The National Wilms Tumor Study (NWTS) was established in 1969 by bringing together investigators from children’s hospitals and clinics throughout North America who were participating in government sponsored cooperative cancer treatment programs. Its founding Chairman, Dr. Giulio D’Angio, had a vision: of curing childhood cancer, and in particular the embryonal kidney cancer known as Wilms tumor, so that survivors could lead normal adult lives, free from the late occurring side effects associated with intensive drug and radiation therapies. The NWTS was one of the first “multi modal” cooperative groups and included not only oncologists but also surgeons, pathologists, radiation therapists, radiologists, epidemiologists, statisticians and other specialists as full members. During the course of five clinical trials, with the last patient enrolled in 2002, tumor mortality rates were cut in half so that today nearly 90% of children with Wilms and other kidney tumors can expect to survive at least until their teenage years, with excellent prospects thereafter. The founding pathologist, Dr. Bruce Beckwith, contributed enormously to this success by identifying a small subgroup of children with tumors of “unfavorable histology” in which over half the tumor deaths occurred. This allowed treatments, particularly with radiation therapy, to be reduced if not omitted for the great majority of patients who did not need them for cure. Treatments, particularly chemotherapy, could then be intensified for the smaller number of patients who did need them.
Today the focus of the NWTS is on the long term follow-up of survivors from the five clinical trials, and of their offspring. Its primary mission is to chart their mortality rates in comparison to those for the general population and to determine the cumulative incidence of secondary malignant neoplasms, congestive heart failure, restrictive pulmonary disease, end stage renal disease, adverse reproductive outcomes and other medical conditions that are likely to have resulted either from treatment or from the same biological factors that led to the Wilms tumor in the first place. The study attempts to identify the particular treatments and biological risk factors that predispose to these “late effects”. Treatments so identified can then be avoided to the extent possible in future therapeutic regimens and survivors at “high risk” for late effects can be routinely monitored for their possible occurrence.
Another primary goal is to study the patterns of familial disease, particularly the (fortunately very low) risk of Wilms tumor in the offspring of survivors, so that former patients may be counseled (and reassured) regarding their ability to conceive and bear healthy children. The very rich database containing uniform pathology diagnoses, detailed treatment records and medically verified outcomes is explored in depth for clues regarding pathogenesis and etiology. Epidemiologic analysis of gender and age at diagnosis, birth weight, histologic subtype of tumor, precursor lesions and treatment outcomes leads to biological hypotheses that can be tested in the laboratory to help establish fundamental mechanisms of tumor formation. The NWTS collaborates with both epidemiologists and molecular geneticists as a case-finding resource, identifying the most informative patients for inclusion in field studies regarding possible environmental risk factors or in laboratory studies designed to identify new Wilms tumor genes.
Through continued follow-up of a unique patient population that spans over three decades of diagnoses, the NWTS Late Effects Study hopes to confirm that the vision of its founder has become a reality: “Cure is not enough.”