Evaluation of Late Adverse Events in Long-Term Wilms' Tumor Survivors

Purpose To evaluate the prevalence and severity of adverse events (AEs) and treatment-related risk factors in long-term Wilms' tumor (WT) survivors, with special attention to radiotherapy. Methods and Materials The single-center study cohort consisted of 185 WT survivors treated between 1966 and 1996, who survived at least 5 years after diagnosis. All survivors were invited to a late-effects clinic for medical assessment of AEs. AEs were graded for severity in a standardized manner. Detailed radiotherapy data enabled us to calculate the equivalent dose in 2 Gy fractions (EQD2 ) to compare radiation doses in a uniform way. Risk factors were evaluated with multivariate logistic regression analysis. Results Medical follow-up was complete for 98% of survivors (median follow-up, 18.9 years; median attained age, 22.9 years); 123 survivors had 462 AEs, of which 392 had Grade 1 or 2 events. Radiotherapy to flank/abdomen increased the risk of any AE (OR, 1.08 Gy−1 [CI, 1.04–1.13]). Furthermore, radiotherapy to flank/abdomen was associated with orthopedic events (OR, 1.09 Gy−1 [CI, 1.05–1.13]) and second tumors (OR, 1.11 Gy−1 [CI, 1.03–1.19]). Chest irradiation increased the risk of pulmonary events (OR, 1.14 Gy−1 [CI, 1.06–1.21]). Both flank/abdominal and chest irradiation were associated with cardiovascular events (OR, 1.05 Gy−1 [CI, 1.00–1.10], OR, 1.06 Gy−1 [CI, 1.01–1.12]) and tissue hypoplasia (OR, 1.17 Gy−1 [CI, 1.10–1.24], OR 1.10 Gy−1 [CI, 1.03–1.18]). Conclusion The majority of AEs, overall as well as in irradiated survivors, were mild to moderate. Nevertheless, the large amount of AEs emphasizes the importance of follow-up programs for WT survivors.