Hidalgo Eveline Teresa, Snuderl Matija, Orillac Cordelia, Kvint Svetlana, Serrano Jonathan, Wu Peter, Karajannis Matthias A, Gardner Sharon L
Division of Pediatric Neurosurgery, Department of Neurosurgery, Hassenfeld Children's Hospital, NYU Langone Health, New York, USA.
Department of Pathology, NYU Langone Health, New York, USA.
Childs Nerv Syst. 2020 Jan;36(1):133-144. doi: 10.1007/s00381-019-04305-x. Epub 2019 Aug 2.
Molecular subgroups of pediatric brain tumors associated with divergent biological, clinical, and prognostic features have been identified. However, data regarding the impact of subgroup affiliation on the outcome of children with malignant brain tumors treated with radiation-sparing protocol is limited. We report long-term clinical outcomes and the molecular subgroups of malignant brain tumors in young children whose first-line treatment was high-dose chemotherapy without irradiation.
Tumor subclassification was performed using the Illumina HumanMethylation450 BeadChip (450k) genome-wide methylation array profiling platform. Clinical information was obtained from chart review.
Methylation array profiling yielded information on molecular subgroups in 22 children. Median age at surgery was 26 months (range 1-119 months). Among medulloblastomas (MB), all 6 children in the infant sonic hedgehog (SHH) subgroup were long-term survivors, whereas all 4 children in subgroup 3 MB died. There was one long-term survivor in subgroup 4 MB. One out of five children with ependymoma was a long-term survivor (RELPOS). Both children with primitive neuroectodermal tumors died. One child with ATRT TYR and one child with choroid plexus carcinoma were long-term survivors.
The efficacy of high-dose chemotherapy radiation-sparing treatment appears to be confined to favorable molecular subgroups of pediatric brain tumors, such as infant SHH MB. Identification of molecular subgroups that benefit from radiation-sparing therapy will aid in the design of prospective, "precision medicine"-driven clinical trials.
已确定与不同生物学、临床和预后特征相关的小儿脑肿瘤分子亚组。然而，关于亚组归属对接受保放疗方案治疗的恶性脑肿瘤患儿预后影响的数据有限。我们报告了一线治疗为高剂量化疗而非放疗的幼儿恶性脑肿瘤的长期临床结局和分子亚组情况。
使用Illumina HumanMethylation450 BeadChip（450k）全基因组甲基化阵列分析平台进行肿瘤亚分类。通过病历审查获取临床信息。
甲基化阵列分析得出了22名儿童的分子亚组信息。手术时的中位年龄为26个月（范围1 - 119个月）。在髓母细胞瘤（MB）中，婴儿型音猬因子（SHH）亚组的所有6名儿童均为长期存活者，而3型MB亚组的所有4名儿童均死亡。4型MB亚组中有1名长期存活者。5名室管膜瘤患儿中有1名是长期存活者（RELPOS）。2名原始神经外胚层肿瘤患儿均死亡。1名ATRT TYR患儿和1名脉络丛癌患儿为长期存活者。
高剂量化疗保放疗治疗的疗效似乎仅限于小儿脑肿瘤的有利分子亚组，如婴儿型SHH MB。确定从保放疗治疗中获益的分子亚组将有助于设计前瞻性的、由“精准医学”驱动的临床试验。
