Detection of cell-free circulating tumor DNA in patients with glioblastma undergoing treatment with first-line chemoradiotherapy

Glioblastoma (GBM) is the most common primary brain tumor in adults and is uniformly fatal. During standard adjuvant treatment for GBM following initial surgical resection of the tumor, patients are treated with a combination of radiation and chemotherapy. During and after this adjuvant treatment, patients are monitored for disease progression with serial magnetic resonance imaging (MRI) scans of the brain. Unfortunately, radiographic changes detected by MRI are often nonspecific and slow to change, even in the face of progressing or regressing disease. As a result, it can be difficult to discriminate between pseudoprogression, an inflammatory response to radiation, also referred to as "treatment effect", and actual cancer growth. Given the overall poor sensitivity and specificity of neuroimaging to monitor tumors over time, a minimally invasive real-time biomarker that provides quantitative information regarding tumor burden is sorely needed. In multiple non-central nervous system (CNS) tumors, liquid biopsy is increasingly being utilized for non-invasive patient monitoring through blood samples containing plasma cell-free tumor DNA (cfDNA). In 2014, a landmark study demonstrated that hematogenous dissemination of was an intrinsic feature of this GBM, thus raising the possibility of using cfDNA as a means of monitoring disease activity and non-invasively testing for tumor DNA mutations in CNS tumors. However, there are currently no published studies that have used a high sensitivity DNA detection assay to quantify cfDNA in patients with GBM. The ability to reliably detect and quantify cfDNA in GBM as a surrogate of tumor burden and disease activity would lead to significantly improved clinical care for patients with this devastating illness. In this two-part study, we plan to quantify and sequence plasma cfDNA in patients with GBM using a novel high sensitivity DNA detection kit and next generation sequencing assay. In doing so, we aim to to gain preliminary insight into 1) the utility of cfDNA as a non-invasive biomarker of tumor burden in GBM, 2) the degree of concordance between tumor DNA mutations detected in the plasma versus those detected in tissue, and 3) the role of cfDNA as a prognostic marker in GBM. The first part of the study will examine previously collected, banked blood specimens from the UPenn Neurosurgery Tumor Tissue Bank, and the second part will prospectively collect and study serial blood specimens from patients undergoing standard therapy for GBM at Penn.