Paulino has thoughtfully reviewed the etiology, diagnosis, and management of Wilms' tumor. Investigators from the National Wilms' Tumor Study Group (NWTSG) first divided Wilms' tumors into two groups: those with a favorable histology and those with an unfavorable histology.
The unfavorable histology group included those Wilms' tumors with focal or diffuse anaplasia and two histologic patterns now recognized to be entities distinct from Wilms' tumor--clear cell sarcoma of the kidney and rhabdoid tumor of the kidney. These two non-Wilms' tumors are associated with central nervous system metastases and second primary tumors that originate within the central nervous system.[4,5] Thus, imaging of the central nervous system must be included in the pretreatment staging of these two subgroups of patients.
In addition to the studies cited by Paulino, investigators from the Emma Kinderzuikenhuis in Amsterdam, using criteria identical to those employed in the report from St. Jude Children's Research Hospital, reported that only 8.8% (7/79) of children who received preoperative combination chemotherapy achieved tumor shrinkage sufficient to make them candidates for partial rather than total nephrectomy. Thus, there is no compelling evidence that neoadjuvant chemotherapy will result in less radical surgery in a significant number of patients.
The Dana-Farber Pilot Study
The pilot study conducted at the Dana-Farber Cancer Institute was based on the results of treatment at The Childrens Hospital, Boston from 1929 through 1977. It was there that a favorable outcome for infants treated with surgery alone was first noted. Subsequent analyses of data from the NWTSG demonstrated that intensive chemotherapy regimens did not improve the prognosis for infants younger than 24 months with stage I, favorable histology Wilms' tumors that weighed less than 550 grams. These children with stage I, favorable histology Wilms' tumors also tended to have favorable prognostic variables, as defined by Weeks et al.
The radiation therapy doses required for children with clear cell sarcoma of the kidney and Wilms' tumor with anaplasia have been modified, based on the data referenced by Paulino. Thus, in NWTS 5, the age-adjusted doses are not employed for the treatment of these two groups of children. All children receive a nominal abdominal radiation therapy dose of 1,050 cGy.
Paulino reviews the chemotherapeutic management of Wilms' tumor as recommended by NWTS 1, 2, and 3. In regard to standard (daily, divided dose) vs "pulse-intensive" (intermittent single dose) schedules for dactinomycin(Drug information on dactinomycin) and doxorubicin(Drug information on doxorubicin), NWTS 4  showed no statistically significant difference in relapse-free or overall survival between the two regimens. Hematologic toxicity was less severe and the dose intensity was greater for those treated using the pulse-intensive schedule. Thus, the pulse-intensive regimen is now recommended as standard treatment.
In addition to the skeletal sequelae discussed by Paulino, two other important long-term complications of treatment are second primary tumors  and cardiac toxicity related to treatment with doxorubicin. The cumulative percentage of children treated with doxorubicin for Wilms' tumor on NWTS 2 and 3 who developed congestive heart failure was 1.7% at 15 years after diagnosis. The onset was 1.3 to 11.7 years after diagnosis of Wilms' tumor, with half of the eight cases occurring 8.8 to 11.7 years after diagnosis. The percentage increased to 5.4% of those whose treatment included whole-lung irradiation, compared to 1.0% of those whose treatment did not. Both prior treatment with radiation and prior treatment with doxorubicin increased the relative risk of developing a second malignant tumor.