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: 7212873
• 负责人: NORMAN E BRESLOW
• 金额: $ 102.75万
• 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 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7212873
• 关键词: Abdomen; Adult; Affect; Biological Assay; Birth Rate; Birth Weight; Breast Feeding; Cancer Patient; Child; Childhood; Chronic; Chronic Disease; Clinical; Clinical Pathology; Clinical Trials; Complex; Condition; Congenital Abnormality; Congestive Heart Failure; Data; Data Analyses; Diabetes Mellitus; Disease; Dose; End Point; Enrollment; Epigenetic Process; Etiology; Event; Familial disease; Family member; Frequencies; Future Generations; Genes; Genetic; Genetic Heterogeneity; Goals; Health; Hereditary Malignant Neoplasm; Heritability; Histologic; Incidence; Infant; Integration Host Factors; International; Kidney Failure; Knowledge; Laboratories; Late Effects; Life; Live Birth; Long-Term Effects; Longitudinal Studies; Loss of Heterozygosity; Lung; Lung diseases; Malignant Childhood Neoplasm; Malignant Neoplasms; Medical; Molecular; Monitor; Mothers; Nephroblastoma; Numbers; Operative Surgical Procedures; Outcome; Participant; Pathogenesis; Patients; Pharmaceutical Preparations; Physicians; Population; Predisposition; Pregnancy Complications; Pregnancy Outcome; Prevention strategy; Quality of life; Radiation; Radiation therapy; Rate; Recurrence; Resources; Respiratory Failure; Rest; Risk; Risk Factors; Siblings; Subgroup; Survivors; Syndrome; Therapeutic; Time; WT1 gene; base; chemotherapy; early childhood; follow-up; genetic epidemiology; imprint; mortality; reproductive; statistics; tumorigenesis

DESCRIPTION (provided by applicant): This proposal is to study the long term health of 9,240 patients enrolled during 1969-2002 on National Wilms Tumor Study (NWTS) clinical trials and to monitor their offspring for cancer and birth defects. With current therapy, 90% of children with Wilms tumor (WT) will be cured. Survivors, however, are at risk for delayed complications of their disease or treatment that may compromise their quality of life. Therapy for WT has changed over time but still includes surgery, multi-agent chemotherapy and (for some) radiation therapy. The disease typically occurs in early childhood; thus many years of follow-up are required to appreciate its consequences for adult survivors. As the complex genetic and epigenetic events involved in the etiology and pathogenesis of WT are unraveled, we may also discover the mechanisms underlying its long-term sequelae and thus help to develop appropriate preventive strategies. Our specific goals are to determine the incidence, spectrum and risk factors, including disease, treatment and host factors, for selected life- threatening endpoints affecting WT survivors: a) congestive heart failure; b) respiratory failure; c) renal failure; d) second malignant neoplasms; and e) diabetes. We will determine the incidence and causes of late mortality in WT patients and, where possible, compare mortality and chronic disease rates with national population rates. We will study birth rates in WT survivors, pregnancy outcomes and complications, and congenital malformations in their offspring. Heritability and recurrence risks will be estimated through study. of familial disease and follow-up of offspring. We will exploit the unique NWTS resource, including.:: -; systematically collected information on birth weights, congenital anomalies, nephrog.enic rests, histologic . type, radiation doses, therapeutic drugs and clinical outcomes, to better characterize, subgroups of patients that may differ with respect to the etiology and pathogenesis of their WT and their susceptibility to long term complications. We will collaborate with molecular biologists by facilitating access to particularly informative patients and by combining the laboratory, clinical, pathology and epidemiologic data for analysis. By elucidating the late complications of WT and its treatment, and by identifying susceptible subgroups, this study will enable future generations of childhood cancer patients and their physicians to select optimum treatments based on knowledge of long term risks as well as short term benefits.

描述（由申请人提供）：该提案是研究1969年至2002年在国家Wilms肿瘤研究（NWTS）临床试验中招收的9,240名患者的长期健康状况，并监测其对癌症和先天缺陷的后代。使用目前的治疗，将治愈90％的Wilms肿瘤（WT）儿童。然而，幸存者有可能损害其疾病或治疗的延迟并发症的风险，可能会损害其生活质量。 WT的治疗随着时间的流逝而发生了变化，但仍包括手术，多药化疗以及（某些）放射治疗。该疾病通常发生在幼儿时期；因此，需要多年的随访才能欣赏其对成年幸存者的后果。随着WT病因和发病机理中涉及的复杂遗传和表观遗传事件被揭示，我们还可以发现其长期后遗症的基础机制，从而有助于制定适当的预防策略。我们的具体目标是确定影响WT幸存者的选定危险终点的发病率，频谱和危险因素，包括疾病，治疗和宿主因素：a）充血性心力衰竭； b）呼吸衰竭； c）肾衰竭； d）第二个恶性肿瘤；和e）糖尿病。我们将确定WT患者晚期死亡率的发生率和原因，并在可能的情况下将死亡率和慢性病率与全国人口率进行比较。我们将研究WT幸存者的出生率，妊娠结局和并发症以及其后代的先天性畸形。遗传力和复发风险将通过研究估算。家族疾病和后代的随访。我们将利用唯一的NWTS资源，包括.:: - ;系统地收集了有关出生体重，先天性异常，肾上腺素的信息。类型，辐射剂量，治疗药物和临床结局，以更好地表征其WT的病因和发病机理的患者亚组，以及他们对长期并发症的敏感性。我们将与分子生物学家合作，通过促进特别有用的患者的访问，并结合实验室，临床，病理和流行病学数据进行分析。通过阐明WT及其治疗的晚期并发症，并通过识别易感亚组，这项研究将使子孙后代的儿童癌症患者及其医生能够根据对长期风险的知识以及短期收益选择最佳治疗方法。