Success in Wilms Tumor Highlights Clinical Trial Cooperation in Pediatrics

Ryan Bendoff with Dr. Susan Cohn, before the CureSearch Walk at Soldier Field, Saturday, September 7. Photo by Jean Lachat

Ryan Bendoff with Dr. Susan Cohn, before the CureSearch Walk at Soldier Field, Saturday, September 7. Photo by Jean Lachat.

By Susan Cohn, MD

The steady improvement in survival rates of patients with Wilms tumor is really one of the big success stories in pediatric oncology.

The most common kidney tumor in kids, Wilms can be a difficult cancer to diagnose because it is largely asymptomatic. It’s usually discovered when a parent notices a hard lump in the abdomen when bathing their child, prompting a trip to the doctor, a scan, and the discovery of the tumor.

Wilms Tumor Survival Rates

In early 1900s, less than 10% of children diagnosed with the disease survived. Now, survival rates for children with Wilms tumor exceed 90%. And if the histology is favorable and the disease is in stage 1, it’s 97%.

These high rates of cure are due to the treatment advances over the past 40 years achieved through successive studies conducted by the National Wilms Tumor Study Group (NWTSG) and the International Society of Pediatric Oncology (SIOP).

However, there continue to be cohorts of children who are not cured with current treatment strategies. Efforts to identify patients who are at high-risk for poor response to current treatments are ongoing.

Ryan was diagnosed with Wilms tumor in July 2011. After having his kidney removed, he underwent daily radiation of his abdomen for two weeks, followed by intermittent chemotherapy for six months. After completing treatment in mid-2012, Ryan is living a normal life again with a greater than 95% chance of a lifelong cure.

Read more about Ryan and his return to camp this summer.

A previous NWTSG clinical trial demonstrated that the presence of genetic abnormalities in chromosomes 1p and 16q were associated with decreased survival in patients with favorable histology Wilms tumor.

Based on these results, one of the questions that is being tested in our current Children’s Oncology Group (COG) trial is whether augmenting therapy for patients with genetic abnormalities of chromosomes 1p and 16q will improve outcome.

It is well recognized that the high cure rate for Wilms tumor comes at a cost, with 25% of survivors having serious chronic health conditions 25 years from diagnosis.

Second malignant solid tumors and congestive heart failure are among the late sequelae that are seen in seen in a subset of Wilms tumor survivors. Further, female Wilms tumor survivors who received flank radiation are at increased risk for pregnancy-related hypertension, premature labor, fetal malposition and delivery of infants with low birth weights.

Thus, in parallel to conducting trials testing intensified therapy for patients with higher-risk disease, clinical trials focused on reducing therapy for patients at low-risk for relapse are ongoing.
A decade ago, clinical trials demonstrated that radiation could be safely eliminated in certain cohorts of patients.

Currently, we are testing whether chemotherapy can be eliminated in patients less than two years of age with small favorable histology Wilms tumors that weigh less than 550 grams in the Children’s Oncology Group (COG) clinical trial (AREN0532).

In addition, in AREN0533 we are testing whether it is safe to eliminate lung radiation in higher-risk patients whose lung disease responds rapidly to chemotherapy.

Further research focused on understanding the biological processes that contribute to the clinical behavior of Wilms tumor and its response to current treatment modalities is needed.

As the pathways of tumorigenesis are elucidated, new biomarkers that will further refine risk will be discovered and novel molecular therapeutic targets that will lead to more personalized treatment are likely to be identified. The success to date in Wilms tumor treatment exemplifies the power of interdisciplinary, cooperative clinical research.

However, we cannot stop now. We must continue to learn from each patient so that we can develop even more effective, less toxic treatments.

Susan Cohn, MD, is a Professor of Pediatrics and Director of Clinical Research in the Section of Pediatric Hematology/Oncology at the University of Chicago Medicine. She is a highly respected expert in pediatric cancers and blood diseases, and a leading authority on neuroblastoma, a cancer of nerve cells, and the most common type of cancer found in infants.