# Late Morbidity and Mortality in Survivors of Childhood Ependymoma: A Report from the Childhood Cancer Survivor Study (CCSS)

## TL;DR

This study finds that long-term health outcomes for childhood ependymoma survivors have not improved despite changes in treatment approaches over time.

## Contribution

The study provides the most comprehensive evaluation of long-term outcomes in ependymoma survivors and highlights the impact of treatment changes on late mortality and morbidity.

## Key findings

- Late mortality rates remained similar across decades despite treatment changes.
- Whole-brain radiation was associated with higher late mortality and chronic health conditions.
- Reduced radiation volumes were linked to lower late mortality and morbidity.

## Abstract

This study provides the most comprehensive evaluation to date of long term outcomes among five year survivors of pediatric ependymoma. Between 1970 and 1999, treatment for pediatric ependymoma evolved to reduce cranial radiation volumes and incorporate chemotherapy for some patients. But, late morbidity and mortality have not improved among pediatric ependymoma survivors despite these treatment changes. Reduced cranial radiation volume was associated with a reduced risk for late mortality and decreased grade 3–4 chronic health conditions. Our findings reveal that rates of late mortality and serious chronic health conditions have not substantially improved over the decades studied though reduced whole-brain radiation exposure is associated with lower late mortality and morbidity, supporting efforts to minimize radiation fields when safe and feasible.

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.