NATIONAL WILMS TUMOR STUDY--5

现代治疗方法已导致生存率的重大改善 患有肾母细胞瘤的儿童。随机临床试验由 国家Wilms肿瘤研究小组已经证明，90%的儿童 I期和II期组织学良好的肾母细胞瘤可以治疗 仅行肾切除术和联合化疗， 长春新碱和更生霉素，而治疗与肾切除术， 放疗和长春新碱三联化疗， 放线菌素D和多柔比星可导致 85%的患者为III期和IV期，组织学良好的Wilms肿瘤。 儿童间变性肾母细胞瘤伴透明细胞瘤的预后 肾肉瘤（CCSK）的改善与阿霉素的增加 （CCSK）和阿霉素和环磷酰胺（间变性）的组合 长春新碱和放线菌素D临床和病理特征 在最初诊断时不允许识别这些 在每个阶段都注定要复发的患者。该识别 必须允许给予更积极的治疗方案， 一小群注定会复发而不会暴露于 使用当前治疗方法预后良好的患者 与更积极的化疗相关的额外风险 养生法在一项试点研究中确定了生物变量， 可能与复发的风险有关。我们将在一份确认性的 研究是否：（1）染色体16 q或1 p区域杂合性丢失; 和/或（2）使用流式细胞术测定的增加的DNA含量预测 儿童的两年无复发生存率显著更差， 组织学良好的肾母细胞瘤。我们将评估 化疗方案，包括更大的剂量强度， 环磷酰胺和依托泊苷的添加用于治疗 患有肾间变性肾母细胞瘤和肾透明细胞肉瘤的儿童。 我们将评估依托泊苷、卡铂联合治疗的活性， 和环磷酰胺治疗儿童肾横纹肌样瘤。我们 将采用统一的策略来治疗复发的儿童， 以确定这些生物因素是否与风险有关， 复发也可预测对修复治疗的反应。大多数人的生存 儿童治疗肾母细胞瘤允许遗传和治疗的研究 与疾病病因和/或发生相关的因素 治疗的并发症。我们将与所有患者保持联系， 允许研究肾母细胞瘤的遗传模式， 治疗对生育和妊娠结局的影响， 充血性心力衰竭和发生第二次恶性 肿瘤的

Modern treatment methods have led to major improvements in survival rates of children with Wilms tumor. Randomized clinical trials conducted by the National Wilms Tumor Study Group have demonstrated that 90% of children with stage I and II favorable histology Wilms tumor can be treated successfully with only nephrectomy and combination chemotherapy consisting of vincristine and dactinomycin, while treatment with nephrectomy, radiation therapy and three-drug chemotherapy with vincristine, dactinomycin and doxorubicin results in long-term relapse-free survival of 85% of patients with stage III and IV, favorable histology Wilms tumor. The prognosis for children with anaplastic Wilms tumor and clear cell sarcoma of the kidney (CCSK) has improved with the addition of doxorubicin (CCSK) and doxorubicin and cyclophosphamide (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 may correlate with risk of relapse. We will determine in a confirmatory study if: (1) loss of heterozygosity for chromosomal regions 16q or 1p; and/or (2) increased DNA content determined using flow cytometry predicts significantly worse two-year relapse-free survival in children with favorable histology Wilms tumor. 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 Wilms tumor and clear cell sarcoma of the kidney. We will evaluate the activity of the combination of etoposide, carboplatin 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 Wilms tumor allows the study of genetic and treatment factors associated with the etiology of the disease and/or the occurrence of complications of therapy. We will maintain contact with all patients to allow study of the pattern of inheritance of Wilms tumor, the effect of therapy on fertility and pregnancy outcome, the risk factors for congestive heart failure and for the occurrence of second malignant tumors.