Translating buccal nanocytology for lung cancer screening into clinical practice

将口腔纳米细胞学肺癌筛查转化为临床实践

• 批准号: 10376883
• 负责人: Vadim Backman
• 金额: $ 67.11万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10376883
• 关键词: Address; Age; American; Architecture; Area; Biological Markers; Biophotonics; Blinded; Boston; Bronchoscopy; Cancer Etiology; Cancer Patient; Cells; Cessation of life; Cheek structure; Chromatin; Chromatin Structure; Clinical; Clinical Data; Clinical Research; Clinical Trials; Consultations; Data; Death Rate; Development; Diagnosis; Diagnostic; Disease; Early Diagnosis; Electron Microscopy; Ensure; Esophagus; Excision; Gender; Genetic; Goals; Grant; Heterogeneity; Individual; Laboratories; Lead; Lesion; Life; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Medical Device; Medical center; Microscopy; Molecular; Mucous Membrane; Nuclear; Operative Surgical Procedures; Optics; Oral mucous membrane structure; Patients; Population; Prevalence; Procedures; Protocols documentation; ROC Curve; Risk; Sampling; Savings; Sensitivity and Specificity; Smoke; Smoker; Smoking History; Specificity; Swab; Techniques; Technology; Testing; Time; Translating; Validation; X-Ray Computed Tomography; base; cancer subtypes; candidate marker; carcinogenesis; case control; clinical practice; computed tomography screening; cost; cost effective; demographics; diagnostic accuracy; diagnostic technologies; disease diagnosis; former smoker; improved; industry partner; instrumentation; interest; low dose computed tomography; lung cancer screening; lung carcinogenesis; minimally invasive; nanoarchitecture; nanocytology; nanoscale; novel; patient stratification; patient subsets; preservation; prevent; primary care setting; risk stratification; screening; technology development; tool; tumor

Project Summary The overarching goal of the Academic Industrial Partnership grant is to develop a population risk-stratification tool that will allow efficacious and cost-effective lung cancer screening. Lung cancer represents an ideal malignancy for screening because of its prevalence, identifiable risk groups (current/former smokers) and ability to surgically cure the disease if diagnosed early. However, there are no robust screening techniques with options such as low-dose CT (LDCT) scans fraught with cost and harm from large numbers of false positives. In order to make lung cancer screening viable, it is imperative to develop a test to pre-screen for LDCT by identifying the subset of patients who are likely to harbor lung cancers and would benefit from LDCT. The test must be sensitive to early disease (e.g. Stage I), low-cost, and able to be carried out in a primary care setting. The goal of this project is to develop such a test. One attractive approach is to exploit field carcinogenesis, the concept that the same genetic/environmental milieu that results in a lesion in one area of the lung will impact upon the entire aero digestive mucosa. The buccal (cheek) mucosa is a “molecular mirror” of lung carcinogenesis, although current techniques are inadequate to translate this phenomenon into a minimally intrusive screening test. The preliminary data show that the alteration of nanoscale architecture in buccal cells is exquisitely sensitive to field carcinogenesis and hence may serve as a robust biomarker for lung cancer. These nano-architectural changes can be detected in a practical and highly accurate fashion via a novel biophotonics technology, partial wave spectroscopic (PWS) microscopy (“nanocytology”). In this study, PWS technology will be refined and a prediction rule developed based on the PWS-detectable nanoscale alterations that is optimized for early stage, curable lung cancer. The goal of the proposed project is to finalize the remaining technology development aspects to translate nanocytology into a practical, accurate, and low- cost test, bring it to the point where it is viable for population screening, and conduct a pre-definitive clinical validation. The team envision that upon completion of this project, nanocytology will be ready for a definitive clinical trial leading to a launch in clinical practice. This novel paradigm could transform the clinical practice of lung cancer screening and thereby mitigate the large toll of this malignancy in Americans.

项目摘要 学术工业伙伴关系赠款的总体目标是开发人口风险分层 将允许有效且具有成本效益的肺癌筛查的工具。肺癌代表一个理想 由于其普遍性，可识别的风险群体（当前/前吸烟者）和 如果早期诊断出手术治愈该疾病的能力。但是，没有强大的筛选技术 诸如低剂量CT（LDCT）扫描诸如大量虚假的成本和伤害的选择 积极的。为了使肺癌筛查可行，必须制定测试以预屏幕 LDCT通过确定可能携带肺癌并将从LDCT中受益的患者的子集。 该测试必须对早期疾病（例如I期），低成本敏感，并且可以在初级保健中进行 环境。该项目的目的是开发这样的测试。一种有吸引力的方法是利用字段 致癌作用，这一概念是，相同的遗传/环境环境导致在一个地区的一个区域导致病变 肺部将影响整个空气消化粘膜。颊（脸颊）粘膜是“分子镜” 肺癌发生的，尽管当前技术不足以将这种现象转化为 最小侵入性筛查测试。初步数据表明，纳米级体系结构的改变 颊细胞对场癌变完全敏感，因此可以用作肺的强大生物标志物 癌症。这些纳米构造变化可以通过一种实用且高度准确的方式通过 新型生物素技术，部分波光谱（PWS）显微镜（“纳米细胞学”）。在这项研究中， PWS技术将进行完善，并根据PWS可检测的纳米级制定预测规则 针对早期可治愈的肺癌进行了优化的改变。拟议项目的目标是最终确定 其余的技术开发方面将纳米细胞学转化为实用，准确且低 - 成本测试，将其用于人口筛查可行的地步，并进行预定义的临床 验证。团队设想，该项目完成后，纳米细胞学将为确定性做好准备 临床试验导致临床实践的发射。这个新颖的范式可以改变 肺癌筛查，从而减轻美国人这种恶性肿瘤的巨大损失。