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: 3199049
• 负责人: NORMAN E BRESLOW
• 金额: $ 15.95万
• 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 1996-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3199049
• 关键词: Wilms' tumor; 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; human subject; linkage mapping; longitudinal human study; medical complication; neoplasm /cancer chemotherapy; neoplasm /cancer genetics; neoplasm /cancer radiation therapy; neoplasm /cancer relapse /recurrence; 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.

这是为了长期跟进而修订的提案 国家维尔姆斯肿瘤研究 (NWTS) 的幸存者及其后代 从而阐明肾母细胞瘤的遗传起源，估计 不良妊娠结局和先天性缺陷的风险 确定患者第二肿瘤和心脏病的发生率 童年时接受癌症治疗。 NWTS 是一项大型协作试验 该组织于 1969 年组织，目前注册的估计有 70% 或更多 在美国被诊断出患有维尔姆斯氏瘤的儿童。 患者 从诊断起进行为期五年的临床试验， 到那时，那些幸存的人就可以被认为已经治愈了 初期疾病。 该提案旨在制定并实施有效的 五年后继续采取后续行动，以便吸取教训 从这一宝贵的儿童和年轻人群体中学到的知识不会 迷失于科学，并完善这些方法作为其他人的模型 从事类似的研究。 这项纵向研究有待确定后期影响 包括第二恶性肿瘤、良性肿瘤、严重心脏病、 生殖结果、先天性缺陷和癌症，包括 家族性肾母细胞瘤，可能在后代中发生。 治疗 NWTS 中使用的干预措施是四种化疗药物的组合 有和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 辐射的使用和剂量不同的亚组 治疗和具体的化疗类型。 肾母细胞瘤的数据 将收集家庭成员和后代以确定 人口频率、主导程度和假定的渗透率 “威尔姆斯基因”并协助他人定位该基因或多个基因 通过连锁分析。 后期影响数据将根据 治疗类型和持续时间，自开始治疗以来经过的年数 治疗、年龄和宿主因素。 患者将通过以下方式进行随访： 每年与幸存者保持联系的自动化系统 积极寻找失联的患者及家属 后续行动。 有关健康状况和其他关键事件的信息将 从定期体检和病史中获得， 用于获取详细信息的调查问卷和医疗记录审查 生殖结果和关键医疗状况的诊断。