NATIONAL WILMS TUMOR STUDY -5

现代治疗方法已导致肾母细胞瘤（WT）儿童生存率的重大改善。 由国家Wilms肿瘤研究小组进行的随机临床试验已经证明，90%的I期和II期组织学良好的WT儿童可以成功治疗。仅用肾切除术、放射治疗和长春新碱、更生霉素和多柔比星的三药化疗就可以成功治疗WT，导致85%的III期和IV期组织学良好的WT患者的长期无复发生存。在长春新碱和更生霉素联合治疗的基础上加用多柔比星（CCSK）和多柔比星及环磷酰胺（间变性），可改善间变性WT和肾透明细胞肉瘤（CCSK）儿童的预后。临床和病理学特征不允许在初始诊断时识别在每个阶段内注定要复发的那些患者。这种识别是必要的，以允许向注定要复发的一小群患者施用更积极的治疗方案，而不使使用当前治疗方法具有良好预后的那些患者暴露于与更积极的化疗方案相关的额外风险。在一项试点研究中已经确定了与复发风险相关的生物变量。我们将在一项验证性研究中确定：（1）染色体区域16 q或1 p1杂合性缺失和/或（2）使用流式细胞术测定的DNA含量增加是否预示组织学良好WT儿童的两年无复发生存率显著较差。我们将评估化疗方案的有效性，其中包括更大剂量强度的环磷酰胺和添加依托泊苷治疗儿童间变性WT和肾透明细胞肉瘤。我们将评估足叶乙甙、卡铂和环磷酰胺联合治疗儿童肾横纹肌样瘤的疗效。我们将采用统一的策略治疗复发的儿童，以确定与复发风险相关的生物学因素是否也预测对恢复治疗的反应。大多数接受WT治疗的儿童的存活率允许研究与疾病病因和/或治疗并发症发生相关的遗传和治疗因素。

Modern treatment methods have led to major improvements in survival rates of children with Wilms tumor (WT). Randomized clinical trials conducted by the National Wilms Tumor Study Group have demonstrated that 90% of children with stage I and II favorable histology WT can be treated successfully WT can be treated successfully with only nephrectomy, radiation therapy and three-drug chemotherapy with vincrintine, dactinomycin and doxorubicin results in long-term relapse- free survival of 85% of patients with stage III and IV, favorable histology WT. The prognosis for children with anaplastic WT and clear cell sarcoma of the kidney (CCSK) has improved with the addition of doxorubicin (CCSK) and doxorubicin and cycophosphamide (anaplasia) to the combination of vincristine and dactinomycin. Clinical and pathological features have not allowed identification at the time of initial diagnosis of those patients destined to relapse within each stage This identification is necessary to allow administration of more aggressive treatment regimens to the small group of patients who are destined to relapse without exposing those patients with an excellent prognosis using current treatment methods to the additional risk associated with more aggressive chemotherapeutic regimens. Biological variables have been identified in a pilot study which correlate with risk of relapse. We will determine in a confirmatory study if: (1) loss of heterozygosity for chromosomal regions 16q or 1p1 and/or (2) increased DNA content determined using flow cytometry predicts significantly worse two-year relapse-free survival in children with favorable histology WT. We will evaluate the effectiveness of chemotherapy regimens which include greater dose intensity of cyclophosphamide and the addition of etoposide for the treatment of children with anaplastic WT and clear cell sarcoma of the kidney. We will evaluate the activity of the combination of etoposide, carboplatinum and cyclophosphamide in children with rhabdoid tumor of the kidney. We will employ a uniform strategy for the treatment of children who relapse to determine if those biological factors associated with the risk of relapse also predict response to retrieval therapy. The survival of most children treated for WT allows the study of genetic and treatment factors associated with the etiology of the disease and/or the occurrence of complications of therapy.