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

项目摘要 2019年美国将确诊近3.7万例口腔癌新发病例，近一半将 五年内死亡。这种疾病的致命性部分归因于大多数病例处于晚期 诊断时的阶段。手术切除仍然是治疗的主要方式，但局部和区域 复发仍然是手术切除后最常见的问题;晚期口腔癌患者 癌症在前3年的复发率高达60-80%。肿瘤切除不当是一种 这是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，并通过在远离手术切缘的部位存在“卫星”恶性细胞（“跳跃病变”） 从作为“现场癌变”现象的结果而发生的原发性癌性损伤中去除。目前， 外科医生通常依赖于他们自己的判断或在白色光下的观察来确定外科手术 利润率阴性切缘的确认基于随机选择的术中冷冻样本 切片分析，留下大部分手术切缘未检查。此外，冷冻切片分析可以 耗时、昂贵，并且具有高的假阴性率。一种更有效和精确的方法是 needed. 光学技术可用于区分原位良性与恶性组织病变。弹性 散射光谱（ESS）是一种点光谱测量技术，可以以很大的 良恶性组织之间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它亚细胞 功能. ESS提供了实时、客观和快速评估组织形态的优点; 光学光谱学相当于组织病理学读数。过去的研究表明，ESS 在口腔癌手术期间， 切除术本研究的第一个目的是通过进一步训练ESS算法来扩展这项工作 在更大的前瞻性数据集上，以便该技术可以证明临床上可接受的准确性 标准本研究的第二个目的是设计和测试能够区分 正常和异常组织之间的深边缘（肿瘤和肿瘤床）的两个方面。一 将从波士顿医疗中心和波士顿VA医院招募120名患者。 ESS测量将与异型增生等级和炎症的组织病理学评估共同注册 类型. 这项技术的进一步完善将导致ESS仪器的验证， 术中切缘引导。我们的假设是，进一步完善我们的ESS算法将大大 提高外科医生确定哪些组织应该进行冷冻切片的准确性， 与传统方法相比，外科医生在口腔癌切除术中评估适当手术边缘 一个人反过来，这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.