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.