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• W2124908105 abstract "Purpose/Objective: To investigate the correlation of radiation-induced brain tissue changes after RS of AVM patients with dose distribution variables and to quantify dose-response relations of late radiation effects in the brain.Materials/Methods: Data from 71 AVM patients who had stereotactic linac RS at DKFZ between ’93 and ’98 were analyzed. Patients were treated with 11–14 non-coplanar fields shaped by a micro-MLC (leaf width: 1.6mm at isocenter distance). A median dose of 18Gy (range 13.3–22Gy) was prescribed to the 80% isodose that completely encompassed the target. Patients were followed in intervals of 3 months in the first year and then every 6 months with MRI. The endpoint of radiation-induced tissue changes on follow-up neuroimaging (i.e. necrosis, edema, blood-brain-barrier breakdown (BBBB)) was evaluated. Each endpoint was further differentiated into 2 levels with respect to the extent of the image change (small vs. large). To ensure a consistent scoring of radiation effects in the data sample, all pretreatment and f-u imaging studies were reviewed by the same physicians. No patient developed necrosis. Correlation of each endpoint and the combined endpoint edema and/or BBBB was investigated for prescribed dose (Dprescr), the size of the AVM target volume (Vtarget) and several dose-volume variables derived from each patient’s dose distribution, including the mean dose in a specified volume of 20cc that was given the highest dose (Dmean20) and the absolute and percent brain volumes (including the AVM target) receiving a dose of at least 8, 10, and 12 Gy (V8-V12, and V8rel-V12rel, respectively). These variables were also determined excluding the AVM target from the considered volume (subscript excl). The correlation of all variables with outcome was assessed in univariate Cox proportional hazards models (significance for p≤0.5). To quantify dose-response relations, patients were ranked according to Dmean20 (the best variable) and classified into 4 groups of equal size. For each group, the actuarial incidence of each endpoint 2 years after RS was determined from Kaplan-Meier estimates. Dose-response curves were fit with a sigmoid shape logistic function and characterized by D50, the dose for 50% adverse effects, and γ50, the normalized slope of the dose-response curve at D50.Results: Dprescr alone is not predictive for outcome (Table). Vtarget is only significantly correlated with large edema and large edema/BBBB. V12 and Dmean20 are correlated with all endpoints except for large BBBB. Univariate hazards models based on Dmean20 or V12 yield better fits than a bivariate model based on Dprescr and Vtarget. Outcome is best predicted by Dmean20, except for large edema for which V12 is slightly better. Excluding the AVM target from the considered volume leads to small changes only. For all endpoints, V12rel correlates worse with outcome compared to V12. Throughout the analysis, V8, V10, and V12 yield similar results and neither of these variables can be favored over the other. D50 values of fitted dose-response curves for tissue changes of large extent are considerably higher than those describing small tissue changes (Table).Conclusions: Radiation-induced tissue changes after AVM RS are predicted by single dose distribution variables that are a function of both dose and volume. These can be used to quantify dose/volume-response relations. Studies of this nature will eventually help to quantitatively assess the tolerance of the brain to partial irradiation. Purpose/Objective: To investigate the correlation of radiation-induced brain tissue changes after RS of AVM patients with dose distribution variables and to quantify dose-response relations of late radiation effects in the brain. Materials/Methods: Data from 71 AVM patients who had stereotactic linac RS at DKFZ between ’93 and ’98 were analyzed. Patients were treated with 11–14 non-coplanar fields shaped by a micro-MLC (leaf width: 1.6mm at isocenter distance). A median dose of 18Gy (range 13.3–22Gy) was prescribed to the 80% isodose that completely encompassed the target. Patients were followed in intervals of 3 months in the first year and then every 6 months with MRI. The endpoint of radiation-induced tissue changes on follow-up neuroimaging (i.e. necrosis, edema, blood-brain-barrier breakdown (BBBB)) was evaluated. Each endpoint was further differentiated into 2 levels with respect to the extent of the image change (small vs. large). To ensure a consistent scoring of radiation effects in the data sample, all pretreatment and f-u imaging studies were reviewed by the same physicians. No patient developed necrosis. Correlation of each endpoint and the combined endpoint edema and/or BBBB was investigated for prescribed dose (Dprescr), the size of the AVM target volume (Vtarget) and several dose-volume variables derived from each patient’s dose distribution, including the mean dose in a specified volume of 20cc that was given the highest dose (Dmean20) and the absolute and percent brain volumes (including the AVM target) receiving a dose of at least 8, 10, and 12 Gy (V8-V12, and V8rel-V12rel, respectively). These variables were also determined excluding the AVM target from the considered volume (subscript excl). The correlation of all variables with outcome was assessed in univariate Cox proportional hazards models (significance for p≤0.5). To quantify dose-response relations, patients were ranked according to Dmean20 (the best variable) and classified into 4 groups of equal size. For each group, the actuarial incidence of each endpoint 2 years after RS was determined from Kaplan-Meier estimates. Dose-response curves were fit with a sigmoid shape logistic function and characterized by D50, the dose for 50% adverse effects, and γ50, the normalized slope of the dose-response curve at D50. Results: Dprescr alone is not predictive for outcome (Table). Vtarget is only significantly correlated with large edema and large edema/BBBB. V12 and Dmean20 are correlated with all endpoints except for large BBBB. Univariate hazards models based on Dmean20 or V12 yield better fits than a bivariate model based on Dprescr and Vtarget. Outcome is best predicted by Dmean20, except for large edema for which V12 is slightly better. Excluding the AVM target from the considered volume leads to small changes only. For all endpoints, V12rel correlates worse with outcome compared to V12. Throughout the analysis, V8, V10, and V12 yield similar results and neither of these variables can be favored over the other. D50 values of fitted dose-response curves for tissue changes of large extent are considerably higher than those describing small tissue changes (Table). Conclusions: Radiation-induced tissue changes after AVM RS are predicted by single dose distribution variables that are a function of both dose and volume. These can be used to quantify dose/volume-response relations. Studies of this nature will eventually help to quantitatively assess the tolerance of the brain to partial irradiation." @default.
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• W2124908105 title "Radiation-induced brain tissue changes after radiosurgery (RS) of patients with cerebral arteriovenous malformations (AVM): correlation with dose distribution variables and dose response" @default.
• W2124908105 doi "https://doi.org/10.1016/s0360-3016(03)01213-6" @default.
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