Radioguided Detection of Lymph Node Metastasis in Non-Small Cell Lung Cancer

描述（由申请人提供）：肺癌是美国男性和女性癌症死亡的最常见原因。淋巴结分期为局部非小细胞肺癌（NSCLC）患者提供了最重要的预后信息。目前评估淋巴结的方法（苏木精-伊红染色）可能会遗漏微转移。我们的第一个目的是建立一个实用的术中伽玛探头检测静脉注射18氟-氟脱氧葡萄糖（FDG）在胸部淋巴结，从而提高淋巴结分期的准确性在非小细胞肺癌。分子标志物将NSCLC患者分为预后良好和预后不良组的潜在能力可以改变个体患者的治疗选择。因此，我们的第二个目标是确定可以预测淋巴结转移（包括微转移）的生物标志物。我们打算通过进行一项涉及100例可切除NSCLC患者的临床试验来实现这些目标。所有患者将接受术前正电子发射断层扫描（PET）。将PET确定的肿瘤分期与静脉注射FDG后使用术中伽马探针确定的分期进行比较。将评估伽马探针引导微转移检测的能力。将常规的淋巴结组织学染色与使用强化病理学技术的淋巴结超分期进行比较。将在原发性肿瘤中进行4种生物标志物-细胞周期蛋白B1、细胞周期蛋白E、存活素和血管内皮生长因子（VEGF）的测定，并将其与淋巴结转移相关。这个研究项目将是一个全面的职业发展计划的一个组成部分，旨在准备我作为一个独立的以病人为导向的调查。这项研究旨在检测肺癌向淋巴结的微观扩散，并从分子水平预测癌症的侵袭性。这些信息将有助于治疗决策。

DESCRIPTION (provided by applicant): Lung cancer is the most frequent cause of cancer death in both men and women in the United States. Lymph node staging provides the most important prognostic information in patients with locoregional non-small cell lung cancer (NSCLC). Current methods of evaluating lymph nodes (hematoxylin-eosin staining) can miss micrometastases. Our first aim is to establish the utility of an intra-operative gamma probe to detect intravenously injected 18F-Fluorodeoxygulcose (FDG) in thoracic lymph nodes, thus improving the accuracy of lymph node staging in NSCLC. The potential ability of molecular markers to stratify patients with NSCLC into good and poor prognostic groups can alter therapeutic choices for individual patients. Thus, our second aim is to identify biological markers that may predict lymph node metastases (including micrometastases). We intend to achieve these goals by conducting a clinical trial involving 100 patients with resectable NSCLC. All the patients will have a pre-operative positron emission tomogram (PET). The PET-determined stage of the tumor will be compared with the stage determined by the use of an intra-operative gamma probe after intravenous FDG injection. The ability of the gamma probe to guide the detection of micrometastases will be assessed. Routine histologic staining of nodes will be compared to ultrastaging of the lymph node using intensive pathologic techniques. Assays of 4 biomarkers - cyclin B1, cyclin E, survivin and vascular endothelial growth factor (VEGF) - in the primary tumors will be done and correlated with lymph node metastases. This research project will be an integral part of a comprehensive career development program designed to prepare me as an independent patient-oriented investigator. This study is designed to detect microscopic spread of lung cancer to lymph nodes and to molecularly predict the aggressiveness of the cancer. This information will then facilitate therapeutic decisions.