1010 - Incidence of Secondary Neoplasms among Long-Term Survivors of Pediatric Brain Tumors following Radiation Therapy: Reference Data from a Single Clinical Practice Covering Diverse Diagnostic and Treatment Categories
Presenter(s)
T. E. Merchant, J. E. Martin-Boggs, J. C. Chiang, S. Wu, and Y. Li; St. Jude Children's Research Hospital, Memphis, TN
Purpose/Objective(s): To estimate the 20-year cumulative incidence of secondary neoplasms, including leukemia, among children with brain tumors treated with radiotherapy, and to evaluate clinical and treatment-related factors associated with secondary tumor development and their impact on long-term survival.
Materials/Methods: 608 pediatric patients with brain tumors representing five distinct primary tumor types and diverse treatment scenarios were evaluated for the development of secondary neoplasms. Attribution of radiotherapy to secondary tumor formation was determined through imaging registration when applicable; diagnoses were histologically confirmed when possible or, inferred based on imaging characteristics and clinical course, including fatal outcomes. More than 90% of survivors were contacted within 12 months of the analysis. Cumulative incidence rates were calculated accounting for the competing risk of first tumor progression in children with ependymoma and germinoma, and without competing risk for the other diagnostic groups and treatment scenarios.
Results: Table 1 summarizes follow-up data and the estimated 20-year cumulative incidence of radiation-induced leukemia, meningioma, and other malignant neoplasms across multiple diagnoses and treatment contexts. These include craniopharyngioma; germinoma treated with craniospinal or focal radiotherapy and chemotherapy; ependymoma in children younger than 3 years of age; ependymoma treated with a second course of radiotherapy; low-grade glioma (with or without NF1); and medulloblastoma treated with photon craniospinal irradiation and chemotherapy.
The 20-year cumulative incidence of death attributable to second primary tumors was 7.58% for germinoma, 4.15% for craniopharyngioma, 6.34% for ependymoma in children younger than 3 years, 10.99% for ependymoma treated with reirradiation, 4.84% for low-grade glioma without NF1, 32.12% for low-grade glioma with NF1, and 7.78% for medulloblastoma.
Conclusion: These findings provide benchmark estimates for the risk of secondary tumor development. Understanding the incidence and latency of secondary neoplasms in children with brain tumors treated with radiotherapy is essential for informed consent, for developing strategies to reduce long-term treatment-related risks, and for comparing historical and contemporary approaches that aim to reduce radiation dose and treatment volumes or incorporate newer therapeutic modalities.
| Table 1: 20-year cumulative incidence | N | Modality | Follow-up Median Years | Leukemia % (SE) | Meningioma % (SE) | Malignant Neoplasms % (SE) |
| Craniopharyngioma | 101 | XRT | 18.9 | - | 2.6 (1.8) | 5.1 (2.2) |
| Germinoma | 78 | XRT?PBT | 9.0 | 1.4 (1.4) | 1.4 (1.4) | 6.0 (4.4) |
| Ependymoma Age < 3 years | 101 | XRT | 22.6 | - | 3.7 (2.1) | 4.2 (2.1) |
| Ependymoma Reirradiation | 150 | XRT?PBT | 7.6 | 1.5 (1.0) | 7.4 (3.6) | 7.6 (3.2) |
| Low-grade Glioma NF1- | 83 | XRT | 24.7 | - | 4.9 (2.8) | 6.8 (3.0) |
| Low-grade Glioma NF1+ | 15 | XRT | 22.4 | - | - | 37.4 (14.3) |
| Medulloblastoma | 80 | XRT | 24.0 | 2.5 (1.8) | 9.1 (3.6) | 5.1 (2.5) |