Determination Of Dose-response Relations For AVM Obliteration After Treatment With Gamma Knife

Keywords: gamma knife, outcome, arteriovenous malformation, dose escalation, dose planning

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     The present study aims at deriving the radiobiological parameters of the dose-response relation for achieving obliteration of arteriovenous malformations (AVM) following single fraction stereotactic radiotherapy. Furthermore, the accuracy by which different radiobiological models predict the probability of AVM obliteration is investigated as well as the impact of hemorrhage history, location and volume of the AVM on its radiosensitivity.
     The study patient material consists of 85 patients who received radiation for AVM therapy.
      Radiation induced AVM obliterations were assessed on the basis of post-irradiation angiographies and other radiological findings. For each patient the dose distribution delivered to the clinical target volume and the clinical treatment outcome were available. These data were used in a maximum likelihood analysis and Monte Carlo simulation to calculate the best estimates of the parameters D50 and ? of different radiobiological models. D50 is the dose which gives a response probability of 50% and ? is the maximum normalized value of the dose-response gradient. The parameters D50 and ? characterize the shape of the AVM dose-response relation. The confidence intervals of these parameters were also calculated and their individual influence on the dose-response curve was studied.
     The radiobiological model was proved suitable in predicting the treatment outcome pattern of the studied patient material. The radiobiological parameters of the model were calculated for different AVM location, bleeding history and size. For one of the models examined, the best estimates of the parameters for peripheral AVMs were D50 = 24.2 Gy and ( = 0.86, whereas for centrally located AVMs the values of the model parameters were D50 = 20.9 Gy and ( = 1.91. Similarly, for AVM larger than 2 cm3, the values of the parameters were D50 = 24.6 Gy and ( = 0.67, whereas for AVM smaller than 2 cm3 the values of the model parameters were D50 = 19.7 Gy and ( = 1.37. These values were estimated using further statistical methods and biological models. A sensitivity analysis shown clinically acceptable ranges of variability.
     The correlation between the dosimetric data and their corresponding clinical effect could be accurately modeled using the examined radiobiological models.
      The derived response parameters can be introduced into the clinical routine with the calculated accuracy assuming same target definition and delineation. The known volume dependence of AVM radiosensitivity was confirmed. Moreover, a trend relating AVM location with its radiosensitivity was observed.


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