Table 2.

A selection of relevant studies, listed in order of publication, suggesting a potential application of cfDNA-based liquid biopsies for purposes of response assessment and prognostic stratification in patients with primary and secondary CNS tumours

Reference	n	Population	Tumour type	Biological fluid	Biomarker	Sequencing method	Clinical application	Main findings of the study
De Mattos-Arruda et al.14	12	Adults	Primary and secondary CNS tumours	CSF	Mutations and CNVs	NGS ddPCR	Response assessment	MAF of CSF tcfDNA decreased after surgery and increased at progression
Panditharatna et al.12	48	Children AYA	Diffuse midline gliomas	Plasma	H3K27M mutations	ddPCR	Response assessment	MAF tracked tumour evolution and predicted relapse
Juratli et al.18	38	Adults	Newly-diagnosed and recurrent GBM	CSF Plasma	TERTp mutations	ddPCR	Prognosis	MAF are predictive of OS
Miller et al.15	85	Adults	LGG and GBM	CSF	tcfDNA detection	NGS	Prognosis	The presence of tcfDNA was associated with shorter OS
Escudero et al.57	13	Children Adolescents	Medulloblastoma	CSF Plasma	tcfDNA	WES ddPCR	Response assessment	CSF tcfDNA allows the study of minimal residual disease
Muralidharan et al.22	157	Adults	Lower grade gliomas and GBM	Plasma	TERTp mutations	ddPCR	Response assessment	MAF paralleled clinical and radiological evolution
Fontanilles et al.73	52	Adults	Newly diagnosed GBM or gliosarcoma	Plasma	cfDNA concentration	–	Response assessment	Median cfDNA concentrations tracked tumour evolution
Bagley et al.72	62	Adults	Newly diagnosed GBM	Plasma	cfDNA concentration	–	Prognosis	Preoperative cfDNA concentration correlated with PFS and OS
Liu et al.29	134	Children	Newly diagnosed medulloblastoma	CSF	tcfDNA detection	NGS	Response assessment Prognosis	Patients with detectable tcfDNA during treatment had worse PFS
Li et al.78	92	Adults	Newly diagnosed NSCLC with brain metastases	CSF Plasma	tcfDNA detection	NGS	Response assessment Prognosis	Patients with CSF tcfDNA at baseline had shorter OS
Cantor et al.32	28	Children	H3K27M-mutant gliomas	CSF Plasma	H3K27M mutations	ddPCR	Response assessment Prognosis	MAF variations correlate with PFS and predict targeted therapy response
Kojic et al.19	12	Children Preadolecents	Malignant primary brain tumours	CSF	tcfDNA	WES ddPCR	Response assessment	ctDNA correlated with disease course and clinical outcomes

AYA = adolescents and young adults; cfDNA = cell-free DNA; CNVs = copy number variations; ddPCR = digital droplet PCR; GBM = glioblastoma; LGG = lower grade gliomas; MAF = mutant allelic frequencies; n = number of patients included; NGS = next generation sequencing; NSCLC = non-small cell lung cancer; OS = overall survival; PFS = progression-free survival; tcfDNA = tumour-derived cell-free DNA; TERTp = TERT promoter; WES = whole exome sequencing.