Dome Jeffrey S, Perlman Elizabeth J, Graf Norbert
From the Division of Oncology, Children's National Medical Center, Washington DC; Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL; Department of Pediatric Oncology and Hematology, Saarland University, Homburg, Germany.
Am Soc Clin Oncol Educ Book. 2014:215-23. doi: 10.14694/EdBook_AM.2014.34.215.
Wilms tumor, or nephroblastoma, has provided a paradigm for progressive improvement in clinical outcomes achieved through serial cooperative group studies. With modern surgery, chemotherapy, and radiation therapy approaches, the overall survival rate for patients with Wilms tumor has reached 90%. Remarkably, the increase in survival has been achieved with a reduction in therapy for most patient subgroups, leading not only to more survivors, but also to healthier survivors. A key contributor to improved outcomes has been the development of clinical and biologic prognostic markers that have enabled risk-directed therapy. Whereas the early cooperative group studies used only tumor stage for risk stratification, current Children's Oncology Group (COG) and International Society of Pediatric Oncology (SIOP) protocols employ a multitude of prognostic factors to guide therapy. Prognostic factors used in the current generation of COG studies include stage, histology, patient age, tumor weight, completeness of lung nodule response, and loss of heterozygosity at chromosomes 1p and 16q. Future COG studies seek to incorporate gain of chromosome 1q and methylation pattern of chromosome 11p15 into the risk classification schema. Prognostic factors used in the current SIOP studies include stage, histology, tumor volume, and responsiveness to therapy. Future SIOP studies seek to incorporate absolute blastemal volume and novel molecular markers for resistant blastema into the risk stratification approach.
肾母细胞瘤，即肾胚胎瘤，为通过系列合作组研究实现临床结局的逐步改善提供了范例。采用现代手术、化疗和放疗方法后，肾母细胞瘤患者的总生存率已达到90%。值得注意的是，大多数患者亚组在减少治疗的情况下实现了生存率的提高，这不仅带来了更多的幸存者，还带来了更健康的幸存者。临床和生物学预后标志物的发展是改善结局的一个关键因素，这些标志物使得能够进行风险导向治疗。早期合作组研究仅将肿瘤分期用于风险分层，而目前儿童肿瘤学组（COG）和国际儿科肿瘤学会（SIOP）的方案采用多种预后因素来指导治疗。当前一代COG研究中使用的预后因素包括分期、组织学、患者年龄、肿瘤重量、肺结节反应的完整性以及1号染色体短臂（1p）和16号染色体长臂（16q）的杂合性缺失。未来的COG研究试图将1号染色体长臂（1q）的获得和11号染色体短臂15区（11p15）的甲基化模式纳入风险分类方案。当前SIOP研究中使用的预后因素包括分期、组织学、肿瘤体积和对治疗的反应性。未来的SIOP研究试图将原始细胞绝对体积和针对耐药原始细胞的新型分子标志物纳入风险分层方法。
