-dimensional dose distribution; the equivalent biological dose is obtained according to the outline delineation of a tumor target area and normal organs and by combining three-dimensional physical dose distribution and biological effect factors, and a dose volume histogram (DVH diagram) of the tumor and normal tissues and organs is obtained through calculation, so that a theoretical basis is provided for novel targeted drug design and accurate BNCT clinical treatment plan biological transformation.
Description
Technical Field
The invention relates to the technical field of radiotherapy, in particular to a boron neutron capture treatment biological dose calculation method.
Background
According to the latest Chinese cancer data (Chinese cancer report) issued by the national cancer center, about ten thousand people are diagnosed as cancer every day, and the cancer is known as the first killer threatening the health of people in China. Radiotherapy, as one of the three main approaches to cancer treatment, is always aimed at: increasing the dose to the tumor area during radiotherapy kills the tumor while decreasing the dose to normal tissue to reduce damage to normal tissue. The ideal precise radiotherapy technique should kill tumor cells with high selectivity and high lethality in micron scale, while BNCT hasA radiotherapy technique of this character by injecting a boron-containing compound into the body through the blood circulation into the target area (tumor region), the specific boride and tumor have a strong affinity and will quickly concentrate in the tumor region and rarely or even not enter normal tissues. When a tumor region is irradiated with epithermal neutrons or a thermal neutron beam, neutrons are captured by boron and occur in the tumor region10B(n，α)7Li is reacted. Produced alpha particles and7the Li particles have high energy transmission linear density (LET), and can kill tumor cells within the range of less than or equal to 10 mu m without damaging surrounding normal tissues and organs, thereby achieving the aim of targeted therapy.
BNCT dose calculation is also more complex than photon radiotherapy, with dose contributions coming from both high and low LET rays. For low LET radiation, cell damage is mainly caused by the indirect action of free radicals, whereas high LET particles cause cell damage mainly by direct action. Wherein the neutron is10The dose produced by the B interaction is referred to as the boron dose. Due to the non-uniform distribution of boron-containing drugs in subcellular scale and neutrons and10secondary particles (alpha particles and)7Li particles) are short-range, and therefore the biological effect of boron dosing is strongly correlated with the sub-cellular size distribution of the boron-containing drug. The calculation of the biological effect (complex biological effect) for BNCT boron dose is mainly based on animal experiments. In addition, some researchers propose the use of the MKM model, the accuracy of which is controversial and lacks universality. For different boron concentrations and distributions, different tissue depths and different human tissues, the biological effects are selected improperly, which causes great differences. At present, for the study on BNCT microdosing science, the calculated physical quantity usually cannot represent a biological endpoint, so that the distribution condition of the targeted boron drug is considered and an accurate RBE and CBE evaluation method is combined to realize the accurate evaluation of the exposure dose of different types of tumors and surrounding tissues and organs under boron neutron capture treatment. Meanwhile, a secondary cancer risk probability model and TCP and NTCP biological models are combined for making a clinical treatment planning system and evaluating and optimizing the curative effect of the medicamentProviding a more comprehensive and scientific basis.
Disclosure of Invention
The invention aims to provide a boron neutron capture treatment biological dose calculation method, which specifically evaluates BNCT biological effects based on targeted boron drug submicron-scale distribution information, constructs a three-dimensional geometric model according to personalized image data information of a patient, and obtains three-dimensional physical dose distribution in a phantom based on Monte Carlo simulation; drawing according to the outlines of the target area and the normal organ, obtaining equivalent biological dose distribution by combining physical dose distribution and biological effect factors, and calculating to obtain a DVH (digital video disk) diagram of each organ; further predicting the secondary cancer risk of the normal tissue and organ through a secondary cancer risk probability model; in addition, the NTCP and TCP models are combined to evaluate the complication probability and tumor control probability of normal tissues.
The invention provides a boron neutron capture treatment biological dose calculation method, which is characterized by comprising the following steps:
(1) obtaining the distribution rule of boron-containing drugs in a subcellular scale;
(2) acquiring the distribution of microdosing parameters and establishing a numerical calculation method or a numerical calculation model of RBE and/or CBE values according to the distribution condition of boron-containing drugs in the subcellular scale, the tissue cell type and the micro-nano scale environmental factors;
(3) constructing an individualized radiation simulation human body model of a tumor patient based on medical image data, constructing a three-dimensional geometric model containing boron drug spatial distribution information, and obtaining boron neutron capture treatment lower body intra-mode three-dimensional physical dose distribution by utilizing irradiation of thermal neutrons or epithermal neutron beams;
(4) according to the outline delineation of the target area of the tumor and the normal organ, further obtaining equivalent biological dose distribution of the tumor and the surrounding normal tissue organ, and calculating to obtain a DVH (dynamic velocity indicator) image of the tumor/normal tissue organ;
optionally, (5) on the basis of obtaining the equivalent biological dose of normal tissues and organs around the tumor, further evaluating the risk of secondary cancer of the normal tissues and organs around the tumor by using a secondary cancer risk probability model;
optionally, (6) on the basis of obtaining biological dose distribution of the tumor and surrounding normal tissues and organs, combining the DVH graph, and by means of characterization of a Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) model, determining the tumor control probability and the normal tissue complication probability under a treatment scheme, and achieving comprehensive and objective evaluation of boron neutron capture treatment effect.
Preferably, the method comprises steps (1) - (4).
Preferably, the method comprises steps (1) - (5).
Preferably, the method comprises steps (1) - (6).
Preferably, in the step (1), the distribution of the boron-containing drug in the subcellular scale is obtained by using a cell structure imaging technology in combination with a neutron autoradiography.
Preferably, the step (1) comprises: the method is characterized in that a high-resolution cell structure imaging technology is combined with a field center repositioning method, and the trajectory distribution of alpha particles generated by capture reaction is measured based on a neutron autoradiography, so that the distribution condition of the targeted boron-containing medicine in a subcellular scale is reversely deduced.
Preferably, in step (1), the cells comprise tumor cells and/or normal tissue cells.
Preferably, the normal tissue cells include normal tissue cells surrounding tumor cells.
Preferably, in the step (1), a method and a program for re-positioning the center of the field of view are established by optimizing the marking mode of the solid nuclear track detector and combining a coordinate system of a laser confocal microscope, so that accurate measurement of the cell structure image and the track image at the same position is ensured.
Preferably, in the step (1), different types of tumor cells can be selected, the culture and fixation mode of the monolayer non-overlapping cell sample on the solid nuclear track detector is researched, and a reliable method for culturing and fixing the monolayer cell sample on the solid nuclear track detector is established.
Preferably, in step (1), the cells with complete structure are selected for imaging by using a laser confocal microscope, and the positioning of the center of the field of view is realized by combining the marker points and the coordinate system.
Preferably, in the step (1), a neutron beam (reactor/accelerator neutron beam) is selected to irradiate the sample, the corresponding relation between the track density and the neutron flux is determined, and then the optimal neutron irradiation flux and time are determined; and after the irradiation is finished, cleaning the cell sample on the solid nuclear track detector, and determining the optimal etching solution and conditions by using PEW and sodium hydroxide solution as etching solution. And repositioning the cell position and acquiring a track image, further performing background subtraction and image enhancement, and accurately matching the fused cell structure image and the track image.
Preferably, in the step (2), the micro-nano scale environmental factor may take into consideration the oxygen concentration in the cell and/or the influence of the type and content of the free radicals.
Preferably, in the step (2), the monte carlo simulation may be one or more combinations of Geant4, TOPAS, MCDS, MCNP, PHITS, and FLUKA.
Preferably, in the step (2), by
The calculation formula can calculate the relative biological effect of each ray type, wherein RBEDSBRepresenting the relative biological effect of DNA double strand breaks as the biological damage endpoint, DγRepresenting a reference radiation dose required when a certain DNA double-strand break yield is taken as a standard; dpRepresenting the exposure dose required for the type of radiation being measured for the same yield of DNA double strand breaks.
Preferably, the biological damage comprises DNA damage.
Preferably, the types of DNA damage are base damage, single strand breaks and double strand breaks.
Preferably, said biological damage repair comprises DNA damage repair.
Preferably, the DNA damage repair may be one or both of base excision repair, nucleotide excision repair, homologous recombination and non-homologous end joining.
Preferably, the process of repairing DNA damage can analyze the probability of correct repair, incorrect repair, mutation under repair paths such as base excision repair, nucleotide excision repair or homologous recombination, non-homologous end joining, and the like, by models such as MCER, MEDRAS, DMAMARIS, and the like.
Preferably, in step (2), the distribution of the microdosing parameters can be calculated by simulation of the specific energy and linear energy distribution of the radiation sensitive region by any one or more of Monte Carlo software such as Geant4, MCDS + MCNP, PHITS, FLUKA, etc.
Preferably, in step (2), the microdosing parameter distribution can be calculated by one or more combination simulations of Monte Carlo simulations such as Geant4, MCDS + MCNP, PHITS, FLUKA, etc.
Preferably, the Monte Carlo may be one or more of Geant4, TOPAS, MCDS, MCNP, PHITS, and FLUKA.
Preferably, in the step (2), the microdosing parameter distribution can be obtained by performing experimental measurement by using a Tissue Equivalent Proportional Counter (TEPC).
Preferably, in the step (2), the RBE and/or CBE numerical calculation model can be used for constructing a biological effect calculation method by taking the DNA double-strand break yield as a damage endpoint according to the DNA damage mechanism.
Preferably, in the step (2), the RBE and/or CBE numerical calculation model may be constructed by combining an optimized microdose chemokinetic model (MKM) with microdose chemokinetic parameter distribution, and then using the cell survival fraction as a biological endpoint.
Preferably, in the step (2), the RBE and/or CBE numerical calculation model can be combined with DNA damage frequency distribution through a Local Effect Model (LEM) to construct a biological effect calculation method by taking the DNA double-strand break yield as a damage endpoint.
Preferably, in step (3), the monte carlo simulation is one or more of the monte carlo simulations such as Geant4, TOPAS, MCNP, PHITS, FLUKA, and the like.
Preferably, in the step (3), the physical dose includes a boron dose, a neutron dose, and a gamma dose.
Preferably, the neutron dose consists of a fast neutron dose and a thermal neutron dose.
Preferably, the fast neutron dose is generated by the nuclear reaction of hydrogen elements and fast neutrons.
Preferably, the thermal neutron dose is generated by nuclear reaction of nitrogen and thermal neutrons.
Preferably, in step (4), the equivalent biological dose of the tumor and the surrounding normal tissue and organ is equal to the physical dose of the tumor/normal tissue and organ multiplied by RBE and/or CBE.
Preferably, in step (4), the equivalent biological Dose is equal to DoseRBE＝ DoseboronCBEboron+DosethermalRBEthermal+DosefastRBEfast+ Dosegamma(or by means of a second calculation formula DoseRBE＝DoseαRBEα+ DoseLiRBELi+DosefastRBEfast+DosethermalRBEthermal+Dosegamma) Therein, DoseRBERepresenting the total biological dose of BNCT of a single organ (which means that the physical dose values of all components are multiplied by the corresponding RBE or CBE and then added), and CBEboronIndicating the Complex biological Effect of boron drugs, DosethermalRepresenting the thermal neutron dose, RBE, produced by the reaction of thermal neutrons with nitrogenthermalRepresenting the relative biological effect of thermal neutrons, DosefastRepresenting the dose of fast neutrons, RBE, produced by elastic scattering of the fast neutrons and hydrogen elementsfastRepresenting the relative biological effects of fast neutrons and DosegammaRepresenting gamma Dose, DoseαRepresents the physical dose caused by alpha particles generated by boron neutron capture reaction; RBEαRepresenting the relative biological effect of alpha particles, DoseLiRepresenting production of boron neutron-capture reactions7Physical dose induced by Li particles; RBELiRepresents7Relative biological effects of Li particles.
Preferably, in the step (4), on the basis of calculating equivalent biological dose distribution and DVH map of tumor and normal tissue organs, parameters such as maximum dose value and average dose value of each organ can be further obtained, and feasibility evaluation on BNCT treatment is realized according to NCCN literature reference.
Preferably, optionally, in step (5), the risk of secondary cancer of the normal tissue and organ around the tumor is evaluated according to the LAR factor in a secondary cancer risk probability model, wherein the secondary cancer risk probability model is from the BEIR model and/or the Schneider model.
Preferably, optionally, in step (6), the NTCP model is any one or combination of NTCP-Lyman or NTCP-RSM.
Preferably, in step (6), the TCP model may be any one or a combination of LQ-Poisson-TCP basic model, LQ-Poisson-TCP two-parameter model, Zaider-TCP model or Logit-TCP model.
In another aspect, the present invention provides a method according to the first aspect of the present invention for use in boron neutron capture therapy, comprising:
calculating the BNCT biological dose based on the spatial distribution of the boron drug and according to the personalized information of the patient; and further combining a secondary cancer risk probability model or a TCP and NTCP model to realize comprehensive and objective evaluation on the boron neutron capture treatment effect.
In another aspect, the invention provides an apparatus comprising:
a processor; and
a memory storing computer instructions which, when executed by the processor, cause the processor to perform the method of the first aspect of the invention.
Another aspect of the invention provides a non-transitory computer storage medium storing a computer program which, when executed by one or more processors, causes the processors to perform the method of the first aspect of the invention.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments.
Drawings
FIG. 1 is a flow chart of a boron neutron capture therapy biological dose calculation method.
Detailed Description
The invention provides a BNCT biological dose calculation method. The method of the invention is based on the neutron autoradiography technology to realize the accurate measurement of the tumor cell size and the boron concentration distribution of the tumor/normal tissue blood vessels; according to different boron drug distribution characteristics, neutron energy spectrums and tissue material characteristics, corresponding relations between boron distribution and neutron energy and relative biological effects or compound biological effects of various ray components of BNCT are constructed through Monte Carlo simulation and a micro-dose biology model; constructing an individualized radiation simulation human body model of a patient based on medical image data so as to obtain three-dimensional dose distribution; drawing outlines of a tumor target area and a normal organ, obtaining equivalent biological dose by combining three-dimensional physical dose distribution and biological effect factors, and calculating to obtain a DVH (dynamic velocity indicator) image of the tumor and the normal tissue organ; evaluating the normal tissue complication probability and the tumor control probability by combining the biological dose distribution and a radiobiological model; the secondary cancer risk of normal tissues and organs is predicted through a secondary cancer risk probability model on the basis of biological dose distribution, and a theoretical basis is provided for biological transformation of novel targeted drug design and accurate BNCT clinical treatment plans.
The following detailed description of the present invention, taken in conjunction with the accompanying drawings and examples, is provided to enable the invention and its various aspects and advantages to be better understood. However, the specific embodiments and examples described below are for illustrative purposes only and are not limiting of the invention.
It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.
Boron neutron capture treatment biological dose calculation method
The invention provides a boron neutron capture therapy biological dose calculation method, which is preferably non-diagnostic and non-therapeutic.
In a preferred embodiment of the present invention, the method comprises the following steps (1), (2), (3), (4) and optionally (5), (6):
step (1): obtaining the distribution rule of boron-containing drugs in a subcellular scale;
preferably, the distribution of the boron-containing drug in the subcellular scale is obtained by adopting a cell structure imaging technology combined with a neutron autoradiography.
Preferably, the step (1) comprises: the high-resolution cell structure imaging technology is combined with a field center relocation method, and the trajectory distribution of alpha particles generated by capture reaction is measured based on a neutron autoradiography, so that the distribution condition of the targeted boron drug in the subcellular scale is reversely deduced.
Preferably, the cells comprise tumor cells and/or normal tissue cells.
Preferably, the normal tissue cells include normal tissue cells surrounding tumor cells.
Preferably, in the step (1), a method and a program for re-positioning the center of the field of view are established by optimizing the marking mode of the solid nuclear track detector and combining a coordinate system of a laser confocal microscope, so that accurate measurement of the cell structure image and the track image at the same position is ensured.
Preferably, in the step (1), different types of tumor cells can be selected, the culture and fixation mode of the monolayer non-overlapping cell sample on the solid nuclear track detector is researched, and a reliable method for culturing and fixing the monolayer cell sample on the solid nuclear track detector is established.
Preferably, in step (1), the cells with complete structure are selected for imaging by using a laser confocal microscope, and the positioning of the center of the field of view is realized by combining the marker points and the coordinate system.
Preferably, in the step (1), a neutron beam (reactor/accelerator neutron beam) is selected to irradiate the sample, the corresponding relation between the track density and the neutron flux is determined, and then the optimal neutron irradiation flux and time are determined; and after the irradiation is finished, cleaning the cell sample on the solid nuclear track detector, and determining the optimal etching solution and conditions by using PEW and sodium hydroxide solution as etching solution. And repositioning the cell position and acquiring a track image, further performing background subtraction and image enhancement, and accurately matching the fused cell structure image and the track image.
Step (2): obtaining the distribution of microdosing parameters and establishing a numerical calculation method or a numerical calculation model of RBE and/or CBE values through Monte Carlo simulation, experimental measurement and biological injury repair theories according to the distribution condition of boron-containing drugs in a subcellular scale, tissue cell types and micro-nano scale environmental factors;
preferably, the micro-nano scale environmental factors may take into consideration the oxygen concentration in the cell and/or the type and content of free radicals.
Preferably, the Monte Carlo simulation can be one or more of Geant4, TOPAS, MCDS, MCNP, PHITS, and FLUKA.
Preferably, said biological damage repair comprises DNA damage repair.
Preferably, the DNA damage repair may be one or both of base excision repair, nucleotide excision repair, homologous recombination and non-homologous end joining.
Preferably, by
The calculation formula can calculate the relative biological effect of each ray type, wherein RBEDSBRepresenting the relative biological effect of DNA double strand breaks as the biological damage endpoint, DγRepresenting a reference radiation dose required when a certain DNA double-strand break yield is taken as a standard; dpRepresenting the exposure dose required for the type of radiation being measured for the same yield of DNA double strand breaks.
Preferably, the types of DNA damage are base damage, single strand breaks and double strand breaks.
Preferably, the process of DNA damage repair can analyze the probability of correct repair, incorrect repair, mutation under repair paths such as base excision repair, nucleotide excision repair or homologous recombination, non-homologous end joining, and the like, by models such as MCER, MEDRAS, DMAMARIS, and the like.
Preferably, in step (2), the distribution of the microdosing parameters can be calculated by simulating the specific energy and linear energy distribution of the radiation-sensitive area by any one or more of Monte Carlo software such as Geant4, MCDS + MCNP, PHITS, FLUKA, etc.; or
Preferably, in the step (2), the microdosing parameter distribution can be obtained by performing experimental measurement by using a Tissue Equivalent Proportional Counter (TEPC).
Preferably, in the step (2), the RBE and/or CBE numerical calculation model can construct a biological effect calculation method by using the DNA double-strand break yield as a damage end point through a DNA damage mechanism; or
Preferably, in the step (2), the RBE and/or CBE numerical calculation model may be constructed by combining the optimized MKM model with microdosing parameter distribution, and then constructing a biological effect calculation method with the cell survival fraction as a biological endpoint; or
Preferably, in the step (2), the RBE and/or CBE numerical calculation model can be combined with the DNA damage frequency distribution through an LEM model to construct a biological effect calculation method by taking the DNA double-strand break yield as a damage endpoint.
And (3): constructing an individualized radiation simulation human body model of a tumor patient based on medical image data, constructing a three-dimensional geometric model containing boron drug spatial distribution information, introducing Monte Carlo simulation, and obtaining three-dimensional physical dose distribution in a lower body model for boron neutron capture treatment by utilizing irradiation of thermal neutrons or epithermal neutrons;
preferably, in step (3), the monte carlo simulation is one or more of the monte carlo simulations such as Geant4, TOPAS, MCNP, PHITS, FLUKA, and the like.
Preferably, in step (3), the physical dose of the tumor and the surrounding normal tissues and organs under boron neutron capture treatment comprises a boron dose, a neutron dose and/or a gamma dose.
Preferably, the neutron dose consists of a fast neutron dose and a thermal neutron dose.
Preferably, the fast neutron dose is generated by the nuclear reaction of hydrogen elements and fast neutrons.
Preferably, the thermal neutron dose is generated by nuclear reaction of nitrogen and thermal neutrons.
And (4): according to the contour delineation of the target area and the normal organ, and the RBE and/or CBE in the step (2) and the three-dimensional physical dose distribution in the step (3), further obtaining the equivalent biological dose of the tumor and the surrounding normal tissue organ, and calculating to obtain a DVH (dynamic velocity indicator) image of the tumor/normal tissue organ;
obtaining the secondary cancer risk of normal tissues and organs around the tumor through a secondary cancer risk probability model; and/or determining the tumor control probability and the normal tissue complication probability under a treatment scheme through the characterization of a DVH (visual velocity indicator) diagram, a TCP (transmission control protocol) and NTCP (neural network control) model and a secondary cancer risk probability model, and realizing the comprehensive and objective evaluation of the boron neutron capture treatment effect.
Preferably, the tumor/normal tissue organ equivalent biological dose is equal to the tumor/normal tissue organ physical dose which is treated in the step (3) and is obtained by multiplying the RBE and/or CBE which is/are obtained in the step (2).
Preferably, said per organ equivalent biological Dose is equal to DoseRBE＝ DoseboronCBEboron+DosethermalRBEthermal+DosefastRBEfast+ Dosegamma(or by means of a second calculation formula DoseRBE＝DoseαRBEα+ DoseLiRBELi+DosefastRBEfast+DosethermalRBEthermal+Dosegamma) Therein, DoseRBERepresenting the BNCT total biological dose of a single organ (meaning that the physical dose values of the components are multiplied by the corresponding RBE or CBE and added), CbEboronIndicating the Complex biological Effect of boron drugs, DosethermalRepresenting the thermal neutron dose, RBE, produced by the reaction of thermal neutrons with nitrogenthermalRepresenting the relative biological effect of thermal neutrons, DosefastRepresenting the dose of fast neutrons, RBE, produced by elastic scattering of the fast neutrons and hydrogen elementsfastRepresenting the relative biological effects of fast neutrons and DosegammaRepresenting gamma Dose, DoseαRepresents the physical dose caused by alpha particles generated by boron neutron capture reaction; RBEαRepresenting the relative biological effect of alpha particles, DoseLiRepresenting production of boron neutron-capture reactions7Physical dose induced by Li particles; RBELiRepresents7Relative biological effects of Li particles.
Preferably, on the basis of obtaining equivalent biological dose distribution and DVH map of tumor and normal tissue organ by calculation, parameters such as maximum dose value and average dose value of each organ can be further obtained, and feasibility evaluation on BNCT treatment is realized according to NCCN literature reference.
Optionally, step (5): on the basis of obtaining equivalent biological dose distribution of the tumor and surrounding normal tissues and organs, obtaining the secondary cancer risk of the surrounding normal tissues and organs of the tumor through a secondary cancer risk probability model;
preferably, in step (5), the risk of secondary cancer of the normal tissue organ around the tumor is evaluated according to the LAR factor in a secondary cancer risk probability model, wherein the secondary cancer risk probability model is derived from the BEIR model and/or the Schneider model.
Optionally, step (6): on the basis of obtaining equivalent biological dose distribution of tumors and surrounding normal tissues and organs, a DVH (dynamic Voltage Shift keying) graph is combined, and the tumor control probability and the normal tissue complication probability under a treatment scheme are determined through the representation of a TCP (Transmission control protocol) and NTCP (non-transient partial pressure) model, so that the boron neutron capture treatment effect is comprehensively and objectively evaluated;
preferably, in step (6), the NTCP model is any one or combination of NTCP-Lyman or NTCP-RSM;
preferably, in step (6), the TCP model may be any one or a combination of LQ-Poisson-TCP basic model, LQ-Poisson-TCP two-parameter model, Zaider-TCP model, or Logit-TCP model.
In a preferred embodiment of the invention, the boron neutron capture treatment biological dose calculation method comprises the following steps:
the method comprises the following steps: imaging the cells with complete structures by adopting a high-resolution cell structure imaging technology, and accurately imaging positions by combining a field center repositioning method; measuring and obtaining the trace distribution of alpha particles generated by boron neutron capture reaction based on a neutron autoradiography, and reversely deducing the distribution condition of the targeted boron drug at the subcellular scale; acquiring a distribution rule of the targeted drug in a subcellular scale through accurate coupling and matching of the track image and the cell structure image;
step two: constructing a cell micro-nano scale structure model containing boron drug distribution information in a Monte Carlo method based on the micro-distribution of the targeted boron drug in the subcells obtained in the first step to obtain the micro-dosimetry parameter distribution and the rule characteristics of the cell radiation sensitive organ, and establishing a RBE and CBE calculation method by combining an optimized MKM model and a cell survival curve; or predicting the biological effect of radiation of each ray component of the BNCT by using the MCDS or Geant4 or MCDS + MCNP or TOPAS and the DNA double-strand break yield as a damage node according to a definition method of relative biological effect by combining the micro distribution of boron drugs and neutron energy; or constructing a biological effect calculation method by combining an LEM model with DNA damage frequency distribution and taking the DNA double-strand break yield as a damage terminal point;
step three: the method comprises the steps of obtaining boron drug distribution information in a patient body by scanning a CT image of the patient and combining with a patient boron concentration distribution obtaining method such as a PET image and the like, constructing a three-dimensional geometric model with three-dimensional spatial distribution information of a target boron drug, importing a Monte Carlo simulation program, and obtaining three-dimensional physical dose distribution in a lower body model for boron neutron capture treatment by utilizing thermal neutrons or super thermal neutron beam irradiation;
step four: on the basis of the second step and the third step, according to the target area and the contour drawing of the normal organ, and combining RBE and/or CBE and three-dimensional physical dose distribution, further obtaining the equivalent biological dose of the tumor and the surrounding normal tissue organ, and calculating to obtain a DVH (dynamic velocity indicator) image of the tumor/normal tissue organ;
step five: on the basis of obtaining equivalent biological dose distribution of the tumor and surrounding normal tissues and organs in the step four, obtaining the secondary cancer risk of the normal tissues and organs around the tumor through a secondary cancer risk probability model;
step six: and on the basis of obtaining equivalent biological dose distribution of the tumor and surrounding normal tissues and organs, determining the tumor control probability and the normal tissue complication probability under the treatment scheme by combining the DVH diagram and the representation of the TCP and NTCP models, and realizing comprehensive and objective evaluation on the boron neutron capture treatment effect.
In the above steps, in the second step, the frequency distribution of DNA damage caused by each ray component of BNCT can be rapidly calculated by MCDS simulation, and the oxygen content of cells and the influence of radical scavenger on radiation-induced DNA damage can be calculated by the simulation method; in the second step, the influence of factors such as a physicochemical process, an energy threshold, a chemical process duration, geometric model setting and the like on the DNA damage result can also be simulated and analyzed by utilizing Geant 4. In the sixth step, the NTCP model is any one of NTCP-Lyman or NTCP-RSM, the TCP model can be any one of an LQ-Poisson-TCP basic model, an LQ-Poisson-TCP two-parameter model, a Zaider-TCP model or a Logit-TCP model, and calculation results of different models can be compared to determine which model is more reasonable clinically so as to be used in a personalized mode.
The application also provides an application of the boron neutron capture treatment biological dose calculation method in boron neutron capture treatment, which comprises the following steps: calculating the BNCT biological dose based on the spatial distribution of the boron drug and according to the personalized information of the patient; and further combining a secondary cancer risk probability model or a TCP and NTCP model to realize comprehensive and objective evaluation on the boron neutron capture treatment effect.
The present application further provides an apparatus, comprising: a processor; and a memory. Wherein the memory stores computer instructions that, when executed by the processor, cause the processor to perform the boron neutron capture therapy bio-dose calculation method of the present invention.
Further, the present application provides a non-transitory computer storage medium storing a computer program that, when executed by one or more processors, causes the processors to perform the boron neutron capture therapy bio-dose calculation method of the present invention.
It should be noted that the division of the unit in the embodiment of the present application is schematic, and is only a logic function division, and there may be another division manner in actual implementation.
The main technical effects of the invention comprise:
1) the invention provides a method for calculating BNCT biological dose based on boron drug spatial distribution and according to personalized information of a patient.
2) The invention combines the boron-containing medicine spatial distribution and neutron energy spectrum information, evaluates the radiation biological effect of boron neutron capture treatment from various angles such as physics, biological damage mechanism, micro-dose model and the like, and improves the universality and correctness of the BNCT biological effect evaluation method.
3) In the invention, a Dose Volume Histogram (DVH) is taken as a preclinical curative effect evaluation basis, and a secondary cancer risk probability model is further combined to evaluate the secondary cancer risk of surrounding normal tissues and organs after different types of tumors are treated by BNCT, so that a theoretical basis is provided for the formulation and perfection of a clinical treatment plan.
4) The method provided by the invention not only takes the DVH as a preclinical curative effect evaluation basis, but also further combines a radiation biological model to give a predicted value of tumor control probability and normal tissue complication probability, comprehensively evaluates the boron neutron capture treatment curative effect, and more intuitively provides support for medical personnel to specify a diagnosis and treatment scheme.
The invention will be further illustrated with reference to the following specific examples. It should be understood that the following specific examples are provided to illustrate the detailed embodiments and specific procedures, but the scope of the present invention is not limited to these examples.
Example 1
Referring to fig. 1, the present embodiment provides a boron neutron capture therapy biological dose calculation method, including the following steps:
step 101: based on neutron autoradiography technology and cell structure imaging technology, obtaining the boron concentration distribution accurate determination of tumor/normal tissue organs;
firstly, a field center re-positioning method and a program are established by optimizing the marking mode of a solid nuclear track detector and combining a coordinate system of a laser confocal microscope, so that accurate repeated measurement of a cell structure image and a track image at the same position is ensured, and then an accurate matching fusion technology for obtaining the cell structure image and the track image is developed. Different types of tumor cells can be selected, preferably a tumor-bearing mouse model is taken as an example, the culture and fixation mode of a monolayer non-overlapping cell sample on the solid nuclear track detector is researched, and the reliable method for culturing and fixing the monolayer cell sample on the solid nuclear track detector is established. And selecting cells with complete structures by using a laser confocal microscope for imaging, and positioning the center of the field of view by combining the mark points and a coordinate system. Irradiating a sample by using a neutron beam (reactor/accelerator neutron beam), determining the corresponding relation between the track density and the neutron flux, and then determining the optimal neutron irradiation flux and time; and after the irradiation is finished, cleaning the cell sample on the solid nuclear track detector, and determining the optimal etching solution and conditions by using PEW and sodium hydroxide solution as etching solution. And repositioning the cell position and acquiring a track image, further performing background subtraction and image enhancement, and accurately matching the fused cell structure image and the track image.
Step 102: obtaining the micro-dosimetry parameter distribution and establishing a numerical calculation method or a numerical calculation model of RBE and CBE values through Monte Carlo simulation and a radiobiological damage mechanism according to the boron-containing medicament submicron-scale space distribution information, the tissue cell type, the micro-nano scale environment and other factors in the step 101;
specifically, the cell type can be brain glioma cell, squamous tongue carcinoma cell, CHO cell, V79 cell or melanoma cell, etc.; the micro-nano scale environmental factors can consider the oxygen concentration in cells and/or the types and the contents of free radicals and the like; the Monte Carlo simulation can be one or more of Geant4, TOPAS, MCDS, MCNP, PHITS and FLUKA; the biological damage repair comprises DNA damage repair; the DNA damage repair can be one or two of base excision repair, nucleotide excision repair, homologous recombination and non-homologous end connection; the RBE and CBE numerical calculation model can be one or more of MKM, LEM, repair-error repair-fixation (RMF) and linear quadratic form (LQ) models, can also be a calculation method using DNA double-strand break as a damage terminal point, and can also be a combination of the methods.
Step 103: constructing a radiation simulation human body model containing boron drug distribution information based on medical image data, combining Monte Carlo simulation, and irradiating different types of tumors by using different types of neutron source conditions to obtain the three-dimensional dose distribution condition in a body model;
specifically, three-dimensional dose distribution corresponding to different ray components in a corresponding body mould is obtained under different treatment schemes of different cases; the different treatment schemes can be different neutron source conditions, different irradiation directions, different radiation field numbers and the like; the different physical dose components comprise boron dose, neutron dose and gamma dose; the neutron dose comprises a fast neutron dose and/or a thermal neutron dose.
Step 104: based on the three-dimensional dose distribution condition in the phantom in the step 103 and the RBE and/or CBE obtained in the step 102, obtaining equivalent biological dose distribution of corresponding tumors and surrounding normal tissues and organs according to the contour delineation of the target region and the normal organs, and calculating to obtain a DVH (dynamic velocity indicator) map of the tumors and the normal tissues and organs;
specifically, the physical dose distribution of the tumor/surrounding normal tissue organs is obtained by one-to-one correspondence of the three-dimensional dose distribution matrix in the body mould and the organ matrix obtained by outline delineation; multiplying each part of physical dose component by the corresponding RBE or CBE to determine each part of equivalent biological dose distribution corresponding to the tumor/normal tissue organ; and further summing to obtain the total biological dose distribution of the tumor/surrounding normal tissues and organs so as to calculate the DVH (digital visual acuity) images of the target area and each normal organ, acquiring data such as the maximum dose value, the average dose value and the like from the DVH images, and realizing feasibility evaluation on the BNCT treatment scheme according to literature reference.
Step 105: calculating LAR factors by combining a secondary cancer risk probability model on the basis of calculating equivalent biological dose distribution of normal tissues and organs around the tumor, so as to evaluate the secondary cancer risk probability of the normal tissues and organs under different treatment schemes;
step 106: on the basis of calculating to obtain equivalent biological dose distribution of tumor and normal tissue and organ, the representation of TCP and NTCP models is utilized to realize comprehensive and objective evaluation on the BNCT treatment effect;
specifically, the NTCP model selects any one of NTCP-Lyman or NTCP-RSM; the TCP model can be any one of an LQ-Poisson-TCP basic model, an LQ-Poisson-TCP two-parameter model, a Zaider-TCP model or a Logit-TCP model.
The invention is further illustrated by the following specific examples:
UMR-106 cell samples were first cultured for 4 hours in samples of BPA (L-boronophenyanaine) with a boron concentration of 80ppm, and the boron accumulation uniformity and boron concentration values were qualitatively and quantitatively analyzed by neutron autoradiography, respectively. The obtained results show that the boron-containing nanoparticles can be uniformly accumulated in the UMR-106 cell sample at a concentration of 80ppm, the concentration of the cell sample reaches about 69.7ppm, and the accumulated boron concentration of the BPA culture solution UMR-106 cell sample with the boron concentration higher than 80ppm in the sample is about 40 ppm. Because the neutron autoradiography has the capability of providing visual distribution of boron concentration, the method for accurately measuring the cell-scale boron distribution is established by further improving the resolution of a track image and combining the optical microscopic imaging technology of cell scale.
The following details how RBE and/or CBE in BNCT treatment can be assessed by Monte Carlo particle transport simulation in combination with the Monte Carlo lesion simulation (MCDS) method.
Considering several dose components in boron neutron capture reactions, here, alpha and7li particles, monoenergetic protons, and recoil protons, alpha particle energy includes 93.7% of 1.47MeV and 6.3% of 1.78MeV,7the Li particle energy included 93.7% 0.84MeV and 6.3% 1.01 MeV; the energy of the monoenergetic proton is 0.54MeV, while the energy spectrum of the recoil proton is mainly determined by the type of the neutron source, Massa in this embodimentThe chusetts Institute of Technology (MIT) reactor neutron source and the boron-containing drug BPA are examples.
Considering alpha and7the range of Li particles is short, about one cell size, the position of boron drug distribution and the alpha sum generated by capture reaction7The initial positions of the Li particles are the same. First, by simulating with Geant4, taking the size of tongue cancer cell as an example, the radius of nucleus is 3 μm, the thickness of cytoplasm is 2 μm, and alpha are obtained on the surface of nucleus by particle transport7Energy spectrum distribution of Li particles (taking the case of enrichment of BPA drug in cells as an example). And meanwhile, irradiating the tissue equivalent material by an MIT neutron source to obtain a recoil proton energy spectrum. On the basis, the energy spectrum is used as an initial source item, the oxygen content of cells is set in an MCDS software script file, parameters such as cell size, simulated cell number and the like are set, the DNA damage condition under different cell oxygen concentrations is calculated, and the DNA damage condition is used137Cs as reference radiation, by
The calculation formula can calculate the relative biological effect of each ray type, wherein RBEDSBRepresenting the relative biological effect of a DNA double strand break as a biological end point, DγRepresenting a reference radiation dose required when a certain DNA double-strand break yield is taken as a standard; dpRepresenting the exposure dose required for the type of radiation being measured for the same yield of DNA double strand breaks.
To briefly explain the structural information of a patient, the present description uses the already constructed radiation simulation phantom as an example to perform dose calculation using monte carlo kit TOPAS, in which the definition of the incident source term includes: the type and shape of the particle beam, the type of the particle source, the energy level and energy scattering angle of the particle beam, the size of the beam field in the direction of the X, Y axis, and other parameters. In the simulations of different tumor patients, the incident sources were all circular and corresponded to the center of the tumor. Through the Monte Carlo particle transport process, four different output files can be defined corresponding to four dose components (boron dose, thermal neutron dose, fast neutron dose, and gamma dose) of BNCT, and five different output files can be defined corresponding to five different dose components (boron dose, thermal neutron dose, fast neutron dose, and gamma dose) of BNCTThe output file corresponds to five dosage components (alpha dosage, alpha dosage,7Li dose, thermal neutron dose, fast neutron dose, gamma dose). Thereby, a three-dimensional dose distribution in the phantom for each radiation component can be obtained. Obtaining corresponding organ matrix according to the outline delineation of tumor and normal organ, obtaining physical Dose distribution of each organ under each ray component through the corresponding relation between the Dose matrix and the organ matrix, combining the obtained RBE and/or CBE, and utilizing equivalent biological Dose calculation formula, DoseRBE＝ DoseboronCBEboron+DosethermalRBEthermal+DosefastRBEfast+ Dosegamma(or by means of a second calculation formula DoseRBE＝DoseαRBEα+ DoseLiRBELi+DosefastRBEfast+DosethermalRBEthermal+Dosegamma) Therein, DoseRBERepresenting the total biological dose of a single organ (by multiplying and adding the physical dose values of the components by the corresponding RBE and/or CBE), CBEboronIndicating the Complex biological Effect of boron drugs, DosethermalRepresenting the thermal neutron dose, RBE, produced by the reaction of thermal neutrons with nitrogenthermalRepresenting the relative biological effect of thermal neutrons, DosefastRepresenting the dose of fast neutrons, RBE, produced by elastic scattering of the fast neutrons and hydrogen elementsfastRepresenting the relative biological effects of fast neutrons and DosegammaRepresenting gamma Dose, DoseαRepresents the physical dose caused by alpha particles generated by boron neutron capture reaction; RBEαRepresenting the relative biological effect of alpha particles, DoseLiRepresenting production of boron neutron-capture reactions7Physical dose induced by Li particles; RBELiRepresents7Relative biological effects of Li particles. The dose value of each component is multiplied by the corresponding biological effect or relative biological effect of the compound to obtain equivalent biological dose (also called dose equivalent value in secondary cancer probability assessment) of tumor and normal tissue organs.
The probability of risk of secondary cancer under this BNCT illumination condition for the normal tissue organ of interest is calculated from the lifetime attributed risk factor (LAR factor) in the BEIR report, as in equations (1) and (2), in conjunction with a probability of risk model for secondary cancer. Taking a 10-year-old female brain tumor as an example, for three different irradiation schemes (left and right, up and down, and three different irradiation directions at the back and front), a corresponding DVH map and LAR factors of each normal organ can be calculated. The feasibility of this treatment regimen can be judged by DVH plots based on NCCN dose limit requirements. In addition, the LAR factor result can determine which irradiation scheme has the lowest risk of secondary cancer of normal tissues and organs, thereby providing a certain theoretical reference for the design of a clinical treatment plan scheme.
Wherein in formula (1), D represents the average dose to which the organ is subjected; beta is aSγ, η are specific parameters of ERR and EAR factors related to patient gender, organ type; e is the age of the patient when subjected to radiation, e is (e-30)/10 when e is less than 30, e is 0 when e is greater than 30; a is the age at which the patient develops secondary cancer.
In formula (2), ERR (D, e, a) and EAR (D, e, a) can be obtained by formula (1);
represents the baseline incidence of different cancer types; s (a) and s (e) represent survival rates at ages a and e, respectively; l represents the incubation period for secondary cancer, typically 5 years for solid tumors and 2 years for leukemias; DDREF is a dose (rate) effector, with a DDREF value of 1.5 when the dose value of the organ is less than 100 mGy; the weight coefficients 0.7 and 0.3 of the LAR formula are recommended by the BEIR report and are applicable to most tissues and organs, while the weight coefficients 0.7 and 0.3 of the LAR factor are interchanged for lung, and only the excess absolute risk factor (EAR) is considered in the LAR factor for mammary gland and only the excess relative wind is considered in the LAR factor for thyroid glandRisk factor (ERR).
On the other hand, from the biological point of view, the boron neutron capture treatment effect and the radiotoxicity of normal tissues were evaluated by TCP and NTCP radiobiological models. Specifically, the NTCP model selected in this example is the NTCP-Lyman model.
NTCP-Lyman model: in formula (3), m is the slope of the dose-response curve at 50% of the complications; n is the volume effect coefficient; d50(V＝1)Dose response curve 50% of the corresponding dose when whole organ is irradiated; d50(V)Dose to generate 50% NTCP for partial volume irradiation, DmaxIs the maximum dose value in the dose-response curve.
D50(V)＝D50(V＝1)×V-n#(3)
Reading D of normal tissue organ of interest in dose-response curves by matlab for different types of tumors50(V＝1)And DmaxThe probability of normal tissue complications can be obtained by referring to the m and n values given in clinical cases and substituting the values into the formula (3).
Specifically, the TCP model selected in this example is the LQ-Poisson-TCP base model.
LQ-Poisson-TCP base model: in the formula (4), alpha is the single click lethality coefficient of the LQ formula; beta is the double-click lethality coefficient of the LQ formula; ρ is the tumor clone origin cell number density. d represents the tumor exposure dose; v represents the tumor volume.
TCP＝exp{-ρ×v×exp(-n(αd+βd2))}#(4)
The tumor control rates corresponding to different irradiated doses can be obtained by substituting the radiation sensitivity parameters alpha and beta of the corresponding LQ model in clinically relevant cases or literature data into the formula (4). A reasonable dose can be given by combining the probability of normal tissue complications and the probability of tumor control.
The feasibility of the BNCT treatment scheme is comprehensively evaluated from the aspects of dosimetry and biology, an optimal treatment scheme is provided for patients, and a theoretical basis is provided for the biological transformation of the design of novel targeted drugs and the accurate BNCT clinical treatment plan.
While the invention has been described in terms of a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the spirit and scope of the invention.
Claims (16)
1. An apparatus for a boron neutron capture therapy bio-dose calculation method, comprising:
a processor; and
a memory storing computer instructions that, when executed by the processor, cause the processor to perform a method of boron neutron capture therapy bio-dose calculation, the method comprising the steps of:
(1) obtaining the distribution rule of boron-containing drugs in a subcellular scale;
(2) acquiring the distribution of microdosing parameters and establishing a numerical calculation method or a numerical calculation model of RBE and/or CBE values according to the distribution condition of boron-containing drugs in the subcellular scale, the tissue cell type and the micro-nano scale environmental factors;
(3) constructing an individualized radiation simulation human body model of a tumor patient based on medical image data, constructing a three-dimensional geometric model containing boron drug spatial distribution information, and obtaining boron neutron capture treatment lower body intra-mode three-dimensional physical dose distribution by utilizing irradiation of thermal neutrons or epithermal neutron beams;
(4) and (3) according to the outline delineation of the target area of the tumor and the normal organ, further acquiring equivalent biological dose distribution of the tumor and the surrounding normal tissue organ, and calculating to obtain a DVH (dynamic velocity indicator) image of the tumor/normal tissue organ.
2. The apparatus of claim 1, wherein the method further comprises the step (5): and further evaluating the risk of secondary cancer of the normal tissue organs around the tumor by using a secondary cancer risk probability model on the basis of obtaining the equivalent biological dose of the normal tissue organs around the tumor.
3. The apparatus of claim 1, wherein the method further comprises the step (6): on the basis of obtaining equivalent biological dose distribution of tumor and surrounding normal tissues and organs, the tumor control probability and the normal tissue complication probability under a treatment scheme are determined through characterization of a tumor control probability TCP and a normal tissue complication probability NTCP model by combining a DVH (dynamic velocity H) diagram, and comprehensive and objective evaluation on boron neutron capture treatment effect is realized.
4. The apparatus of claim 1, wherein in step (2), the microdosing parameter distribution is calculated by one or more combined simulations of Geant4, MCDS + MCNP, PHITS, FLUKA monte carlo simulations; or in the step (2), the distribution of the microdosing parameters can be obtained by experimental measurement of a Tissue Equivalent Proportional Counter (TEPC).
5. The apparatus of claim 1, wherein in the step (2), the numerical calculation model of RBE and/or CBE is used to construct a calculation method of biological effect by using DNA double strand break yield as damage end point through DNA damage repair; or in the step (2), the RBE and/or CBE numerical calculation model can be combined with the microdosing parameter distribution through an optimized Microdosing Kinetic Model (MKM), and then a biological effect calculation method is constructed by taking the cell survival fraction as a biological endpoint; or in the step (2), the RBE and/or CBE numerical calculation model can be combined with DNA damage frequency distribution through a Local Effect Model (LEM) to construct a biological effect calculation method by taking the DNA double-strand break yield as a damage endpoint.
6. The apparatus according to claim 2, wherein in step (5), the risk of secondary cancer of the normal tissue and organ surrounding the tumor is evaluated based on the LAR factor in a probability model of risk of secondary cancer, wherein the probability model of risk of secondary cancer is derived from the BEIR model and/or the Schneider model.
7. The apparatus of claim 3, wherein in step (6), the NTCP model is NTCP-Lyman or NTCP-RSM.
8. The apparatus of claim 3, wherein in step (6), the TCP model is an LQ-Poisson-TCP base model, an LQ-Poisson-TCP two-parameter model, a Zaider-TCP model, or a Logit-TCP model.
9. A non-transitory computer storage medium storing a computer program that, when executed by one or more processors, causes the processors to perform a method of boron neutron capture therapy bio-dose calculation, the method comprising the steps of:
(1) obtaining the distribution rule of boron-containing drugs in a subcellular scale;
(2) acquiring the distribution of microdosing parameters and establishing a numerical calculation method or a numerical calculation model of RBE and/or CBE values according to the distribution condition of boron-containing drugs in the subcellular scale, the tissue cell type and the micro-nano scale environmental factors;
(3) constructing an individualized radiation simulation human body model of a tumor patient based on medical image data, constructing a three-dimensional geometric model containing boron drug spatial distribution information, and obtaining boron neutron capture treatment lower body intra-mode three-dimensional physical dose distribution by utilizing irradiation of thermal neutrons or epithermal neutron beams;
(4) and (3) according to the outline delineation of the target area of the tumor and the normal organ, further acquiring equivalent biological dose distribution of the tumor and the surrounding normal tissue organ, and calculating to obtain a DVH (dynamic velocity indicator) image of the tumor/normal tissue organ.
10. The non-transitory computer storage medium of claim 9, wherein the method further comprises the step (5): and further evaluating the risk of secondary cancer of the normal tissue organs around the tumor by using a secondary cancer risk probability model on the basis of obtaining the equivalent biological dose of the normal tissue organs around the tumor.
11. The non-transitory computer storage medium of claim 9, wherein the method further comprises step (6): on the basis of obtaining equivalent biological dose distribution of a tumor and surrounding normal tissues and organs, a DVH (dynamic velocity H) graph is combined, the Tumor Control Probability (TCP) and the Normal Tissue Complication Probability (NTCP) under a treatment scheme are determined through representation of a Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) model, and comprehensive and objective evaluation on boron neutron capture treatment effects is achieved.
12. The non-transitory computer storage medium of claim 9, wherein in step (2), the microdosing parameter distribution is calculated by one or more combinatorial simulations of Geant4, MCDS + MCNP, PHITS, FLUKA monte carlo simulations; or in the step (2), the distribution of the microdosing parameters can be obtained by experimental measurement of a Tissue Equivalent Proportional Counter (TEPC).
13. The non-transitory computer storage medium of claim 9, wherein in step (2), the RBE and/or CBE numerical calculation model is used to construct a bioeffect calculation method with DNA double strand break yield as the damage endpoint through DNA damage repair; or in the step (2), the RBE and/or CBE numerical calculation model can be combined with the microdosing parameter distribution through an optimized Microdosing Kinetic Model (MKM), and then a biological effect calculation method is constructed by taking the cell survival fraction as a biological endpoint; or in the step (2), the RBE and/or CBE numerical calculation model can be combined with DNA damage frequency distribution through a Local Effect Model (LEM) to construct a biological effect calculation method by taking the DNA double-strand break yield as a damage endpoint.
14. The non-transitory computer storage medium of claim 10, wherein in step (5), the risk of secondary cancer in the normal tissue and organ surrounding the tumor is evaluated according to the LAR factor in a secondary cancer risk probability model, wherein the secondary cancer risk probability model is derived from the BEIR model and/or the Schneider model.
15. The non-transitory computer storage medium of claim 11, wherein in step (6), the NTCP model is NTCP-Lyman or NTCP-RSM.
16. The non-transitory computer storage medium of claim 11, wherein in step (6), the TCP model is LQ-Poisson-TCP basic model, LQ-Poisson-TCP two-parameter model, Zaider-TCP model, or Logit-TCP model.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110011840.8A CN112618970B (en) | 2021-01-06 | 2021-01-06 | Device and medium for boron neutron capture treatment biological dose calculation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110011840.8A CN112618970B (en) | 2021-01-06 | 2021-01-06 | Device and medium for boron neutron capture treatment biological dose calculation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112618970A CN112618970A (en) | 2021-04-09 |
| CN112618970B true CN112618970B (en) | 2022-03-15 |
Family
ID=75291140
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110011840.8A Active CN112618970B (en) | 2021-01-06 | 2021-01-06 | Device and medium for boron neutron capture treatment biological dose calculation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112618970B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113642386A (en) * | 2021-07-02 | 2021-11-12 | 广州金域医学检验中心有限公司 | Method, device, equipment and medium for evaluating nasopharyngeal carcinoma treatment effect based on deep learning |
| CN113933889A (en) * | 2021-10-13 | 2022-01-14 | 散裂中子源科学中心 | Preparation and data reading method of combined type Fricke gel dosimeter |
| CN114129910B (en) * | 2021-11-18 | 2023-10-31 | 中国医学科学院肿瘤医院深圳医院 | Calculation method of nanometer metal radiation sensitization bioequivalence dose |
| CN116598010B (en) * | 2023-05-16 | 2024-01-09 | 兰州大学 | Method for analyzing influence of energy-carrying particles on normal cells in sulfur neutron capture treatment |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1658878A1 (en) * | 2004-11-17 | 2006-05-24 | The European Community, represented by the European Commission | BNCT treatment planning |
| CN103394167A (en) * | 2013-08-01 | 2013-11-20 | 山东省肿瘤医院 | BED (biological effective dose)-based prediction method for complications caused by tumor radiotherapy |
| CN104107062A (en) * | 2013-04-17 | 2014-10-22 | 深圳市医诺智能科技发展有限公司 | Radiotherapeutic effect evaluation method and system |
| JP2016214760A (en) * | 2015-05-25 | 2016-12-22 | 株式会社東芝 | Treatment device for boron neutron capture therapy, and control method thereof |
| CN106980136A (en) * | 2016-01-15 | 2017-07-25 | 南京中硼联康医疗科技有限公司 | Radiation detecting system and radiation line detecting method for neutron capture treatment system |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105445777B (en) * | 2015-12-01 | 2018-06-05 | 南京航空航天大学 | A kind of boron neutron capture therapy Dosimetry |
| CN109308733A (en) * | 2017-07-27 | 2019-02-05 | 南京中硼联康医疗科技有限公司 | Geometrical model method for building up and dose calculation methodology based on medical image data |
| WO2020111085A1 (en) * | 2018-11-26 | 2020-06-04 | 国立大学法人筑波大学 | Treatment planning system for boron neutron capture therapy (bnct), bnct system, and bnct |
-
2021
- 2021-01-06 CN CN202110011840.8A patent/CN112618970B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1658878A1 (en) * | 2004-11-17 | 2006-05-24 | The European Community, represented by the European Commission | BNCT treatment planning |
| CN104107062A (en) * | 2013-04-17 | 2014-10-22 | 深圳市医诺智能科技发展有限公司 | Radiotherapeutic effect evaluation method and system |
| CN103394167A (en) * | 2013-08-01 | 2013-11-20 | 山东省肿瘤医院 | BED (biological effective dose)-based prediction method for complications caused by tumor radiotherapy |
| JP2016214760A (en) * | 2015-05-25 | 2016-12-22 | 株式会社東芝 | Treatment device for boron neutron capture therapy, and control method thereof |
| CN106980136A (en) * | 2016-01-15 | 2017-07-25 | 南京中硼联康医疗科技有限公司 | Radiation detecting system and radiation line detecting method for neutron capture treatment system |
Non-Patent Citations (1)
| Title |
|---|
| 基于蒙特卡罗方法的硼中子俘获治疗非小细胞肺癌剂量学研究;郁海燕;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20180315;全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112618970A (en) | 2021-04-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112618970B (en) | Device and medium for boron neutron capture treatment biological dose calculation method | |
| JP6754841B2 (en) | How to set a geometric model based on medical image data | |
| US11087524B2 (en) | Method for establishing smooth geometric model based on data of medical image | |
| TWI646945B (en) | Deconstruction method of tissue element mass ratio based on medical image and establishment method of geometric model | |
| CN109308733A (en) | Geometrical model method for building up and dose calculation methodology based on medical image data | |
| WO2022078175A1 (en) | Boron neutron capture therapy system and treatment plan generation method therefor | |
| Gemmel et al. | Calculation and experimental verification of the RBE-weighted dose for scanned ion beams in the presence of target motion | |
| CN103536302B (en) | Based on 3-dimensional dose distributional difference analytical method and the system of TPS | |
| WO2022001594A1 (en) | Radiotherapy system and therapy plan generation method therefor | |
| Ševčik | Monte Carlo simulation and experimental verification of photon radiation-induced polymerization in dosimetric materials | |
| Shukla | Dosimetry in Magnetic Fields Using Ionization Chambers | |
| CARLO | PIETRO PISCIOTTA | |
| McNiven | Improving the Accuracy of Ionization Chamber Dosimetry in Small Megavoltage X-ray Fields | |
| Wootton et al. | Basic Radiation Physics | |
| Battistoni et al. | Development of the FLUKA Monte Carlo code for particle therapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |