CSF biomarkers of neurotoxicity in childhood cancer survivors after cranial radiotherapy or surgery

IF 4.4 2区医学 Q1 CLINICAL NEUROLOGY

Annals of Clinical and Translational Neurology Pub Date : 2024-07-19 DOI:10.1002/acn3.52152

Erik Fernström, Marianne Jarfelt, Malin Blomstrand, Birgitta Lannering, Markus Axelsson, Pontus Wasling, Thomas Björk-Eriksson, Henrik Zetterberg, Marie Kalm

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Abstract

Objective

Treatment of pediatric brain tumors is associated with potential long-term cognitive sequelae. Patients treated with craniospinal irradiation for posterior fossa tumors are at high risk. New biomarkers that could help to differentiate treatment effects from other causes of cognitive dysfunction would be valuable in tailoring optimal survivorship care. Biomarkers that reflect biological mechanisms behind treatment-associated cognitive decline would also be important in the evaluation of future treatment regimens for pediatric brain or skull base tumors.

Methods

In this biomarker-finding study, 10 adult survivors of pediatric medulloblastoma, skull base tumors, and posterior fossa low-grade glioma underwent study specific lumbar puncture at a minimum of 17 years following treatment. We analyzed cerebrospinal fluid biomarkers reflecting neuron and astrocyte integrity, amyloid metabolism, inflammation, extracellular matrix, synaptic integrity, and blood–brain barrier function. The values were compared with biomarker levels in healthy controls of comparable age.

Results

Biomarkers reflecting neuronal injury (neurofilament light chain protein), astrocyte injury or activation (glial fibrillary acidic protein) as well as inflammation (YKL-40) were significantly elevated in cancer survivors compared to controls. Biomarkers reflecting amyloid metabolism showed a pattern of decrease in patients treated for medulloblastoma.

Interpretation

The results suggest a potential chronic low-grade neurodegeneration and astrocyte activation in patients treated for pediatric brain or skull base tumors. Protein biomarkers of CNS disease could potentially be used to increase our understanding of the contribution from different tumor treatments with regard to long-term symptoms in cancer patients.

Abstract Image

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颅脑放疗或手术后儿童癌症幸存者神经毒性的 CSF 生物标志物。

目的：小儿脑肿瘤的治疗与潜在的长期认知后遗症有关。接受颅骨照射治疗后窝肿瘤的患者是高危人群。新的生物标志物可帮助区分治疗效果和认知功能障碍的其他原因，这对定制最佳的生存护理非常有价值。反映治疗相关认知功能下降背后生物机制的生物标志物对于评估未来小儿脑肿瘤或颅底肿瘤的治疗方案也很重要：在这项寻找生物标志物的研究中，10 名小儿髓母细胞瘤、颅底肿瘤和后窝低级别胶质瘤的成年幸存者在治疗后至少 17 年接受了特定的腰椎穿刺研究。我们分析了反映神经元和星形胶质细胞完整性、淀粉样蛋白代谢、炎症、细胞外基质、突触完整性和血脑屏障功能的脑脊液生物标志物。结果显示：反映神经元损伤的生物标志物水平与年龄相当的健康对照组的生物标志物水平进行了比较：结果：与对照组相比，癌症幸存者体内反映神经元损伤（神经丝蛋白轻链）、星形胶质细胞损伤或激活（胶质纤维酸性蛋白）以及炎症（YKL-40）的生物标志物明显升高。反映淀粉样蛋白代谢的生物标志物在接受髓母细胞瘤治疗的患者中呈下降趋势：结果表明，接受小儿脑肿瘤或颅底肿瘤治疗的患者可能会出现慢性低度神经变性和星形胶质细胞活化。中枢神经系统疾病的蛋白质生物标志物可用于加深我们对不同肿瘤治疗对癌症患者长期症状的影响的了解。

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来源期刊

Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)

CiteScore

9.10

自引率

1.90%

发文量

218

审稿时长

8 weeks

期刊介绍： Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.