BACKGROUND Central nervous system tumors remain the leading cause of cancer-related mortality amongst children with solid tumors, with medulloblastoma (MB) representing the most common pediatric brain malignancy. Despite best current therapies, patients with recurrent MB experience have an alarmingly high mortality rate and often have limited therapeutic options beyond inadequate chemotherapy or experimental clinical trials. Therefore, a systematic review of the literature regarding treatment strategies employed in recurrent pediatric MB will evaluate previous salvage therapies in order to guide future clinical trials. The aim of this systematic review will be to investigate the efficacy and safety of salvage therapies for the management of children with progressive, treatment-refractory, or recurrent MB. METHODS We will conduct literature searches (from 1995 onwards) in MEDLINE, EMBASE, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and Cochrane Central Register of Controlled Trials. Studies examining the survival and toxicity of therapies administered to treatment-refractory pediatric MB patients will be included. Two reviewers will independently assess the search results based on predefined selection criteria, complete data abstraction, and quality assessment. The primary outcomes of this review will be overall and progression-free survival. Secondary outcomes will include safety and toxicity of each therapy administered. The study methodological quality (or bias) will be appraised using an appropriate tool. Due to the nature of the research question and published literature, we expect large inter-study heterogeneity and therefore will use random effects regression analysis to extract the combined effect. In additional analyses, we will investigate the role of re-irradiation and mono- vs. poly-therapy in recurrent disease, and whether molecular subgrouping of MB influences salvage therapy. DISCUSSION This systematic review will provide an overview of the current literature regarding salvage therapies for relapsed MB patients. Investigation of clinically tested therapies for children with recurrent MB has significant implications for clinical practice. By reviewing the efficacy and toxicity of MB salvage therapies, this study will identify effective therapeutic strategies administered to recurrent MB patients and can inform future clinical trials aimed to improve patient survivorship and quality of life. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42020167421.

中文翻译：

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进行性、难治性或复发性儿童髓母细胞瘤的挽救治疗：系统评价方案。

背景中枢神经系统肿瘤仍然是实体瘤儿童癌症相关死亡的主要原因，其中髓母细胞瘤（MB）代表最常见的儿科脑恶性肿瘤。尽管目前有最好的治疗方法，但患有复发性 MB 的患者死亡率却高得惊人，而且除了化疗或实验性临床试验不足之外，治疗选择往往有限。因此，对有关复发性儿科 MB 治疗策略的文献进行系统回顾将评估以前的挽救疗法，以指导未来的临床试验。本次系统评价的目的是调查挽救疗法对于治疗进展性、难治性或复发性 MB 儿童的有效性和安全性。方法 我们将在 MEDLINE、EMBASE、ClinicalTrials.gov、WHO 国际临床试验注册平台和 Cochrane 对照试验中央注册处进行文献检索（从 1995 年起）。将包括检查难治性儿科 MB 患者治疗的存活率和毒性的研究。两名评审员将根据预定义的选择标准、完整的数据抽象和质量评估独立评估搜索结果。本次审查的主要结果是总体生存期和无进展生存期。次要结果将包括每种疗法的安全性和毒性。研究方法学质量（或偏差）将使用适当的工具进行评估。由于研究问题和已发表文献的性质，我们预计研究间存在较大异质性，因此将使用随机效应回归分析来提取综合效应。在其他分析中，我们将研究再照射和单药治疗与多药治疗在复发性疾病中的作用，以及 MB 的分子亚型是否影响挽救治疗。讨论 本系统综述将概述有关复发性 MB 患者抢救治疗的当前文献。对患有复发性 MB 的儿童进行临床测试的疗法的研究对临床实践具有重要意义。通过回顾 MB 挽救疗法的功效和毒性，本研究将确定对复发性 MB 患者实施的有效治疗策略，并为未来旨在提高患者生存率和生活质量的临床试验提供信息。系统审查注册 PROSPERO CRD42020167421。