Validation and Translation of MasSpec Pen Technology for Intraoperative Evaluation of Non-small Cell Lung Cancer

摘要 非小细胞肺癌(NSCLC)是美国癌症相关死亡的主要原因 手术仍然是一个关键的治疗选择。非小细胞肺癌的合适切除范围高度依赖于 关于术中决策。具体地说，NSCLC的诊断通常是在术中确定的。 通过有限切除可疑的肺结节，术中诊断是必要的 在同一过程中进行更大的、针对癌症的切除。此外，术中评估 在非小细胞肺癌手术中，需要切除范围的百分比，以确保在离开 手术室(OR)。因此，在手术中准确诊断非小细胞肺癌和确定手术切缘的能力 在非小细胞肺癌患者的护理中是至关重要的。然而，目前用于术中评估的技术 NSCLC诊断和切缘的关键是冰冻切片分析，这是一项具有百年历史的劳动密集型和 容易出错的。冰冻切片分析也延长了手术时间，使患者面临更高的风险 手术并发症。新技术可以为外科医生提供快速而准确的 在手术室中诊断非小细胞肺癌和高精度评估手术切缘是迫切需要改进的 病人的外科护理和结果。我们已经报道了一项创新技术的发展， MasSpec Pen(MSPen)，用于癌症组织的快速和无损诊断。MSPen部署了单个 从组织中轻轻提取分子的水滴，然后用质谱仪(MS)进行分析 和统计分类器，在几秒钟内提供诊断。我们已经证明，MSPEN可以准确地 利用银行组织诊断非小细胞肺癌的准确率为97%。我们还展示了MSPen系统可以 翻译成OR供外科医生用于快速体内和体外组织分析。通过协作 贝勒医学院的学术科学家和外科医生与位于 MSPen Technologies Inc.，我们现在建议改进和验证MSPen以用于术中诊断和 非小细胞肺癌手术切缘评估。我们的目标是优化和转换新的MSPen技术 NSCLC检测，测试其功能，并在OR设置中验证其性能，从而提供潜在的 改进了向外科医生-最终用户-提供术中肺组织分析的平台。我们的具体目标是：目标 1.优化MSPen技术在非小细胞肺癌手术中的应用我们将开发下一代 用于开放式和机器人非小细胞肺癌手术的MSPen平台；目的2.验证MSPen用于非小细胞肺癌诊断。 我们将进行一项前瞻性的观察性研究，允许胸外科医生验证这项技术 非小细胞肺癌在手术室的诊断；目的3.验证MSPEN对术中非小细胞肺癌切缘的评估。 我们将验证MSPen技术在体内和体外手术切缘评估中的作用，包括 具有代表性的组织边缘，目前在临床护理中被忽视。我们的提议有可能 在提高肺癌患者的外科护理标准方面为外科医生提供变革性的好处。

SUMMARY Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States for which surgery remains a critical treatment option. The appropriate extent of resection for NSCLC is highly dependent on intra-operative decision-making. Specifically, the diagnosis of NSCLC is often determined intra-operatively by a limited resection of a suspicious pulmonary nodule, and intraoperative diagnosis is required before proceeding to a larger, cancer-specific resection during the same procedure. Further, intraoperative evaluation of resection margins is required in NSCLC surgeries to assure complete cancer removal before leaving the operating room (OR). Thus, the ability to accurately diagnose NSCLC and determine surgical margins in the OR is critical in the care for patients with NSCLC. However, the current technology used for intraoperative evaluation of NSCLC diagnosis and margins is frozen section analysis, a century-old technique that is labor-intensive and prone to error. Frozen section analysis also extends operative time, subjecting patients to increased risks of surgical complications. New technologies that can provide surgeons with the ability to rapidly and accurately diagnose NSCLC in the OR and evaluate surgical margins with high accuracy are critically needed to improve surgical care and outcomes for patients. We have reported the development of an innovative technology, the MasSpec Pen (MSPen), for rapid and non-destructive diagnosis of cancer tissues. The MSPen deploys a single droplet of water to gently extract molecules from tissues, which are then analyzed by mass spectrometry (MS) and statistical classifiers to provide diagnosis in seconds. We have demonstrated that the MSPen can accurately diagnose NSCLC using banked tissues with 97% accuracy. We have also shown that the MSPen system can be translated to the OR for use by surgeons for rapid in vivo and ex vivo tissue analysis. Through a collaborative partnership between academic scientists and surgeons at Baylor College of Medicine and the R&D team at MSPen Technologies Inc., we now propose to refine and validate the MSPen for intraoperative diagnosis and surgical margin evaluation in NSCLC. Our objective is to optimize and translate new MSPen technology for NSCLC detection, test its functionality, and validate its performance in the OR setting, thus delivering a potentially improved platform for intraoperative lung tissue analysis to surgeons - the end users. Our specific aims are: Aim 1. Optimize the MSPen Technology for intraoperative use in NSCLC operations. We will develop a next-gen MSPen platform for use in open and robotic NSCLC surgeries; Aim 2. Validate the MSPen for NSCLC diagnosis. We will conduct a prospective observational study allowing thoracic surgeons to validate the technology for NSCLC diagnosis in the OR; Aim 3. Validate the MSPen for intraoperative surgical margin evaluation in NSCLC. We will validate the MSPen technology for surgical margin evaluation in vivo and ex vivo, including the most representative tissue margins that are currently disregarded in clinical care. Our propose has the potential to offer transformative benefits to surgeons in advancing the surgical standard of care for patients with lung cancer.