Late health outcomes in survivors of Wilms tumor: A report from the St. Jude Lifetime (SJLIFE) cohort study.

Abstract

10038 Background: We aimed to characterize late health, neurocognitive, and physical performance outcomes among survivors of Wilms tumor. Methods: Wilms tumor survivors (n = 280), ≥ 5 years from diagnosis, participating in SJLIFE were clinically assessed along with a community control sample (n = 625). Health outcomes were graded per a modified Common Terminology Criteria for Adverse Events (grade 1 [mild] to grade 4 [life threatening]). Standardized neurocognitive testing was graded using age-adjusted z-scores. Aerobic function (six-minute walk), mobility (timed up and go) and flexibility (sit and reach) were assessed. Associations between treatment exposures and prevalent conditions were examined by multivariable logistic regression, adjusted for current age, sex and race. Results: Survivors (59% female, 73% white), median age 3 years (range 0-15) at diagnosis and 31 years (9-58) at evaluation, were comprehensively evaluated on the St. Jude campus. Two-thirds (67%) were treated with doxorubicin (median dose 175 mg/m2 range 52-490), 167 (60%) received abdominal radiation (median dose 12 Gy range 8.8-61.2) and 25% received chest radiation (12 Gy range 9-44). By age 40 years, survivors averaged 12.7 (95% confidence interval [CI] 11.7-13.8) grade 1-4 and 7.5 (CI 6.7-8.2) grade 2-4 conditions, compared to 4.2 (CI 3.9-4.6) and 2.3 (CI 2.1-2.5), respectively, among controls. The most prevalent medical conditions (grade ≥ 2) are reported in the table. Abnormal glucose metabolism was associated with abdominal radiation (relative risk [RR] 5.1 CI 1.4-19.0); restrictive pulmonary defects with chest radiation (RR 24.0 CI 3.2-180); and cardiomyopathy (RR 15.6 CI 1.9-128), pulmonary diffusion (RR 4.5 CI 1.3-15.1), and chronic kidney disease (RR 4.5 CI 1.3-16.1) with doxorubicin exposure. Survivors had a three-fold higher risk (standardized incidence ratio 3.5, CI 2.2-6.6) for subsequent neoplasms. Impairments (grade ≥ 2) in executive function (20% vs. 12%), attention (17% vs. 9%), memory (21% vs. 10%), and processing speed (20% vs. 8%) were more frequent in survivors than controls (p < 0.05). Impairments in aerobic function (13.6%), mobility (13.6%), and flexibility (11.1%) were higher than expected (p < 0.01). Significant associations were not identified between treatment exposures and neurocognitive or physical performance outcomes. Conclusions: Systematic clinical assessment identified a significant burden of chronic health conditions and previously unrecognized neurocognitive and physical performance limitations in survivors of Wilms tumor.[Table: see text]