Cerebral Radiation Necrosis in Pediatric Patients

Abstract

Radiation necrosis is a well-described toxicity following radiation therapy in the brain. There is little data regarding the incidence of radiation necrosis in pediatric patients. We retrospectively reviewed our experience with 101 children with solid brain tumors. Radiation necrosis was diagnosed by examination of magnetic resonance imaging. Median follow-up for all patients was 13 months (range 3-51). Radiation necrosis occurred in 5% (5/101) of cases with a median time to onset of 1.2 months. In three of these children, the child was symptomatic, requiring management with steroids and bevacizumab. Radiation necrosis did not correlate with the administration of chemotherapy, age at treatment, or planning treatment volume. Our experience with pediatric patients treated with radiotherapy for solid brain tumor suggests that children may have an increased likelihood to develop radiation necrosis compared to adults.

Radiation Necrosis in Pediatric Patients with Brain Tumors Treated with Proton Radiotherapy

“…In 1 study of 101 children treated with photon radiation therapy, 5% of patients developed radiation necrosis based on clinicoradiologic follow-up. 2 In another study of 49 patients with malignant brain tumors treated with photon radiation therapy, high-dose thiotepa, and autologous stem cell rescue, 37% of patients developed posttreatment abnormal brain imaging findings, which were defined broadly to include contrast-enhancing lesions, T2-weighted or FLAIR hyperintense lesions, hemorrhage, or subdural fluid, though the percentage of radiation necrosis was not reported. 3 In our series, 31% of patients developed radiation necrosis based on imaging, indicating a trend toward a higher incidence of necrosis with PBT compared with the incidence reported for photon radiation therapy, which was similar to the high percentage in a series of 17 patients treated with PBT, of whom 47% developed an imaging diagnosis of radiation necrosis.…”

“…This compares with radiation necrosis described at a median of 1.2 months (range, 0.5-8.0 months) and 8 months (range, 2-39 months) in 2 large series of patients with pediatric brain tumors treated with photon radiation therapy and a median time of 3.9 months in a smaller series of patients treated with PBT. 2,3 It remains uncertain which factors in patients with pediatric brain tumor account for the difference in time to development of radiation necrosis compared with adult patients, which is more typical at or greater than 12 months. 1,24 Based on the proposed pathogenesis of radiation necrosis, there may be differences in the vascular endothelium, progenitor cells, oligodendrocytes, microglia, local microenvironment, and inflammatory response in the developing brain compared with adults accounting for the differences in timing.…”

“…Most of the literature regarding radiation necrosis involves adult patients, but the incidence of radiation necrosis in the pediatric brain tumor population with photon radiation therapy has also been described with an incidence of 5% and is potentially exacerbated by chemotherapy so that radiation necrosis may be attributable to the combination of radiation therapy and chemotherapy. 2,3 Although radiation therapy remains an important form of treatment for pediatric brain tumors, the brains of young children may respond differently to radiation therapy compared with adults. Potential etiologies reported from a limited number of animal studies have demonstrated differences in progenitor cells, local microenvironment, inflammatory response, and effects on oligodendrocytes and microglia.…”

Severe Radiation Necrosis Successfully Treated With Bevacizumab in an Infant with Low‐Grade Glioma and Tumor‐Associated Intractable Trigeminal Neuralgia

“…The incidence of radiation necrosis in adults is reported between 5 and 10%. There is limited data on the incidence in children, but current studies report 3.7–5% risk, based largely on children with high‐grade brain tumors . A retrospective review of 236 children with medulloblastoma and other CNS embryonal tumors showed a necrosis incidence of 3.7% at 5 years .…”

Cellular and molecular mechanisms of radiation-induced brain injury: can peripheral markers be detected?

“…Любопытно, что с возрастом в мозге крыс происходит снижение экспрессии провоспалительных медиаторов в ответ на лучевое воздействие [34]. В то же время существуют данные, указывающие на снижение риска развития лучевого некроза у взрослых пациентов по сравнению с детьми [48]. Таким образом, большое число многосторонних данных указывает на ключевую роль нейровоспалительных процессов в патогенезе развития разнообразных лучевых повреждений мозга, включая лучевой некроз и когнитивные нарушения.…”