Department of Pediatric and Adolescent Oncology, Gustave Roussy, Villejuif, France.
Department of Biostatistics and Epidemiology, Gustave Roussy, University Paris-Saclay, Villejuif, France.
Neuro Oncol. 2021 Jul 1;23(7):1163-1172. doi: 10.1093/neuonc/noaa301.
High-risk medulloblastoma is defined by the presence of metastatic disease and/or incomplete resection and/or unfavorable histopathology and/or tumors with MYC amplification. We aimed to assess the 3-year progression-free survival (PFS) and define the molecular characteristics associated with PFS in patients aged 5-19 years with newly diagnosed high-risk medulloblastoma treated according to the phase II trial PNET HR+5.
All children received postoperative induction chemotherapy (etoposide and carboplatin), followed by 2 high-dose thiotepa courses (600 mg/m2) with hematological stem cell support. At the latest 45 days after the last stem cell rescue, patients received risk-adapted craniospinal radiation therapy. Maintenance treatment with temozolomide was planned to start between 1-3 months after the end of radiotherapy. The primary endpoint was PFS. Outcome and safety analyses were per protocol (all patients who received at least one dose of induction chemotherapy).
Fifty-one patients (median age, 8 y; range, 5-19) were enrolled. The median follow-up was 7.1 years (range: 3.4-9.0). The 3 and 5-year PFS with their 95% confidence intervals (95% CI) were 78% (65-88) and 76% (63-86), and the 3 and 5-year OS were 84% (72-92) and 76% (63-86), respectively. Medulloblastoma subtype was a statistically significant prognostic factor (P-value = 0.039) with large-cell/anaplastic being of worse prognosis, as well as a molecular subgroup (P-value = 0.012) with sonic hedgehog (SHH) and group 3 being of worse prognosis than wingless (WNT) and group 4. Therapy was well tolerated.
This treatment based on high-dose chemotherapy and conventional radiotherapy resulted in a high survival rate in children with newly diagnosed high-risk medulloblastoma.
高危型髓母细胞瘤的定义为存在转移性疾病和/或不完全切除和/或不良组织病理学和/或存在 MYC 扩增的肿瘤。我们旨在评估新诊断的高危型髓母细胞瘤患儿（年龄为 5-19 岁）的 3 年无进展生存率（PFS），并定义与 PFS 相关的分子特征，这些患儿根据 II 期试验 PNET HR+5 接受治疗。
所有患儿均接受术后诱导化疗（依托泊苷和卡铂），随后接受 2 个高剂量噻替哌疗程（600mg/m2）联合造血干细胞支持。在最后一次干细胞挽救后最晚 45 天，患者接受风险适应性颅脊髓放疗。在放疗结束后 1-3 个月，计划开始进行替莫唑胺维持治疗。主要终点是 PFS。结果和安全性分析是基于方案（所有接受至少一剂诱导化疗的患者）。
51 例患者（中位年龄 8 岁；范围：5-19 岁）入组。中位随访时间为 7.1 年（范围：3.4-9.0 年）。3 年和 5 年 PFS 及其 95%置信区间（95%CI）分别为 78%（65-88）和 76%（63-86），3 年和 5 年 OS 分别为 84%（72-92）和 76%（63-86）。髓母细胞瘤亚型是一个具有统计学意义的预后因素（P 值=0.039），大细胞/间变性预后较差，分子亚组（P 值=0.012）中 sonic hedgehog（SHH）和 3 组的预后比 wingless（WNT）和 4 组差。治疗耐受良好。
基于大剂量化疗和常规放疗的这种治疗方法使新诊断的高危型髓母细胞瘤患儿的生存率较高。
