Janice R. Takashima

Surgery-related factors and local recurrence of Wilms tumor in National Wilms Tumor Study 4.

OBJECTIVE To assess the prognostic factors for local recurrence in Wilms tumor. SUMMARY BACKGROUND DATA Current therapy for Wilms tumor has evolved through four studies of the National Wilms Tumor Study Group. As adverse prognostic factors were identified, treatment of children with Wilms tumor has been tailored based on these factors. Two-year relapse-free survival of children in the fourth study (NWTS-4) exceeded 91%. Factors once of prognostic import for local recurrence may lose their significance as more effective therapeutic regimens are devised. METHODS Children evaluated were drawn from the records of NWTS-4. A total of 2482 randomized or followed patients were identified. Local recurrence, defined as recurrence in the original tumor bed, retroperitoneum, or within the abdominal cavity or pelvis, occurred in 100 children. Using a nested case-control study design, 182 matched controls were selected. Factors were analyzed for their association with local failure. Relative risks and 95% confidence intervals were calculated, taking into account the matching. RESULTS The largest relative risks for local recurrence were observed in patients with stage III disease, those with unfavorable histology (especially diffuse anaplasia), and those reported to have tumor spillage during surgery. Multiple regression analysis adjusting for the combined effects of histology, lymph node involvement, and age revealed that tumor spillage remained significant. The relative risk of local recurrence from spill was largest in children with stage II disease. The absence of lymph node biopsy was also associated with an increased relative risk of recurrence, which was largest in children with stage I disease. The survival of children after local recurrence is poor, with an average survival rate at 2 years after relapse of 43%. Survival was dependent on initial stage: those who received more therapy before relapse had a worse prognosis. CONCLUSIONS This study has demonstrated that surgical rupture of the tumor must be prevented by the surgeon, because spills produce an increased risk of local relapse. Both local and diffuse spills produce this risk. Stage II children with local spill appear to require more aggressive therapy than that used in NWTS-4. The continued critical importance of lymph node sampling in conjunction with nephrectomy for Wilms tumor is also established. Absence of lymph node biopsy may result in understaging and inadequate treatment of the child and may produce an increased risk of local recurrence.

Early and Late Mortality After Diagnosis of Wilms Tumor

PURPOSE To assess rates and causes of mortality in patients with Wilms tumor (WT). METHODS Through 2002, 6,185 patients enrolled onto the National Wilms Tumor Study between 1969 and 1995 were actively observed. Deaths were classified on the basis of medical records as the result of original disease, late effects (including second malignant neoplasms [SMNs], cardiac causes, pulmonary disease, and renal failure), or other causes. Standardized mortality ratios (SMRs) and Cox regression were used to assess the effects of sex, age, and calendar period of diagnosis on mortality. RESULTS Within 5 years of WT diagnosis, 819 deaths occurred, and 159 deaths occurred among 4,972 known 5-year survivors. The SMR was 24.3 (95% CI, 22.6 to 26.0) for the first 5 years, was 12.6 (95% CI, 10.0 to 15.7) for the next 5 years, and remained greater than 3.0 thereafter. For deaths in the first 5 years, the mortality risk decreased by 5-year calendar period of diagnosis (rate ratio [RR] = 0.78 per period). No such trend occurred for later deaths. Among 5-year survivors, 62 deaths were attributed to late effects of treatment or disease, including 27 to SMNs. A trend of decreased risk with calendar period of diagnosis was observed for late-effects mortality (RR = 0.86; 95% CI, 0.67 to 1.10) and for SMN mortality (RR = 0.82; 95% CI, 0.55 to 1.21). CONCLUSION Although the survival outlook for WT patients has improved greatly over time, survivors remain at elevated risk for death many years after their original diagnosis.

Risk Factors for End Stage Renal Disease in Non-WT1-Syndromic Wilms Tumor

PURPOSE We assessed risk factors for end stage renal disease in patients with Wilms tumor without known WT1 related syndromes. We hypothesized that patients with characteristics suggestive of a WT1 etiology (early onset, stromal predominant histology, intralobar nephrogenic rests) would have a higher risk of end stage renal disease due to chronic renal failure. We predicted a high risk of end stage renal disease due to progressive bilateral Wilms tumor in patients with metachronous bilateral disease. MATERIALS AND METHODS End stage renal disease was ascertained in 100 of 7,950 nonsyndromic patients enrolled in a National Wilms Tumor Study during 1969 to 2002. Risk factors were evaluated with cumulative incidence curves and proportional hazard regressions. RESULTS The cumulative incidence of end stage renal disease due to chronic renal failure 20 years after Wilms tumor diagnosis was 0.7%. For end stage renal disease due to progressive bilateral Wilms tumor the incidence was 4.0% at 3 years after diagnosis in patients with synchronous bilateral Wilms tumor and 19.3% in those with metachronous bilateral Wilms tumor. For end stage renal disease due to chronic renal failure stromal predominant histology had a HR of 6.4 relative to mixed (95% CI 3.4, 11.9; p<0.001), intralobar rests had a HR of 5.9 relative to no rests (95% CI 2.0, 17.3; p=0.001), and Wilms tumor diagnosis at less than 24 months had a HR of 1.7 relative to 24 to 48 months and 2.8 relative to greater than 48 months (p=0.003 for trend). CONCLUSIONS Metachronous bilateral Wilms tumor is associated with high rates of end stage renal disease due to surgery for progressive Wilms tumor. Characteristics associated with a WT1 etiology markedly increased the risk of end stage renal disease due to chronic renal failure despite the low risk in non-WT1 syndromic cases overall.

Pulmonary Disease after Treatment for Wilms Tumor: A Report from the National Wilms Tumor Long-Term Follow-Up Study

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).

Renal failure does not preclude cure in children receiving chemotherapy for Wilms tumor: A report from the National Wilms Tumor Study Group

Children with Wilms tumor can develop renal failure during treatment. Since there are few published data concerning the appropriate chemotherapy for this situation, we reviewed the experience of children who developed renal failure while being treated on National Wilms Tumor Study Group (NWTSG) studies 1–4 (1969–1994).

Pulmonary disease after treatment for wilms tumor

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).

Surgery-Related Factors and Local Recurrence of Wilms Tumor in National Wilms Tumor Study 4

From the *Department of Surgery, Childrens Hospital, Boston, Massachusetts; tDepartment of Biostatistics, University of Washington, Seattle, Washington; tDivision of Pediatric Surgery, University of Texas-Houston Medical School, Houston, Texas; §Department of Pediatric Surgery, Denver Childrens Hospital, Denver, Colorado; JINational Wilms Tumor Study Group Data & Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington; ¶Department of Pathology, Loma Linda University, Loma Linda, California; #Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; and **Department of Pediatrics, Roswell Park Cancer Institute, Buffalo, New York, and the School of Medicine and Biomedical Sciences, University at Buffalo, State University ofNew York, Buffalo, New York