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 5 0.003). These trends may reflect the decreasing use of radiation therapy and increasing intensity of chemotherapy in modern protocols for treatment of WT.Wilms tumor (WT) is an embryonal tumor of the kidney that affects approximately 1 child in every 10,000 before the age of 15 years in Europe and North America.1 During the 20th century, with the development first of curative radiation therapy (RT) techniques and then of effective chemotherapy regimens, WT case fatality rates declined from 90 to 10%. 2The increasing numbers of survivors of WT and other childhood cancers, however, have substantial risk of developing adverse medical conditions related to treatment of their disease.3 One of the most serious late consequences of treatment

Second malignancies after childhood noncentral nervous system solid cancer: Results from 13 cancer registries

“…This finding may reflect the different cancerogenic mechanisms that lead to solid tumors or leukemia, following radiotherapy and chemotherapy, respectively. 11 In our study, we observed an increased risk of digestive organs, bones and thyroid cancer but also brain cancer, and we did not observe an increased leukemia risk. Given the high incidence of secondary brain cancer, and because we could not distinguish between different types of renal tumors, we checked the latency between the renal and the secondary brain tumors to investigate the possibility of rhabdoid tumors' brain metastases.…”

“…30 A recent study that combined three cohorts of children with Wilms tumor for a total of 13,351 subjects followed for a median time of 11.6 years, observed the occurrence of 174 solid tumors, among which the most frequent were tumors of digestive organs, bones, breast, thyroid and 28 leukemias. 11 This study partially overlaps with ours, because one of the three cohorts consisted of 1,574 cases recorded in the cancer registries of Norway, Denmark, Iceland, Sweden and Finland from 1960 up to 2004. The study found that for solid tumors, the risk increased with age and time since Wilms' tumor diagnosis but decreased with calendar period of diagnosis.…”

“…The registries contributed data for different time periods in the years 1943 to 2000, with a median observation period of 32 years. This dataset partially overlaps with the populations included in previous studies from the Nordic countries 9,11,13 and Slovenia.…”

“…24 On the other hand, chemotherapy regimens have, in some instances, become more intensive, such as in limb-sparing surgery in the treatment of osteosarcoma. 44 In a recent large study on second cancers after Wilms' tumors, 11 the authors have also pointed out that if the risk of subsequent solid tumors has started to decrease, this is not so for secondary leukemia, likely associated with chemotherapy, which appears to keep rising, and that SIRs for solid tumors remain high even after they have started to decline 10 to 19 years after the childhood cancer and do not exhibit a definite downward trend.…”

“…On the other hand, information on the longterm risk of second malignancies after the rarest types of childhood cancer is more limited because large groups of patients have to be followed up for more than three or four decades. 3,4,9,11 We have estimated the risk of second malignancies after childhood NCNSSC by taking advantage of a unique source of data consisting of a large cohort of survivors from 13 population-based registries located in Europe, North America, Asia and Oceania. The aim of our study is to investigate the magnitude of risk and type of second cancer in relation to the type of childhood NCNSSC, calendar period of NCNSSC diagnosis and time elapsed since NCNSSC diagnosis.…”