CBM-13CHARACTERIZATION OF CELL-FREE CIRCULATING TUMOR DNA IN LOW GRADE AND MALIGNANT GLIOMAS

Abstract

BACKGROUND: Glioblastoma is the most common primary malignant brain tumor, with poor survival despite standard therapy. Genetic profiling of tumor tissue can identify targeted therapies to increase treatment options, though such testing presents with limitations. Cell-free circulating tumor DNA (ctDNA) testing was recently developed and carries remarkable diagnostic potential for targeted therapy. CtDNA testing needs to be further characterized in glioma patients to establish its utility. METHODS: 133 consecutive samples of gliomas (15 grade II, 20 grade III and 98 grade IV) were tested prospectively at a CLIA-certified, CAP-accredited clinical laboratory with Guardant360 ctDNA panel. Testing is sensitive to 1-2 molecules of mutated ctDNA in a 10 mL blood sample with 99.9999% specificity. Samples were analyzed for amplifications in 3 genes (EGFR, ERBB2, MET) and single nucleotide variants (SNVs) by a 54 or expanded 68-gene panel, with a combination of comprehensive and critical exon sequencing. RESULTS: 2/15 (13.3%) samples from patients with grade II gliomas harbored detectable genomic alterations, whereas 6/20 (30.0%) of grade III and 38/98 (38.8%) of grade IV samples contained alterations. The most common genes with detectable alterations in the 98 glioblastoma samples were p53 (15), APC (8), EGFR (5), and MET (5). Data for date of next progression was available for 40 of the 98 glioblastoma samples. 16 of the 40 samples were tested within 30 days of the next recurrence; 9/16 (56%) detected genomic alterations. The remaining 24 samples were tested more than 30 days before the next recurrence; only 5/24 (21%) had detectable alterations. CONCLUSIONS: CtDNA testing is more sensitive to detecting genetic variations in glioblastomas as opposed to lower grade gliomas. The presence of detectable alterations was increased in the 30 days prior to the next documented recurrence. This increased sensitivity may suggest the utility of ctDNA as an early detector of progression.