Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Ann Clin Transl Neurol. 2024 Sep;11(9):2382-2391. doi: 10.1002/acn3.52152. Epub 2024 Jul 19.
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.
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.
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.
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.
小儿脑瘤的治疗可能会导致潜在的长期认知后遗症。接受颅脊柱照射治疗后颅窝肿瘤的患者风险较高。新的生物标志物可以帮助区分治疗效果和其他认知功能障碍的原因，这对于制定最佳生存护理方案非常有价值。反映治疗相关认知能力下降背后生物学机制的生物标志物，对于评估小儿脑或颅底肿瘤的未来治疗方案也非常重要。
在这项寻找生物标志物的研究中，10 名接受过小儿髓母细胞瘤、颅底肿瘤和后颅窝低级别胶质瘤治疗的成年幸存者，在治疗后至少 17 年接受了特定的腰椎穿刺。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。将这些值与具有可比性年龄的健康对照组的生物标志物水平进行比较。
与对照组相比，反映神经元损伤（神经丝轻链蛋白）、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）的生物标志物在癌症幸存者中明显升高。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现下降趋势。
这些结果表明，接受小儿脑或颅底肿瘤治疗的患者可能存在潜在的慢性低度神经退行性变和星形胶质细胞激活。中枢神经系统疾病的蛋白质生物标志物可能有助于增加我们对不同肿瘤治疗对癌症患者长期症状的贡献的理解。
