Cell-free DNA and circulating TERT promoter mutation for disease monitoring in newly-diagnosed glioblastoma
- PDF / 1,827,572 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 15 Downloads / 207 Views
(2020) 8:179
Open Access
RESEARCH
Cell‑free DNA and circulating TERT promoter mutation for disease monitoring in newly‑diagnosed glioblastoma Maxime Fontanilles1,2,10* , Florent Marguet3,4, Ludivine Beaussire1, Nicolas Magne5, Louis‑Ferdinand Pépin6, Cristina Alexandru2, Isabelle Tennevet2, Chantal Hanzen7, Olivier Langlois8, Fabrice Jardin3, Annie Laquerrière3,4, Nasrin Sarafan‑Vasseur1, Fréderic Di Fiore1,2,9† and Florian Clatot1,2†
Abstract The clinical implications of plasmatic cell-free and tumor DNA (cfDNA and ctDNA) are challenging in glioblastoma. This prospective study included 52 consecutive newly diagnosed glioblastoma (n = 49) or gliosarcoma (n = 3) patients treated with concomitant temozolomide and radiotherapy (RT-TMZ), followed by a TMZ maintenance phase. Plasma samples were collected at baseline, before RT-TMZ (pre-RT-TMZ) and at the end of adjuvant TMZ, or at the time of progression in cases of progressive disease (PD). The cfDNA concentration was measured with a fluoromet‑ ric method, and ctDNA was detected using targeted droplet digital PCR. The main objectives were to analyze the associations between cfDNA and ctDNA measurements during the course of treatment with PD and survival. There was a significant decrease in median cfDNA concentration from baseline to pre-RT-TMZ—19.4 versus 9.7 ng/mL (p T and 1,295,250 C > T, respectively C228T and C250T). Thus, TERTp mutations may be a potential biomarker for diagnosis [12] and disease monitoring in glioblastoma. In this context, the aim of this prospective study was to evaluate the cfDNA concentration and the detection rate of ctDNA at diagnosis and during the course of treatment, as well as their correlation with tumor progression, in patients treated for a newly diagnosed glioblastoma.
Materials and methods
Page 2 of 10
time of progression, before the end of adjuvant TMZ. All patients were followed according to the RANO criteria [14] using brain MRI every 3 months from the end of the RT-TMZ phase. All MRIs performed at baseline were reviewed for tumor volume determination. They were analyzed on a T2-Flair and T1 postcontrast sequences after manual segmentation using Advantage Windows 4.6® (General Electric Healthcare, Milwaukee, Wisconsin, United States). The analysis of tumor volume was performed in T1 postcontrast sequences according necrotic areas. The maximal relative cerebral blood volume (rCBV) was also measured by perfusion-weighted imaging, when available, by drawing several regions of interest in high-rCBV areas in the tumor and was compared to the contralateral non-affected brain parenchyma [15, 16]. Samples of 6 mL of whole blood were collected at three different time points into tubes containing ethylenediaminetetraacetic acid (EDTA) based on previous studies [17, 18]. Within 2 h after blood collection, the tubes were centrifuged at 3000 rpm for 10 min; the plasma was then extracted and stored at − 80 °C until use. Tumor samples were obtained during diagnostic procedures (resection or biopsy). After collection, the tumor samples w
Data Loading...
