Differential Diagnosis of recurrent GBM versus Radiation Necrosis using MDSCbiomarkers

复发性胶质母细胞瘤(GBM)诊断的一个主要临床挑战是评估对 治疗。虽然标准的放化疗提高了存活率，但它也使复发的评估复杂化。 事实上，放射效应表现为强化的肿块，与复发的肿瘤无法区分，发生在 近30%的GBM患者。髓系来源的抑制细胞是重要的免疫抑制细胞 出现在实体肿瘤内及其周围，包括基底膜，以及许多癌症的外周血中 病人。局部肿瘤微环境的募集被认为介导了对宿主的主动抑制 肿瘤的免疫反应。这些观察使MDSCs有可能用于检测复发的 以非侵入性方式监测治疗反应，同时避免不便、成本和 更昂贵的磁共振成像(MRI)和/或侵入性活检的风险。考虑到侵入性，风险 手术干预的费用和涉及的放射挑战，微创的“液体活组织检查”， 具有高度的敏感性和特异性，代表了一种变革性的技术。我们的初步数据显示， 基于MDSC的生物标记物DVI可以将复发的GBM患者与其他原因的GBM区分开来 仅用外周血增强肿块，包括放射性坏死、疤痕和假性进展。 为了进一步评估这项测试的敏感性和特异性，我们提出了以下目标：1)验证 DVI在鉴别真复发性肾小球基底膜(RGBM)与其他MRI病因中的敏感性和特异性 影像增强；2.)确定DVI相对于传统成像的性能特征 区分接受治疗的患者的真实复发(RGBM)和治疗效果；以及3)识别潜在的 机制(S)据此，VNN_2水平受GBM的调节。能够进行临床上安全和简单的测试 DVI的量化将提高目前鉴别RN和GBM肿瘤复发的诊断标准 并且可以很容易地被全国临床流式细胞仪实验室改编和实施。有能力 客观地评估液体活组织检查对治疗的反应将是变革性的，并导致两者都更好 通过避免危险和昂贵的外科手术来治疗和提高护理的价值。

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.