• N E Breslow, J R Takashima, J A Whitton, J Moksness, G J D'Angio, and D M Green.
• Department of Biostatistics, University of Washington, Fred Hutchinson Cancer Research Center, Seattle 98195-7232, USA.
• J. Clin. Oncol. 1995 Aug 1; 13 (8): 1851-9.

PurposeThe study was undertaken to determine the incidence of second malignant neoplasms (SMNs) in patients treated for Wilms' tumor and demonstrate how the incidence varied with the initial treatment protocol.Patients And MethodsBetween October 1969 and December 1991, 5,278 assessable patients were enrolled onto the National Wilms' Tumor Study (NWTS) and by the end of 1993 had contributed 39,461 person-years to a follow-up study. Expected numbers of second cancers were calculated by applying national incidence rates to person-years classified by age, sex, and calendar year.ResultsForty-three SMNs were observed, whereas only 5.1 were expected (standardized incidence ratio [SIR], 8.4; 95% confidence interval [CI], 6.1 to 11.4). Fifteen years after the Wilms' tumor diagnosis, the cumulative incidence of a SMN was 1.6% and increasing steadily. Abdominal irradiation received as part of the initial therapy increased the risk of a SMN (SIR, 1.43/10 Gy; 95% CI, 1.13 to 1.81). Doxorubicin potentiated the radiation effect. Among 234 patients who received doxorubicin and greater than 35 Gy of abdominal radiation, eight SMNs were observed, whereas only 0.22 were expected (SIR, 36; 95% CI, 16 to 72). Treatment for relapse further increased the SMN risk by a factor of 4 to 5.ConclusionThese results demonstrate the importance of current efforts to limit the use of intensive chemotherapy and radiation therapy, which are now applied only to patients with the most aggressive disease. Continuing close surveillance of the great majority of Wilms' tumor patients who become long-term survivors is essential for early diagnosis of SMNs and other late sequelae of therapy.

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