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Development of anaplastic changes in low-grade astrocytomas of childhood
1Division of Neurosurgery, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Insights
Radiation therapy for pediatric low-grade astrocytomas may increase the risk of developing anaplastic astrocytomas. This study highlights a potential link between prior radiation treatment and the subsequent development of malignant brain tumors in children.
Area of Science:
- Pediatric neuro-oncology
- Radiation oncology
- Pediatric neuropathology
Background:
- Low-grade astrocytomas are common pediatric brain tumors.
- Treatment often involves surgery and/or radiation therapy.
- Long-term outcomes and secondary malignancies are critical considerations.
Observation:
- Six children developed anaplastic astrocytomas after treatment for low-grade astrocytomas.
- Initial treatments included surgery and radiation therapy (50-52.5 Gy).
- Anaplastic transformation occurred 2-10 years post-initial treatment.
Findings:
- Histopathology revealed anaplastic astrocytoma or glioblastoma multiforme.
- Tumors recurred at primary sites or within the radiation field.
- Four of six children died within 10 months of diagnosis of the anaplastic tumor.
Implications:
- Radiation therapy may play a role in the development of secondary anaplastic astrocytomas in children.
- Further research is needed to understand the mechanisms of radiation-induced oncogenesis.
- This finding has implications for optimizing treatment strategies in pediatric low-grade gliomas.
Abstract:
The authors present their experience with six children who developed anaplastic astrocytomas after receiving treatment for low-grade astrocytomas. Five children were from a series of 55 children with optic chiasmatic-hypothalamic gliomas who have been studied since 1976. The sixth child initially had a low-grade astrocytoma of the thalamus. The mean age of the children at initial presentation was 5.3 years. Five children were treated with surgery and radiation therapy; one child with a chiasmatic-hypothalamic glioma received radiation therapy alone. The amount of external radiation therapy used in all children was 50-52.5 Gy delivered in standard fractionations over approximately 6 weeks to include the volume of the original tumor plus a margin of 2 cm. The time to anaplastic transformation varied between 2 and 10 years (mean, 6.4 years). At tumor recurrence, the children had seizures or symptoms and signs of raised intracranial pressure. The location of the second tumor in all patients was either at the primary site or within the field of radiation therapy. Five of the six children underwent a second craniotomy and subtotal resection of their malignant gliomas. One child had positive cerebrospinal fluid cytology and multiple intraspinal metastatic tumor nodules detected by magnetic resonance imaging. On histopathological examination, four children had anaplastic astrocytoma, and two had glioblastoma multiforme. Four of the six children have died of their anaplastic astrocytomas (mean time from diagnosis of anaplastic astrocytoma to death, 10 months). Two children underwent chemotherapy and spinal irradiation for their anaplastic astrocytomas, and are currently alive and undergoing treatment. The possible mechanisms by which anaplastic tumors have developed in children treated previously for low-grade astrocytomas is discussed. The data suggest that radiation therapy may have played an integral role in the genesis of anaplastic astrocytomas in these children.