Abstract：
OBJECTIVE: Radiation-induced cerebrovascular toxicity is a well-documented sequelae that can be both life-altering and potentially fatal. We performed a meta-analysis of the relevant literature to create practical models for predicting the risk of cerebral vasculopathy after cranial irradiation.
METHODS: A literature search was performed for studies reporting pediatric radiation therapy (RT) associated cerebral vasculopathy. When available, we used individual patient RT doses delivered to the Circle of Willis (CW) or optic chiasm (as a surrogate), as reported or digitized from original publications, to formulate a dose-response. A logistic fit and a Normal Tissue Complication Probability (NTCP) model was developed to predict future risk of cerebrovascular toxicity and stroke, respectively. This NTCP risk was assessed as a function of prescribed dose.
RESULTS: The search identified 766 abstracts, 5 of which were used for modeling. We identified 101 of 3989 pediatric patients who experienced at least one cerebrovascular toxicity: transient ischemic attack, stroke, moyamoya, or arteriopathy. For a range of shorter follow-ups, as specified in the original publications (approximate attained ages of 17 years), our logistic fit model predicted the incidence of any cerebrovascular toxicity as a function of dose to the CW, or surrogate structure: 0.2% at 30 Gy, 1.3% at 45 Gy, and 4.4% at 54 Gy. At an attained age of 35 years, our NTCP model predicted a stroke incidence of 0.9% to 1.3%, 1.8% to 2.7%, and 2.8% to 4.1%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared with a baseline risk of 0.2%-0.3%). At an attained age of 45 years, the predicted incidence of stroke was 2.1% to 4.2%, 4.5% to 8.6%, and 6.7% to 13.0%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared with a baseline risk of 0.5%-1.0%).
CONCLUSIONS: Risk of cerebrovascular toxicity continues to increase with longer follow-up. NTCP stroke predictions are very sensitive to model variables (baseline stroke risk and proportional stroke hazard), both of which found in the literature may be systematically erring on minimization of true risk. We hope this information will assist practitioners in counseling, screening, surveilling, and facilitating risk reduction of RT-related cerebrovascular late effects in this highly sensitive population.
METHODS: A literature search was performed for studies reporting pediatric radiation therapy (RT) associated cerebral vasculopathy. When available, we used individual patient RT doses delivered to the Circle of Willis (CW) or optic chiasm (as a surrogate), as reported or digitized from original publications, to formulate a dose-response. A logistic fit and a Normal Tissue Complication Probability (NTCP) model was developed to predict future risk of cerebrovascular toxicity and stroke, respectively. This NTCP risk was assessed as a function of prescribed dose.
RESULTS: The search identified 766 abstracts, 5 of which were used for modeling. We identified 101 of 3989 pediatric patients who experienced at least one cerebrovascular toxicity: transient ischemic attack, stroke, moyamoya, or arteriopathy. For a range of shorter follow-ups, as specified in the original publications (approximate attained ages of 17 years), our logistic fit model predicted the incidence of any cerebrovascular toxicity as a function of dose to the CW, or surrogate structure: 0.2% at 30 Gy, 1.3% at 45 Gy, and 4.4% at 54 Gy. At an attained age of 35 years, our NTCP model predicted a stroke incidence of 0.9% to 1.3%, 1.8% to 2.7%, and 2.8% to 4.1%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared with a baseline risk of 0.2%-0.3%). At an attained age of 45 years, the predicted incidence of stroke was 2.1% to 4.2%, 4.5% to 8.6%, and 6.7% to 13.0%, respectively at prescribed doses of 30 Gy, 45 Gy, and 54 Gy (compared with a baseline risk of 0.5%-1.0%).
CONCLUSIONS: Risk of cerebrovascular toxicity continues to increase with longer follow-up. NTCP stroke predictions are very sensitive to model variables (baseline stroke risk and proportional stroke hazard), both of which found in the literature may be systematically erring on minimization of true risk. We hope this information will assist practitioners in counseling, screening, surveilling, and facilitating risk reduction of RT-related cerebrovascular late effects in this highly sensitive population.
摘要：
目的：辐射诱导的脑血管毒性是一种有据可查的后遗症，可以改变生活并可能致命。我们对相关文献进行了荟萃分析，以创建实用模型来预测颅脑照射后脑血管病变的风险。
方法：对报道儿科放射治疗（RT）相关脑血管病变的研究进行了文献检索。如果可用,我们使用个别患者的RT剂量递送到威利斯环（CW）或视交叉（作为替代），从原始出版物中报告或数字化，制定剂量反应。开发了逻辑拟合和正常组织并发症概率（NTCP）模型来预测脑血管毒性和中风的未来风险。分别。这种NTCP风险被评估为处方剂量的函数。
结果：搜索确定了766篇摘要，其中5个用于建模。我们确定了3989名儿科患者中的101名至少经历了一种脑血管毒性：短暂性脑缺血发作，中风,moyamoya,或动脉病变。对于一系列较短的随访，如原始出版物中所规定的(大约达到17岁)，我们的逻辑拟合模型预测了任何脑血管毒性的发生率作为CW剂量的函数，或替代结构：30Gy时为0.2%，在45Gy时为1.3%，和54Gy的4.4%。35岁时，我们的NTCP模型预测中风发生率为0.9%至1.3%，1.8%至2.7%，和2.8%至4.1%，分别在30Gy的规定剂量下，45Gy,和54Gy（基线风险为0.2%-0.3%）。在45岁的时候，预测的中风发生率为2.1％至4.2％，4.5%至8.6%，和6.7%至13.0%，分别在30Gy的规定剂量下，45Gy,和54Gy（基线风险为0.5%-1.0%）。
结论：脑血管毒性的风险随着随访时间的延长而持续增加。NTCP卒中预测对模型变量（基线卒中风险和比例卒中风险）非常敏感，文献中发现的这两种方法可能在最小化真实风险方面存在系统性错误。我们希望这些信息能够帮助从业者进行咨询，筛选,监视,在这个高度敏感的人群中，有助于降低RT相关脑血管后期效应的风险。
方法：对报道儿科放射治疗（RT）相关脑血管病变的研究进行了文献检索。如果可用,我们使用个别患者的RT剂量递送到威利斯环（CW）或视交叉（作为替代），从原始出版物中报告或数字化，制定剂量反应。开发了逻辑拟合和正常组织并发症概率（NTCP）模型来预测脑血管毒性和中风的未来风险。分别。这种NTCP风险被评估为处方剂量的函数。
结果：搜索确定了766篇摘要，其中5个用于建模。我们确定了3989名儿科患者中的101名至少经历了一种脑血管毒性：短暂性脑缺血发作，中风,moyamoya,或动脉病变。对于一系列较短的随访，如原始出版物中所规定的(大约达到17岁)，我们的逻辑拟合模型预测了任何脑血管毒性的发生率作为CW剂量的函数，或替代结构：30Gy时为0.2%，在45Gy时为1.3%，和54Gy的4.4%。35岁时，我们的NTCP模型预测中风发生率为0.9%至1.3%，1.8%至2.7%，和2.8%至4.1%，分别在30Gy的规定剂量下，45Gy,和54Gy（基线风险为0.2%-0.3%）。在45岁的时候，预测的中风发生率为2.1％至4.2％，4.5%至8.6%，和6.7%至13.0%，分别在30Gy的规定剂量下，45Gy,和54Gy（基线风险为0.5%-1.0%）。
结论：脑血管毒性的风险随着随访时间的延长而持续增加。NTCP卒中预测对模型变量（基线卒中风险和比例卒中风险）非常敏感，文献中发现的这两种方法可能在最小化真实风险方面存在系统性错误。我们希望这些信息能够帮助从业者进行咨询，筛选,监视,在这个高度敏感的人群中，有助于降低RT相关脑血管后期效应的风险。
