Wilms Tumor

Disease Background

Wilms tumor, also known as nephroblastoma, is a cancer of the kidney that usually occurs in children younger than age 5. The causes are unknown, but it is believed that a genetic abnormality is involved in some cases. Wilms tumors arise from embryonal kidney tissues that have normally disappeared at the time of birth. The kidneys are a matched pair of organs about the size of a fist found on either side of the backbone. The kidneys filter and clean the blood, take out unneeded products, and make urine.

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Wilms tumor occurs in about one in 12,000 children. It is the second most common solid tumor outside of brain tumors in children and makes up 7 percent of all childhood cancers. It is most often diagnosed between the ages of 6 months and 10 years, with the greatest number of children diagnosed by age 5. While there is evidence that some Wilms Tumor children inherit a gene mutation that makes them more susceptible to the cancer, a recent study found that fewer than 10 percent of the cases can be attributed to the only identified gene linked to the cancer.

Our Research

Overview of Hutchinson Center Research

The Hutchinson Center houses the statistical center for the former National Wilms Tumor Study (NWTS), a pediatric oncology research consortium which merged with three other pediatric oncology clinical trials groups in 2002. It maintains one of the longest-running pediatric cancer databases in the United States. Over the course of 37 years, the group has tracked more than 10,000 survivors of Wilms tumor.

The 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 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.

As a result of this extensive follow up of Wilms tumor patients, refinements in treatment have boosted survival rates and yielded insight into potential long-term effects of radiation and chemotherapy on the subsequent development and health of these children.

The NWTS investigators conducted five clinical trials to determine which drugs or drug combinations were most effective as well as to minimize the amount of radiation used in treatment. More than 400 children were entered on these studies each year, representing about 70 percent of the total Wilms cases in the United States. The initial trial aimed to determine whether chemotherapy alone or combination chemotherapy plus radiation therapy is the more effective initial treatment for childhood kidney cancer.

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 the mortality rates for this "cohort" in comparison to those for the general population. Additional major goals are 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.

Effective treatments for Wilms tumor

Modern therapy typically involves surgical removal of the tumor followed by chemotherapy, with or without radiation therapy. At the beginning of the 20th century, about 90 percent of children diagnosed with Wilms tumor died. By the end of the century, nearly 90 percent survived and were able to lead relatively normal lives. That radical change in outcomes can be attributed in part to the NWTS, one of the longest running research study groups in the nation. 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 more than 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.

Statistician Dr. Norman Breslow, another founding member of the NWTS, established the Data and Statistical Center (DSC) at the University of Washington in 1969 and relocated it to the Hutchinson Cancer Center in 1975. From the outset he placed high priority on collecting data through careful follow up of all registered Wilms patients. His research focused on the analysis of biological factors that may help determine outcomes from treatments for Wilms tumor patients.

The DSC houses the world's largest collection of clinical information on Wilms tumor. The database has allowed researchers to document the adverse effects of both chemotherapy and various doses of radiation on skeletal and muscle development, the development of second tumors including breast, colon and primary liver cancers at relatively young ages, and, in the case of female patients, adverse pregnancy outcomes. Today, as a result of this extensive follow up of Wilms tumor patients and the ongoing late effects study, we have greater insight into potential long-term effects of radiation and chemotherapy on the subsequent development and health of these children, and we have developed more effective treatments with fewer long-term side effects.

The research data continues to lead to improvements in Wilms therapy now carried out by the Childrens Oncology Group. The second NWTS Chair, Dr. Daniel Green, shared the pioneering vision of obtaining cure with minimum impact on the patient and the family. The treatment regimen used to consist of five days of chemotherapy repeated over the course of 15 months, but research led by Dr. Green has shown that the treatment can be given in single doses and completed in six months. This makes it much easier for many children to get the best therapy by decreasing the length of treatment, which also saves families hundreds of thousands of dollars.

See also the National Wilms Tumor Study Web site.

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Relevant Articles

• Tracing cancer's family ties
  
  
• The data backbone — In her 26th year, Janice Takashima knows that Wilms study has come a long way since center's pre-computer plotting of points on graph paper
  
  
• Have (enormous) data, will cure — World's-largest tracking of Wilms-tumor patients, statistics allows researchers to boost survival, ease side effects for childhood disease
  
  
• Breslow talk covers Wilms genetics

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