Late Effects of Treatment in Wilms Tumor Survivors and Offspring

描述（由申请人提供）：本提案旨在研究肾母细胞瘤（WT）治疗儿童的长期健康状况，并监测其后代的癌症和出生缺陷。该研究基于1969年至2002年期间在国家Wilms肿瘤研究（NWTS）进行的5项临床试验之一中招募的9，236名患者的独特和良好描述的队列。NWTS研究3-5制定了治疗方案，今天作为“标准治疗”给予绝大多数患者。通过这种疗法，90%的WT儿童被治愈。然而，幸存者面临着疾病或治疗延迟并发症的风险，这可能会影响他们的生活质量。由于这种疾病通常发生在儿童早期，需要几十年的随访才能了解成年幸存者的后果。针对四种危及生命的疾病：继发性恶性肿瘤;充血性心力衰竭;终末期肾病（ESRD）;限制性肺病。大多数事件通过检查医疗记录得到证实。具体目标是根据治疗、疾病和宿主因素确定NWTS-3-5中每种疾病高风险的新患者亚组。例如，有高风险的终末期肾病患者可以考虑进行保留肾脏的手术。从NWTS-5患者中收集的生物样本将用于检验WT 1基因突变不仅在儿童期易患WT，而且在青春期和成年期易患ESRD的假设。系统收集的出生体重、先天性异常、肾源性剩余、组织学类型以及放疗和化疗剂量的信息将用于构建ESRD的风险函数，并研究对充血性心力衰竭和继发性恶性肿瘤的治疗效果是否因肾母细胞瘤的生物亚型而异。该研究将估计女性患者的卵巢衰竭率和男性患者伴侣的活产率和妊娠并发症风险。 WT的遗传性和复发风险，以及下一代出生缺陷的频率，将通过随访一个独特的患者后代队列来估计。

DESCRIPTION (provided by applicant): This proposal is to study the long term health of children treated for Wilms tumor (WT), and to monitor their offspring for cancer and birth defects. The study is based in the unique and well described cohort of 9,236 patients enrolled during 1969-2002 on one of 5 clinical trials conducted by the National Wilms Tumor Study (NWTS). NWTS studies 3-5 developed treatment protocols that today are administered as "standard therapy" to the vast majority of patients. With this therapy, 90% of children with WT are cured. Survivors, however, are at risk for delayed complications of their disease or its treatment that may compromise their quality of life. Since the disease typically occurs in early childhood, many decades of follow-up are required to appreciate the consequences for adult survivors. Four life-threatening conditions are targeted: secondary malignant neoplasms; congestive heart failure; end stage renal disease (ESRD); and restrictive pulmonary disease. Most occurrences are validated by examination of medical records. Specific goals are to identify new subgroups of patients from NWTS-3-5 at high risk for each condition based on treatment, disease and host factors. Patients at high risk for ESRD, for example, may be considered for renal sparing surgery. Biological samples collected from patients on NWTS-5 will be used to test the hypothesis that mutations in the WT1 gene not only predispose to WT in childhood but also to ESRD in adolescence and adulthood. Systematically collected information on birth weights, congenital anomalies, nephrogenic rests, histologic type, and on radiation and chemotherapy doses will be used to construct risk functions for ESRD and to investigate whether treatment effects on congestive heart failure and secondary malignant neoplasms differ according to the biological subtype of Wilms tumor. The study will estimate rates of ovarian failure in female patients and rates of live birth and risks of pregnancy complications in partners of male patients. Heritability and recurrence risks of WT, together with the frequency of birth defects in the next generation, will be estimated through follow-up of a unique cohort of patient offspring.