World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Original Article

Volume 10, Number 4-5, October 2019, pages 169-175

Serum Neurofilament Light, Glial Fibrillary Acidic Protein and Tau Are Possible Serum Biomarkers for Activity of Brain Metastases and Gliomas

Figure 2. sNfL, GFAp and tau concentrations per intracranial neoplasm group. There is statistically significant difference in sNfL, GFAp and tau levels between groups, although concentrations were not clinically meaningful for tau. CNSPD: patients with CNS tumors with progressive disease; CNSSD: patients with CNS with stable disease; CNBM: patients with metastatic cancer with no brain metastasis; BM: patients with metastatic solid tumors with known brain metastasis; C: healthy controls; remote BM: patient without evidence of measurable disease, but with prior treatment of a metastatic brain lesion, more than 2 years before inclusion in the study. sNfL: serum neurofilament light chain; GFAp: glial fibrillary acidic protein; tau: tau protein; CNS: central nervous system.

**Table 1.** Conditions Per Group
CNSPD	CNSSD	CNBM	BM	Remote BM
DLBCL: diffuse large B-cell lymphoma; PCL: primary central nervous system lymphoma; CML: chronic myeloid leukemia; NSCLC: non-small cell lung cancer; HER2: human epidermal growth factor receptor 2; EGFR: epidermal growth factor receptor; CNS: central nervous system; CNSPD: patients with CNS tumors with progressive disease; CNSSD: patients with CNS with stable disease; CNBM: patients with metastatic cancer with no brain metastasis; BM: patients with metastatic solid tumors with known brain metastasis; C: healthy controls; remote BM: patient without evidence of measurable disease, but with prior treatment of a metastatic brain lesion, more than 2 years before inclusion in the study.
DLBCL	Glioblastoma	CML	Breast HR+ HER2-	Esophageal cancer HER2-
Mantle Cell Lymphoma	Glioblastoma	Colorectal cancer	Breast HR+ HER2-
Glioblastoma	Glioblastoma	Colorectal cancer	Breast HR+ HER2-
Glioblastoma	Glioma II	Colangiocarcinoma	NSCLC
Glioblastoma	Glioma III	Esophageal HER2-	NSCLC
Glioblastoma	HIV-PCL	Follicular Lymphoma	NSCLC
Oligodendroglioma	Oligoastrocytoma	Melanoma	NSCLC EGFR mutated
Oligodendroglioma		Polycythemia vera
		Prostate cancer

Table 1. Conditions Per Group

CNSPD

CNSSD

CNBM

Remote BM

DLBCL: diffuse large B-cell lymphoma; PCL: primary central nervous system lymphoma; CML: chronic myeloid leukemia; NSCLC: non-small cell lung cancer; HER2: human epidermal growth factor receptor 2; EGFR: epidermal growth factor receptor; CNS: central nervous system; CNSPD: patients with CNS tumors with progressive disease; CNSSD: patients with CNS with stable disease; CNBM: patients with metastatic cancer with no brain metastasis; BM: patients with metastatic solid tumors with known brain metastasis; C: healthy controls; remote BM: patient without evidence of measurable disease, but with prior treatment of a metastatic brain lesion, more than 2 years before inclusion in the study.

DLBCL

Glioblastoma

CML

Breast HR+ HER2-

Esophageal cancer HER2-

Mantle Cell Lymphoma

Glioblastoma

Colorectal cancer

Breast HR+ HER2-

Glioblastoma

Colorectal cancer

Breast HR+ HER2-

Glioblastoma

Glioma II

Colangiocarcinoma

NSCLC

Glioblastoma

Glioma III

Esophageal HER2-

NSCLC

Glioblastoma

HIV-PCL

Follicular Lymphoma

NSCLC

Oligodendroglioma

Oligoastrocytoma

Melanoma

NSCLC
EGFR mutated

Oligodendroglioma

Polycythemia vera

Prostate cancer

**Table 2.** Characteristics of the Study Participants
Group	CNSPD	CNSSD	CNBM	BM	Remote BM	C
NA: non-available; CNS: central nervous system; CNSPD: patients with CNS tumors with progressive disease; CNSSD: patients with CNS with stable disease; CNBM: patients with metastatic cancer with no brain metastasis; BM: patients with metastatic solid tumors with known brain metastasis; C: healthy controls; remote BM: patient without evidence of measurable disease, but with prior treatment of a metastatic brain lesion, more than 2 years before inclusion in the study.
No.	8	7	9	7	1	4
Age, median (range), years	45.5 (42 - 74)	58 (40 - 81)	62 (30 - 78)	57 (43 - 75)	61	49 (36 - 62)
Ethnicity (%W)	88	57	89	43	100	50
Lines of systemic treatment, median (range)	2 (1 - 3)	1 (1 - 2)	1 (1 - 3)	1 (0 - 4)	1	NA
Radiation therapy to CNS	6	6	No	7	1	No
Antihistamine	No	1	No	No	No	No
Benzodiazepine	1	1	No	No	No	No
Memantine	No	No	No	1	No	No
Antidepressant	2	1	4	No	No	No
Antipsychotic	No	No	No	No	No	No
Anticonvulsant	3	3	No	No	No	No

Table 2. Characteristics of the Study Participants

Group

CNSPD

CNSSD

CNBM

Remote BM

NA: non-available; CNS: central nervous system; CNSPD: patients with CNS tumors with progressive disease; CNSSD: patients with CNS with stable disease; CNBM: patients with metastatic cancer with no brain metastasis; BM: patients with metastatic solid tumors with known brain metastasis; C: healthy controls; remote BM: patient without evidence of measurable disease, but with prior treatment of a metastatic brain lesion, more than 2 years before inclusion in the study.

No.

Age, median (range), years

45.5 (42 - 74)

58 (40 - 81)

62 (30 - 78)

57 (43 - 75)

49 (36 - 62)

Ethnicity (%W)

100

Lines of systemic treatment, median (range)

2 (1 - 3)

1 (1 - 2)

1 (1 - 3)

1 (0 - 4)

Radiation therapy to CNS

Antihistamine

Benzodiazepine

Memantine

Antidepressant

Antipsychotic

Anticonvulsant

**Table 3.** Median Serum NfL, Tau and GFAp Concentrations Per Group
Group, median (range), pg/mL	CNSPD	CNSSD	CNBM	BM	Remote BM	C
CNS: central nervous system; CNSPD: patients with CNS tumors with progressive disease; CNSSD: patients with CNS with stable disease; CNBM: patients with metastatic cancer with no brain metastasis; BM: patients with metastatic solid tumors with known brain metastasis; C: healthy controls; remote BM: patient without evidence of measurable disease, but with prior treatment of a metastatic brain lesion, more than 2 years before inclusion in the study. NfL: neurofilament light protein; GFAp: glial fibrillary acidic protein; tau: tau protein.
Serum NfL	239.4 (96.7 - 1,101.4)	23.0 (12.6 - 135.3)	11.8 (4.7 - 51.4)	142.3 (67.8 - 284.9)	13.9	7.2 (3.2 - 14.8)
Serum GFAp	2,092.1 (227,8 - 3,435,6)	163.1 (49.7- 538.8)	90.2 (40.4 - 270.1)	557.7 (201.2 - 5,972.8)	97.1	74.5 (46.9 - 147.8)
Serum tau	6.1 (2.5 - 13.3)	9.5 (4.2 - 10.9)	12.5 (4.1 - 20.6)	6.5 (2.5 - 9.6)	7.4	8.25 (6.2 - 13.8)

Table 3. Median Serum NfL, Tau and GFAp Concentrations Per Group

Group, median (range), pg/mL

CNSPD

CNSSD

CNBM

Remote BM

CNS: central nervous system; CNSPD: patients with CNS tumors with progressive disease; CNSSD: patients with CNS with stable disease; CNBM: patients with metastatic cancer with no brain metastasis; BM: patients with metastatic solid tumors with known brain metastasis; C: healthy controls; remote BM: patient without evidence of measurable disease, but with prior treatment of a metastatic brain lesion, more than 2 years before inclusion in the study. NfL: neurofilament light protein; GFAp: glial fibrillary acidic protein; tau: tau protein.

Serum NfL

239.4 (96.7 - 1,101.4)

23.0 (12.6 - 135.3)

11.8 (4.7 - 51.4)

142.3 (67.8 - 284.9)

13.9

7.2 (3.2 - 14.8)

Serum GFAp

2,092.1 (227,8 - 3,435,6)

163.1 (49.7- 538.8)

90.2 (40.4 - 270.1)

557.7 (201.2 - 5,972.8)

97.1

74.5 (46.9 - 147.8)

Serum tau

6.1 (2.5 - 13.3)

9.5 (4.2 - 10.9)

12.5 (4.1 - 20.6)

6.5 (2.5 - 9.6)

7.4

8.25 (6.2 - 13.8)