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Abstract：
\"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.
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.
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.
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.
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.
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.
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.
摘要：
“开始”三，是一项前瞻性临床试验，使用强化诱导，然后进行清髓性化疗和自体造血细胞抢救（AuHCR），以避免或减少髓母细胞瘤幼儿的照射剂量/体积。
手术后，患者接受5个周期的诱导，然后使用卡铂进行清髓性化疗，Thiotepa,依托泊苷和AuHCR。在诊断时或诱导后残留肿瘤的6岁以上儿童保留照射。
在2003年至2009年之间，招募了92名10岁以下的髓母细胞瘤儿童。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％。局部髓母细胞瘤为61±8%和77±7%，传播患者为35±7%和52±7%。结节性/促纤维化（ND）髓母细胞瘤患者的5年EFS和OS（±SE）率为89±6％和89±6％，而经典组为26±6％和53±7％，大细胞/间变性（LCA）髓母细胞瘤为38±13％和46±14％，分别。在多元Cox回归分析中，组织学是调整分期后EFS唯一显著的独立预测因子，切除范围,方案，年龄,性别（P<0.0001）。ND的五年无辐射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，有2人中毒死亡。24名幸存者在诊断后平均4.9年完成神经认知评估。智商和记忆力得分总体在平均范围内，而处理速度和自适应功能的平均水平较低。
我们报告了使用大剂量化疗对患有ND髓母细胞瘤的年幼儿童的平均智商和记忆力的优异存活率和保留。大多数患者在没有照射的情况下存活。
手术后，患者接受5个周期的诱导，然后使用卡铂进行清髓性化疗，Thiotepa,依托泊苷和AuHCR。在诊断时或诱导后残留肿瘤的6岁以上儿童保留照射。
在2003年至2009年之间，招募了92名10岁以下的髓母细胞瘤儿童。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％。局部髓母细胞瘤为61±8%和77±7%，传播患者为35±7%和52±7%。结节性/促纤维化（ND）髓母细胞瘤患者的5年EFS和OS（±SE）率为89±6％和89±6％，而经典组为26±6％和53±7％，大细胞/间变性（LCA）髓母细胞瘤为38±13％和46±14％，分别。在多元Cox回归分析中，组织学是调整分期后EFS唯一显著的独立预测因子，切除范围,方案，年龄,性别（P<0.0001）。ND的五年无辐射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，有2人中毒死亡。24名幸存者在诊断后平均4.9年完成神经认知评估。智商和记忆力得分总体在平均范围内，而处理速度和自适应功能的平均水平较低。
我们报告了使用大剂量化疗对患有ND髓母细胞瘤的年幼儿童的平均智商和记忆力的优异存活率和保留。大多数患者在没有照射的情况下存活。
