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

摘要：在手术切除实体癌时，组织诊断对于切缘评估和 最佳切除。肿瘤的完全切除几乎与所有类型的预后改善有关。 实体恶性肿瘤的症状。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，可以是主观的，要求现场专业的病理专业知识，是劳动-和 耗时，并使患者面临更多的麻醉和手术部位感染的风险。我们队有 报道了一种高度创新的手持和生物兼容的质谱仪的开发， “MasSpec Pen”，用于体外和体内组织的快速和无损诊断(Zhang等人，《科学》 转化医学，2017，9，Eaan 3968)。MasSpec钢笔提供了独特的变革性能力 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 纸巾和几秒钟内。我们相信MasSpec钢笔比现有的钢笔有很大的改进 技术，代表着一种如此创新的进步，将成为 术中应用于癌症诊断和切缘评估。与外科医生和病理学家合作，位于 贝勒医学院，我们建议在此背景下进一步开发和验证MasSpec Pen 它在手术切缘评估中的预期用途。这项建议的目标包括： 目的1.优化MasSpec笔用于乳腺癌和胰腺癌的检测。MasSpec钢笔提供 用于癌症诊断的近乎实时的分子检测能力以及 具有临床应用的吸引力。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下的检测能力 (目标1a)。将对业绩衡量标准(例如敏感性和再现性)进行系统评估。统计 分类器将根据肿瘤的异质性、精细化和性能方面进行扩展 (敏感度、特异度和准确度)使用独立样本集进一步验证(目标1b)。 目的2.验证MasSpec Pen在术中癌症诊断和手术切缘评估中的价值。 MasSpec钢笔允许体内癌症诊断和手术切缘评估的证明 具有深刻的临床意义。癌症检测能力的技术验证和最终调整 在乳腺癌(Aim 2a)和胰腺癌(Aim 2b)手术中将采用体内使用的技术 贝勒医学院。预测性诊断和手术切缘状况将与临床结果进行比较。 对于相同的患者，使用标准的临床方法来评估其临床应用的有效性。

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.