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模式，然后通过侵入性程序进行组织确认。这一过程有些不精确，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结局至关重要。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）液体活检将提高早期非小细胞肺癌组织学恶性肺结节的检测和预后准确性。我们将利用NIH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。这些数据现在促使我们研究检测“诊断前一天”的性能，期望在一项更现实、前瞻性设计的临床研究中获得相似的结果，该研究采用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建立HD-CTC液体活检的测试特征，并识别具有可检测到HD-CTC的恶性结节的患者，以确定液体活检是否可以增加1）确定性治疗前的临床分期和2）确定性诊断和治疗后的预后。我们将通过开发单细胞分子分析来显著增强该检测，以提供明确的表征。将非侵入性，可靠和准确的循环生物标志物与当前的护理标准相结合，不仅可以开发更具成本效益的更准确的临床预测模型，而且还可以使用早期非小细胞肺癌的临床体内模型来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.