Late Morbidity and Mortality in Survivors of Childhood Ependymoma: A Report from the Childhood Cancer Survivor Study (CCSS).
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BACKGROUND/OBJECTIVES: Treatment of childhood ependymoma evolved from 1970 to 1999 by reducing radiation volumes and incorporating chemotherapy. The impact of these changes on long-term health outcomes remains unknown. In this report, we evaluated temporal changes in all-cause and cause-specific late mortality, chronic health conditions (CHCs), and subsequent neoplasms (SNs) in the Childhood Cancer Survivor Study (CCSS) cohort of adult survivors of pediatric ependymoma, diagnosed between 1970 and 1999. METHODS: A total of 404 five-year survivors of ependymoma (47.5% female, 80.7% non-Hispanic White, median 6 (range 0-20) years at diagnosis, 22 (5-49) years from diagnosis) diagnosed between 1970 and 1999 and enrolled in the Childhood Cancer Survivor Study were evaluated for late (>5 years from diagnosis) mortality, SNs, and CHCs. Outcomes were analyzed by diagnosis decade, radiotherapy, and chemotherapy exposure. Gray's test compared cumulative incidences. Multivariable piecewise exponential models estimated relative risks (RRs). RESULTS: Whole-brain radiation exposure decreased over time (42.9% (1970s) to 2.7% (1990s)), while focal radiation (21.4% to 68.9%), and chemotherapy (29.5% to 50.2%) use increased. Fifteen-year all-cause late mortality (incidence, 95% CI) remained similar across decades: 1970s (9.3%, 3.4-18.8%), 1980s (14.7%, 9.4-21.2%), 1990s (10.3%, 6.7-14.9%). All-cause late mortality was higher after treatment with whole-brain radiation (22.5%, 11.2-36.5%) compared to focal radiation (11.4%, 7.5-16.1%) or no brain radiation (3.5%, 0.9-9.1%) (p < 0.001), and with chemotherapy (14.4%, 9.6-20.0%) versus without (6.8%, 3.8-11.0%) (p = 0.004). Compared to no brain radiation, the RR (95% CI) of grade 3-4 CHCs increased among survivors treated with focal (2.6, 1.3-5.4) and whole-brain radiation (3.5, 1.5-8.1), while chemotherapy was not associated with CHCs or SNs. CONCLUSIONS: Despite reduced radiation volumes and increased use of chemotherapy, late mortality and morbidity among pediatric ependymoma survivors remained largely unchanged across treatment decades.