Plasma DSC for early detection of disease and therapeutic efficacy in melanoma

血浆 DSC 用于早期检测黑色素瘤疾病和治疗效果

• 批准号: 8753290
• 负责人: Nichola C. Garbett
• 金额: $ 19.58万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8753290
• 关键词: Address; Aftercare; BRAF gene; Blood; Blood Plasma Volume; CTLA4 gene; Cancer Center; Caring; Cessation of life; Characteristics; Classification; Clinic; Clinical; Clinical assessments; Collection; Control Groups; Data; Databases; Deposition; Detection; Development; Diagnosis; Diagnostic; Differential Scanning Calorimetry; Discrimination; Disease; Early Diagnosis; Enrollment; Excision; Exposure to; Goals; Health Status; Heating; Image; Immunotherapeutic agent; Immunotherapy; Incidence; Individual; Link; Monitor; Neoplasm Metastasis; Operative Surgical Procedures; Outcome; PET/CT scan; Pathology; Patient Care; Patients; Performance; Plasma; Plasma Proteins; Positron-Emission Tomography; Property; Proteome; Proteomics; Protocols documentation; Radiation; Recurrence; Research; Resectable; Resected; Risk; Sampling; Scanning; Second Primary Cancers; Specimen; Staging; Systemic Therapy; Testing; Therapeutic; Therapeutic Agents; Thermodynamics; Time; Tissues; Treatment Efficacy; Tumor Burden; Universities; X-Ray Computed Tomography; burden of illness; clinical care; cost; disease diagnosis; effective therapy; high risk; imaging modality; improved; killings; longitudinal analysis; melanoma; novel; novel diagnostics; novel strategies; public health relevance; repository; response; standard of care; tool; tumor

DESCRIPTION (provided by applicant): Stage IV melanoma kills approximately 40,000 individuals per year globally. Early detection of new metastases is essential since up to three metastastic tumors can be resected for cure and patients with limited disease burden have improved clinical outcomes to immunotherapeutic agents such as ipilimumab (anti- CTLA4). As a result, full-body FDG-PET and CT imaging assessments are routinely conducted every three months for surveillance and every two months for response assessment. However, the utility of these scans is limited by both cost and the contribution of cumulative radiation exposure to secondary malignancies. The development of new non-invasive approaches for melanoma detection and frequent monitoring thus is expected to result in a marked reduction in melanoma-related deaths. The overarching goal of our research is the development of differential scanning calorimetry (DSC) analysis of blood plasma as a new, non- invasive diagnostic to enable more frequent monitoring and facilitate early detection of recurrences and early assessment of therapeutic response. Importantly, the University of Louisville's Melanoma Multi- Disciplinary Clinic and Tissue Repository has a large and growing collection of detailed de-identified clinical information and multiple longitudinal plasma specimens from stage I-IV melanoma patients (>3000 plasma samples and currently 219 resected melanoma metastases) which we propose to access in order to test this novel diagnostic approach. The application of DSC analysis to characterize the blood plasma proteome in our lab has provided an entirely new and complementary bioanalytical approach for the detection and monitoring of disease. DSC monitors heat changes associated with the thermal denaturation of biomolecules yielding a unique profile characteristic of the components, their amounts and interactions. Preliminary data indicate that direct analysis of small volumes of plasma using DSC yields profiles (or thermograms) that are sensitive to differences in the thermodynamic properties of abundant plasma proteins related to health status. DSC thermograms show sensitivity to disease pathology and therapeutic response and therefore could have considerable utility as a new diagnostic approach. The goals of this proposal are to examine the performance of DSC thermograms alongside standard PET/CT imaging for the diagnosis, the early detection of recurrence and the assessment of therapeutic efficacy in melanoma. If we are successful, the proposed research has the potential to contribute to earlier clinical assessment that can directly impact the care of melanoma patients. We propose three aims. Aim 1 addresses the utility of DSC thermograms for the detection and stage differentiation of melanoma compared with PET/CT. Aim 2 will determine the diagnostic performance of DSC analysis of longitudinal plasma samples to detect disease recurrence following surgical resection in stage III patients. In Aim 3, we will determine the utility of DSC for the assessment of early response to treatment in BRAF+ stage IV melanoma patients.

描述（由申请人提供）：全球每年约有 40,000 人死于 IV 期黑色素瘤。早期发现新的转移瘤至关重要，因为最多可以切除三个​​转移性肿瘤以进行治愈，并且疾病负担有限的患者可以改善伊匹单抗（抗 CTLA4）等免疫治疗药物的临床结果。因此，全身 FDG-PET 和 CT 成像评估通常每三个月进行一次以进行监测，每两个月进行一次以进行反应评估。然而，这些扫描的实用性受到成本和累积辐射暴露对继发性恶性肿瘤的影响的限制。因此，开发新的非侵入性黑色素瘤检测和频繁监测方法预计将显着减少与黑色素瘤相关的死亡。我们研究的总体目标是开发血浆差示扫描量热法（DSC）分析作为一种新的非侵入性诊断方法，以实现更频繁的监测并促进复发的早期检测和治疗反应的早期评估。重要的是，路易斯维尔大学的黑色素瘤多学科诊所和组织存储库拥有大量且不断增长的详细的去识别化临床信息和来自 I-IV 期黑色素瘤患者的多个纵向血浆样本（> 3000 个血浆样本和目前 219 个切除的黑色素瘤转移灶） ）我们建议访问它以测试这种新颖的诊断方法。我们实验室应用 DSC 分析来表征血浆蛋白质组，为疾病的检测和监测提供了一种全新的、补充性的生物分析方法。 DSC 监测与生物分子热变性相关的热变化，产生组分、其数量和相互作用的独特轮廓特征。初步数据表明，使用 DSC 直接分析少量血浆可生成对与健康状况相关的丰富血浆蛋白的热力学特性差异敏感的曲线（或热分析图）。 DSC 热分析图显示出对疾病病理学和治疗反应的敏感性，因此作为一种新的诊断方法具有相当大的实用性。该提案的目标是检查 DSC 热分析图与标准 PET/CT 成像的性能，以用于诊断、早期检测复发和评估黑色素瘤的治疗效果。如果我们成功，拟议的研究有可能有助于早期临床评估，从而直接影响黑色素瘤患者的护理。我们提出三个目标。目标 1 阐述了 DSC 热分析图与 PET/CT 相比在黑色素瘤检测和分期方面的实用性。目标 2 将确定纵向血浆样本 DSC 分析的诊断性能，以检测 III 期患者手术切除后的疾病复发。在目标 3 中，我们将确定 DSC 在评估 BRAF+ IV 期黑色素瘤患者早期治疗反应中的效用。