LATE EFFECTS IN WILMS' TUMOR SURVIVORS AND OFFSPRING

对威尔姆斯肿瘤幸存者和后代的迟发影响

• 批准号: 3199047
• 负责人: NORMAN E BRESLOW
• 金额: $ 18.34万
• 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 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3199047
• 关键词: automated medical record system; cancer registry /resource; cancer risk; cardiotoxin; cardiovascular disorder; clinical trials; combination cancer therapy; congenital disorders; disease /disorder proneness /risk; drug adverse effect; female; female reproductive system; fertility; gene frequency; genetic disorder; genetic models; human population genetics; linkage mapping; longitudinal human study; medical complication; neoplasm /cancer chemotherapy; neoplasm /cancer genetics; neoplasm /cancer radiation therapy; neoplasm /cancer relapse /recurrence; nephroblastoma; pediatric neoplasm /cancer; pregnancy disorder; questionnaires; statistics /biometry

This is a revised proposal for the long term follow-up of survivors from the National Wilms' Tumor Study (NWTS) and their offspring so as to elucidate the genetic origins of Wilms' tumors, to estimate the risk of adverse pregnancy outcomes and congenital defects and to determine the rates of second tumors and heart disease in patients treated for cancer in childhood. The NWTS is a large collaborative trial organized in 1969 that currently registers an estimated 70% or more of the children diagnosed with Wilms' tumor in the United States. Patients are followed on the clinical trial for five years from diagnosis, by which time those who have survived may be considered cured of their initial disease. This proposal is to develop and implement efficient means of continued follow-up beyond five years so that the lessons to be learned from this invaluable cohort of children and young adults will not be lost to science, and to perfect these methods as a model for others engaged in similar studies. Late effects to be ascertained in this longitudinal study include second malignant tumors, benign tumors, serious heart disease, reproductive outcomes, and congenital defects and cancer, including familial Wilms' tumors, that may develop in offspring. The treatment interventions used in the NWTS are combinations of four chemotherapeutic agents with and without radiation therapy. This will permit the comparison of rates of occurrence of key events among randomized patient subgroups that differ with respect to the use and dosage of radiation therapy and the specific type of chemotherapy. Data on Wilms' tumors in family members and offspring will be collected so as to determine the population frequency, degree of dominance and penetrance of the putative "Wilms' gene" and to assist others in the location of the gene or genes via linkage analysis. Data on late effects will be analyzed according to type and duration of therapy, years elapsed since initiation of treatment, age and host factors. Patients will be followed by means of an automated system that maintains annual contact with survivors and actively pursues those patients and families who become lost to follow-up. Information on health status and other key events will be obtained from periodic physical exams and medical histories, with questionnaires and reviews of medical records used to obtain details on reproductive outcomes and diagnoses of key medical conditions.

这是对长期随访的修订建议 国家威尔姆斯肿瘤研究（NWTS）及其后代的幸存者 为了阐明威尔姆斯肿瘤的遗传起源，以估计 不良怀孕结局和先天性缺陷的风险 确定患者的第二肿瘤和心脏病的发生率 在儿童时期接受癌症治疗。 NWTS是一项大型协作试验 1969年组织的目前估计估计有70％或更多 在美国被诊断出患有威尔姆斯肿瘤的孩子。 患者 从诊断后进行了五年的临床试验，通过 那些幸存的人可以被视为治愈他们的 初始疾病。 该建议是开发和实施高效 持续跟进的手段超过五年，以使课程成为 从这个宝贵的儿童和年轻人中学到的 迷失于科学，并完善这些方法作为他人的典范 进行了类似的研究。 在这项纵向研究中要确定的后期效果 包括第二个恶性肿瘤，良性肿瘤，严重的心脏病， 生殖结果以及先天性缺陷和癌症，包括 家族性威尔姆斯的肿瘤可能会在后代发展。 治疗 NWT中使用的干预措施是四种化学治疗的组合 有或没有放射治疗的药物。 这将允许 随机患者中关键事件发生率的比较 相对于辐射的使用和剂量不同的亚组 治疗和特定类型的化学疗法。 有关威尔姆斯肿瘤的数据 将收集家庭成员和后代，以确定 推定的人口频率，优势程度和外观 “ Wilms的基因”，并协助他人在基因或基因的位置 通过链接分析。 将根据延迟效果的数据根据 疗法的类型和持续时间，自开始以来已经过去的时间 治疗，年龄和宿主因素。 患者将随之而来 一种自动化系统，该系统与幸存者和幸存者的年度联系 积极追求那些迷失的患者和家庭 后续。 有关健康状况和其他关键事件的信息将是 从定期的身体检查和医学历史中获得 问卷和有关医疗记录的评论，用于获取有关的详细信息 生殖结果和关键医疗状况的诊断。