A Molecular Diagnostic Assay for Accurately Differentiating Melanoma from Benign Lesions

准确区分黑色素瘤和良性病变的分子诊断方法

• 批准号: 9905050
• 负责人: DAVID L HACHEY
• 金额: $ 99.87万
• 依托单位: FRONTIER DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9905050
• 关键词: Amendment; Antigens; Area; Benign; Biological Assay; Biopsy; Caliber; Cells; Classification; Client; Clinical; Computer software; Custom; Data; Data Analyses; Data Set; Detection; Development; Diagnosis; Diagnostic; Diagnostic Services; Digestion; Early Diagnosis; Ensure; Evaluation; Formalin; Goals; Gold; Image; Incentives; Informatics; Laboratories; Legal patent; Lesion; Malignant - descriptor; Mass Spectrum Analysis; Measurement; Measures; Melanocytic Neoplasm; Metadata; Methodology; Microscopic; Microtomy; Molecular; Monitor; Nevus; Outcome; Paraffin Embedding; Pathologist; Pathology Report; Patient Care; Patients; Performance; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Physical shape; Physicians; Preparation; Procedures; Proteins; Protocols documentation; Quality Control; Reagent; Reporting; Reproducibility; Research; Retrieval; Sampling; Secure; Security; Sensitivity and Specificity; Side; Skin; Skin Cancer; Small Business Innovation Research Grant; Software Tools; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Standardization; Statistical Data Interpretation; Technology; Testing; Time; Tissues; Training; Treatment Cost; United States; Validation; accurate diagnosis; analytical method; base; clinical diagnostics; cloud software; cohort; cost; cost effective; data acquisition; diagnosis standard; diagnostic assay; disease classification; follow-up; frontier; histopathological examination; instrumentation; interest; machine learning algorithm; mass spectrometer; meetings; melanoma; molecular diagnostics; molecular imaging; mortality risk; off-patent; operation; prototype; quality assurance; skin lesion; tissue preparation; web interface

Abstract. Melanoma is the third most common form of skin cancer with estimated 87,110 new cases diagnosed in the United States in the year 2017. Current routine diagnostic approaches utilize microscopic evaluation of thinly sectioned patient biopsies, but in certain cases diagnosis can be contentious even among experts. The overall goal of this multi-phase SBIR project is to develop, validate, and commercialize MelanoMap™, Frontier Diagnostics' patented assay for the diagnosis of melanoma using a matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) platform—and to have this assay available to pathologists in the U.S. as a laboratory developed test. MALDI IMS is a state-of-the-art technology that generates molecular images of tens to thousands of biomolecules from tissue sections in a single analysis. The assay uses formalin-fixed paraffin embedded (FFPE) biopsies used in routine histopathological diagnosis. The proposed assay has pathologists select regions of skin biopsies for analysis via a remote web interface. The acquired IMS data from those regions unambiguously identifies malignant melanoma or benign nevus. Phase I of this proposal will demonstrate the feasibility of this technology platform to achieve cost-effective diagnosis of melanoma from patient skin biopsies at sample volumes acceptable for a clinical laboratory. Specific Aim 1 focuses on the development of a scalable and robust analytical protocol in both sample preparation and informatics to accurately diagnose melanoma with MALDI IMS. In specific aim 2, we will test the methodology developed in Specific Aim 1 on a cohort of melanocytic lesions with known clinical outcome and subsequently validate the classification accuracy of the proposed test In Phase II, the protocols developed in Phase I will be integrated into a diagnostic service workflow. This phase will focus on quality control measures, client facing cloud software, clinical diagnostic reporting, and completing the analysis of a 500-patient sample set for final assay validation. Specific Aim 3 of this proposal (initial aim of Phase II) will establish and implement test tissues into standard workflows that will provide performance metrics for standard operation of a test meeting Clinical Laboratory Improvement Amendments (CLIA) standards. Protocols will be developed to monitor reagents, the reproducibility of sample preparation, and mass spectrometer performance on daily basis. Specific Aim 4 will expand software capabilities to include a secure web interface for clients ordering the test and the laboratory performing the test. The software will meet regulatory compliance, perform statistical analysis, and generate and communicate reports of the MALDI IMS analysis. Specific Aim 5 proposes to expand the sample set used in the initial assay from Specific Aim 2 to include a set of 300 patient samples from our clinical collaborators with 5 or more years follow-up data. The test will be independently validated by an additional 200 patient samples with definitive diagnoses.

抽象的。 黑色素瘤是第三种最常见的皮肤癌，估计有87,110例新诊断病例 2017年的美国。目前的常规诊断方法利用薄层的微观评估 切片的患者活组织检查，但在某些情况下，即使在专家之间，诊断也可能存在争议。整体而言 这个分多阶段进行的SBIR项目的目标是开发、验证和商业化MelanoMap™，Frontier 诊断公司使用基质辅助激光解吸/电离诊断黑色素瘤的专利分析 成像质谱学(MALDI IMS)平台-并向美国的病理学家提供这种分析。 作为实验室开发的测试。MALDI IMS是一种最先进的技术，可以生成 在一次分析中，可以从组织切片中提取数万到数千个生物分子。化验使用固定的福尔马林 石蜡包埋(FFPE)活检用于常规组织病理学诊断。建议的化验方法已经 病理学家通过远程网络接口选择皮肤活检的区域进行分析。获取的IMS数据 从这些区域明确识别恶性黑色素瘤或良性痣。 该方案的第一阶段将论证该技术平台实现成本效益的可行性 临床实验室可接受的样本数量的患者皮肤活检的黑色素瘤诊断。 具体目标1侧重于在两个样本中开发可扩展和健壮的分析方案 MALDI IMS准确诊断黑色素瘤的准备和信息学。在具体目标2中，我们将测试 针对一组已知临床结果的黑素细胞病变，在特定目标1中开发了方法学 并随后验证了所提出的测试的分类准确性 在第二阶段，第一阶段制定的协议将被整合到诊断服务工作流程中。这 阶段将侧重于质量控制措施、面向客户的云软件、临床诊断报告和 完成对500名患者样本集的分析，以进行最终的化验验证。本提案的具体目标3 (第二阶段的初始目标)将建立测试组织并将其实施到标准工作流程中，以提供 符合临床实验室改进修正案的测试的标准操作的性能度量 (CLIA)标准。将制定监测试剂、样品制备的重现性、 和质谱计的日常性能。特定目标4将扩展软件功能，以包括 为订购测试的客户和执行测试的实验室提供安全的Web界面。该软件将 遵守法规，执行统计分析，生成并传达MALDI的报告 IMS分析。特定目标5建议将初始化验中使用的样本集从特定目标2扩大到 包括一组来自我们的临床合作者的300个患者样本，这些样本具有5年或更长时间的随访数据。这个 测试将通过另外200个确诊患者样本进行独立验证。