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

SIMPLE SUMMARY: Approximately 20% of patients with cancer develop brain metastases (BM). Early BM diagnosis is critical to enable less invasive or toxic approaches. Sensitive and easy-to-use blood-based BM biomarkers may allow early diagnosis and appropriate timely treatment and may improve overall survival. This study aimed to evaluate the potential roles of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) for diagnosing and monitoring BM. We found significant differences in the sNfL and the sGFAP levels between patients with and without BMs. The optimal cutoff-levels of sNfL and sGFAP had sensitivities of 91% and 91%, respectively, and combining the two biomarkers (sNfL or sGFAP) improved the sensitivity to up to 98%, with an overall accuracy higher than 91%. Thus, sNfL and sGFAP may be used as biomarkers for BM screening in patients with cancer. 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.