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Background: The standard treatment of pulmonary metastases in patients with Wilms tumor (WT) includes 12-gray radiotherapy (RT) to the entire chest. To the authors' knowledge, the risk of breast cancer (BC) in a large cohort of female survivors of WT has not previously been reported., Methods: A total of 2492 female participants in National Wilms Tumor Studies 1 through 4 (1969-1995) were followed from age 15 years through the middle of 2013 for incident BC. The median age at the time of last contact was 27.3 years. The authors calculated cumulative risk at age 40 years (CR40), hazard ratios (HR) by Cox regression, standardized incidence ratios (SIRs) relative to US population rates, and 95% confidence intervals (95% CIs)., Results: The numbers of survivors with invasive BC divided by the numbers at risk were 16 of 369 (CR40, 14.8% [95% CI, 8.7-24.5]) for women who received chest RT for metastatic WT, 10 of 894 (CR40, 3.1% [95% CI, 1.3-7.41]) for those who received only abdominal RT, and 2 of 1229 (CR40, 0.3% [95% CI, 0.0-2.3]) for those who received no RT. The SIRs for these 3 groups were 27.6 (95% CI, 16.1-44.2) based on 5010 person-years (PY) of follow-up, 6.0 (95% CI, 2.9-11.0) based on 13,185 PY of follow-up, and 2.2 (95% CI, 0.3-7.8) based on 13,560 PY of follow-up, respectively. The risk was high regardless of the use of chest RT among women diagnosed with WT at age ≥10 years, with 9 of 90 women developing BC (CR40, 13.5% [95% CI, 5.6-30.6]; SIR, 23.6 [95% CI, 10.8-44.8] [PY, 1463])., Conclusions: Female survivors of WT who were treated with chest RT had a high risk of developing early BC, with nearly 15% developing invasive disease by age 40 years. Current guidelines that recommend screening only those survivors who received ≥20 Gy of RT to the chest might be reevaluated., (© 2014 American Cancer Society.)

Purpose: This study was undertaken to evaluate the incidence of pulmonary disease among patients treated with radiation therapy (RT) for pulmonary metastases (PM) from Wilms tumor (WT)., Patients and Methods: We reviewed records of 6,449 patients treated on National Wilms Tumor Studies-1, -2, -3, and -4 whose flow sheets or annual status reports documented one of several pulmonary conditions. Cases were fully evaluable if pulmonary function test (PFT) results were available, pulmonary fibrosis was identified on a chest radiograph or was listed as the primary or a contributing factor to death. Partially evaluable cases were those for whom PFT results could not be obtained. We evaluated the relationship between RT factors and the occurrence of pulmonary disease using hazard ratios (HRs) and cumulative incidence, treating death as a competing risk., Results: Sixty-four fully evaluable and 16 partially evaluable cases of pulmonary disease were identified. The cumulative incidence of pulmonary disease at 15 years since WT diagnosis was 4.0% (95% confidence interval [CI] 2.6-5.4%) among fully evaluable and 4.8% (95% CI 3.3-6.4%) among fully and partially evaluable patients who received lung RT for PM at initial diagnosis. Rates of pulmonary disease were substantially higher among those who received lung RT for PM present at initial diagnosis or relapse compared to those who received no RT or only abdominal RT (HR 30.2, 95% CI 16.9-53.9)., Conclusion: The risk of pulmonary disease must be considered in evaluating the risk:benefit ratio of lung RT for the management of PM from WT., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Metastatic lung disease in Wilms tumor (WT) patients was traditionally identified by chest radiograph (CXR). It is unclear whether patients with small lesions, detectable only by computed tomography ("CT-only" lesions), require the more intensive therapy, including doxorubicin and lung irradiation, given to patients with metastases detectable by CXR., Procedures: This study involved 417 patients with favorable histology WT and isolated lung metastases (detected by CXR or CT) who were registered on National Wilms tumor Study (NWTS)-4 or -5. Outcomes by method of detection (CXR vs. CT-only), use of lung radiation, and 2- or 3-drug chemotherapy (dactinomycin and vincristine ± doxorubicin) were determined and compared using the log-rank test., Results: There were 231 patients with lung lesions detected by CXR and 186 by CT-only. Of the patients with CT-only nodules, 37 received only 2 drugs and 101 did not receive lung radiation. Five-year event-free survival (EFS) was greater for patients receiving three drugs (including doxorubicin) with or without lung radiation than for those receiving two drugs (80% vs. 56%; P = 0.004). There was no difference seen in 5-year overall survival (OS) between the 3- and 2-drug subsets (87% vs. 86%; P = 0.91). There were no significant differences in EFS (82% vs. 72%; P = 0.13) or OS (91% vs. 83%; P = 0.46) for patients with CT-only nodules whether they received lung radiation or not., Conclusions: Our results suggest that patients with CT-only lung lesions may have improved EFS but not OS from the addition of doxorubicin but do not appear to benefit from pulmonary radiation., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: To define the optimal treatment for children with Wilms tumor who have pulmonary nodules identified on chest computed tomography (CT) scan, but have a negative chest radiograph, we evaluated the outcome of all such patients randomized or followed on National Wilms Tumor Study (NWTS)-3 and -4., Patients and Methods: We estimated the event-free and overall survival percentages of 53 patients with favorable histology tumors and pulmonary densities identified only by CT scan (CT-only) who were treated as Stage IV with intensive doxorubicin-containing chemotherapy and whole-lung irradiation, and compared these to the event-free and overall survival percentages of 37 CT-only patients who were treated less aggressively based on the extent of locoregional disease with 2 or 3 drugs, and without whole-lung irradiation., Results: The 4-year event-free and overall survival percentages of the 53 patients with CT-only nodules and favorable histology Wilms tumor who were treated as Stage IV were 89% and 91%, respectively. The 4-year event-free and overall survival percentages for the 37 patients with CT-only nodules and favorable histology who were treated according to the extent of locoregional disease were 80% and 85%, respectively. The differences observed between the 2 groups were not statistically significant. Among the patients who received whole-lung irradiation, there were fewer pulmonary relapses, but more deaths attributable to lung toxicity., Conclusions: The current data raise the possibility that children with Wilms tumor and CT-only pulmonary nodules who receive whole lung irradiation have fewer pulmonary relapses, but a greater number of deaths due to treatment toxicity. The role of whole lung irradiation in the treatment of this group of patients cannot be definitively determined based on the present data. Prolonged follow-up of this group of patients is necessary to accurately estimate the frequency of late, treatment-related mortality.

To determine the effect of surgical excision of pulmonary metastases from Wilms' tumor on postrelapse survival, we retrospectively analyzed the clinical courses of 211 patients with stages I to III, favorable or unfavorable histology Wilms' tumor entered on National Wilms' Tumor Study-1, -2, or -3 whose first recurrence was limited to the lungs. There was no difference in the 4-year postrelapse survival percentage of favorable-histology patients with a solitary pulmonary metastasis who did or did not undergo surgical removal of the metastasis in addition to pulmonary irradiation and chemotherapy. Although histological confirmation of pulmonary relapse is frequently indicated, the present data suggest that therapeutic removal of pulmonary metastases from patients with relapsed Wilms' tumor does not increase the percentage of patients who survive for 4 years postrelapse, compared with treatment with whole-lung irradiation and chemotherapy.

Comparisons were made between 236 Wilms' tumor patients with metastasis to the lungs and/or liver at initial diagnosis who were registered on the National Wilms' Tumor Study (NWTS) during 1969 to 1983, and 1755 patients who did not have overt metastases at diagnosis. Patients with evidence of regional spread of disease beyond the kidney, especially if to the renal vein or lymph nodes, were much more likely to have overt metastases present at diagnosis than those with apparently localized disease. The presence of metastases was also correlated with age at diagnosis, ranging from 1% among infants younger than 1 year of age to 24% for those aged 6 years or older. The percentage of tumor deaths for patients with metastases at diagnosis (Stage IV) and a primary tumor of favorable histology (FH) declined from 29% at 2 years postdiagnosis on the first therapeutic trial (NWTS-1) to 9% for the most recent one (NWTS-3), and is now comparable to that for patients without metastases but with nonresectable local invasion at diagnosis (Stage III). The local extent of disease also influenced the survival outcome for Stage IV/FH patients. Survival was poor for those with anaplastic or sarcomatous (unfavorable) histology, regardless of local staging or trial. There was no difference in survival according to metastatic site (liver +/- lung vs. lung only) if present prior to treatment. By contrast, patients who developed liver metastases during or after treatment had an especially poor chance for survival as compared with those who developed lung deposits at those times.