Advanced Development of the MasSpec Pen for Cancer Diagnosis and Surgical Margin Evaluation

摘要：在实体癌手术切除过程中，组织诊断对于边缘评估至关重要， 最佳切除肿瘤的完全切除与几乎所有类型的预后改善有关 恶性实体肿瘤然而，术中评估肿瘤范围的标准临床方法 切除，冰冻切片分析，可能是主观的，需要现场专业病理学专业知识，是劳动力， 耗时，并使患者面临增加的麻醉和手术部位感染的风险。我们的团队已被 报道了一种高度创新的手持式生物相容性质谱仪的开发， “MasSpec Pen”，用于离体和体内组织的快速和非破坏性诊断（Zhang等人，Science Translational Medicine，2017，9，eaan3968）。MasSpec笔提供了独特的变革能力， 直接从组织样本中评估疾病状态的分子预测因子，而不会对 几秒钟内就能完成我们相信MasSpec笔提供了比现有的实质性改进 技术，并代表了一个进步，这是如此创新，将成为一个颠覆性的飞跃， 术中用于癌症诊断和边缘评估。与外科医生和病理学家合作， 在贝勒医学院，我们建议在此背景下进一步开发和验证MasSpec Pen 其在手术切缘评价中的预期术中用途。这项建议的目标包括： 目标1.优化用于乳腺癌和胰腺癌检测的MasSpec笔。MasSpec Pen提供 用于癌症诊断的近真实的分子检测能力沿着 对临床应用有吸引力。将进行技术改进，以提高术中使用的性能， 并进一步确定和开发在各种肿瘤细胞浓度和组织深度的检测能力 (Aim 1a）。将系统评价性能指标（例如灵敏度和重现性）。统计 分类器将在考虑肿瘤异质性、细化及其性能的情况下进行扩展 （灵敏度，特异性和准确性）进一步验证使用独立的样本集（目标1b）。 目标二。使用MasSpec Pen进行术中癌症诊断和手术切缘评估。 MasSpec Pen可用于体内癌症诊断和手术切缘评估的证明， 具有深远的临床意义。癌症检测能力的技术验证和 在乳腺癌（Aim 2a）和胰腺癌（Aim 2b）手术期间， 贝勒医学院。预测性诊断和手术切缘状态将与临床结果进行比较 使用标准临床方法对相同患者进行评估，以评价其临床用途。

ABSTRACT: Tissue diagnosis is critical during surgical removal of solid cancers for margin evaluation and optimal excision. Complete resection of the tumor is associated with an improved prognosis for almost all types of solid malignancies. However, the standard clinical approach for intraoperative assessment of extent of tumor excision, frozen section analysis, can be subjective, require on site specialty pathology expertise, is labor- and time- consuming, and exposes patients to increased risks of anesthesia and surgical site infection. Our team has reported the development of a highly innovative handheld and biocompatible mass spectrometry device, the “MasSpec Pen”, for rapid and non-destructive diagnosis of ex vivo and in vivo tissues (Zhang et al, Science Translational Medicine, 2017, 9, eaan3968). The MasSpec Pen provides the unique and transformative ability to assess molecular predictors of disease state directly from tissue samples without causing harm or damage to the tissues and in seconds. We believe the MasSpec Pen offers substantial improvements over existing technologies and represents an advance that is so innovative that will become a disruptive leap forward for intraoperative use in cancer diagnosis and margin evaluation. In collaboration with surgeons and pathologists at the Baylor College of Medicine, we propose to further develop and validate the MasSpec Pen within the context of its intended intraoperative use in surgical margin evaluation. The objectives of this proposal include: Aim 1. Optimize the MasSpec Pen for breast and pancreatic cancer detection. The MasSpec Pen provides near real time molecular detection capabilities for cancer diagnosis along with operational features that are attractive for clinical use. Technical refinements will be pursued to improve performance for intraoperative use, and to further determine and develop detection capabilities at various tumor cell concentration and tissue depths (Aim 1a). Performance measures (e.g. sensitivity and reproducibility) will be systematically evaluated. Statistical classifiers will be expanded considering aspects of tumor heterogeneity, refined, and their performance (sensitivity, specificity and accuracy) further validated using independent sample sets (Aim 1b). Aim 2. Validate the MasSpec Pen for intraoperative cancer diagnosis and surgical margin evaluation. The demonstration that the MasSpec Pen allows in vivo cancer diagnosis and surgical margin evaluation has profound clinical implications. Technical validation of cancer detection capabilities and final tuning of the technology for in vivo use will be pursued during breast (Aim 2a) and pancreatic (Aim 2b) cancer surgeries at Baylor College of Medicine. Predictive diagnosis and surgical margin status will be compared to clinical results for the same patients using standard clinical approaches to evaluate its clinical usefulness for clinical use.