CN103394167A - BED (biological effective dose)-based prediction method for complications caused by tumor radiotherapy - Google Patents
BED (biological effective dose)-based prediction method for complications caused by tumor radiotherapy Download PDFInfo
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Abstract
The invention provides a BED (biological effective dose)-based prediction method for complications caused by tumor radiotherapy. The method comprises the following steps of improving the conventional NTCP (normal tissue complication probability) model by using the concept of a BED, and performing fractionated dose correction on the model by introducing an alpha/beta factor; reviewing and analyzing dose-volume parameters of irradiation to a certain organ after a group of patients receive radiotherapy and follow-up results, which are obtained by clinical observation after the radiotherapy, about the occurrence of the complications on the organ, and performing synchronous fitting on model parameters and the alpha/beta factor by utilizing the improved NTCP model; and substituting the NTCP model parameters and the alpha/beta factor, which are obtained by fitting, and the dose-volume information of the organs of a group of patients to receive the radiotherapy into the improved NTCP model, and calculating a probability value of occurrence of the complications on the organs of the patients in the group. Therefore, the probability of occurrence of the complications on the organ after the tumor patients in the group receive different fractionated doses of irradiation is predicted.
Description
Technical field
The present invention relates to a kind of radiotherapy clinical complication Predicting Technique, specifically a kind of Forecasting Methodology of the complication of the tumour radiotherapy based on biological effect dosage.
Background technology
The purpose of tumour radiotherapy is by improving target area (tumor) dosage and reducing target area normal surrounding tissue (jeopardizing organ) radiation injury, improve the Partial controll rate of tumor, thus further improve the cancer patient survival rate, improve life in patients.Yet, the tumor invasion position is usually located in patient body, when penetrating human body, ray must pass some normal structure, and the lateral scattering of x-ray also increased the dosage of target area normal surrounding tissue raying, even the most accurate radiotherapy technology also can't be avoided the mistake of target area normal surrounding tissue is irradiated at present.And the organ in human body is comparatively responsive to x-ray radiation, and the organ of certain volume is subject to the irradiation of doses, will show the impaired of organ dysfunction, thereby makes human body show complication.
Dosage in tumour radiotherapy is cut apart pattern:
According to the Biological characteristics of tumor cell, radiotherapy, in implementation process, according to the difference of fractionated dose, is divided into routine and cuts apart, cuts apart greatly and three kinds of patterns of hyperfractionated, wherein
Routine is cut apart and is referred to that fractionation of radiation dosage is 2.0Gy, once a day, is to adopt maximum dosage to cut apart pattern; Cut apart greatly and refer to that fractionation of radiation dosage is greater than 2.0Gy, irradiate interval more than or equal to one day, biological effect dosage is higher, to the damage of tumor normal surrounding tissue more conventional cut apart larger;
Hyperfractionated refers to that fractionation of radiation dosage, less than 2.0Gy, irradiates twice every day, and interval was greater than 6 hours, and biological effect dosage is lower, with routine, cuts apart and compares, and can protect better the tumor normal surrounding tissue.
For different patients, according to position, the pathology, by stages different of tumor, different fractionated dose therapeutic schemes will be adopted, thereby the degree of impairment of the tumor surrounding normal organ that causes is also by different.
Irradiation complication:
The irradiation complication that some is acute, as the acute lung injury that causes in the radiotherapy in lung cancer process, appear in the process that the patient accepts radiotherapy, the treatment progress that may delay thus the patient, more serious may affect radiocurable smooth enforcement, threaten patient's life, thereby reduce TCP, reduced survival; Some, irradiation complication, appeared in the time of 3 months to 5 years of accepting after radiotherapy as the bladder damage in late period that causes in the carcinoma of prostate Patients During Radiotherapy in late period, reduced patient's life quality, for the patient has brought more misery.
Irradiation complication is carried out to feasibility and the meaning thereof of prediction:
To each example, prepare to accept radiocurable patient, all need to before implementing treatment, to it, carry out CT scan, and the faultage image that scanning obtains is sent to the radiotherapy planning system, carry out carrying out again radiotherapy plan after three-dimensional reconstruction.The design process of tumour radiotherapy physics teacher to radiotherapy planning, the incident direction, ray energy, the irradiation field that are the x-ray that clinac penetrates while treating by simulated emission are opened the parameters such as wild shape, the simulation radiation dose is the distribution situation in each organ and tissue in human body, and by the dose-volume rectangular histogram, the exposure dosage of each organ around tumor is carried out to qualitative assessment.Tumour radiotherapy physics teacher is by quality assurance equipment, and the analog result of dose distribution is detected, and guarantees that the actual dose distribution results that obtains after the actual acceptance irradiation of analog result and human body is consistent.Like this, just can be before the patient to accept actual therapeutic, the radiation dose that will accept the patient carries out qualitative assessment accurately, and on this basis, for the probability that normal structure develops complications, predicts.
In this case, the doctor of tumor radiotherapy section can be according to predicting the outcome, and before implementing treatment, in time adjust the radiotherapy scheme, the damage of prophylaxis of tumours normal surrounding tissue targetedly, thus reduce or avoid the generation of irradiation complication.
The effect of normal structure complication forecast model:
Normal structure complication probability (NTCP) model is to be based upon dose-volume to close a mathematical model of fastening, can pass through the adjustment model parameter, describe different normal organs and the probability of irradiation complication after accepting certain exposure dose, occurs, the radiotherapy toxic reaction is predicted, also can to different therapeutic schemes, be carried out according to this quantification contrast of biological effect.
Burman is in the complication probability model of application Lyman in 1991 proposition, on the basis of each organ clinical tolerance dosage that Emami provides, by the method for curve fitting and observation, provided 27 kinds of normal organs in the situation that accept the full volumetric uniform irradiation occur 29 kinds of corresponding NTCP model parameters of irradiation complication (
TD 50 (1),
n,
m) and be widely used in clinical practice.In recent years, also there is lot of documents to report and by the NTCP model, to the radiotherapy scheme, carry out the correlational study of quantitative evaluation and comparison.
Biological effect dosage
" biological dose " in radiation therapy process and " physical dosage " are two different concepts.According to No. 30 Report Definition of the international IAEA of Atomic Energy Commission, " biological dose " refers to the measurement to organism rdaiation response degree.Therefore, there is the multidigit researcher to propose physical dosage is converted to the conversion model of biological dose, but only have the model of only a few to have practical value, its neutral line-secondary Linear-Quadrac, the L-Q model is a kind of mathematical model that is widely used in radiobiological studies and clinical radiotherapy most, it is to draw from the cell survival curve direct derivation, so it is not a pure empirical equation.By the biological effect dosage Biological Effective Dose that the L-Q model derives, BED, it is a kind of exactly that according to dosage, to cut apart pattern different and physical dosage is converted to the method for biological dose.At present, this method is widely used in clinical position the conversion to physical dosage and biological dose.
The deficiency that prior art exists:
the deficiency that prior art exists in actual use is, traditional NTCP model can only carry out the complication prediction for the patient who accepts identical fractionated dose in the prediction prediction group, it is a kind of predictive mode of complication based on physical dosage, what accept as all predicted patients is that routine dose is while cutting apart, think that physical dosage is equal to biological dose, can directly adopt the conventional model form to predict, but, if in predicted patient colony, exist some patients like this, they will accept unconventional dosage fractionated irradiation, that brings thus is different from the biological effect that routine dose is cut apart, just can't be embodied, be that traditional NTCP model can't predict respectively that to two parts patient (and clinical experience and statistical data all confirm, different fractionated dose schemes will affect the appearance of irradiation complication to some extent), therefore, this limitation makes the predictive ability decrease of traditional NTCP model, the scope of application is restricted.
For better these characteristics being made explanations, now lift an example explanation: as shown in Figure 2, Fig. 2 (a) and (b) showed that respectively accepting routine dose cuts apart (blueness, Arm A, 35 times * 2.0Gy/ time) and accept Hypofractionation (redness, Arm B, 28 times * 2.5Gy/ time) the integration and differentiation DVH figure of two routine patient's bladder exposure dosage.Because two routine patients have accepted identical total prescribed dose (70Gy), therefore, on scheming, can't find out after two routine patient's bladders are accepted to irradiate the difference that may show complication.Yet clinical experience and statistical result showed, accept the patient of Hypofractionation, and its probability that develops complications is greater than accepting the conventional patient of cutting apart, and difference has significance.In this case, because traditional NTCP model is subject to irradiating the accumulation DVH figure of total amount fully based on patient's organ, do not consider the impact of different fractionated dose schemes on complication, therefore, the probability that develops complications for above-mentioned two routine patients, the same predicting the outcome will be provided, and this result does not conform to the actual conditions.
Summary of the invention
The objective of the invention is to overcome the deficiency that prior art exists, provide a kind of for the different fractionated dose program prediction patients rear method that irradiation complication occurs of receiving treatment.
Method of the present invention realizes in the following manner, utilize " biological effect dosage " Biological Effective Dose, the BED concept, to traditional normal structure complication probability Normal Tissue Complication Probability, the NTCP model is made
Improve, introduce α/β factor pair model and carry out the fractionated dose correction; Then, one group of patient of retrospective analysis accepts the Follow-up results that clinical observation obtains after certain organ is irradiated after radiotherapy dose-volume parameter and treatment this organ develops complications, utilize the NTCP model after improving, model parameter and the α/β factor are carried out to synchronous match; Finally, NTCP model parameter and the α/β factor that match is obtained, NTCP model after improving with the dose-volume information substitution that will accept radiocurable one group of this organ of patient, calculate the probit that this organ of this group patient develops complications, thereby realize that to this group tumor patient the probability that this organ develops complications is predicted after accepting different fractionated doses irradiations.Concrete steps are as follows:
(1)
Traditional NTCP model is improved
1) biological dose conversion: to maximal dose and the dose bin of dosage unit corresponding to each volume element volume bin that describes in traditional NTCP model, according to bioequivalence dosage Biological Effective Dose, the concept of BED is carried out the biological dose conversion, and formula is
Wherein,
For the patient
The dosage of the maximal dose that certain organ is irradiated or a dosage unit, α/β are the factors of carrying out the fractionated dose correction,
The patient
Minute number of times of receiving treatment,
Be after formula 1 conversion, obtain with
The biological dose of equivalence;
(2) to improving rear NTCP model parameter and the α/β factor, carry out match
1) obtain dose distribution: from the radiotherapy planning system, derive and describe the dose-volume rectangular histogram that the human body organ is accepted radiation dose, and this figure is converted to differential form by integrated form, with this, obtain volume element corresponding to each volume element of this organ, i.e. its radiation dose (unit: Gy) that receives;
2) estimated parameter value: the match to model parameter need be adopted maximum likelihood estimate.For each the routine patient from the retrospective analysis group
, its NTCP value can be expressed as the form of model parameter, the α/β factor and differential post dose, volume element function, that is:
(formula 2)
For being used for the retrospective analysis group patient data of model of fit parameter, its log-likelihood function
Be expressed as
Wherein, for the patient
If radiation complication appears in clinical observation,
Otherwise
.Then, utilize optimization tool, make likelihood function
Get maximum, i.e. match obtains describing model parameter value and the α/β factor values that this organ develops complications;
(3) complication is predicted
1) preparation from the prediction prediction group is accepted to radiocurable each routine patient and design radiotherapy treatment planning, and according to the described method of preamble, by the dose distribution of radiotherapy planning system simulation organ, and derive with differential form the radiation dose that each volume element of this organ receives;
2) the dose-volume factor of each routine this organ of patient in the prediction prediction group that simulation is obtained (being volume element and corresponding dosage unit), and NTCP model parameter value and α/β factor values after the improvement that obtains of preamble match, the NTCP model of substitution after improving in the lump, calculate the NTCP value that this organizes each routine patient, namely obtain the probit that irradiation complication appears in each routine patient, realize the prediction to complication.
excellent effect of the present invention is:use method prediction radiotherapy of the present invention to cause the probability that tumor surrounding normal organ develops complications, can be before the patient accepts actual therapeutic, for the patient colony that will accept the various dose splitting scheme and treat, the prediction of distinguishing individuation is provided, embodied the significant difference that the various dose splitting scheme shows producing irradiation complication, for the radiotherapy department doctor provides assessment tool easily and effectively, what is more important, in clinical practice, effectively reduce the patient and accept the probability that develops complications after radiotherapy, improved patient's life quality, and improved to a certain extent survival.
The present invention predict carcinoma of prostate radiotherapy cause predicting the outcome of bladder complication in late period and with the contrast of traditional method prediction effect, as shown in the table.
The accompanying drawing explanation
Fig. 1 is radiotherapy complication Forecasting Methodology flow chart;
Fig. 2 accepts the patient that various dose cuts apart after mode treatment to have identical dose distribution map;
Fig. 3 is the integration and differentiation DVH figure of corresponding diagram 2 after proofreading and correct by the inventive method.
The specific embodiment
Below in conjunction with accompanying drawing, method of the present invention is described in further detail.
(1) traditional NTCP model is improved
1) certain normal organ is after its certain volume has been accepted certain radiation dose, and the probability (NTCP) that may show complication is as follows:
Wherein,
In formula 7
With
Respectively the patient
The irradiated volume element of organ and corresponding dosage unit,
,
With
Three parameters of NTCP model;
2) for the maximal dose in formula 5
With each the dosage unit in formula 7
, utilize respectively formula 1 to change, physical dosage is converted to biological dose, obtain accordingly
With
3) use
With
In difference replacement formula 5 and formula 7
With
, complete the improvement to traditional NTCP model, on the basis of original three parameters, introduced the different fractionated doses of α/β factor pair and proofreaied and correct, thereby made traditional NTCP model carry out the complication prediction for the patient colony that accepts different fractionated doses;
(2) to improving rear NTCP model parameter and the α/β factor, carry out match
Situation about developing complications for a certain normal organ, choose one group and have the same area tumor and accepted radiocurable patient, collect dose-volume information (DVH) and this organ that each this organ of routine patient is subject to radiation and necessarily following up a case by regular visits to situation about developing complications on time point;
1) for this, organize each routine patient
, its NTCP value can be expressed as the form of model parameter, the α/β factor and differential post dose, volume element function, that is:
For being used for the retrospective analysis group patient data of model of fit parameter, its log-likelihood function
Be expressed as
Wherein, for the patient
If radiation complication appears in clinical observation,
Otherwise
2) utilize optimization tool, as genetic algorithm, simulated annealing and simplex algorithm etc., make likelihood function
Get maximum, i.e. the global optimum of likelihood function point, the value of each corresponding model parameter and the α/β factor is exactly develop complications model parameter value and the α/β factor values of probability of this organ of description of obtaining of match with it;
(3) complication is predicted
1) for each the routine patient in the prediction prediction group, formulate radiotherapy planning, and therefrom derive organ to be predicted is subject in radiotherapy planning radiation dose-volume information, and integrated form is converted to differential form, namely obtains the dosage unit that each volume element of this organ is corresponding;
2) for each the routine patient in the prediction prediction group, by volume element and the dosage unit that obtains in previous step, with for this organ injury and the NTCP model parameter that match obtains, in NTCP model after the substitution improvement, calculate in the lump, obtain the NTCP value for each routine patient, namely obtain the probit that irradiation complication appears in each routine patient, realize the prediction to complication.
Inventive method accuracy and feasibility checking
For effectiveness and the accuracy of verifying Forecasting Methodology provided by the present invention, now enumerate one group in clinical position actual observation to tumor radiotherapy patient situation about developing complications, and predict with the method.
Enter group 192 examples and accept radiocurable patients with prostate cancer, all patients has all been accepted the irradiation of 70Gy prescribed dose, wherein, 89 routine patients (Arm A) have accepted fractionated dose is the conventional fractionated irradiation of 2.0Gy/ time, and it is the large fractionated irradiation of 2.5Gy/ time that 103 routine patients (Arm B) have accepted fractionated dose.We follow up a case by regular visits to and have recorded the patient and accept after radiotherapy the 3rd year, the situation of bladder damage in late period occurs, and wherein: Arm A has 8 routine patients to develop complications, and Arm B has 21 routine patients to develop complications.Here, whether develop complications, with the LENT/SOMA standard that international radiotherapy tissue proposes, weigh, think and occur that the patient more than or equal to LENT/SOMA secondary complication symptom enters the complication performance group, otherwise enter not performance group of complication.Details is as follows:
Arm A: enter group 89 examples, 2.0Gy/ time * 35 times=70Gy of prescribed dose, 5 times/week, to treat after 3 years and have 8 routine patients to develop complications, the complication sickness rate is 8.99%;
Arm B: enter group 103 examples, 2.5Gy/ time * 28 times=70Gy of prescribed dose, 4 times/week, to treat after 3 years and have 21 routine patients to develop complications, the complication sickness rate is 20.39%.
Because Arm A and two groups of patients of Arm B have accepted identical radiation prescribed dose (70Gy), therefore, if do not consider dosage, do not cut apart the impact that pattern is brought, two groups of patients occur that the probability of irradiation complication should be identical, yet observed result but has sizable difference (8.99% vs. 20.39%), this just requires us when analogue being carried out to the complication prediction, uses NTCP forecast model and prediction flow process thereof after the present invention improves.
We utilize the NTCP model after traditional NTCP model and the present invention improve, and above-mentioned situation has been done respectively to prediction, and result is as shown in table 1.
For calculating parameter, two kinds of Forecasting Methodologies, in fit procedure, have obtained similar NTCP model parameter value (namely
TD 50 (1),
n,
The m value), and the difference of two groups just is, traditional NTCP model does not use the α/β factor to carry out the fractionated dose correction, and method provided by the invention is improved traditional NTCP model, has introduced the α/β factor and has participated in forecasting process.
From predicting the outcome of table 1, can see, traditional NTCP model predicts the outcome for Arm A and Arm B's, all in 15.1% left and right, and the overall complication probability of this result while just Arm A and Arm B patient being mixed into to one group of patient, namely
This result has been covered different fractionated dose schemes and has been produced the appreciable impact that complication is brought after on radiotherapy, and after having used the NTCP model and correlation predictive flow process after the present invention improves, Arm A and Arm B have been provided respectively to 8.93% and 20.45% predict the outcome, very approaching with observable 8.99% and 20.39% the actual sickness rate of complication.
In order to embody more intuitively the change that brings after the α/β factor correction, we carry out the α/β factor correction to listed two routine patient's bladder exposure dose-volume histogram curve in Fig. 2, namely by after bladder maximum point dosage is carried out to the α/β factor correction with each volume element matched doses unit, again delineate dose volume histogram, result as shown in Figure 3.Fig. 3 (a) and (b) respectively corresponding Fig. 2 (a) and integration and differentiation DVH (b).As seen from Figure 3, originally two curves that overlaped, after the different fractionated doses of α/β factor pair are proofreaied and correct, the high dose area of accepting its bladder exposure dosage of patient (Arm B) that large fractionated dose the irradiates segment distance that moved right, embody and cut apart greatly fractionated dose and have higher biological effect dosage, and many pieces of documents show, drop on the variation of Supravesical high dose area volume, by the appearance of appreciable impact bladder complication.Therefore, Fig. 3 well explain accept the large fractionated irradiation patient bladder higher reason of probability that develops complications.
Except the disclosed technical characterictic of description of the present invention, be the known technology of those skilled in the art.
Claims (1)
1. the Forecasting Methodology of the complication of the tumour radiotherapy based on biological effect dosage, towards the tumor patient that will accept different fractionated doses irradiations, before it accepts actual therapeutic, to treatment, may cause the complication probability of its generation to be predicted, it is characterized in that, at first, traditional normal structure complication probability NTCP model is improved, it can be predicted for the patient colony of different fractionated doses; Then, utilize one group of patient's treatment and the rear follow up data for the treatment of, NTCP model parameter and the α/β factor after improving are carried out to synchronous match; Finally, utilize fitting result, to accepting the probability that radiocurable one group of patient develops complications, predict,
Concrete steps are as follows:
(1) biological dose conversion: maximal dose and the dose bin of dosage unit corresponding to each volume element volume bin in traditional NTCP model, describing, according to the concept of bioequivalence dosage BED, carry out the biological dose conversion, conversion formula is
(formula 1)
Wherein,
For the patient
The dosage of the maximal dose that certain organ is irradiated or a dosage unit, α/β are the factors of carrying out the fractionated dose correction,
The patient
Minute number of times of receiving treatment,
Be after formula 1 conversion, obtain with
The biological dose of equivalence;
(2) to improving rear NTCP model parameter and the α/β factor, carry out match
Obtain dose distribution: from the radiotherapy planning system, derive and describe the dose-volume rectangular histogram DVH that the human body organ is accepted radiation dose, and this figure is converted to differential form by integrated form, with this, obtain volume element corresponding to each volume element of this organ, be its radiation dose that receives, unit: Gy;
Estimated parameter value: adopt maximum likelihood estimate to carry out match to model parameter, for each the routine patient from the retrospective analysis group
, its NTCP value can be expressed as the form of model parameter, the α/β factor and differential post dose, volume element function, that is:
For being used for the retrospective analysis group patient data of model of fit parameter, its log-likelihood function
Be expressed as
Wherein, for the patient
If radiation complication appears in clinical observation,
Otherwise
Then, utilize optimization tool, make likelihood function
Get maximum, i.e. match obtains describing model parameter value and the α/β factor values that this organ develops complications;
(3) complication is predicted
Preparation from the prediction prediction group is accepted to radiocurable each routine patient and design radiotherapy treatment planning, by the dose distribution of radiotherapy planning system simulation organ, and derive with differential form the radiation dose that each the volume element simulation of this organ receives;
The dose-volume factor of each routine this organ of patient in the prediction prediction group that simulation is obtained, be volume element and corresponding dosage unit, and NTCP model parameter value and α/β factor values after the improvement that obtains of preamble match, the NTCP model of substitution after improving in the lump, calculate the NTCP value that this organizes each routine patient, namely obtain the probit that irradiation complication appears in each routine patient, realize the prediction to complication.
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| CN112618970A (en) * | 2021-01-06 | 2021-04-09 | 南京航空航天大学 | Boron neutron capture treatment biological dose calculation method |
| CN112618970B (en) * | 2021-01-06 | 2022-03-15 | 南京航空航天大学 | Device and medium for boron neutron capture treatment biological dose calculation method |
| CN117690596A (en) * | 2024-02-04 | 2024-03-12 | 福建自贸试验区厦门片区Manteia数据科技有限公司 | Organ tolerance dose determination device, electronic apparatus, and storage medium |
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