Validation of Light Scattering Spectroscopy for Intra-operative Margin Guidance during Oral Cancer Resection

项目总结 2019年，美国将新增近3.7万例口腔癌确诊病例，其中近一半将 五年后就会死去。这种疾病的致命性部分归因于大多数病例都是晚期。 确诊时为分期。手术切除仍然是主要的治疗方式，但局部和区域性的 手术切除后复发仍然是最常见的问题；晚期口腔癌患者 癌症在头3年的复发率高达60%-80%。不适当的肿瘤切除是一种 这种局部复发的常见原因。这可以用目前使用的不精确的方法来解释。 用于评估手术切缘和远处部位是否存在“卫星”恶性细胞(“跳跃性病变”) 原发癌变是“野生性癌变”现象的结果。目前， 外科医生通常依靠自己的判断或在白光下的视觉来确定手术 利润率。阴性边缘的确认基于随机选择的术中冰冻样本 切片分析，留下了大部分手术切缘没有检查。此外，冰冻切片分析可以 耗时长、费用高、假阴性率高。一种更有效和更精确的方法是 需要的。 光学技术可以用来区分原位的良性和恶性组织病变。弹力 散射谱(ESS)是一种点光谱测量技术，它可以探测到大量的 良恶性组织的敏感性亚细胞形态差异。这些差异 包括核大小、染色质粒度或密度、细胞器大小和密度以及其他亚细胞 功能。ESS提供了对组织形态进行实时、客观和快速评估的优势； 光学光谱学相当于组织病理学读数。过去的研究证明了ESS的能力 在口腔癌手术中，在活体内准确区分正常和异常的口腔粘膜 切除手术。目前这项研究的第一个目标是通过进一步培训ESS算法来扩展这项工作 在一个更大的预期数据集上，以便该技术可以证明临床上可以接受的准确性 标准。本研究的第二个目的是设计和测试能够区分的新型仪器 在深缘(肿瘤和肿瘤床)两侧的正常和异常组织之间。一 120名患者将从波士顿医疗中心和波士顿退伍军人管理局医院招募。 ESS措施将与异型增生分级和炎症的组织病理学评估共同登记 打字。 这项技术的进一步改进将导致ESS仪器的验证，能够促进 术中保证金指导。我们的假设是，ESS算法的进一步完善将极大地 提高外科医生确定哪些组织应该进行冰冻切片的准确性，这将有助于 与传统方法相比，外科医生在口腔癌切除术中评估合适的手术范围 独自一人。这反过来又将显著降低局部复发率及其相关的发病率和死亡率。

PROJECT SUMMARY Nearly 37,000 new cases of oral cancer will be diagnosed in the United States in 2019, and nearly half will die in 5 years. The lethality of this disease is partially attributed to the fact that most cases are in advanced stages when diagnosed. Surgical resection remains a primary modality for treatment but local and regional recurrence remains the most common problem after surgical resection; patients with advanced stage oral cancer experience recurrence rates as high as 60-80% in the first 3 years. Inadequate tumor excision is a common cause for such local recurrence. This could be explained by the imprecise methods currently used for assessing surgical margins and by the presence of “satellite” malignant cells (“skip lesions”) in sites away from the primary cancerous lesion which occur as a result of the “field cancerization” phenomenon. Currently, surgeons often depend on their own judgment or visualization under white light to determine surgical margins. Confirmation of negative margins is based on randomly selected samples for intraoperative frozen section analysis, leaving much of the surgical margin unexamined. Moreover, frozen section analysis can be time consuming, expensive, and have a high false negative rate. A more efficient and precise approach is needed. Optical technologies can be used to distinguish in situ benign from malignant tissue lesions. Elastic Scattering Spectroscopy (ESS) is a point spectroscopic measuring technique that can detect with great sensitivity sub-cellular morphologic differences between benign and malignant tissue. These differences include nuclear size, chromatin granularity or density, organelle sizes and densities, and other sub-cellular features. ESS provides the advantage of real-time, objective and quick assessment of tissue morphology; the optical-spectroscopy equivalent of histopathological readings. Past research demonstrated the ability of ESS to differentiate with good precision normal versus abnormal oral mucosa, in-vivo, during oral cancer surgical resection. The first aim of this current study is to expand on that work by further training the ESS algorithms on a much larger prospective dataset so that the technology can demonstrate clinically acceptable accuracy standards. The second aim of this study is to design and test novel instrumentation capable of differentiating between normal and abnormal tissue on both aspects of the deep margin (tumor and tumor bed). One hundred and twenty patients will be enrolled from Boston Medical Center and from the Boston VA hospitals. ESS measures will be co-registered with histopathological assessments of dysplasia grade and inflammation type. Further refinement of this technology will result in the validation of ESS instrumentation capable of facilitating intraoperative margin guidance. Our hypothesis is that further refinement of our ESS algorithms will greatly improve surgeons' accuracy in determining which tissue should go to frozen section, and will help the surgeon assess proper surgical margins during excision of oral cancers compared to traditional approaches alone. This, in turn, will significantly reduce local recurrence rates and its associated morbidity and mortality.