我们将针对 M 髓母细胞瘤的策略应用于所有高危亚组，包括 LC/A 组织学、TP53 突变、MYC/MYCN 扩增。3 岁以上的患者在手术后接受分期和组织生物学分析、序贯高大剂量甲氨蝶呤(HD-MTX)、大剂量依托泊苷(HD-VP16)、大剂量环磷酰胺(HD-Cyclo)、大剂量卡铂(HD-Carbo)。超分割加速颅脊髓放疗( HART-CSI），每日两次，1.3 Gy 分次，达到根据患者年龄和化疗（CT）放疗前反应定制的总剂量：10 岁以下且完全缓解（CR）或 31.2 Gy获得部分缓解 (PR) 或没有转移性疾病，其他/老年患者为 39 Gy。对后颅窝/残留转移 (M ) 沉积物的增强剂量分别达到 60 Gy/9 Gy，但如果出现以下情况则应避免转移结节非常大或患者非常年轻。如果在放疗前 (RT) 阶段后未达到 CR/PR，并且在所有 M0 患者中 - HART 之前/之后，则给予两个疗程的高剂量噻替派。进行了分组89 名患者入组，中位年龄 8.8 岁，中位随访 136 个月。5/15 年总生存率 (OS) 和无事件生存率 (EFS) 分别为 75.9/66.5% 和 68.2 /65.3%，分别；5/28 死亡事件与复发无关（3 例发生继发性恶性肿瘤）。性别、年龄小于 10 岁、组织学亚型、存在 MYC/MYCN 扩增、CSI 剂量减少、RT 省略加强、清髓治疗的实施、转移的存在/不存在均不会影响预后。HART 前 CT 后进展的患者 (14/89) 和 HART 后疾病稳定 (SD) PD (10/89) 对预后产生负面影响 (P < 0.001)。对 66/89 名患者样本进行的分组显示，与第 3 组和第 4 组（分别为 15 名和 29 名患者）相比，Sonic Hedgehog (SHH) 肿瘤患者（#15、2 名具有 TP53 突变）的 EFS 显着较差，7) 中的第 3/4 组。如果根据 CT 反应分层，则 10 岁以下的患者接受较低的 CSI 剂量。该策略在正在进行的 SIOPE 方案中部分采用，证实在所有高风险类别中，与之前报告的结果相比，EFS 和 OS 有所改善； SHH 肿瘤似乎最具侵袭性。© 作者 2024。由牛津大学出版社代表神经肿瘤学会出版。

We applied the strategy for M+ medulloblastoma across all high-risk subgroups, including LC/A histology, TP53 mutations, MYC/MYCN amplification.Patients over 3-years-old received,after surgery,staging and histo-biological analysis,sequential high-dose-methotrexate(HD-MTX),high-dose-etoposide(HD-VP16),high-dose-cyclophosphamide(HD-Cyclo),high-dose-carboplatin(HD-Carbo).Hyperfractionated-accelerated-radiotherapy-craniospinal(HART-CSI),administered in twice daily 1.3 Gy-fractions reached a total dose tailored to the patients' age and pre-radiation response to chemotherapy(CT): 31.2 Gy if under 10-years-old and complete response(CR) or partial response(PR) obtained or absence of metastatic disease,39 Gy in other/older patients.Boosts to posterior fossa/residual metastatic(M+) deposits were given up to a total dose of 60 Gy/9 Gy,respectively,but avoided if metastatic nodules were very big or patients very young.Two courses of high-dose-thiotepa were delivered in case of not CR/PR after pre-radiotherapy(RT) phase and in all M0 patients either - pre/post HART.Subgrouping was performed where tissue was available.Eighy-nine patients were enrolled,median age 8.8 years,median follow up 136 months.Overall-survival(OS) and event-free-survival(EFS) at 5/15 years were 75.9/66.5% and 68.2/65.3%, respectively;5/28 fatal events were not related to relapse(three developed secondary malignancies).Sex,age less than 10 years,histological subtype,presence of MYC/MYCN amplification,reduction in CSI dose,omission of RT-boosts,implementation of myeloablative therapy,presence/absence of metastases did not impact prognosis.Patients progressing after pre-HART CT(14/89) and stable-disease(SD)+PD after HART(10/89) negatively affected outcome(P<0.001).Subgrouping in 66/89 patients' samples demonstrated a significantly worse EFS for patients with Sonic Hedgehog(SHH)-tumors(#15, 2 with constitutional TP53-mutations) vs. group 3 and 4(15 and 29 patients, respectively, group3/4 in 7).Patients younger than 10 received lower CSI doses if stratified according to CT response.This strategy, partly adopted in the ongoing SIOPE protocol,confirmed improved EFS and OS over previously reported outcomes in all high-risk categories;SHH tumors appeared the most aggressive.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.