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）：本提案旨在研究 1969 年至 2002 年期间参加国家肾母细胞瘤研究 (NWTS) 临床试验的 9,240 名患者的长期健康状况，并监测他们的后代是否患有癌症和出生缺陷。通过目前的治疗，90% 的肾母细胞瘤 (WT) 儿童将被治愈。然而，幸存者面临着疾病或治疗迟发并发症的风险，这可能会影响他们的生活质量。 WT 的治疗随着时间的推移而发生变化，但仍然包括手术、多药化疗和（对于某些）放射治疗。这种疾病通常发生在儿童早期；因此，需要多年的后续行动才能了解其对成年幸存者的影响。随着WT病因和发病机制中涉及的复杂遗传和表观遗传事件的解开，我们还可能发现其长期后遗症的机制，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 幸存者的选定危及生命终点的发病率、谱系和风险因素，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) 肾功能衰竭； d) 第二恶性肿瘤； e) 糖尿病。我们将确定 WT 患者晚期死亡的发生率和原因，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畸形。将通过研究估计遗传性和复发风险。家族性疾病的发生和后代的随访。我们将利用独特的 NWTS 资源，包括：: -;系统地收集有关出生体重、先天性异常、肾病休息、组织学信息。类型、放射剂量、治疗药物和临床结果，以更好地描述在 WT 的病因和发病机制以及对长期并发症的易感性方面可能不同的患者亚组。我们将与分子生物学家合作，帮助接触信息丰富的患者，并结合实验室、临床、病理学和流行病学数据进行分析。通过阐明 WT 的晚期并发症及其治疗方法，并确定易感亚组，这项研究将使后代儿童癌症患者及其医生能够根据长期风险和短期效益的知识选择最佳治疗方法。