Temporal Trends of Subsequent Central Nervous System Malignancies Among Survivors of Childhood Cancer

Authors

Robert T Galvin
Yan Chen
Yan Yuan
Tabitha Cooney
Rebecca Howell
Susan Smith
Michael A Arnold
Miriam Conces
Wendy Leisenring
Gregory T Armstrong
Joseph P Neglia
Lucie M Turcotte

Language

English

Publication Date

5-1-2025

Journal

Journal of the National Cancer Institute

DOI

10.1093/jnci/djaf005

PMID

39792043

PMCID

PMC12058266

PubMedCentral® Posted Date

1-10-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background: It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms of the central nervous system (CNS), a frequently fatal late effect of cancer therapy.

Methods: Five-year survivors of primary childhood cancers diagnosed between 1970 and 1999 in the Childhood Cancer Survivor Study with CNS subsequent malignant neoplasms were identified. Cumulative incidence rates and standardized incidence ratios were compared among survivors diagnosed between 1970-1979 (n = 6223), 1980-1989 (n = 9680), and 1990-1999 (n = 8999). Multivariable models assessed risk factors for CNS subsequent malignant neoplasms.

Results: A total of 157 CNS subsequent malignant neoplasms (1970s, 52; 1980s, 63; 1990s, 42) were identified, excluding meningiomas, which were most often malignant gliomas. The proportion of survivors receiving any cranial radiotherapy exposure was reduced over time (1970s, 77.0%; 1980s, 54.3%; 1990s, 33.9%), while the proportion receiving more than 35 Gy cranial radiotherapy showed a smaller reduction (11.4%, 10.8%, and 8.5%, respectively). Twenty-year cumulative incidence and standardized incidence ratios for CNS subsequent malignant neoplasms by treatment decade were 0.32% (95% confidence interval = 0.18% to 0.46%) and 6.6 (95% CI = 5.0 to 8.7); 0.55% (95% CI = 0.41% to 0.70%) and 8.3 (95% CI = 6.6 to 10.4); and 0.43% (95% CI = 0.31% to 0.55%) and 9.2 (95% CI = 7.0 to 12.0), respectively, with no statistically significant decreases between eras. Multivariable analyses showed increased risk for cranial radiotherapy dose levels more than 10 Gy and for primary diagnoses of medulloblastoma and/or primitive neuro-ectodermal tumor (hazard ratio [HR] = 18.7, 95% CI = 9.2 to 37.9) and astrocytoma (HR = 10.1, 95% CI = 5.3 to 19.5). Three-year cumulative incidence of death after CNS subsequent malignant neoplasms, by treatment decade, were 76%, 74%, and 73%, respectively.

Conclusion: CNS subsequent malignant neoplasm incidence has not decreased despite fewer survivors exposed to CNS-directed radiotherapy. CNS subsequent malignant neoplasm remains a substantial source of mortality for affected patients.

Keywords

Humans, Incidence, Female, Central Nervous System Neoplasms, Male, Child, Adolescent, Child, Preschool, Risk Factors, Neoplasms, Second Primary, Adult, Cranial Irradiation, Infant, Young Adult, United States, Survivors, Time Factors, Cancer Survivors, Neoplasms

Published Open-Access

yes

Recommended Citation

Galvin, Robert T; Chen, Yan; Yuan, Yan; et al., "Temporal Trends of Subsequent Central Nervous System Malignancies Among Survivors of Childhood Cancer" (2025). Faculty, Staff and Student Publications. 5859.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5859