Clinical validation of the HD-CTC fluid biopsy in early detection of lung cancer.

描述（由申请人提供）：目前，非小细胞肺癌（NSCLC）的临床诊断依赖于多种成像方式，然后通过侵入性手术进行组织确认。这个过程有些不精确，因为手术后患者的病理诊断可能与术前评估不一致，并可能导致患者预后不良，因为准确分期早期癌症对良好预后至关重要。我们假设，在接受肺癌评估的患者对照临床队列中严格验证最近开发的高清晰度循环肿瘤细胞（HD- CTC）液体活检，将提高非小细胞肺癌组织学的早期肺恶性结节的检测准确性和预后。我们将利用美国国立卫生研究院支持的概念验证数据，该数据已证明HD-CTC液体活检能够在诊断时检测大多数患者的疾病来源细胞。这些数据促使我们在“诊断前一天”研究该检测的性能，期望在一项更现实的、前瞻性设计的临床研究中获得类似的结果，该研究由非恶性肺结节患者组成的匹配对照。我们的目的是在一组接受肺癌评估的患者中准确地建立HD-CTC液体活检的测试特征，并确定那些有可检测到HD-CTC的恶性结节患者，以确定液体活检是否可以增加1)确定治疗前的临床分期和2)确定诊断和治疗后的预后。我们将通过开发单细胞分子分析来提供明确的特征，从而显著增强测试。将无创、可靠和准确的循环生物标志物与当前的护理标准相结合，不仅可以开发更准确、成本效益高的临床预测模型，而且可以通过早期非小细胞肺癌的临床、体内模型增强我们对肿瘤生物学和转移的理解。

DESCRIPTION (provided by applicant): Currently, the clinical diagnosis of non-small cell lung cancer (NSCLC) relies on a number of imaging modalities followed by a tissue confirmation with an invasive procedure. This process is somewhat imprecise because a patient's pathologic diagnosis after surgery may be discordant from pre-operative assessment and may contribute to poor patient prognosis since accurately staging early cancers is essential to good outcome. We hypothesize that rigorously validating the recently developed High Definition Circulating Tumor Cell (HD- CTC) Fluid Biopsy in a controlled clinical cohort of patients undergoing evaluation for lung cancer will improve the accuracy of detection and prognosis in early-stage, malignant nodules of the lung with non-small cell lung cancer histology. We will capitalize on NIH-supported proof of concept data, which has demonstrated that the HD-CTC Fluid Biopsy is capable of detecting disease derived cells in the majority of patients at the time of diagnosis. These data now motivate us to investigate the performance of the assay "the day before diagnosis" with the expectation of achieving similar results in a more realistic, prospectively designed, clinical study with matched controls consisting of patients who have non-malignant lung nodules. Our aim is to accurately establish the test characteristics of the HD-CTC fluid biopsy in a group of patients undergoing evaluation for lung cancer and to identify those patients with malignant nodules that have detectable HD-CTCs to determine whether the fluid biopsy can augment 1) clinical staging prior to definitive treatment and 2) prognosis after definitive diagnosis and treatment. We will significantly enhance the test by developing single cell molecular analysis to provide definitive characterization. Integrating non-invasive, reliable and accurate circulating biomarkers with the current standard of care will not only allow for the development of more accurate clinical prediction models that are cost-effective, but may also augment our understanding of tumor biology and metastasis using a clinical, in vivo model of early non-small cell lung cancer.