Abstract

Background

“Head Start” III, was a prospective clinical trial using intensive induction followed by myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) to either avoid or reduce the dose/volume of irradiation in young children with medulloblastoma.

Methods

Following surgery, patients received 5 cycles of induction followed by myeloablative chemotherapy using carboplatin, thiotepa, and etoposide with AuHCR. Irradiation was reserved for children >6 years old at diagnosis or with residual tumor post-induction.

Results

Between 2003 and 2009, 92 children <10 years old with medulloblastoma were enrolled. Five-year event-free survival (EFS) and overall survival (OS) rates (±SE) were 46 ± 5% and 62 ± 5% for all patients, 61 ± 8% and 77 ± 7% for localized medulloblastoma, and 35 ± 7% and 52 ± 7% for disseminated patients. Nodular/desmoplastic (ND) medulloblastoma patients had 5-year EFS and OS (±SE) rates of 89 ± 6% and 89 ± 6% compared with 26 ± 6% and 53 ± 7% for classic and 38 ± 13% and 46 ± 14% for large-cell/anaplastic (LCA) medulloblastoma, respectively. In multivariate Cox regression analysis, histology was the only significant independent predictor of EFS after adjusting for stage, extent of resection, regimen, age, and sex (P <0.0001). Five-year irradiation-free EFS was 78 ± 8% for ND and 21 ± 5% for classic/LCA medulloblastoma patients. Myelosuppression was the most common toxicity, with 2 toxic deaths. Twenty-four survivors completed neurocognitive evaluation at a mean of 4.9 years post-diagnosis. IQ and memory scores were within average range overall, whereas processing speed and adaptive functioning were low-average.

Conclusion

We report excellent survival and preservation of mean IQ and memory for young children with ND medulloblastoma using high-dose chemotherapy, with most patients surviving without irradiation.

中文翻译：

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“Head Start”III 治疗结节性促纤维增生性髓母细胞瘤幼儿的优异结果：一项多机构前瞻性临床试验。

 抽象的

 背景

“Head Start”III 是一项前瞻性临床试验，使用强化诱导，然后进行清髓化疗和自体造血细胞拯救 (AuHCR)，以避免或减少髓母细胞瘤幼儿的照射剂量/体积。

 方法

手术后，患者接受 5 个周期的诱导，然后使用卡铂、噻替派和依托泊苷与 AuHCR 进行清髓化疗。放射治疗保留用于诊断时 >6 岁的儿童或诱导后有残留肿瘤的儿童。

 结果

2003 年至 2009 年间，招募了 92 名 <10 岁患有髓母细胞瘤的儿童。所有患者的五年无事件生存率 (EFS) 和总生存率 (OS) (±SE) 分别为 46 ± 5% 和 62 ± 5%，局限性髓母细胞瘤为 61 ± 8% 和 77 ± 7%，35对于播散性患者，为 ± 7% 和 52 ± 7%。结节性/促纤维增生性 (ND) 髓母细胞瘤患者的 5 年 EFS 和 OS (±SE) 率为 89 ± 6% 和 89 ± 6%，而经典型为 26 ± 6% 和 53 ± 7%，以及 38 ± 13% 和 46大细胞/间变性 (LCA) 髓母细胞瘤分别为 ± 14%。在多变量 Cox 回归分析中，在调整分期、切除范围、治疗方案、年龄和性别后，组织学是 EFS 唯一显着的独立预测因子 ( P <0.0001)。 ND 患者五年无照射 EFS 为 78 ± 8%，经典/LCA 髓母细胞瘤患者为 21 ± 5%。骨髓抑制是最常见的毒性，导致 2 例中毒死亡。 24 名幸存者平均在诊断后 4.9 年完成神经认知评估。智商和记忆力总体得分处于平均范围内，而处理速度和适应性功能则处于较低平均水平。

 结论

我们报告说，使用高剂量化疗的 ND 髓母细胞瘤幼儿的平均智商和记忆力均得到了良好的保留，并且大多数患者无需接受放射治疗即可存活。