Evaluation of Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Screening and Monitoring Biomarkers for Brain Metastases

Abstract

We evaluated the potential serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) roles in diagnosing and monitoring brain metastases (BMs). We included 70 patients with newly diagnosed BMs, 71 age- and cancer type-matched patients without BMs, and 67 healthy controls (HCs). We compared sNfL and sGFAP levels among the groups using a single-molecule array immunoassay. We prospectively followed 26 patients with BMs every 2–3 months by measuring sNfL and sGFAP levels and performing magnetic resonance imaging (MRI) scans. The sNfL and the sGFAP levels were higher in patients with BMs (medians: sNfL, 63.7 µL; sGFAP, 819.5 pg/µL) than in those without BMs (sNfL, 13.3 µL; sGFAP, 154 pg/µL; p < 0.001) and HCs (sNfL, 12.5 µL; sGFAP, 135 pg/µL; p < 0.001). The sNfL and the sGFAP cutoff levels had a sensitivity and a specificity of 91%. The sGFAP cutoff level had a sensitivity of 91% and a specificity of 97%. The sNfL and the sGFAP levels were related to the BM size but not to the primary cancer type. After BM treatment, sNfL and sGFAP levels decreased with reduced BM lesions on MRI; however, they increased when BMs progressed. sNfL and sGFAP are potential biomarkers for BM screening in cancer patients.

Neurofilaments contribution in clinic: state of the art

“…Several publications have thus focused on the use of NfL as a diagnostic and prognostic blood marker. High blood levels of NfL in brain metastases (Hepner et al, 2019 ; Kim et al, 2021 ; Lin et al, 2022 ) was reported, these levels being correlated with the number and size of metastases (Lin et al, 2022 ). A decrease in levels of NfL was also detected following treatment (Kim et al, 2021 ).…”

“…For metastases diagnosis, NfL threshold values may be defined according to age: for example, NfL levels >22 pg/ml (measured by the Simoa approach) in cancer patients aged 51–60 years may predict the presence of brain metastases (Kim et al, 2021 ). Other biomarkers are also being evaluated, in particular the GFAP protein which would, according to Darlix et al ( 2021 ) outperform NfL as a diagnostic and prognostic factor for brain metastases in breast cancer patients.…”

Blood Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Promising Screening Biomarkers for Brain Metastases in Patients with Lung Cancer

“…Moreover, disruptions in the blood–brain barriers may allow GFAP or NfL to cross through CSF to circulation. Previous studies have demonstrated that sNfL and sGFAP levels are associated with the number and size of BM lesions [ 13 , 15 ]. The diagnostic performance of sNfL and sGFAP is better in patients with symptomatic BM than in those without symptoms [ 15 ].…”

“…Previous studies have demonstrated that sNfL and sGFAP levels are associated with the number and size of BM lesions [ 13 , 15 ]. The diagnostic performance of sNfL and sGFAP is better in patients with symptomatic BM than in those without symptoms [ 15 ]. Previous findings have demonstrated that elevated sNfL and sGFAP levels at the time of BM diagnosis were associated with poor patient outcomes [ 13 , 14 ], which can be explained by the association between sNfL and sGFAP levels and the extent of BM lesions; thus, the more advanced the BM, the worse the prognosis.…”

“…Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are promising candidates, with NfL indicating central nervous system axonal loss and GFAP reflecting astrocyte activation [ 10 , 11 ]. Several recent studies have indicated higher blood NfL or GFAP levels in patients with BMs than in those without BMs [ 12 , 13 , 14 , 15 ]. However, the previous studies were limited by small sample size, a lack of control for confounding factors such as age, and the potential effects of treatment on NfL and GFAP levels.…”