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; 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）：IV期黑色素瘤每年在全球大约杀死40,000人。早期发现新转移是必不可少的，因为可以切除多达三个转移性肿瘤来治愈，并且疾病负担有限的患者对免疫治疗剂（例如ipilimumab）（抗CTLA4）的临床结局有改善。结果，全身FDG-PET和CT成像评估通常每三个月进行一次监视，每两个月进行一次响应评估。但是，这些扫描的效用受成本和累积辐射暴露于继发性恶性肿瘤的贡献的限制。因此，新的非侵入性检测方法的发展和频繁监测预计将导致黑色素瘤相关死亡的显着降低。我们研究的总体目标是对血浆的差异扫描量热法（DSC）分析作为一种新的，非侵入性的诊断，以实现更频繁的监测并促进早期发现的复发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仓库拥有越来越多的详细的去识别临床信息，以及来自I级IV期黑色素瘤患者的多个纵向血浆标本（> 3000个血浆样本> 3000个血浆样本和目前219个切除的黑素瘤转移酶），以访问这种新型方法，以访问这种新颖的方法。 DSC分析在我们实验室中表征血浆蛋白质组的应用为检测和监测疾病提供了一种全新的互补生物分析方法。 DSC监视与生物分子的热变性相关的热变化，该变性产生了组件的独特特征，其量和相互作用。初步数据表明，使用DSC对小体积的血浆进行直接分析可产生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概况。 DSC热图显示对疾病病理和治疗反应的敏感性，因此可能具有相当大的效用作为一种新的诊断方法。该提案的目标是检查DSC热图与标准PET/CT成像以及诊断的标准PET/CT成像以及黑色素瘤中治疗功效的评估。如果我们成功，则提出的研究有可能为直接影响黑色素瘤患者护理的较早临床评估做出贡献。我们提出了三个目标。 AIM 1解决了与PET/CT相比，DSC热图在黑色素瘤的检测和分化方面的实用性。 AIM 2将确定纵向血浆样品的DSC分析的诊断性能，以检测III期患者手术切除后疾病复发。在AIM 3中，我们将确定DSC评估BRAF+期IV期黑色素瘤患者对治疗的早期反应的效用。