Late Effects of Treatment in Wilms Tumor Survivors and Offspring

治疗对肾母细胞瘤幸存者和后代的后期影响

• 批准号: 8889201
• 负责人: Wendy M Leisenring
• 金额: $ 61.61万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8889201
• 关键词: Abdomen; Address; Adolescence; Adult; Age; Biological; Birth Rate; Birth Weight; Cancer Patient; Child; Child health care; Childhood; Conduct Clinical Trials; Congenital Abnormality; Congestive Heart Failure; Constitutional; Cyclophosphamide; Development; Diagnosis; Disease; Dose; Doxorubicin; End stage renal failure; Enrollment; Etoposide; Female; Frequencies; Future Generations; Gender; General Population; Goals; Heritability; Histologic; Histology; Incidence; Integration Host Factors; Kidney; Kidney Failure; Kidney Transplantation; Knowledge; Late Effects; Lesion; Life; Live Birth; Longitudinal Studies; Low Birth Weight Infant; Lung diseases; Malignant Childhood Neoplasm; Malignant Neoplasms; Medical Records; Monitor; Mutation; Nephroblastoma; Operative Surgical Procedures; Patient Care; Patients; Performance; Physicians; Population Control; Pregnancy; Pregnancy Complications; Protocols documentation; Quality of life; Radiation; Receiver Operating Characteristics; Recurrence; Regimen; Rest; Retrieval; Risk; Risk Estimate; Sampling; Second Primary Cancers; Subgroup; Survivors; Syndrome; Testing; Transplantation; Treatment Protocols; WT1 gene; Weight; base; chemotherapy; chest irradiation; cohort; congenital anomaly; cost; early childhood; follow-up; graft failure; hazard; high risk; irradiation; male; mortality; next generation; offspring; ovarian failure; response; surveillance strategy; treatment effect; treatment strategy; trend

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.

描述(申请人提供)：这项建议是为了研究接受肾母细胞瘤(Wilms Tumor，WT)治疗的儿童的长期健康状况，并监测他们的后代癌症和出生缺陷。这项研究是基于1969年至2002年期间登记的9236名患者中独特的和描述良好的队列，这些患者是由国家肾母细胞肿瘤研究(NWTS)进行的5项临床试验之一。NWTS的3-5项研究制定了治疗方案，如今这些方案作为“标准疗法”应用于绝大多数患者。通过这种疗法，90%的WT儿童被治愈。然而，幸存者面临着他们的疾病或治疗的延迟并发症的风险，这可能会危及他们的生活质量。由于这种疾病通常发生在儿童早期，需要数十年的随访才能认识到成年幸存者的后果。四种危及生命的疾病被列为目标：继发性恶性肿瘤、充血性心力衰竭、终末期肾病(ESRD)和限制性肺部疾病。大多数事件都是通过检查医疗记录来确认的。具体目标是根据治疗、疾病和宿主因素确定每种情况下NWTS-3-5高危患者的新亚组。例如，ESRD的高危患者可以考虑进行肾脏保留手术。从NWTS-5患者身上收集的生物样本将被用来检验WT1基因突变不仅在儿童时期易患WT，而且在青春期和成年后易患ESRD的假设。系统收集的有关出生体重、先天异常、肾源性休息、组织类型以及放化疗剂量的信息将被用来构建ESRD的风险函数，并调查对充血性心力衰竭和继发性恶性肿瘤的治疗效果是否因Wilms肿瘤的生物学亚型而异。这项研究将估计女性患者的卵巢衰竭比率，以及男性患者的伴侣的活产率和妊娠并发症的风险。 WT的遗传性和复发风险，以及下一代出生缺陷的频率，将通过对一组独特的患者后代的随访来估计。