Table 3.
Summary of studies of ctDNA in plasma in patients with gliomas.
| Author (Year) | N | ctDNA Reservoir |
ctDNA Detection Method | % of ctDNA-Positive Patients | % of ctDNA Positive Controls | Type of ctDNA Mutations Detected | Main Findings |
|---|---|---|---|---|---|---|---|
| Lavon (2010) [31] | Astro: N = 41 Oligo: N = 34 |
Plasma | 10q LOH MGMT and PTEN methylation |
Astrocytomas: -10q LOH: 51% -MGMTmet: 24% -PTENmet: 0% Oligodendrogliomas: -10q LOH: 79% -1p LOH: 17% -19q LOH: 4% -MGMTmet: 24% |
24% serum positive with no viable tumor on MRI | - | Moderate sensitivity and specificity for LGG and HGG |
| Boisselier (2012) [14] | Gliomas: N = 39 (n = 25 IDH1m) HC: N = 14 |
Plasma | COLD dPCR (IDH1-R132H) | Total: 60% (15/25) LGG: 37.5% (3/8) HGG: 70.6% (12/17) |
0 HC (0/14) | IDH1-R132H | Higher detection rate among HGG vs. LGG (70.6% vs. 37.5%) Higher detection rate and higher DNA concentration among high vs. low volume tumors |
| Bettegowda (2014) [30] | Intra- and extracranial cancers: N = 177 Gliomas: N = 27 |
Plasma | NGS | <10% | - | - | Extracranial malignancies: ctDNA detected in 82% Intracranial malignancies: ctDNA detected in <50% of MB and in >10% of gliomas |
| Schwaederle (2017) [29] | Intra- and extra-cranial cancers: N = 670 Gliomas: N = 152 |
Plasma | NGS | 15% (pts with characterized actionable alterations) |
- | - | Extra- and intra-cranial malignancies: ctDNA detected in 48% Gliomas: ctDNA detected in 15% |
| Nassiri (2021) [22] | IDHm gliomas: N = 70 IDHwt gliomas: N = 52 Menin- giomas: N = 60 Hemangio- pericytomas: N = 9 Low-grade glial-neuronal tumors: N = 14 Brain mets of UK primary: N = 9 |
Plasma | cfMeDIP-seq | - | - | - | High sensitivity and discriminative capacity between: Gliomas vs. other cancers vs. HC IDHm vs. IDHwt HGG vs. LGG High correlation between plasma and tumor methylation signatures |
| Current study (2022) | N = 10 (6 IDH1m, 4 IDH1wt) |
Plasma | BEAMing for IDH1m | 50% (3/6) | 0 IDH1wt (0/4) | IDH1-R132H (n = 2) IDH1-R132C (n = 1) |
Same mutant loci detected in IDH1 plasma (BEAMing) and tumor (NGS) All ctDNA+ pts had active disease on MRI In 1 pt BEAMing detected in plasma 1 of the 2 co-existing IDH1 mutations in tissue (R132H, R132C). |
Astro: astrocytoma, BEAMing: Beads, Emulsion, Amplification and Magnetics, cfMeDIP-seq: cell-free methylated DNA immunoprecipitation and high-throughput sequencing, ctDNA: circulating tumor DNA, dPCR: digital PCR, HC: healthy controls, HGG: high-grade gliomas, IDH: isocitrate dehydrogenase, IDHm: IDH mutant, IDHwt: IDH wild-type, LGG: low-grade gliomas, LOH: loss of heterozygosity, mets: metastases, MGMT: O6-methylguanine–DNA methyltransferase, NGS: next-generation sequencing, oligo: oligodendroglioma, pt: patient, pts: patients, UK: unknown. (-): indicates either not reported or not applicable.