Cystlike Lesions as a Late Sequela of Radiotherapy in Pediatric Patients

Abstract

BACKGROUND AND PURPOSE: The developing nervous system is particularly vulnerable to late adverse effects of cranial radiation therapy, such as leukoencephalopathy, microbleeds, and cavernomas. Cystlike lesions have been rarely described and characterized in the literature. We aimed to characterize cystlike lesions, their risk factors, and association with other late adverse effects. MATERIALS AND METHODS:Children treated for brain tumors during a 30-year period (n ¼ 139) were included. We documented imaging findings, focusing on cystlike lesion development and its relationship with clinical history and other imaging findings. Multivariable analysis was performed using logistic regression and negative binomial regression models.RESULTS: Cystlike lesions developed in 16.5% of patients treated with radiotherapy, with a median of 2 years until the development of the first lesion. For every 4-year age increase, there were 50% decreased odds of developing lesions and a 50% decrease in the average count of lesions. Females demonstrated a 4.00 rate ratio of developing a higher number of lesions. Patients who underwent chemoradiotherapy had 3.20 increased odds of developing cystlike lesions compared with patients with radiation therapy alone. A larger proportion of patients treated with methotrexate (25%) developed cystlike lesions, but this was not statistically significant. Cystlike lesions tended to develop in cerebral locations where leukoencephalopathy was worse. A strong relationship was found between the development of cystlike lesions and leukoencephalopathy severity.CONCLUSIONS: Cystlike lesions are frequent and under-reported late adverse effects of cranial radiation therapy in children. Younger age, chemoradiotherapy, and the severity of leukoencephalopathy represent risk factors for the development of cystlike lesions.ABBREVIATIONS: CLL ¼ cystlike lesions; LE ¼ leukoencephalopathy; MTX ¼ methotrexate; RT ¼ radiotherapy C entral nervous system tumors are the most common solid tumors in children, accounting for up to 22% of tumors in patients between 0 and 14 years of age. 1 The 5-year relative cancer survival rate in these patients has been increasing in the past decades. 2 Childhood cancer therapy causes chronic health problems in almost 75% of survivors, which can become clinically visible several years after treatment and are frequently irreversible and progressive. 1

Case report: Exploring chemoradiotherapy-induced leukoencephalopathy with 7T imaging and quantitative susceptibility mapping

“…However, even CT may be highly toxic for the pediatric brain ( 8 ). In particular, methotrexate (MTX) is known for its significant adverse effects on the CNS, with concomitant brain radiation and young age identified as risk factors for MTX-associated issues ( 9 ). Although the majority of chemotherapy agents does not cross the intact blood brain barrier (BBB), the amount of neurotoxicity produced by a multimodal therapy regimen potentially reduces the integrity of the barrier.…”

“…Neuroimaging abnormalities have been reported in several studies following CT, RT, or multimodal therapy. These abnormalities encompass common conditions such as leukoencephalopathy (LE) and vasculopathies, microbleeds and cavernomas, but also more rarely observed cyst-like lesions (CLL) ( 9 , 11 ). Children who receive RT at younger ages may be especially vulnerable to radiation-induced LE ( 4 ) and the risk of LE is correlated with the dose and volume of the brain which has been exposed to radiation.…”