However, this success is not without a price. Survivors of Wilms' tumor are at an increase risk for developing other types of cancer later in life. These secondary malignant neoplasms (SMNs) are one of the most serious of the long-term effects of childhood cancer treatment. Is the successful treatment of Wilms' tumor a pyrrhic victory?
A new study from the National Wilms' Tumor Study Group (NWTSG), published in the August issue of Journal of Clinical Oncology, analyzes more than 5,000 patients registered over a 22-year period. The study was undertaken to determine the incidence of SMNs in Wilms' tumor patients, and how the incidence varied depending on the initial treatment used.
The Good News
"The Wilms' Tumor Study Group report provides parents and oncologists with the ability to review our successes in treating this form of childhood cancer," said Norman E. Breslow, Ph.D., professor of biostatistics, University of Washington (Seattle). "The study also gives us the opportunity to observe, over the long term, the implications of different therapies, and allows physicians and parents to make more informed decisions about appropriate treatment."
Already, results from previous NWTSG reports have led oncologists to limit the use of intensive chemotherapy and radiation therapy, which are now applied only to those patients with the most aggressive disease.
In an editorial accompanying the study Anna T. Meadows, M.D., professor of pediatrics, and director, division of oncology, Children's Hospital of Philadelphia (Philadelphia), raises the possibility that some SMNs may be related to a genetic predisposition in some children to develop cancer.
"One cannot help but wonder whether some patients with Wilms' tumor develop SMNs because they carry a genetic mutation for it, or one that makes them more susceptible to the cancer-causing effects of therapy," said Dr. Meadows. "These cancer-causing mutations could not be revealed, however, until curative therapies for Wilms' tumor were developed, allowing children to survive long enough to be at risk for a second malignancy."
The Bad News
According to Dr. Breslow and his colleagues, the cumulative risk of developing a SMN was 1.6% at 15 years since the Wilms' tumor diagnosis. The risk of developing a leukemia or lymphoma was 0.4% by year 8, after which no further cases occurred. However, the risk of developing a solid tumor continued to increase sharply with time.
The study confirms that radiation therapy does have a cancer-causing (oncogenic) effect in Wilms' tumor patients, as has been demonstrated in studies of other childhood cancers. The oncogenic effect appears to be dose-dependent, that is, the higher the amount of radiation used to treat the patient, the higher the patient's risk of developing a SMN.
The study also provides further evidence that doxorubicin, a drug introduced into NWTSG trials in 1975 and used to treat 40% of patients since, further increases the risk of SMNs. The authors point out that six of nine patients who developed secondary leukemia received doxorubicin, as well as radiation, as part of the initial treatment course. In addition, two of nine patients treated for relapse received doxorubicin, one of whom also received radiation therapy. Thus, eight of nine patients who developed leukemia as a SMN received doxorubicin at some point during treatment for Wilms' tumor, and all but one also received radiation.
Another factor affecting the increased risk of SMNs was treatment following a recurrence. These three factors -- radiation, doxorubicin, and treatment of a relapse -- alone or in combination appear to account for 86% of the SMNs recorded.
The National Wilms' Tumor Study Group
The NWTSG has been in continuous operation since 1969, when a series of randomized trials was designed to achieve two objectives: improve survival in patients with advanced disease, and lessen the toxicity of treatment, especially late-occurring toxicity.
Considerable effort has been expended by the NWTSG in locating and contacting those registered patients who have survived in order to insure unbiased estimates of the different effects related to variations in therapy. Continuing close surveillance of all childhood cancer survivors is essential for the early diagnosis of SMNs and other late consequences of therapy. To that end, approximately 20,000 five-year survivors are being enrolled in the Childhood Cancer Survivor Study, which will assess second cancers and other late sequelae of treatment.
"Continued observation of childhood cancer survivors is good medicine," said Dr. Meadows. "An added benefit to he study of children with cancer, especially those who develop second cancers is that it has provided us with a better understanding of the etiology of cancer generally."
Journal of Clinical Oncology is the leading peer-review journal in the field of medical oncology, and publishes original research on a monthly basis. It is the Official Journal of the American Society of Clinical Oncology, the largest association of cancer researchers and clinicians in the United States and worldwide.
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