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.
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