Differential Diagnosis of recurrent GBM versus Radiation Necrosis using MDSCbiomarkers

使用 MDSC 生物标志物鉴别诊断复发性 GBM 与放射性坏死

• 批准号: 10330027
• 负责人: THOMAS S MCCORMICK
• 金额: $ 22.13万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10330027
• 关键词: Address; Adult; Appearance; Biological Markers; Biopsy; Blood; Blood Tests; Brain Neoplasms; CD14 gene; Cancer Patient; Caring; Cells; Cellular Immunity; Characteristics; Cicatrix; Clinical; Coin; Combined Modality Therapy; Data; Diagnosis; Differential Diagnosis; Disease; Early Diagnosis; Etiology; FDA approved; Flow Cytometry; Glioblastoma; Glioma; HLA-DR Antigens; Healthcare Systems; Humoral Immunities; Image; Image Enhancement; Immune response; Immunologic Markers; Immunosuppression; Incidence; Interventional radiology; Laboratories; Lead; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of brain; Mediating; Membrane Proteins; Molecular; Monitor; Myeloid-derived suppressor cells; Neurologist; Operative Surgical Procedures; Patients; Performance; Progression-Free Survivals; Radiation necrosis; Radiation therapy; Recruitment Activity; Recurrence; Recurrent tumor; Reproducibility; Research Design; Risk; Sensitivity and Specificity; Solid Neoplasm; Surface; Survival Rate; Technology; Testing; Third-Party Payer; Treatment Failure; Tumor Tissue; anti-tumor immune response; base; chemoradiation; clinical practice; cost; diagnostic criteria; imaging study; improved; indexing; liquid biopsy; minimally invasive; monocyte; neoplastic cell; novel; peripheral blood; protein biomarkers; radiation effect; recruit; research study; response; treatment effect; treatment response; tumor; tumor microenvironment; wasting

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.

诊断复发性胶质母细胞瘤（GBM）的一个主要临床挑战是评估对以下治疗的反应： 治疗虽然标准化放疗提高了生存率，但它也使复发评估复杂化。 事实上，放射效应表现为与复发性肿瘤难以区分的增强肿块， 近30%的GBM患者。髓源性抑制细胞（MDSC）是重要的免疫抑制细胞 出现在实体瘤（包括GBM）及其周围，以及许多癌症的外周血中 患者募集到局部肿瘤微环境被认为介导宿主的主动抑制 肿瘤的免疫反应。这些观察结果使得MDSC可能用于检测复发性 GBM和以非侵入性方式监测对治疗的反应，同时避免了不方便、成本和 更昂贵的磁共振成像（MRI）和/或侵入性活检的风险。考虑到入侵性，风险 以及手术干预的成本和所涉及的放射学挑战，微创“液体活检”， 具有高灵敏度和特异性代表了一种变革性技术。我们的初步数据表明， 称为DVI的基于MDSC的生物标志物可以将复发性GBM患者与其他病因的GBM患者区分开来。 仅使用外周血增强肿块，包括放射性坏死、瘢痕和假性进展。 为了进一步评估该测试的灵敏度和特异性，我们提出以下目标：1.验证 DVI用于区分GBM真实复发（rGBM）与其他MRI病因的敏感性和特异性 成像增强; 2.）确定DVI相对于传统成像的性能特征， 在治疗中的患者中区分真实复发（rGBM）与治疗效果;以及3）识别潜在的 因此，VNN 2水平由GBM调节。能够进行临床安全和简单的测试 量化DVI将提高目前区分RN和GBM肿瘤复发的诊断标准 并且可以容易地由全国范围内的临床流式细胞术实验室调整和实施。的能力 使用液体活检客观评估治疗反应将是一种变革， 通过避免危险和昂贵的外科手术，提高治疗的价值。

项目成果

A Liquid Biopsy to Assess Brain Tumor Recurrence: Presence of Circulating Mo-MDSC and CD14+ VNN2+ Myeloid Cells as Biomarkers That Distinguish Brain Metastasis From Radiation Necrosis Following Stereotactic Radiosurgery.

• DOI: 10.1093/neuros/nyaa334
• 发表时间: 2020-08
• 期刊: Neurosurgery
• 影响因子: 4.8
• 作者: D. Soler;Amber E. Kerstetter-Fogle;Theresa Elder;Alankrita Raghavan;J. Barnholtz-Sloan;K. Cooper;T. McCormick;A. Sloan