Neurofilament Light Chain as A Biomarker for Brain Metastases

SIMPLE SUMMARY: Early detection of brain metastases is warranted to allow timely intervention that can improve local control and survival time. Neurofilament light chain (NfL) is a neuron-specific protein released after neuronal decay, and we evaluated blood-borne NfL as a biomarker in 43 lung cancer patients with brain metastases and 25 without brain metastasis. NfL was elevated in patients with brain metastasis and serial measurements uncovered increasing NfL levels with a median of three months before a brain metastasis was found on a brain scan. Our findings imply that measuring chances of NfL in the blood could be a potential biomarker for early detection of brain metastases. ABSTRACT: Background: Brain metastases are feared complications in cancer. Treatment by neurosurgical resection and stereotactic radiosurgery are only available when metastatic lesions are limited and early detection is warranted. The neurofilament light chain (NfL) is a sensitive neuron-specific biomarker released following neuronal decay. We explored serum NfL as a biomarker of brain metastases. Methods: Serum was collected from 43 stage IV lung cancer patients with brain metastases and 25 stage I lung cancer patients. Serum was collected at time of cancer diagnosis and at time of brain metastasis diagnosis. In nine patients with brain metastases, additional samples were available between the two time points. NfL was quantified by Single Molecule Array (Simoa)™. Results: The median NfL level was significantly higher in patients with brain metastases than in patients without (35 versus 16 pg/mL, p = 0.001) and separated patients with an area under the curve of 0.77 (0.66–0.89). An increase in NfL could be measured median 3 months (range: 1–5) before the brain metastasis diagnosis. Further, a high level of NfL at time of brain metastasis diagnosis correlated with an inferior survival (hazard ratio: 2.10 (95% confidence interval: 1.11–3.98)). Conclusions: This study implies that NfL could be a potential biomarker of brain metastases.