Purpose: It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms (SMNs) of the central nervous system (CNS), a frequently fatal late effect of cancer therapy.
Methods: Five-year survivors of primary childhood cancers diagnosed between 1970-1999 in the Childhood Cancer Survivor Study with a subsequent CNS SMN were identified. Cumulative incidence rates and standardized incidence ratios (SIR) 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 SMN.
Results: 157 CNS SMNs (1970s, 52; 1980s, 63; 1990s, 42) were identified, excluding meningiomas, which were most often malignant gliomas. The proportion of survivors receiving any cranial radiotherapy (CRT) exposure was reduced over time (1970s 77.0%, 1980s 54.3%, 1990s 33.9%), while the proportion receiving >35Gy CRT showed a smaller reduction (11.4%, 10.8%, and 8.5%, respectively). Twenty-year cumulative incidence (95% CI) and SIR (95% CI) for CNS SMN by treatment decade were 0.32% (0.18-0.46%) and 6.6 (5.0-8.7); 0.55% (0.41-0.70%) and 8.3 (6.6-10.4); and 0.43% (0.31-0.55%) and 9.2 (7.0-12.0), respectively, with no statistically significant decreases between eras. Multivariable analyses showed increased risk for CRT dose levels >10Gy and for primary diagnoses of medulloblastoma/PNET (HR 18.7, 9.2-37.9) and astrocytoma (HR 10.1, 5.3-19.5). Three-year cumulative incidence of death after CNS SMN, by treatment decade, were 76%, 74%, and 73%, respectively.
Conclusion: CNS SMN incidence has not decreased despite fewer survivors exposed to CNS-directed radiotherapy. CNS SMNs remain a substantial source of mortality for affected patients.
© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected].