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

Authors

Katharine R Lange
Peter de Blank
Mengqi Xing
Sedigheh Mirzaei
Deo Kumar Srivastava
Kevin Oeffinger
Joseph Neglia
Kevin Krull
Paul C Nathan
Rebecca Howell
Kirsten K Ness
Lucie M Turcotte
Wendy Leisenring
Gregory T Armstrong
Tara Brinkman
Daniel C Bowers
Mehmet Fatih Okcu

Language

English

Publication Date

11-15-2025

Journal

Cancers

DOI

10.3390/cancers17223669

PMID

41301035

PMCID

PMC12650955

PubMedCentral® Posted Date

11-15-2025

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Keywords

late morbidity and mortality, pediatric ependymoma, radiation and chemotherapy

Published Open-Access

yes

Recommended Citation

Lange, Katharine R; de Blank, Peter; Xing, Mengqi; et al., "Late Morbidity and Mortality in Survivors of Childhood Ependymoma: A Report from the Childhood Cancer Survivor Study (CCSS)" (2025). Faculty, Staff and Student Publications. 5860.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5860