Table 2.

Studies on cell-free DNA sequencing in plasma or CSF of CNS metastases

Study	Site of CNS Malignancy	n	Primary	Biological Fluid Sampled	Sequencing Method	CNS Malignancy Mutation Detection Rate
Swinkels et al, 2000	LM	2	Lung adenocarcinoma	CSF	Mutant- allele- specific amplification (PCR)	KRAS mutation detectable in CSF 2/2 (100%)
De Mattos et al, 2015	P	12	6 breast cancer, 2 lung cancer, 4 glioblastoma	CSF plasma	Targeted sequencing	CNS disease only: 58% CSF, 0% plasma; CNS and non-CNS disease: 60% CSF, 55.5% plasma
Momtaz et al, 2016	P, LM	11	Patients with BRAF-mutated malignancies	CSF	Targeted sequencing	BRAF mutations detected in CSF of 6/11 (54%)
Pentsova et al, 2016	P, LM	41	11 lung cancer, 11 breast cancer, 6 melanoma, 1 bladder cancer, 2 gastrointestinal, 2 ovarian, 1 neuroendocrine, 2 thyroid, 2 prostate, 2 renal, 1 sarcoma	CSF	Targeted sequencing	Mutations detectable in CSF of 20/32 (63%) patients with parenchymal mets 3/4 (75%) patients with LM
Marchio et al, 2017	LM	2	Lung adenocarcinoma	CSF plasma	Targeted sequencing	KRAS mutations detectable in CSF 2/2 (100%)
Siravegna et al, 2017	P	1	HER 2 + breast CSF adenocarcinoma	CSF plasma	Digital droplet PCR whole exome sequencing	ERBB2 CNYC TP53 PIK3CA
Fan et al, 2018	LM	11	EGFR-mutated NSCLC	CSF	Targeted sequencing	EGFR mutations detectable in CSF 11/11 (100%); mutations were not concordant in 1/11 (9%)
Li et al, 2018	LM	42	EGFR-mutated NSCLC	CSF	Targeted sequencing	EGFR mutations detectable in CSF of 92% (n = 28)
Huang et al, 2018	LM	1	CUP adenocarcinoma	CSF	Targeted sequencing	HER2 and MPL amplification PIK3CA, CDKN2A and P53 mutations

Abbreviations: P = parenchyma; LM = leptomeninges; PIK3CA = phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; HER2 = human epidermal growth factor receptor 2; MPL = myeloproliferative leukemia; CDKN2A = cyclin-dependent kinase inhibitor 2A.