质子治疗儿童常见颅内肿瘤疗效和安全性的系统评价和Meta分析

摘要

目的 评价质子治疗儿童常见颅内肿瘤的疗效和安全性.方法 检索Web of Science、Embase、Cochrane Library、PubMed和中国生物医学文献数据库,检索截止时间为2016年9月,纳入质子治疗儿童常见颅内肿瘤的临床研究.对纳入的文献进行质量评价,采用MetaAnalyst及STATA 12.0进行合并分析,对无法合并的结局指标采用描述性分析.结果 11篇研究进入系统评价,9篇为病例系列报告,2篇为非随机对照试验,共纳入接受质子治疗的颅内肿瘤患儿531例,颅咽管瘤2篇(45例),星形细胞瘤2篇(59例),髓母细胞瘤4篇(228例),室管膜瘤2篇(120例),未分病理类型报道1篇(79例).①总生存率(0S):分别有5、10和6篇文献报道了2、3和5年OS.2篇非随机对照试验中,3年OS质子治疗组分别为94.1％和94.0％,光子治疗组分别为96.8％和92.5％;1篇报道了5年OS,质子治疗组和光子治疗组分别为82.0％和87.6％.病例系列报告的文献间存在异质性(I2＞50％,P＜0.1),亚组采取随机效应模型合并,2、3和5年的OS分别为94％ (95％CI:0.90～ 0.97)、90％(95％CI:0.86～ 0.93)和87％ (95％CI:0.82～0.93).②局部控制率(LC):分别有3、4和2篇文献报道了2、3和5年LC,文献间有异质性(,＞50％,P＜0.1),亚组采取随机效应模型合并,2、3和5年的LC分别为93％(95％CI:0.88～0.98)、86％ (95％CI:0.81～0.92)和77％ (95％CI:0.70～0.85).③第二原发性恶性肿瘤(SMN):4篇文献报道了1例髓母细胞瘤治疗后并发急性髓细胞性白血病.④不良反应:9篇文献报道了不良反应,1篇未进行分级报道,8篇文献(465例)报道了3级以上听力损伤16例,3级以上视力损伤6例,需要激素替代治疗的内分泌功能障碍16例.结论 质子治疗儿童颅内肿瘤患者前,尚需高质量、大样本的临床验证.%Objective To assess the efficacy and safety of the proton therapy for intracranial tumors in childhood.Methods The electronic bibliographic databases were searched,including Cochrane library,PubMed,Embase,Web of science,Chinese Biomedical Database to assemble the studies of the proton therapy for the most common intracranial tumors in childhood.The MetaAnalyst Beta 3.13 and STATA 12.0 software were used to combine the extracted data.Results Eleven studies were included,9 case series reports and 2 case control studies,a total of 531 patients received proton therapy,including 2 of craniopharyngioma (45 patients),2 of astrocytoma (59 patients),5 of medulloblastoma (228 patients),2 of ependymoma (120 patients),1 report of no pathological type (79 patients).①Overall survival (OS):There were 2,3 and 5 years of OS in 5,10 and 6 reports 2 casecontrol studies,3 years OS proton therapy was 94.1％ and 94％,photon therapy was 96.8％ and 92.5％;5 years OS of 1 report,proton therapy and photon therapy were 82％ and 87.6％.The heterogeneity was found in case series reports of documents (I2 ＞ 50％,P＜0.1),by sub group random effects model with 2,3 and 5 years of OS were 94％(95％CI:0.90-0.97),90％(95％CI:0.86-0.93) and 87％(95％CI:0.82-0.93).②Local control rate (LC):there were 2,3 and 5 years of LC in 3,4 and 2 reports,The heterogeneity was found in case series reports of documents (I2 ＞50％,P＜0.1),by sub group random effects model with 2,3 and 5 years of LC are 93％ (95％CI:0.88-0.98),86％ (95％CI:0.81-0.92) and 77％ (95％CI:0.70-0.85).③The second primary malignant tumor (SMN):4 reported the SMN,only 1 patient of medulloblastoma induced acute myelogenous leukemia with PT and no patient in other reports.④Toxicoty:9 papers reported the toxicoties after PT.One paper was not hierarchical report,16 patients of grade 3 above the level of hearing impairment and 6 patients of vascular injury,16 patients of the endocrine dysfunction of replacement therapy were reported in 8 papers (465 patients).Conclusion Available data demonstrated that the most common intracranial tumors in childhood are effectively and safely treated with proton therapy.Although current results are promiseing,more evidence is required before the proton therapy can become the standard threatment for intracranial tumors in childhood.