CN109499013A - Biological effect dosing method and system in a kind of tumour radiotherapy - Google Patents
Biological effect dosing method and system in a kind of tumour radiotherapy Download PDFInfo
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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
- A61N5/1048—Monitoring, verifying, controlling systems and methods
- A61N5/1071—Monitoring, verifying, controlling systems and methods for verifying the dose delivered by the treatment plan
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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
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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
- A61N2005/1035—Simulated annealing
Abstract
The invention discloses biological effect dosing method and systems in a kind of tumour radiotherapy.The determining method includes: to establish cells survival curve descriptive model by increasing corrected parameter；Obtain cell survival data, fitted model parameters；Biological effect dose modal is established according to the cells survival curve descriptive model；Biological effect dosage is determined according to the biological effect dose modal.Biological effect dosage can accurately be determined using biological effect dosing method in tumour radiotherapy provided by the present invention and system, to more accurately carry out the conversion between different radiation treatment plans；In the cells survival curve descriptive model obtained, each parameter has its corresponding biological significance, while cells survival curve descriptive model is simple, is easy to clinical expansion.
Description
Technical field
The present invention relates to medical domain, more particularly to biological effect dosing method in a kind of tumour radiotherapy and
System.
Background technique
" biological dose " and " physical dosage " in radiation therapy process concept that be two different.According to International Atomic energy
No. 30 Report Definition of committee IAEA, " biological dose " refers to the measurement of organism rdaiation response degree.Cells survival is described
Curve model describes the survival condition of cell in tumour cell and normal tissue cell radiation therapy process, is commonly used to be fitted
The survivorship curve that the in vitro and in vivo survival experiment of Clone formation cell obtains.The biology derived by cells survival curve model
Effect dose (biological effect dose, BED) model be generally applicable to calculate the equivalent dose of different gradation schemes,
The prediction and tumor by local control of Normal Tissue Complication (Normal Tissue Complication Probability, NTCP)
The calculating of rate (Tumor Control Probability, TCP) processed.
With radiotherapy apparatus, the development of technology, hypo fractionradiotherapy --- divide including widow, body portion stereotactic radiotherapy
The treatment mode of (stereotacticbodyradiotherapy, SBRT) is gradually paid attention to, hypo fractionradiotherapy be
It is greater than the radiotherapy mode of the single dose of conventional therapy when radiotherapy by single fraction irradiation, tumour cell is not only proliferated to probability drop again
To minimum, raising tumor control rate, and the radiotherapy course for the treatment of can be shortened, reduce treatment cost.Primary and metastatic lung, liver
The clinical study results of the malignant tumours such as dirty, prostate show, big fractionation radiotherapy significant effect.Single-bolus high-dose and conventional radiotheraphy
Two kinds of radiotherapy modes are all that the DNA double chain break due to caused by radiation exposure leads to the damage of cell, thus control tumour and
Cause normal tissue injury.It is a difference in that when implementing conventional radiotheraphy, since single dose is small, often treats by several times with treatment
The long reason of journey, can improve the reparation of cell, the redistribution of cell cycle and proliferation between gradation, this be unfavorable for the control of tumour but
The damage of normal tissue can be reduced.Hypo fractionradiotherapy is since single treatment dosages are big, gradation number is few and treatment course
Short reason can reduce the reparation, cell cycle redistribution and proliferation of cell in treatment, this is conducive to the control of tumour but simultaneously
Increase the damage of normal tissue.
In the existing scaling module that physical dosage is converted to biological dose, linear-secondary (Linear-
Quadratic, LQ) model is a kind of mathematical model for being widely used in radiobiological studies and clinical radiotherapy, it is
It is obtained from the survival curve direct derivation of cell.The biological effect dosage derived by LQ model inference is a kind of according to agent
The method that amount Fractionation regimen is different and converts biological dose for physical dosage.
LQ model is one and receives the experience that data variation curve obtains after different continuing dosages irradiate by being fitted cell
Formula.As shown in Figure 1, LQ curve meets these experimental results of Chinese hamster cell in culture very much in logarithmic linear figure,
Maximum dose level is 6Gy, but continues thereafter with bending, and observing experimental result at high doses becomes linear, and model is thought to radiate meeting
Lead to fatal injury and sublethal damage.Cell DNA double-strand break is the fatal injury event for leading to cell inactivation, double
Chain fracture, which can be single particle energy deposition, causes double-strand to be destroyed, referred to as α damage, proportional with radiological dose；Or 2 grains
Son synergistic effect causes double-strand to be destroyed, referred to as β damage, square proportional with radiological dose.Sublethal damage is due to putting
Radion leads to DNA Single-Strand Breakage in Cells, if cell can be repaired without further irradiating.After cell exposure,
Its overall impairment must be the comprehensive effect of α damage and β damage, can be described as:
S=exp (- α D- β D2) (1)
Wherein, what S was indicated is the CNN surviving fraction of cell, and D is to apply according to dosage, and α indicates that the single particle of unit dose makes carefully
The average probability that born of the same parents kill；β indicates the average probability that two particles of unit dose kill cell.When α damage and β damage are general
When rate is identical, α D=β D2, D=α/β, the α/β obtained herein is the biological characteristic dosage (unit: Gy) of the exposure tissue.Often
Kind tissue has its corresponding biological characteristic dosage, and α/β is bigger, and the tissue is more sensitive to ray, is presented as early response organization, such as
Tumor tissues, the epithelial cell of majority；α/β is smaller, which more resists ray, is presented as late response organization, such as prostate
Tumour (α/β is less than 2Gy), lung, spinal cord.
The biological effect dosage that LQ model inference goes out generates equal when referring to infinite more, the fractionated dose infinitesimal of gradation number
Theoretical accumulated dose needed for biological effect.BED has pushed tumour radiotherapy biological dose to the qualitative assessment side based on experiment
To development.BED is that cell survival fraction S takes after logarithm (- 1/ α) times, it may be assumed that
N indicates that irradiation number, D indicate that fractionated dose, α/β indicate the biological characteristic dosage to equivalent tissue.Zoopery
Show in the research of mouse small intestine pit cell Different Dose Rates Radiobiological effects, it is different that LQ model can be very good fitting
The survivorship curve of cell under dosage rate.Simultaneously clinically it has been proved that LQ model can be just when 1~64 irradiation of partitioning into skin
When quantitative description they repair in biological effect dosage；It is sent out in 157 Nasopharyngeal Carcinoma Patients conventional fractionated radiation therapy researchs
It is existing, there is apparent BED relationship in nasopharyngeal carcinoma fractionation radiotherapy, dosage is lower, and office's control and survival rate are lower, but produced by doses
BED change with treatment time, the course for the treatment of is longer, office control and survival rate it is lower.
Nearly ten years, with the raising of equipment and technical level, radiotherapy can be by x-ray dose in highly conformable mode
Any position of body is accurately projected, therapeutic process can be completed within of short duration a couple of days, drop while improving biological effect
Low medical treatment cost, this makes radiotherapy doctor rekindle interest to big cutting techniques, and relevant clinical queue experiment also gives
Encouraging result.
But think that the time interval between gradation can be such that the sublethal damage of cell obtains completely in LQ model
It repairs, but as single mode therapeutic dose is continuously increased, single dose promotes bring biological effect and is but ignored.Cell
Will form the damage of two categories in radiative process: the first kind is fatal injury, and the second class is sublethal damage.It is lethal
Theory is explained with lethal can use in Asia, thinking to have crucial target in cell in theory, only ray particle is hit
In all target, cell just can be dead.Fatal injury in cell may be considered all targets and all be hit, sub- lethal damage
Wound is that part target is hit but do not hit all in cell.Theory in LQ model thinks sublethal damage meeting self-regeneration,
But as the promotion of single dose in radiotherapy, cell can generate a large amount of sublethal damage in a short time, this is just
Cause: 1. cells are when carrying out DNA self-regeneration, since the radix of sublethal damage becomes more, so that cell errors repair
Quantity becomes more；2. cell can be utilized for the biological enzyme repaired in progress self-regeneration and protein is limited in a short time
, this sublethal damage for allowing for cell cannot be repaired and be further converted to fatal injury；3. in radiotherapy
When with dosage continuous promotion, some sublethal damages, which are directly become fatal injury by further irradiation, to be caused carefully
Born of the same parents' apoptosis.Which results in high dose area tradition LQ model cannot correct cell survival condition.Due to LQ model be
Single low dose exposure is derived by model, and the increase with single dose is not accounted in LQ model, therefore, nothing
Method accurately calculates biological effect dosage；In addition, the parameter in LQ model has it mutually to cope with biological significance, but in fitting
It was found that model obtained biological parameter when being fitted the cell line of some pairs of ray relative insensitivities cannot be indicated accurately
Its real biological susceptibility.
Summary of the invention
The object of the present invention is to provide biological effect dosing method and systems in a kind of tumour radiotherapy, to solve
Increase in traditional LQ model due to not accounting for single dose, and lead to not accurate evaluation go out radiate control
The problem of biological effect dosage during treatment.
To achieve the above object, the present invention provides following schemes:
Biological effect dosing method in a kind of tumour radiotherapy, comprising:
Obtain corrected parameter；The corrected parameter include single dose, sublethal damage to fatal injury convert
Conversion function and correction function；
Cells survival curve descriptive model is established according to the corrected parameter；
Biological effect dose modal is established according to the cells survival curve descriptive model；
Biological effect dosage is determined according to the biological effect dose modal.
Optionally, described that cells survival curve descriptive model is established according to the corrected parameter, it specifically includes:
According to formula S=exp ((- α d- β d2)/(1+dγ)) establish cells survival curve descriptive model；Wherein, S is cell
CNN surviving fraction；It is single dose for d；α is the average probability of the fatal injury as caused by single particle in radiative process；
β is the average probability that two particles cause fatal injury；γ be due to sublethal damage conversion caused by quadratic term not
Disconnected reduced model parameter.
Optionally, described that biological effect dose modal is established according to the cells survival curve descriptive model, it specifically includes:
The cells survival curve descriptive model is fitted using least square method, the cells survival after determining fitting
Curve descriptive model；
Biological effect dose modal is established according to the cells survival curve descriptive model after the fitting.
Optionally, it is described biological effect dosage is determined according to the biological effect dose modal after, further includes:
It is according to the biological effect dose modal that the irradiation under the conditions of fractionated dose equivalence to unlimited fractionation of radiation is of equal value
Dosage, and according to formula n1d1(1+βd1/α)/(1+d1 γ)=n2d2(1+βd2/α)/(1+d2 γ) the different radiation treatment plans of conversion；
n1For the gradation number of the first therapeutic scheme；d1For the single dose of the first therapeutic scheme, n2For the gradation of the second therapeutic scheme
Number；d2For the single dose of the second therapeutic scheme.
Biological effect dosage determines system in a kind of tumour radiotherapy, comprising:
Corrected parameter obtains module, for obtaining corrected parameter；The corrected parameter includes single dose, sub- lethal
Damage the conversion function and correction function converted to fatal injury；
Cell curve descriptive model establishes module, describes mould for establishing cells survival curve according to the corrected parameter
Type；
Biological effect dose modal establishes module, for establishing biological effect according to the cells survival curve descriptive model
Dose modal；
Biological effect dosage determining module, for determining biological effect dosage according to the biological effect dose modal.
Optionally, the cell curve descriptive model is established module and is specifically included:
Cell curve descriptive model establishes unit, for according to formula S=exp ((- α d- β d2)/(1+dγ)) establish cell
Survivorship curve descriptive model；Wherein, S is cell survival fraction；It is single dose for d；α is in radiative process by single grain
The average probability of fatal injury caused by son；β is the average probability that two particles cause fatal injury；γ is since Asia causes
The ever-reduced model parameter of quadratic term caused by dead property damage conversion.
Optionally, the biological effect dose modal is established module and is specifically included:
Fitting unit is determined quasi- for being fitted using least square method to the cells survival curve descriptive model
Cells survival curve descriptive model after conjunction；
Biological effect dose modal establishes unit, for being established according to the cells survival curve descriptive model after the fitting
Biological effect dose modal.
Optionally, further includes:
Conversion module, for according to the biological effect dose modal by fractionated dose equivalence to unlimited fractionation of radiation condition
Under irradiation equivalent dose, and according to formula n1d1(1+βd1/α)/(1+d1 γ)=n2d2(1+βd2/α)/(1+d2 γ) conversion difference
Radiation treatment plan；Wherein, n1 is the gradation number of the first therapeutic scheme；d1For the single dose of the first therapeutic scheme, n2For
The gradation number of second therapeutic scheme；d2For the single dose of the second therapeutic scheme.
The specific embodiment provided according to the present invention, the invention discloses following technical effects: the present invention provides one kind
Biological effect dosing method and system in tumour radiotherapy, by introducing single dose, it may be assumed that introduced with single
The variation of cell self-regeneration caused by exposure dose increase turns the sublethal damage ignored in LQ model to fatal injury
It is added in LQ model after the factors quantization of change, so that it is determined that new cells survival curve descriptive model, changes in high dose area
The gradient of model has been apt to it, so that model curve is more in line with Germicidal efficacy data, cells survival curve describes mould before improving
The shortcomings that type is persistently bent decline in high dose area, is unable to the survival condition of accurate description cell；Meanwhile it is raw by new cell
Biological effect in radiotherapy can more accurately be described by depositing the biological effect dose modal that curve descriptive model is derived
Dosage improves previous model the shortcomings that Biocidal effect is over-evaluated or underestimated to high dose area, can accurately calculate biology
Effect dose, to more accurately carry out the conversion between different radiation treatment plans；The parameter that model is fitted has
Its corresponding biological significance, while cells survival curve descriptive model is simple, is easy to clinical expansion.
Detailed description of the invention
It in order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, below will be to institute in embodiment
Attached drawing to be used is needed to be briefly described, it should be apparent that, the accompanying drawings in the following description is only some implementations of the invention
Example, for those of ordinary skill in the art, without any creative labor, can also be according to these attached drawings
Obtain other attached drawings.
Fig. 1 is logarithmic linear figure provided by the present invention；
Fig. 2 is biological effect dosing method flow chart in tumour radiotherapy provided by the present invention；
Fig. 3 is quadratic term provided by the present invention since probability reduces caused by the sub- lethal conversion to fatal injury
Curve graph；
Fig. 4 is the matched curve figure provided by the present invention based on zooblast survival data；
Fig. 5 is the matched curve figure provided by the present invention based on human body cell survival data
Fig. 6 is that biological effect dosage determines system block diagram in tumour radiotherapy provided by the present invention；
Fig. 7 is that biological effect dosage determines system construction drawing in tumour radiotherapy provided by the present invention.
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment shall fall within the protection scope of the present invention.
The object of the present invention is to provide biological effect dosing method and system in a kind of tumour radiotherapy, Neng Gouzhun
Really evaluate the biological effect dosage in radiation therapy process.
In order to make the foregoing objectives, features and advantages of the present invention clearer and more comprehensible, with reference to the accompanying drawing and specific real
Applying mode, the present invention is described in further detail.
Fig. 2 is biological effect dosing method flow chart in tumour radiotherapy provided by the present invention, such as Fig. 2 institute
Show, biological effect dosing method in a kind of tumour radiotherapy, comprising:
Step 201: obtaining corrected parameter；The corrected parameter includes single dose, sublethal damage to lethal
Damage the conversion function and correction function of conversion.
Step 202: cells survival curve descriptive model is established according to the corrected parameter.
In previous research report, when discovery single dose is more than (5~6Gy), the survival curve of part cell be will become
Stronger linear relationship.So semilethal conversion should be changed less than (5~6Gy) significantly, it is being greater than (5~6Gy)
After become steady.So dosage to the sub- lethal relational assumption converted into power-exponent function relationship, i.e. F { d γ }, wherein d is single
Exposure dose, γ are model parameter.In LQ model to it is sub- it is lethal it is relevant be model quadratic term.Due to semilethal turn
It changes, so that quadratic term-β d2Constantly reduce.Assuming that quadratic term is-P β d2, P can be understood as the probability of quadratic term.Do not considering
P (d)=1 before dosage factor, P (d)=F { d γ } after considering single dose increase.Due to P as the increase of dosage constantly subtracts
It is small, so P (d)=P/F { d γ }, i.e. P (d)=1/F { d γ }.Can it directly be indicated with simple form F { d γ }=d γ
Between relationship, so P (d)=1/d γ, for guarantee P between [0,1] less than 1, so the truth of a matter is changed to (1+d γ), most
Termination fruit is R=P=1/ (1+d γ).
As shown in figure 3, under being spaced at the same time, as the increase cell of single dose can stand semilethal reparation
It carves and uses 1/ (1+d of modelγ) indicate.Repair function R and LQ models coupling can be obtained into new cells survival curve and describe mould
Type:
S=exp (- α d- β d21/(1+dγ)) (3)
Wherein α represents the average probability of the fatal injury as caused by single particle in radiative process, and there are two grains for β representative
Son causes the average probability of fatal injury.Wherein γ indicate due to it is sub- it is lethal converted to fatal injury, caused by it is secondary
The ever-reduced model parameter of item.It is found on the basis of a large amount of cell experiment, it is on the effect data of fitting that first order is same
Sample also has better effect multiplied by correction function R.The reason is that correction function describes increasing with dosage by quick for first order
Stable function characteristic is changed to, it is succinct so formula for new model are as follows:
S=exp ((- α d- β d2)/(1+dγ)) (4)
Wherein (decision of parameter is to be fitted determination according to different cell line, or pass through clinical data by α, β and γ
Integrated and pre-processed, estimation then is fitted to parameter) be model characteristic parameter, d is single dose.
α represents the average probability of the fatal injury as caused by single particle in radiative process, and β is represented to be made there are two particle
At the average probability of fatal injury.Wherein γ indicate due to it is sub- it is lethal converted to fatal injury, caused by quadratic term not
Disconnected reduced model parameter.
Obtain cell survival data；The cell survival data include zooblast survival data and human body cell survival
Data.The accuracy and applicability of model are verified by cell survival data；In the realization of specific system, human body can be applied
Cell survival data are fitted.
The existing cell survival data of retrospective analysis, have inside selected one group of zooblast Radiation survival experimental data and one
Group human body cell Radiation survival experimental data, to be fitted accuracy test and Estimating The Model Coefficients to new model.In animal
Chinese hamster fibroma cell line (CHOAA8) and mammary gland of mouse sarcoma cell line (EMT6) are picked inside cell；It is thin in human body
Two kinds of prostate cancer cell lines (CP3 and DU145) is picked in born of the same parents.Least square method pair is used on the basis of two group data sets
Cell survival data are fitted, and fitting result is as shown in Figure 4 and Figure 5, meanwhile, table 1 is four kinds of differences provided by the present invention
Fitting parameter corresponding to cell line and its fitting precision contrast table, as shown in table 1.
Zooblast survival data is Chinese hamster fibroma cell line (CHAOO8, zero) and mammary gland of mouse sarcoma cell line
(EMT6, △), solid line are the matched curve of CHOAA8, and dotted line is the matched curve of EMT6.
Human body cell survival data is prostate cancer cell line (DU145 and CP3, respectively and ☆), solid line DU145
Matched curve, dotted line be CP3 matched curve.
Step 203: biological effect dose modal is established according to the cells survival curve descriptive model.
Biological effect dose computation model is established according to obtained cell survival curve descriptive model, formula (5) is biology
Effect dose model.Biological effect dose modal is taken into natural logrithm in both members, then multiplied by -1/ α, can thus be incited somebody to action
New model is converted into biological effect dose computation model.
BED=d (1+ β d/ α)/(1+dγ) (5)
Wherein, α is the average probability of the fatal injury as caused by single particle in radiative process；β is that two particles are made
At the average probability of fatal injury；γ is the ever-reduced model ginseng of quadratic term caused by being converted due to sublethal damage
Number, d is single dose.
Step 204: biological effect dosage is determined according to the biological effect dose modal.
As shown in Figure 6, whereinFor goodness of fit evaluation function, x is fit value,
Y is the measured value of cell survival fraction, f (Di；{ p } is the calculated value of biological effect dose model, wiFor weight；The present invention can be with
By biological effect dose modal by the irradiation equivalent dose under the conditions of fractionated dose equivalence to unlimited fractionation of radiation, according to formula
(6) conversion between different radiation treatment plans is carried out.
n1d1(1+βd1/α)/(1+d1 γ)=n2d2(1+βd2/α)/(1+d2 γ) (6)
Wherein, α is the average probability of the fatal injury as caused by single particle in radiative process；β is that two particles are made
At the average probability of fatal injury；γ is the ever-reduced model ginseng of quadratic term caused by being converted due to sublethal damage
Number, n1For the gradation number of the first therapeutic scheme；d1For the single dose of the first therapeutic scheme, n2For the second therapeutic scheme
Gradation number；d2For the single dose of the second therapeutic scheme.
Fig. 7 is that biological effect dosage determines system construction drawing in tumour radiotherapy provided by the present invention, such as Fig. 7 institute
Show, biological effect dosage determines system in a kind of tumour radiotherapy, comprising:
Corrected parameter obtains module 701, for obtaining corrected parameter；The corrected parameter includes single dose, Asia
The conversion function and correction function that lethal damage is converted to fatal injury；
Cell curve descriptive model establishes module 702, for establishing the description of cells survival curve according to the corrected parameter
Model.
The cell curve descriptive model is established module 702 and specifically included: cell curve descriptive model establishes unit, is used for
According to formula S=exp ((- α d- β d2)/(1+dγ)) establish cells survival curve descriptive model；Wherein, S is cell survival point
Number；It is single dose for d；α is the average probability of the fatal injury as caused by single particle in radiative process；β is two
A particle causes the average probability of fatal injury；γ is that quadratic term constantly reduces caused by being converted due to sublethal damage
Model parameter.
Biological effect dose modal establishes module 703, for establishing biology according to the cells survival curve descriptive model
Effect dose model.
The biological effect dose modal is established module 703 and is specifically included: fitting unit, for using least square method pair
The cells survival curve descriptive model is fitted, the cells survival curve descriptive model after determining fitting；Biological effect agent
Model foundation unit is measured, for establishing biological effect dose modal according to the cells survival curve descriptive model after the fitting.
Biological effect dosage determining module 704, for determining biological effect dosage according to the biological effect dose modal.
The invention also includes conversion module, it is used for fractionated dose equivalence according to the biological effect dose modal to infinitely
Irradiation equivalent dose under the conditions of fractionation of radiation, and according to formula n1d1(1+βd1/α)/(1+d1 γ)=n2d2(1+βd2/α)/(1+
d2 γ) the different radiation treatment plans of conversion；Wherein, n1For the gradation number of the first therapeutic scheme；d1For the single of the first therapeutic scheme
Exposure dose, n2For the gradation number of the second therapeutic scheme；d2For the single dose of the second therapeutic scheme.
For cell survival status model in description radiation therapy process, additionally it is possible to derive a series of biological effect agent
The calculation method of amount.
It wherein, include mainly two class models, the first kind is continuum model, including linear-secondary (Linear-
Quadratic, LQ) model and generalized linear secondary model (Linear-Quadratic, LQ)；Second class is sectional type model,
It is linear including general survivorship curve (universal survival curve, USC) model and linear-secondary-
(Linear-Quadratic-Linear；LQL) model.
GLQ model thinks that LQ model does not fully consider the variation of sublethal damage over time, in LQ model
The repair process of sublethal damage is only accounted for, and sublethal damage is due to further radiating the case where being converted to fatal injury
It is ignored.It is acceptable in low dose exposure and low dose rate irradiation, and in single-bolus high-dose irradiation and high dose rate
It will result in biggish difference when irradiation.Most important improve of GLQ model is exactly to increase sublethal damage to fatal injury
Transformation index item β2, expression formula are as follows:
Wherein, D is that accumulated dose is irradiated in time t, and dosage rate when I (t) is irradiation, μ is repair rate, β1It indicates sub- to cause
Dead damage ratio, β2Indicate that sublethal damage is converted into the ratio of fatal injury.
USC model is to click model by LQ model and more targets to be composed, the former Accurate Curve-fitting cold spot area cell is deposited
Curve living and the latter combine the characteristics of high dose area more accurately can be fitted experimental data.In order to keep model simpler easily
With USC clicks the asymptote of model using more targets to replace the model.Model setting conversion dosage DT is used as d≤DT
LQ model；As d >=DT, model is clicked using more targets, so that LQ model can seamlessly transit at DT, expression formula are as follows:
DT is conversion dosage, and D0 is the parameter for determining the final slope of curve, and Dq is the extension that more targets click model asymptote
The intercept of line and x-axis.The calculation formula of USC model calculating biological effect dosage:
D is the accumulated dose of irradiation, and d is single dose, and n is irradiation number.
Dosed regions have been divided into two parts by using converting dosage DT by LQL model, pass through introduction in high dose area
One naive model is fitted the linear segment of cells survival curve.The expression formula of LQL model are as follows:
γ indicates that the linear segment in cell survival curve high dose area, the logarithm of per unit dose cell kill in formula
Wound.When assuming that two model tight fits and smooth when being transitioned into linear segment, can be approximately with LQ models fitting by γ
Cells survival curve conversion dosage DT at tangent slope.LQ-L model can be used to calculate bioequivalence dosage, calculate public
Formula are as follows:
The present invention is on the basis of traditional computation model, by the ignored continuous promotion biology effect with single dose
The factor that should change is added in model, solves traditional biological effect dose computation model with the promotion of single dose,
In excessively high estimation radiotherapy the problem of biological effect dosage.
Each embodiment in this specification is described in a progressive manner, the highlights of each of the examples are with other
The difference of embodiment, the same or similar parts in each embodiment may refer to each other.For system disclosed in embodiment
For, since it is corresponded to the methods disclosed in the examples, so being described relatively simple, related place is said referring to method part
It is bright.
Used herein a specific example illustrates the principle and implementation of the invention, and above embodiments are said
It is bright to be merely used to help understand method and its core concept of the invention；At the same time, for those skilled in the art, foundation
Thought of the invention, there will be changes in the specific implementation manner and application range.In conclusion the content of the present specification is not
It is interpreted as limitation of the present invention.
Claims (8)
1. biological effect dosing method in a kind of tumour radiotherapy characterized by comprising
Obtain corrected parameter；The corrected parameter includes turning of converting to fatal injury of single dose, sublethal damage
Change function and correction function；
Cells survival curve descriptive model is established according to the corrected parameter；
Biological effect dose modal is established according to the cells survival curve descriptive model；
Biological effect dosage is determined according to the biological effect dose modal.
2. biological effect dosing method in tumour radiotherapy according to claim 1, which is characterized in that described
Cells survival curve descriptive model is established according to the corrected parameter, is specifically included:
According to formula S=exp ((- α d- β d2)/(1+dγ)) establish cells survival curve descriptive model；Wherein, S is cell survival
Score；It is single dose for d；α is the average probability of the fatal injury as caused by single particle in radiative process；β is
Two particles cause the average probability of fatal injury；γ is that quadratic term constantly subtracts caused by being converted due to sublethal damage
Small model parameter.
3. biological effect dosing method in tumour radiotherapy according to claim 2, which is characterized in that described
Biological effect dose modal is established according to the cells survival curve descriptive model, is specifically included:
The cells survival curve descriptive model is fitted using least square method, the cells survival curve after determining fitting
Descriptive model；
Biological effect dose modal is established according to the cells survival curve descriptive model after the fitting.
4. biological effect dosing method in tumour radiotherapy according to claim 3, which is characterized in that described
After determining biological effect dosage according to the biological effect dose modal, further includes:
According to the biological effect dose modal by the irradiation equivalent dose under the conditions of fractionated dose equivalence to unlimited fractionation of radiation,
And according to formula n1d1(1+βd1/α)/(1+d1 γ)=n2d2(1+βd2/α)/(1+d2 γ) the different radiation treatment plans of conversion；n1For
The gradation number of first therapeutic scheme；d1For the single dose of the first therapeutic scheme, n2For the gradation number of the second therapeutic scheme；
d2For the single dose of the second therapeutic scheme.
5. biological effect dosage determines system in a kind of tumour radiotherapy characterized by comprising
Corrected parameter obtains module, for obtaining corrected parameter；The corrected parameter includes single dose, sublethal damage
The conversion function and correction function converted to fatal injury；
Cell curve descriptive model establishes module, for establishing cells survival curve descriptive model according to the amendment；
Biological effect dose modal establishes module, for establishing biological effect dosage according to the cells survival curve descriptive model
Model；
Biological effect dosage determining module, for determining biological effect dosage according to the biological effect dose modal.
6. biological effect dosage determines system in tumour radiotherapy according to claim 5, which is characterized in that described thin
Born of the same parents' curve descriptive model is established module and is specifically included:
Cell curve descriptive model establishes unit, for according to formula S=exp ((- α d- β d2)/(1+dγ)) establish cells survival
Curve descriptive model；Wherein, S is cell survival fraction；It is single dose for d；α is to be made in radiative process by single particle
At fatal injury average probability；β is the average probability that two particles cause fatal injury；γ is due to sub- lethal
The ever-reduced model parameter of quadratic term caused by damage conversion.
7. biological effect dosage determines system in tumour radiotherapy according to claim 6, which is characterized in that the life
Object effect dose model building module specifically includes:
Fitting unit, for being fitted using least square method to the cells survival curve descriptive model, after determining fitting
Cells survival curve descriptive model；
Biological effect dose modal establishes unit, for establishing biology according to the cells survival curve descriptive model after the fitting
Effect dose model.
8. biological effect dosage determines system in tumour radiotherapy according to claim 7, which is characterized in that also wrap
It includes:
Conversion module, for will be under the conditions of fractionated dose equivalence to unlimited fractionation of radiation according to the biological effect dose modal
Equivalent dose is irradiated, and according to formula n1d1(1+βd1/α)/(1+d1 γ)=n2d2(1+βd2/α)/(1+d2 γ) the different radiation of conversion
Therapeutic scheme；Wherein, n1For the gradation number of the first therapeutic scheme；d1For the single dose of the first therapeutic scheme, n2It is second
The gradation number of therapeutic scheme；d2For the single dose of the second therapeutic scheme.
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