Abstract：
BACKGROUND: Brachytherapy for ocular melanoma is based on the application of eye plaques with different spatial dose nonuniformity, time-dependent dose rates and relative biological effectiveness (RBE).
OBJECTIVE: We propose a parameter called the equivalent uniform RBE-weighted dose (EUDRBE) that can be used for quantitative characterization of integrated cell survival in radiotherapy modalities with the variable RBE, dose nonuniformity and dose rate. The EUDRBE is applied to brachytherapy with 125I eye plaques designed by the Collaborative Ocular Melanoma Study (COMS).
METHODS: The EUDRBE is defined as the uniform dose distribution with RBE = 1 that causes equal cell survival for a given nonuniform dose distribution with the variable RBE > 1. The EUDRBE can be used for comparison of cell survival for nonuniform dose distributions with different RBE, because they are compared to the reference dose with RBE = 1. The EUDRBE is applied to brachytherapy with 125I COMS eye plaques that are characterized by a steep dose gradient in tumor base-apex direction, protracted irradiation during time intervals of 3-8 days, and variable dose-rate dependent RBE with a maximum of about 1.4. The simulations are based on dose of 85 Gy prescribed to the farthest intraocular extent of the tumor (tumor apex). To compute the EUDRBE in eye plaque brachytherapy and correct for protracted irradiation, the distributions of physical dose have been converted to non-uniform distributions of biologically effective dose (BED) to include the biological effects of sublethal cellular repair, Our radiobiological analysis considers the combined effects of different time-dependent dose rates, spatial dose non-uniformity, dose fractionation and different RBE and can be used to derive optimized dose regimens brachytherapy.
RESULTS: Our simulations show that the EUDRBE increases with the prescription depths and the maximum increase may achieve 6% for the tumor height of 12 mm. This effect stems from a steep dose gradient within the tumor that increases with the prescription depth. The simulations also show that the EUDRBE increase may achieve 12% with increasing the dose rate when implant duration decreases. The combined effect of dose nonuniformity and dose rate may change the EUDRBE up to 18% for the same dose prescription of 85 Gy to tumor apex. The absolute dose range of 48-61 Gy (RBE) for the EUDRBE computed using 4 or 5 fractions is comparable to the dose prescriptions used in stereotactic body radiation therapy (SBRT) with megavoltage X-rays (RBE = 1) for different cancers. The tumor control probabilities in SBRT and eye plaque brachytherapy are very similar at the level of 80% or higher that support the hypothesis that the selected approximations for the EUDRBE are valid.
CONCLUSIONS: The computed range of the EUDRBE in 125I COMS eye plaque brachytherapy suggests that the selected models and hypotheses are acceptable. The EUDRBE can be useful for analysis of treatment outcomes and comparison of different dose regimens in eye plaque brachytherapy.
OBJECTIVE: We propose a parameter called the equivalent uniform RBE-weighted dose (EUDRBE) that can be used for quantitative characterization of integrated cell survival in radiotherapy modalities with the variable RBE, dose nonuniformity and dose rate. The EUDRBE is applied to brachytherapy with 125I eye plaques designed by the Collaborative Ocular Melanoma Study (COMS).
METHODS: The EUDRBE is defined as the uniform dose distribution with RBE = 1 that causes equal cell survival for a given nonuniform dose distribution with the variable RBE > 1. The EUDRBE can be used for comparison of cell survival for nonuniform dose distributions with different RBE, because they are compared to the reference dose with RBE = 1. The EUDRBE is applied to brachytherapy with 125I COMS eye plaques that are characterized by a steep dose gradient in tumor base-apex direction, protracted irradiation during time intervals of 3-8 days, and variable dose-rate dependent RBE with a maximum of about 1.4. The simulations are based on dose of 85 Gy prescribed to the farthest intraocular extent of the tumor (tumor apex). To compute the EUDRBE in eye plaque brachytherapy and correct for protracted irradiation, the distributions of physical dose have been converted to non-uniform distributions of biologically effective dose (BED) to include the biological effects of sublethal cellular repair, Our radiobiological analysis considers the combined effects of different time-dependent dose rates, spatial dose non-uniformity, dose fractionation and different RBE and can be used to derive optimized dose regimens brachytherapy.
RESULTS: Our simulations show that the EUDRBE increases with the prescription depths and the maximum increase may achieve 6% for the tumor height of 12 mm. This effect stems from a steep dose gradient within the tumor that increases with the prescription depth. The simulations also show that the EUDRBE increase may achieve 12% with increasing the dose rate when implant duration decreases. The combined effect of dose nonuniformity and dose rate may change the EUDRBE up to 18% for the same dose prescription of 85 Gy to tumor apex. The absolute dose range of 48-61 Gy (RBE) for the EUDRBE computed using 4 or 5 fractions is comparable to the dose prescriptions used in stereotactic body radiation therapy (SBRT) with megavoltage X-rays (RBE = 1) for different cancers. The tumor control probabilities in SBRT and eye plaque brachytherapy are very similar at the level of 80% or higher that support the hypothesis that the selected approximations for the EUDRBE are valid.
CONCLUSIONS: The computed range of the EUDRBE in 125I COMS eye plaque brachytherapy suggests that the selected models and hypotheses are acceptable. The EUDRBE can be useful for analysis of treatment outcomes and comparison of different dose regimens in eye plaque brachytherapy.
摘要：
背景：眼部黑色素瘤的近距离放射治疗是基于不同空间剂量不均匀性的眼部斑块的应用，时间依赖性剂量率和相对生物学有效性（RBE）。
目的：我们提出了一个称为等效均匀RBE加权剂量（EUDRBE）的参数，该参数可用于定量表征具有可变RBE的放射治疗模式中的整合细胞存活，剂量不均匀性和剂量率。EUDRBE适用于由协同性眼部黑素瘤研究（COMS）设计的125I眼部斑块的近距离放射治疗。
方法：EUDRBE定义为RBE=1的均匀剂量分布，对于给定的非均匀剂量分布，变量RBE>1导致细胞存活相等。EUDRBE可用于比较不同RBE剂量分布不均匀的细胞存活率，因为它们与RBE=1的参考剂量进行比较。EUDRBE适用于125ICOMS眼部斑块的近距离放射治疗，其特征在于肿瘤基底-顶点方向的剂量梯度陡峭，在3-8天的时间间隔内进行长期照射，和可变剂量率依赖性RBE，最大值约为1.4。模拟基于对肿瘤的最远眼内范围(肿瘤顶点)开出的85Gy剂量。为了计算眼斑块近距离放射治疗中的EUDRBE并校正长期照射，物理剂量的分布已转化为生物有效剂量（BED）的非均匀分布，包括亚致死细胞修复的生物学效应，我们的放射生物学分析考虑了不同时间依赖性剂量率的综合影响，空间剂量不均匀性，剂量分割和不同的RBE，可用于得出优化的剂量方案。
结果：我们的模拟表明，EUDRBE随处方深度而增加，对于12mm的肿瘤高度，最大增加可能达到6％。这种效应源于肿瘤内随着处方深度增加的陡峭剂量梯度。模拟还显示,当注入持续时间减少时,随着剂量率的增加,EUDRBE增加可以达到12%。对于85Gy的相同剂量处方，剂量不均匀性和剂量率的综合作用可能会使EUDRBE改变高达18％。使用4或5个分数计算的EUDRBE的绝对剂量范围为48-61Gy（RBE），与用于不同癌症的具有兆伏X射线的立体定向身体放射治疗（SBRT）（RBE=1）的剂量处方相当。SBRT和眼斑块近距离放射治疗中的肿瘤控制概率在80％或更高的水平上非常相似，这支持以下假设：为EUDRBE选择的近似值是有效的。
结论：125ICOMS眼斑块近距离放射治疗中EUDRBE的计算范围表明所选择的模型和假设是可以接受的。EUDRBE可用于分析治疗结果和比较眼斑块近距离放射治疗中的不同剂量方案。
目的：我们提出了一个称为等效均匀RBE加权剂量（EUDRBE）的参数，该参数可用于定量表征具有可变RBE的放射治疗模式中的整合细胞存活，剂量不均匀性和剂量率。EUDRBE适用于由协同性眼部黑素瘤研究（COMS）设计的125I眼部斑块的近距离放射治疗。
方法：EUDRBE定义为RBE=1的均匀剂量分布，对于给定的非均匀剂量分布，变量RBE>1导致细胞存活相等。EUDRBE可用于比较不同RBE剂量分布不均匀的细胞存活率，因为它们与RBE=1的参考剂量进行比较。EUDRBE适用于125ICOMS眼部斑块的近距离放射治疗，其特征在于肿瘤基底-顶点方向的剂量梯度陡峭，在3-8天的时间间隔内进行长期照射，和可变剂量率依赖性RBE，最大值约为1.4。模拟基于对肿瘤的最远眼内范围(肿瘤顶点)开出的85Gy剂量。为了计算眼斑块近距离放射治疗中的EUDRBE并校正长期照射，物理剂量的分布已转化为生物有效剂量（BED）的非均匀分布，包括亚致死细胞修复的生物学效应，我们的放射生物学分析考虑了不同时间依赖性剂量率的综合影响，空间剂量不均匀性，剂量分割和不同的RBE，可用于得出优化的剂量方案。
结果：我们的模拟表明，EUDRBE随处方深度而增加，对于12mm的肿瘤高度，最大增加可能达到6％。这种效应源于肿瘤内随着处方深度增加的陡峭剂量梯度。模拟还显示,当注入持续时间减少时,随着剂量率的增加,EUDRBE增加可以达到12%。对于85Gy的相同剂量处方，剂量不均匀性和剂量率的综合作用可能会使EUDRBE改变高达18％。使用4或5个分数计算的EUDRBE的绝对剂量范围为48-61Gy（RBE），与用于不同癌症的具有兆伏X射线的立体定向身体放射治疗（SBRT）（RBE=1）的剂量处方相当。SBRT和眼斑块近距离放射治疗中的肿瘤控制概率在80％或更高的水平上非常相似，这支持以下假设：为EUDRBE选择的近似值是有效的。
结论：125ICOMS眼斑块近距离放射治疗中EUDRBE的计算范围表明所选择的模型和假设是可以接受的。EUDRBE可用于分析治疗结果和比较眼斑块近距离放射治疗中的不同剂量方案。
