Abstract

Background

Infant medulloblastoma represents an enormous challenge in neuro-oncology, due to their simultaneous high-risk of recurrence and high risk of severe neurodevelopmental sequelae with craniospinal irradiation. Currently infant medulloblastoma are treated with intensified protocols, either comprising intraventricular methotrexate or autologous transplant, both of which carry significant morbidity and are not feasible in the majority of the world. We sought to evaluate the molecular predictors of outcome in a cohort of infants homogeneously treated with induction chemotherapy, focal radiation and maintenance chemotherapy.

Methods

In a retrospective analysis, 29 young children treated with a craniospinal irradiation sparing strategy from Hospital Garrahan in Buenos Aires were profiled using Illumina HumanMethylationEPIC arrays, and correlated with survival.

Results

Twenty-nine children (range, 0.3–4.6 y) were identified, comprising 17 sonic hedgehog (SHH), 10 Group 3/4, and 2 non-medulloblastomas. Progression-free survival (PFS) across the entire cohort was 0.704 (95% CI: 0.551–0.899). Analysis by t-distributed stochastic neighbor embedding revealed 3 predominant groups, SHHβ, SHHγ, and Group 3. Survival by subtype was highly prognostic with SHHγ having an excellent 5-year PFS of 100% (95% CI: 0.633–1) and SHHβ having a PFS of 0.56 (95% CI: 0.42–1). Group 3 had a PFS of 0.50 (95% CI: 0.25–1). Assessment of neurocognitive outcome was performed in 11 patients; the majority of survivors fell within the low average to mild intellectual disability, with a median IQ of 73.5.

Conclusions

We report a globally feasible and effective strategy avoiding craniospinal radiation in the treatment of infant medulloblastoma, including a robust molecular correlation along with neurocognitive outcomes.

中文翻译：

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缩小婴儿髓母细胞瘤的治疗差距：一种全球可行方案的分子告知结果。

摘要

背景

婴儿髓母细胞瘤由于其同时复发的高风险和颅脑脊髓照射造成的严重神经发育后遗症的高风险，在神经肿瘤学上代表着巨大的挑战。当前，婴儿髓母细胞瘤已经用强化方案治疗，包括脑室内甲氨蝶呤或自体移植，这两种方案均具有明显的发病率，并且在世界大多数地区不可行。我们试图评估在接受诱导化学疗法，局部放疗和维持化学疗法均一治疗的一组婴儿中结局的分子预测因子。

方法

在一项回顾性分析中，使用Illumina HumanMethylationEPIC阵列分析了布宜诺斯艾利斯Garrahan医院接受颅骨放射线保留策略治疗的29名幼儿，并与存活率相关。

结果

确定了29名儿童（范围0.3-4.6 y），包括17个声波刺猬（SHH），10个3/4组和2个非髓母细胞瘤。整个队列的无进展生存期（PFS）为0.704（95％CI：0.551–0.899）。通过t分布随机邻居嵌入进行的分析显示，有3个主要组，即SHHβ，SHHγ和第3组。按亚型的生存率高，SHHγ的5年PFS分别为100％（95％CI：0.633-1）和SHHβ，具有很高的预后。 PFS为0.56（95％CI：0.42-1）。第3组的PFS为0.50（95％CI：0.25-1）。11例患者进行了神经认知预后评估。大多数幸存者的平均智商中位数为73.5，属于中度至轻度智障的低平均水平。

结论

我们报告了一种全球可行和有效的策略，避免在婴儿髓母细胞瘤的治疗中颅脑放射，包括稳固的分子相关性以及神经认知结果。