Dose-response Curve Of Vestibular Schwannomas Treated By Gamma Knife Radiosurgery

Keywords: vestibular schwannoma, gamma knife, Imaging, outcome, radiosurgery

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     The purpose of this study is to determine the dose-response relation for achieving control of vestibular schwannomas after single fraction Gamma Knife radiosurgery and, furthermore, to estimate the confidence intervals of the radiobiological parameters which mathematically describe the shape of the dose-response curve. The impact of the extent by which target volume decreases, is also investigated.
     The study patient material consists of 40 patients who were treated with Gamma Knife between 2004 and 2006. In patient treatment, the Leksell Gamma Knife (model 4C) unit was employed, utilizing its automated positioning system (APS). The dose distribution delivered to the target and the corresponding treatment outcome were registered for each patient. All the patients had at least 2 years of follow-up. The patients were divided into two subgroups depending on whether target volume after 2 years remained unchanged/decreased (treatment success) or increased (treatment failure) compared to the volume at the time of radiosurgery.
     The size reduction of the target volume was measured by GammaPlan using the fiducial box. The maximum likelihood method was applied for estimating the parameters D50 and ? of the Poisson model. D50 is the dose which is associated with the 50% response probability and g is the maximum value of the dose-response gradient. The values of these parameters describe the shape of the dose-response relation for controlling vestibular schwannomas. The confidence interval of the dose-response curve was also calculated based on the individual confidence intervals of the radiobiological parameters.
     The radiobiological parameters of the model were calculated for a range of target shrinkage proportions. The best estimates of the radiobiological parameters obtained are D50 = 12.0 Gy (7.0 – 14.0 Gy) and ? = 0.75 (low limit – 1.50) for a reference volume of Vref = 4.2 cm3. The value of the maximum likelihood function, lnL was -18.9. The observed control rate in this patient material was 69%, whereas the control rate predicted by the model was 63%. The range of the parameter uncertainties that were determined affected considerably the confidence interval of the determined dose-response curve of vestibular schwannoma control. The radiobiological model applied was proved suitable in predicting the treatment outcome pattern of the studied patient material.
     This is a retrospective study.
     The estimated radiobiological parameters and the associated dose-response curve are suitable for clinical implementation given that the same target definition and delineation is used. The extent of target shrinkage is among the factors that may affect the process of parameter determination.
     The calculated accuracy gives an indication of the uncertainty that will characterize the calculated response probabilities in prospective studies. The dosimetric data and the corresponding treatment outcome could be successfully correlated using the Poisson model.


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