Differential Diagnosis of recurrent GBM versus Radiation Necrosis using MDSCbiomarkers

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One major clinical challenge for diagnosis of recurrent glioblastoma (GBM) is assessment of response to treatment. While standard chemo-radiotherapy improves survival, it also complicates assessment of recurrence. Indeed, radiation effects which present as enhancing masses indistinguishable from recurrent tumor occur in nearly 30% of GBM patients. Myeloid-derived suppressor cells (MDSC) are important immunosuppressive cells that appear in and around solid tumors, including GBM, as well as in the peripheral blood of many cancer patients. Recruitment to the local tumor microenvironment is thought to mediate active suppression of the host immune response by the tumor. These observations make MDSCs potentially useful for detecting recurrence of GBM and monitoring response to therapy in a noninvasive manner, while avoiding the inconvenience, cost, and risk of more expensive Magnetic Resonance Imaging (MRI) and/or invasive biopsy. Given the invasiveness, risk and cost of surgical intervention and the radiological challenges involved, a minimally invasive “liquid biopsy”, with high sensitivity and specificity represents a transformative technology. Our preliminary data suggests that a MDSC based biomarker known as DVI can differentiate patients with recurrent GBM from other etiologies of enhancing masses including radiation necrosis, scar, and pseudoprogression using only peripheral blood. To further assess the sensitivity and specificity of this test, we propose the following aims: 1.) Validate the sensitivity and specificity of DVI for distinguishing true recurrence of GBM (rGBM) from other etiologies of MRI imaging enhancement; 2.) Determine the performance characteristics of DVI relative to conventional imaging at differentiating true recurrence (rGBM) from treatment effect in patients under treatment; and 3) Identify potential mechanism(s) hereby VNN2 levels are modulated by GBM. The ability to perform a clinically safe and easy test to quantify the DVI will advance the current diagnostic criteria for distinguishing RN from GBM tumor recurrence and could be easily adapted and implemented by clinical flow cytometry laboratories nationwide. The ability to objectively assess response to treatment using a liquid biopsy will be transformative and lead to both better treatment and improving the value of care by avoiding risky and expensive surgical procedures.