Secondary malignant neoplasms after Wilms tumor: an international collaborative study

Abstract

A combined cohort of 8,884 North American, 2,893 British and 1,574 Nordic subjects with Wilms tumor (WT) diagnosed before 15 years of age during 1960-2004 was established to determine the risk of secondary malignant neoplasms (SMN). After 169,641 person-years (PY) of observation through 2005, 174 solid tumors (exclusive of basal cell carcinomas) and 28 leukemias were ascertained in 195 subjects. Median survival time after a solid SMN diagnosis 5 years or more from WT was 11 years; it was 10 months for all leukemia. Age-specific incidence of secondary solid tumors increased from approximately 1 case per 1,000 PY at age 15 to 5 cases per 1,000 PY at age 40. The cumulative incidence of solid tumors at age 40 for subjects who survived free of SMNs to age 15 was 6.7%. Leukemia risk, by contrast, was highest during the first 5 years after WT diagnosis. Standardized incidence ratios (SIRs) for solid tumors and leukemias were 5.1 and 5.0, respectively. Results for solid tumors for the 3 geographic areas were remarkably consistent; statistical tests for differences in incidence rates and SIRs were all negative. Age-specific incidence rates and SIRs for solid tumors were lower for patients whose WT was diagnosed after 1980, although the trends with decade of diagnosis were not statistically significant. Incidence rates and SIRs for leukemia were highest among those diagnosed after 1990 (p-trend = 0.003). These trends may reflect the decreasing use of radiation therapy and increasing intensity of chemotherapy in modern protocols for treatment of WT.

Figure 1

Incidence of solid tumors by time since WT diagnosis and cohort, calculated as weighted averages of jumps in cumulative hazards using 5 year bandwidths around each time point. Results for North America were truncated at 30 years due to limited follow-up thereafter.

Figure 2

Incidence of solid tumors (panel a, per 1,000 person-years) and leukemia (panel b, per 10,000 person-years) by time since WT diagnosis, calculated using 5 year bandwidths.

Figure 3

Incidence of solid tumors by time since WT diagnosis and decade of WT diagnosis, calculated using 5 and 10 year (for 1960–69) bandwidths and truncated at 10 year intervals depending on decade of diagnosis.