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Clinical Utility of Plasma Cell-Free DNA in Adult Patients with Newly Diagnosed Glioblastoma: A Pilot Prospective Study
- Source :
- Clin Cancer Res
- Publication Year :
- 2019
-
Abstract
- Purpose: The clinical utility of plasma cell-free DNA (cfDNA) has not been assessed prospectively in patients with glioblastoma (GBM). We aimed to determine the prognostic impact of plasma cfDNA in GBM, as well as its role as a surrogate of tumor burden and substrate for next-generation sequencing (NGS). Experimental Design: We conducted a prospective cohort study of 42 patients with newly diagnosed GBM. Plasma cfDNA was quantified at baseline prior to initial tumor resection and longitudinally during chemoradiotherapy. Plasma cfDNA was assessed for its association with progression-free survival (PFS) and overall survival (OS), correlated with radiographic tumor burden, and subjected to a targeted NGS panel. Results: Prior to initial surgery, GBM patients had higher plasma cfDNA concentration than age-matched healthy controls (mean 13.4 vs. 6.7 ng/mL, P < 0.001). Plasma cfDNA concentration was correlated with radiographic tumor burden on patients' first post-radiation magnetic resonance imaging scan (ρ = 0.77, P = 0.003) and tended to rise prior to or concurrently with radiographic tumor progression. Preoperative plasma cfDNA concentration above the mean (>13.4 ng/mL) was associated with inferior PFS (median 4.9 vs. 9.5 months, P = 0.038). Detection of ≥1 somatic mutation in plasma cfDNA occurred in 55% of patients and was associated with nonstatistically significant decreases in PFS (median 6.0 vs. 8.7 months, P = 0.093) and OS (median 5.5 vs. 9.2 months, P = 0.053). Conclusions: Plasma cfDNA may be an effective prognostic tool and surrogate of tumor burden in newly diagnosed GBM. Detection of somatic alterations in plasma is feasible when samples are obtained prior to initial surgical resection.
- Subjects :
- 0301 basic medicine
Oncology
Adult
Male
Cancer Research
medicine.medical_specialty
Pilot Projects
Newly diagnosed
Plasma cell
Free dna
Article
Circulating Tumor DNA
03 medical and health sciences
Young Adult
0302 clinical medicine
Germline mutation
Internal medicine
medicine
Biomarkers, Tumor
Humans
Longitudinal Studies
Prospective Studies
Prospective cohort study
Aged
Aged, 80 and over
Adult patients
business.industry
High-Throughput Nucleotide Sequencing
Middle Aged
medicine.disease
Prognosis
Magnetic Resonance Imaging
Tumor Burden
Survival Rate
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Mutation
Female
business
Glioblastoma
Chemoradiotherapy
Subjects
Details
- ISSN :
- 15573265
- Volume :
- 26
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Accession number :
- edsair.doi.dedup.....3fe9f3e1182feafaa1fc07b21a626163