Primary Disseminated Multifocal Ewing Sarcoma: Results of the Euro-EWING 99 Trial
Primary Disseminated Multifocal Ewing Sarcoma: Results of the Euro-EWING 99 Trial
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DOI：
10.1200/jco.2009.22.9864
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发表时间：
2010-07-10
影响因子：
45.3
通讯作者：
Juergens, Heribert
中科院分区：
文献类型：
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作者：
Ladenstein, Ruth;Poetschger, Ulrike;Juergens, Heribert
目的采用剂量强化治疗理念，改善原发性弥散性多灶性Ewing肉瘤（PDMES）患者的不良预后。1999年至2005年，281名PDMES患者被纳入Euro-EWING 99 R3研究。中位年龄为16.2岁（范围0.4 - 49岁）。推荐的治疗方法包括6个周期的长春新碱、异环磷酰胺、阿霉素和依托泊苷（VIDE）， 1个周期的长春新碱、放线菌素和异环磷酰胺（VAI），局部治疗（手术和/或放疗）和高剂量的布苏芬-美法兰，随后是自体干细胞移植（HDT/SCT）。结果：中位随访3.8年后，所有281例患者3年无事件生存率（EFS）和总生存率（OS）分别为27% +/- 3%和34% +/- 4%。250例患者（89%）完成了6个VIDE周期；169例患者（60%）接受了HDT/SCT。在46名14岁以下儿童中，从HDT/SCT开始的3年估计EFS为45%。Cox回归分析显示，年龄大于14岁的患者诊断时的风险增加（风险比[HR] = 1.6），原发肿瘤体积大于200ml (HR = 1.8)，超过一个骨转移部位（HR = 2.0），骨髓转移（HR = 1.6）和额外的肺转移（HR = 1.5）。基于这些HR因素的前期风险评分确定了评分= 5的三组（70例患者，P < 0.0001） EFS发生率为50%。结论强化多模式治疗可使PDMES患者存活。年龄、肿瘤体积和转移扩散程度是相关的危险因素。基于这些因素的评分可能有助于采取适应风险的治疗方法。
Purpose To improve the poor prognosis of patients with primary disseminated multifocal Ewing sarcomas (PDMES) with a dose-intense treatment concept.Patients and Methods From 1999 to 2005, 281 patients with PDMES were enrolled onto the Euro-EWING 99 R3 study. Median age was 16.2 years (range, 0.4 to 49 years). Recommended treatment consisted of six cycles of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE), one cycle of vincristine, dactinomycin, and ifosfamide (VAI), local treatment (surgery and/or radiotherapy), and high-dose busulfan-melphalan followed by autologous stem-cell transplantation (HDT/SCT).Results After a median follow-up of 3.8 years, event-free survival (EFS) and overall survival (OS) at 3 years for all 281 patients were 27% +/- 3% and 34% +/- 4% respectively. Six VIDE cycles were completed by 250 patients (89%); 169 patients (60%) received HDT/SCT. The estimated 3-year EFS from the start of HDT/SCT was 45% for 46 children younger than 14 years. Cox regression analyses demonstrated increased risk at diagnosis for patients older than 14 years (hazard ratio [HR] = 1.6), a primary tumor volume more than 200 mL (HR = 1.8), more than one bone metastatic site (HR = 2.0), bone marrow metastases (HR = 1.6), and additional lung metastases (HR = 1.5). An up-front risk score based on these HR factors identified three groups with EFS rates of 50% for score = 5 (70 patients; P < .0001).Conclusion PDMES patients may survive with intensive multimodal therapy. Age, tumor volume, and extent of metastatic spread are relevant risk factors. A score based on these factors may facilitate risk-adapted treatment approaches.